Nanotechnology: Science, Innovation, and Opportunity

By Lynn E. Foster
...............................................
Publisher: Prentice Hall
Pub Date: December 21, 2005
Print ISBN-10: 0-13-192756-6
Print ISBN-13: 978-0-13-192756-8
Pages: 336

Table of Contents | Index

"A fascinating look at the art and science of nanotechnology. Hold on to your hats, the world is
about to change big time. . . . A comprehensive look at nanotechnology from the perspective of
science, investment, IP, and business development with a healthy dose of vision for good measure.
First-rate authors with an excellent presentation of the material. Buy this book." --David Bishop,
Ph.D., V.P. of Nanotechnology Research, Bell Labs, Lucent Technologies

"An absolute must-read for every technology sector being impacted by nanotechnology. This book
presents the true value of these technologies, delivering a comprehensive prospectus on the science
to commercialization of nanotechnology." --Matthew Laudon, Ph.D., Executive Director, Nano
Science & Technology Institute

"This is an excellent book for anyone trying to get a general grasp on the emerging science and
technology of nanotechnology in particular for business executives, engineers, or entrepreneurs
who are trying to decide what this technology can mean to them." --Charles H. Volk, Ph.D., V.P. &
Chief Technologist, Northrop Grumman, Navigation Systems Division

"Larry Gilbert and Michael Krieger's overview of the university technology transfer process is
excellent and provides a realistic perspective and understanding of the commercialization process
for technologies developed in the academic environment." --John Ritter, Director, Office of
Technology Licensing, Princeton University

"For a broad, readable introduction to nanotechnology with its attendant entrepreneurial, social,
and technological implications, this book is a great start. The most interesting chapter from my
perspective was Smalley's on finding abundant, cheap energy sources. Most informative and
refreshing. If you have an interest as an intelligent layperson in nanotechnology and its basic
motivations and methods, this book will serve as a worthy point of departure in your search." --
Mark S. Petrovic, Ph.D., V.P. of Research and Development, EarthLink

"Get this book if you want to explore any part or the whole field of nanotechnology. I was
interested in the many sources of funding for nanotechnology and why each source was doing it.
The authors have shown an awareness that nanotechnology must be nurtured by dedicated people
to achieve its real potential. I recommend this book because it treats the potential of
nanotechnology in depth and realistically: Riches will come, but much effort is needed in the
meantime." --Bill McLellan, winner of Richard Feynman's Nanotechnology Challenge

Inside the Emerging Multibillion-Dollar Nanotechnology Industry

Suddenly, nanotechnology isn't science fiction or mere theory: It's becoming one of the world's
fastest-growing, highest-impact industries. In Nanotechnology: Science, Innovation, and
Opportunity, the field's leading experts offer an up-to-the-minute briefing on where the industry
stands now, how it will unfold over the coming decade, and how it will impact you.

Edited by a key industry advisor, this book covers the latest in nanotech science, technology, and
applications. You'll meet the key players, and discover nanotech at work in fields ranging from
drug delivery to energy efficiency. Here are the opportunities, the challenges, and the implications:
all you need to know about today's nanotech business--and tomorrow's.

Coverage includes

How the convergence of nanoscale science foreshadows revolutionary societal change

Technical and business obstacles that still challenge the industry

Lessons from the early "gold rush" days of biotech: managing the hype

Nanotech as disruptive innovation: implications for investors and venture capitalists

The evolving roles of entrepreneurs, universities, and the U.S. government

Key application areas: materials, microelectronics, sensors, energy, and beyond

Bio-Nano-Information fusion: the potential to transform medicine

Relevant patent law and intellectual property issues

The ethics of nanotechnology

 Nanotechnology: Science, Innovation, and Opportunity
By Lynn E. Foster
...............................................
Publisher: Prentice Hall
Pub Date: December 21, 2005
Print ISBN-10: 0-13-192756-6
Print ISBN-13: 978-0-13-192756-8
Pages: 336

Table of Contents | Index

Copyright
Foreword
Preface
Acknowledgments
About the Author
Contributors
Gerald Gallwas
Richard Smalley
Peter Coffee
Steve Jurvetson
Daniel V. Leff
R. Douglas Moffat
Geoffrey M. Holdridge
Julie Chen
Larry Gilbert
Michael Krieger
Chinh H. Pham
Charles Berman
Jeff Lawrence
Larry Bock
Jim Duncan
Meyya Meyyappan
Mark Reed
Sheryl Ehrman
Brent Segal
Zhong Lin (ZL) Wang
Fiona Case
David J. Nagel
Sharon Smith
George Thompson
Stephen Goodnick
Axel Scherer
Suzie Hwang Pun
Jianjun (JJ) Cheng
Dan Garcia
Dean Ho
 Chih-Ming Ho
Mihail C. Roco
William Sims Bainbridge
Section One. Development Drivers
Chapter 1. Lessons in Innovation and Commercialization from the Biotechnology Revolution
The Story of Biotechnology
Concept 1: Lessons From the S-Curve
Concept 2: Lessons From Commercial Innovation
The S-Curve Summarized
Commercial Innovation Summarized
The Future of Nanotechnology
References
Chapter 2. Nanotechnology and Our Energy Challenge
Transport and Storage
Energy for Everyone
Chapter 3. Fads and Hype in Technology: The Sargasso Sea of "Some Day Soon"
Knowing Success When We See It
The Nature of Hype
Clouding the Picture
A Virtuous Circle
When Science Gets Down to Business
Far From a Fad
References
Section Two. The Players
Chapter 4. Nanotechnology Commercialization: Transcending Moore's Law with Molecular Electronics and Nanotechnology
Technology Exponentials
Moore's Law
Molecular Electronics
The Commercialization of Nanotechnology
Systems, Software, and Other Abstractions
Time Line
The Ethical Debate: Genes, Memes, and Digital Expression
Conclusion
Chapter 5. Investment in Nanotechnology
Venture Capital Investing
Nanotechnology Venture Capital Investment
Nanotechnology Start-up Companies
Public Markets and Nanotechnology Companies
Chapter 6. The Role of the U.S. Government in Nanoscale Science and Technology
The National Nanotechnology Initiative and the 21st Century Nanotechnology Research and Development Act
Research and Development
Education and Workforce Development
Facilities and Instrumentation
Technology Transfer
Responsible Development
References
Chapter 7. Overview of U.S. Academic Research
National Science Foundation Funding Mechanisms
NNI and NSF Research Focus Areas
Future Directions
 Research Focus Areas of Other NNI Agencies
Summary
References
Chapter 8. Understanding University Technology Transfer for Nanotechnology
Unique Rather than Common Elements Characterize Tech Transfer Deals
Why Does a University Transfer Technology?
How is Technology Transferred?
Final Words
Notes
Chapter 9. Intellectual Property Policy and Impact
Types of IP Protection
Statutory Requirements
Conclusion
Reference
Chapter 10. Entrepreneurs in the Technological Ecosystem
Lions, Tigers, and Bears: What is the Role of an Entrepreneur?
The Power of an Idea: What is a Good Idea?
A Single Person can Change the World: What is an Entrepreneur?
Look Forward, Think Backward: What Does an Entrepreneur Do?
The Good, Bad, and Ugly: What Should an Entrepreneur Expect?
Is It Worth It?
Chapter 11. Major Corporations: Technology, Business, and the Culture of Opportunity
Culture, Models, and Cycles
The Holy Grail
Chapter 12. Nanotechnology in Federal Labs
The Role of Federal Research Laboratories
Transferring Technology
Summary
Section Three. Materials and Industries
Chapter 13. Nanoscale Materials
Overview
Nanoparticles
References
Carbon Nanotubes
References
Nanowires
Soft Nanotechnology
Chapter 14. Nanotechnology-Enabled Sensors: Possibilities, Realities, and Diverse Applications
Possibilities
Realities
Diverse Applications
References
Chapter 15. Microelectronics
Nanomanufacturing Product Strategy
Existing Technologies
Reference
Photonics
Conclusion
Chapter 16. Drug Delivery
Nanotechnology in Drug Delivery
 Future Trends in Drug Delivery
References
Chapter 17. Bio-Nano-Information Fusion
Seeing
Manipulation
Characterization
Integration
Emergent Systems
Conclusions
Acknowledgments
References
Section Four. Convergence and Integration
Chapter 18. Convergence and Integration
Framework for Science and Technology Development
Outlook for Industry
Concluding Remarks
Acknowledgments
References
Chapter 19. Ethical Considerations in the Advance of Nanotechnology
The Nature of Ethics
Ethics of Individual Behavior
Nano-Specific Issues
Converging Technologies
Practical Responses
References
Epilogue
Chapter 20. Infinitesimal Machinery
Revisiting "There's Plenty of Room at the Bottom"
What We Can Do Today
Small MachinesHow to Make Them
Small MachinesHow to Use Them
Electrostatic Actuation
Mobile Microrobots
Making Precise Things from Imprecise Tools
Friction and Sticking
Computing with Atoms
Reversible Gates
The Electron as Calculating Engine
Heat in a Quantum Computer
Acronyms and Abbreviations
Index
Copyright
Many of the designations used by manufacturers and sellers to distinguish their products are claimed
as trademarks. Where those designations appear in this book, and the publisher was aware of a
trademark claim, the designations have been printed with initial capital letters or in all capitals.

The authors and publisher have taken care in the preparation of this book, but make no expressed
or implied warranty of any kind and assume no responsibility for errors or omissions. No liability is
assumed for incidental or consequential damages in connection with or arising out of the use of the
information or programs contained herein.

The publisher offers excellent discounts on this book when ordered in quantity for bulk purchases or
special sales, which may include electronic versions and/or custom covers and content particular to
your business, training goals, marketing focus, and branding interests.

For more information, please contact: For sales outside the U.S., please
contact:
U.S. Corporate and Government Sales International Sales
(800) 382-3419 [email protected]
[email protected]

Visit us on the Web: www.prenhallprofessional.com

Library of Congress Cataloging-in-Publication Data

Foster, Lynn E.
Nanotechnology : science, innovation and opportunity / Lynn E. Foster.
p. cm.
Includes bibliographical references and index.
ISBN 0-13-192756-6 (hard cover : alk. paper)
1. Nanotechnology. 2. Nanotechnology--Social aspects. I. Title.
T174.7.F68 2005
620'.5dc22
2005027597

Copyright © 2006 Pearson Education, Inc.

All rights reserved. Printed in the United States of America. This publication is protected by
copyright, and permission must be obtained from the publisher prior to any prohibited reproduction,
storage in a retrieval system, or transmission in any form or by any means, electronic, mechanical,
photocopying, recording, or likewise. For information regarding permissions, write to:

Pearson Education, Inc.

Rights and Contracts Department
One Lake Street
Upper Saddle River, NJ 07458
Text printed in the United States on recycled paper at Courier in Westford, Massachusetts.

First printing, December 2005

Dedication
Dedicated to Richard Feynman: For having a vision of things smaller than any of us and a spirit
bigger than all of us.

And to my wife Miriam: For enduring the vision of one man.

Foreword
When Congress passed and the President signed the 21st Century Nanotechnology Research and
Development Act, or Public Law 108-153, in December 2003, our goal was to help spur and
coordinate research and technology development in this exciting and promising area, one that has
the potential to transform every aspect of our lives. By manipulating matter at a molecular scale,
nanotechnology may allow us to develop new materials and devices that have unique properties
beyond the realm of current conventional technology. Its potential economic effects are also
profound, as some have estimated that its impact on both existing and new industries may easily
exceed tens of billions of dollars by the end of this decade, and a trillion dollars not too many years
beyond. Applications ranging from novel and highly targeted therapeutic treatments for diseases
including cancer to such timely concerns as increased energy efficiency or tools for providing a
cleaner environment certainly emphasize the potentially transformational nature of nanotechnology.

While many potential applications are some years ahead of us, the increasing frequency with which
articles on nanotechnology are appearing in trade publications, investment publications, and in the
mainstream media tell us that the science is already moving beyond the laboratory. Yet as we move
ahead with the development of this frontier technology, it is important that we also pay attention to
the issues beyond fundamental science and discovery that are equally importantissues such as
technology innovation and technology transfer. And it is not just economic issues that need to be
considered. As with any new technology, we need to pay careful attention to minimizing any
potential impact on the environment as we move ahead. As the chapters in this book indicate, while
much work lies ahead, we are making exciting progress in each of these areas.

Senator Joe Lieberman

Senator George Allen
Washington, D.C., November 2005
Preface
During the past century, human life spans have almost doubled, and travel and communication
happen with an ease and speed that would have been considered science fiction only a few
generations ago. Remarkably, the pace of innovation is actually increasing over that of the past.

Science has now advanced to the point that those on the cutting edge of research work with
individual atoms and molecules. This is the defining characteristic of the new metafield of
nanotechnology, which encompasses a broad range of both academic research and industrial
development. At this small scale, the familiar classical physics guideposts of magnetism and
electricity are no longer dominant; the interactions of individual atoms and molecules take over. At
this levelroughly 100 nanometers (a nanometer being a billionth of a meter, and a human hair being
50,000 nanometers wide) and smallerthe applicable laws of physics shift as Newtonian yields to
quantum.

Nanotechnology holds the promise of advances that exceed those achieved in recent decades in
computers and biotechnology. Its applications will have dramatic infrastructural impacts, such as
building tremendously faster computers, constructing lighter aircraft, finding cancerous tumors still
invisible to the human eye, or generating vast amounts of energy from highly efficient solar cells.
Nanotechnology will manifest in innovations both large and small in diverse industries, but the real
benefit will accumulate in small cascades over decades rather than in a sudden, engulfing wave of
change. It is not the "Next Big Thing" but rather will be any number of "next large things".
Nanotechnology may not yield a result as dramatic as Edison's lightbulb but rather numerous gains
as pervasive as the integrated-circuit-controlled lightbulbs in the traffic lights that are ubiquitous in
modern life.

Although the lightbulb breakthroughs will be few, there will be numerous benefits taken for granted,
such as the advantages that the automated intelligence of traffic grids provide to major cities. This
should not be a surprise, because nanotechnology is not an invention but rather a range of fields of
study and applications, defined by size, that use tools, ideas, and intuitions available to innumerable
scientific disciplines. Thus nanotechnology offers tremendous potential for several key reasons.
Materials and processes at that size have unique properties not seen at larger scale, offer
proportionately greater reactive surface area than their larger counterparts, and can be used in or
with living organisms for medical applications. As a result, familiar materials can have completely
different properties at the nanoscale.

For example, carbon atoms form both coal and diamonds, but with different molecular
arrangements. Scientists now know that carbon molecules at the nanoscale can form cylindrical
tubes, called carbon nanotubes, that are much stronger than steel and conduct electricity, neither of
which is possible with the carbon found in coal or diamonds. Carbon nanotubes may one day provide
key breakthroughs in medicine and electronics. Likewise, nanotechnology can provide breakthroughs
in industrial uses. The electrical current produced in solar cells or batteries reflects the flow of
electrons from one surface to another. Nanotechnology has already enabled the demonstration of a
vastly increased surface area of electrodes that allows electrons to flow much more freely, along
with corresponding improvements in battery performance. Safer, cheaper, and cleaner electricity
and electrical storage would obviously have a dramatic impact on our society.

Another reason nanotechnology holds so much promise is that it enables solutions at the same size
scale as biological organisms, such as the individual cells in our bodies. Engineered materials are
possible, such as ultrasmall particles made in the exact size to perform like a "smart bomb" in
delivering drugs in the blood stream. Other applications might detect cancer when it is only a few
cells in size. Future convergence of nanotechnology and biotechnology may combine biological and
man-made devices in a variety of applications, such as batteries for implanted heart pacemakers
that draw electrical current from the wearer's glucose rather than from surgically implanted
batteries.

Yet another important facet of nanotechnologyone that underpins both its promise and the
challengesis that it embraces and attracts so many different disciplines that researchers and
business leaders are working in, among them, chemistry, biology, materials science, physics, and
computer science. Although each field has tremendously talented people, each also has its own
somewhat unique training and terminology. Almost like the parable of the blind men and the
elephant, each group approaches the molecular level with unique skills, training, and language.
Communication and research between academic disciplines and between researchers and their
business counterparts is critical to the advancement of nanotechnology.

With the diversity of professional cultures in mind, a central goal of this book is to promote
communication and cooperation between researchers and industry by including similarly diverse
articles written by experts but accessible to everyone.

The depth of scientific talent and the substantial resources being devoted to nanotechnology are a
tremendous cause for optimism for both near-term and long-term gains. Ultimately nanotechnology
will yield greater impact than information technology or biotechnology has. However, the tempo of
technology is not set by the velocity of novel discoveries, but rather by the pace of what the market
will embrace and pay for. The medium term in nanotechnology will be difficult and delayed by issues
far beyond scientific research or product prototypingnamely, by the long, difficult process of new
products gaining traction in the marketplace. To reach the stage of a viable product, the innovations
will have to overcome issues such as how they are integrated, how much power they consume, and
how they are controlled. Only then will the marketplace vote with dollars on the technology. For
these reasons, another goal of this book is to highlight these issues so that a broader audience can
address them with its respective understanding and resources.

This book is organized into four matrixed sections. Section One is focused on the history and
development drivers of innovation. The first chapter highlights a historical example from the early
days of the biotechnology industry as a cautionary lesson about a new industry developing with new
tools and tremendous promise. The promise of nanotechnology to solve the world's energy problem
is outlined in Chapter 2, along with the impact the solution would have on solving other problems as
well. Chapter 3 is a discussion of the role played by expectations in the development of an industry.

Section Two focuses on the talents, roles, and motivations of the main players and individuals, along
with the organizational factors that drive technologies forward or limit their impact. Chapter 4
presents the vision of a venture capitalist who takes a long-term view of nanotechnology as the
nexus of disruptive innovation, and Chapter 5 outlines current investment decisions in
nanotechnology. Chapter 6 outlines the U.S. government's role in funding research and establishing
policies for the safe and effective use of nanotechnology. Then Chapter 7 discusses specific areas of
academic research, and Chapter 8 explains how technologies developed there are brought to
commercial use. The role of U.S. patent law in commerce follows in Chapter 9, with a discussion of
its impact on the advance of nanotechnology. Chapter 10 explains why entrepreneurs are the key
drivers of change in a new industry and help it advance by taking tremendous personal risks.
Chapter 11 discusses the challenges within a large corporation that is developing technology
products. Finally, Chapter 12 presents an overview of technologies developed in federal laboratories
and describes how they are commercialized.

Section Three considers specific areas of innovation: nanoscale materials (Chapter 13) as well as
other areas where nanotechnology is making a dramatic impact: nano-enabled sensors (Chapter
14), the microelectronics industry (Chapter 15), and drug delivery (Chapter 16). This part concludes
with a chapter (Chapter 17) specifically on the intersection of nanotechnology and biotechnology, a
combination that holds enormous potential to impact medicine and health.
Section Four suggests that the convergence of science at the nanoscale foreshadows a
transformation and revolutionary change in society (Chapter 18) and highlights ethical
considerations in the advance of nanotechnology (Chapter 19).

The Epilogue features a prescient speech given in 1983 by the late Richard Feynman, the legendary
physicist who first envisioned nanotechnology.

Working at the level of individual atoms and molecules allows researchers to develop innovations
that will dramatically improve our lives. The new realm of nanotechnology holds the promise of
improving our health, our industry, and our society in ways that exceed even those of computers or
biotechnology.
Acknowledgments
These acknowledgments must begin with, and I cannot thank enough, distinguished scientist Dr.
Hans Coufal of IBM and the Nanoelectronics Research Initiative for the inspiration and
encouragement to undertake this project.

Innumerable thanks go to the many authors who contributed to this volume. The responsiveness
and generosity of such a distinguished group of researchers and business professionals transformed
the arduous task of bringing this book together into a particularly gratifying one. Special thanks are
also due to Bernard Goodwin of Prentice Hall for his continuing guidance.

Behind my efforts is one person whose day-to-day patience and encouragement were essential: my
wife, Miriam, who has shared the highs and lows of a consuming project. These few words are only a
small fraction of my enormous sense of love, appreciation, and thanks.

Four people worked "above and beyond" on this book, and without their special behind-the-scenes
efforts it would not have been completed: Michael Krieger of Williken Wilson Loh & Stris LLP, Geoff
Holdridge, National Nanotechnology Coordination Office and WTEC, Inc., Matt Laudon of the Nano
Science & Technology Institute, and Brent Segal of Nantero.

Thanks are due also to several people who contributed greatly to this book but were not listed as
authors because of editorial constraints, in particular the following: Art Riggs, City of Hope's
Beckman Research Institute; Howard Schmidt, Rice University; Amit Kenjale, Caltech; Robert
Giasoli, XCOM Wireless and the Micro and Nanotechnology Commercialization Education Foundation;
Jim Gimzewski, University of California, Los Angeles, and the California NanoSystems Institute;
Michael Holton, Smart Technology Ventures; Jim Spohrer, IBM; Daniel Choi, NASA Jet Propulsion
Lab; Marc Madou, University of California, Irvine; Peggy Arps, University of California, Irvine; Susan
Zhou, University of California, Irvine; Tony Cheetham, University of California, Santa Barbara.

Numerous colleagues at Greenberg Traurig, LLP, were a source of information, ongoing support, and
encouragement, as was the firm itself. My nanotechnology universe was broadened by the
opportunity to do programs for the Caltech Enterprise Forum, and by the wisdom and camaraderie
of many of its board members.

Thanks for the foundation of this book are due to Dr. Joe Lichtenhan of Hybrid Plastics, who started
me on the nanotechnology road, and to Jerry Gallwas, Hans Coufal, Malcolm Green, and Sergeant
Major (Retired) Peter Van Borkulo for being mentors to me for so many years. Special appreciation
goes to Cheryl Albus of the National Science Foundation for her constructive skepticism that helped
me separate substance from fad in nanotechnology.

Many others contributed greatly and are due wholehearted thanks for helping bring this book to
completion: Kevin Ausman, Rice University; John Belk, The Boeing Company; Keith Boswell, Virginia
Economic Development Partnership; Peter Burke, University of California, Irvine; Altaf Carim, U.S.
Department of Energy; Scott Carter, Caltech; Gerard Diebner, Greenberg Traurig; Andre Dehon,
Caltech; Alex Dickenson, Luxtera; Sverre Eng, NASA Jet Propulsion Lab (retired); David Forman,
Small Times Media; Wayne Jones, Greenberg Traurig; Sam Gambhir, Stanford; Guanglu Ge,
Caltech; Maurice Gell, University of Connecticut; Peter Gluck, Greenberg Traurig; Peter Grubstein,
NGEN Partners; Joe Helble, Office of Senator Joseph Lieberman and Dartmouth College; Jamie Hjort,
Office of Senator George Allen; Julie Holland, NASA Commercialization Center, California Polytechnic
University; Robert Hwang, U.S. DOE Brookhaven National Laboratory; Srinivas Iyer, Los Alamos
National Laboratory; Barbara Karn, U.S. Environmental Protection Agency; David Knight, Terbine,
Inc.; David Lackner, NASA Ames; Tony Laviano, Loyola Marymount University; Tom Loo, Greenberg
Traurig; Goran Matijasevic, University of California, Irvine; Paul McQuade, Greenberg Traurig; John
Miller, Arrowhead Research; Brian Pierce, Rockwell Scientific; Andy Quintero, The Aerospace
Corporation; Phil Reilly, Macusight, Inc.; Tony Ricco, Stanford; Bart Romanowicz, The Nano Science
& Technology Institute; Ari Requicha, USC; Michael Roukes, Caltech; James Rudd, The National
Science Foundation; Frank Sadler, Office of Senator George Allen; Carlos Sanchez, U.S. Army; John
Sargent, U.S. Department of Commerce; Jeff Schloss, National Institutes of Health; Clayton Teague,
National Nanotechnology Coordination Office; Jim Von Ehr, Zyvex; Kumar Wickramasinghe, IBM;
Stan Williams, HP; Hiroshi Yokoyama, National Institute of Advanced Industrial Science and
Technology, Japan; CJ Yu, Glyport, Inc.

Lynn Foster
Los Angeles, July 2005
About the Author
Lynn E. Foster is the Emerging Technologies Director of Greenberg Traurig, LLP, one of the largest
law firms in the United States. In this position he advises technology companies on technology
transfer, patent licensing, strategic partnerships and raising capital.

Prior to joining Greenberg Traurig, Mr. Foster held technology industry positions in corporate,
entrepreneurial, and government settings, among them managing software development in the
aerospace industry, heading a start-up, and managing a seed-stage commercialization grant
program. He serves on Advisory Boards for the Nano Science and Technology Institute and the
International Engineering Consortium, as well as the Executive Committee of the Caltech Enterprise
Forum. He authored the first Nanotechnology Trade Study and has directed eight Nanotechnology
conferences and trade missions. He also has 20 years of active and reserve service with the U.S.
Army, including service in the first Gulf War and Bosnia. He holds an M.B.A. and a B.S. in production
and operations management.
Contributors
Gerald Gallwas

Richard Smalley

Peter Coffee

Steve Jurvetson

Daniel V. Leff

R. Douglas Moffat

Geoffrey M. Holdridge

Julie Chen

Larry Gilbert

Michael Krieger

Chinh H. Pham

Charles Berman

Jeff Lawrence

Larry Bock

Jim Duncan

Meyya Meyyappan

Mark Reed

Sheryl Ehrman

Brent Segal

Zhong Lin (ZL) Wang

Fiona Case

David J. Nagel

Sharon Smith

George Thompson

Stephen Goodnick
Axel Scherer

Suzie Hwang Pun

Jianjun (JJ) Cheng

Dan Garcia

Dean Ho

Chih-Ming Ho

Mihail C. Roco

William Sims Bainbridge

Gerald Gallwas
Gerald Gallwas was a member of the original team in the mid-1960s that founded and managed the
growth of what became the clinical diagnostic business of Beckman Instruments. The team
pioneered a new technology based on kinetic rate measurements applied to first-order chemical
reactions for clinically significant blood constituents.

As the business grew, he served in many roles, from new product development to directing clinical
field trials in the United States, Europe, and Japan. This led to extensive involvement with
professional and trade organizations as well as regulatory agencies. He retired after 30 years of
service as Director of Program Management, overseeing multimillion-dollar new product
development programs. Since that time, he has consulted widely in the United States and Europe on
new product development, strategic and business planning, organizational development, and
marketing. Gallwas holds a B.S. in chemistry from San Diego State University.
Richard Smalley
Nobel Laureate Richard E. Smalley received his B.S. in 1965 from the University of Michigan. After
an intervening four-year period in industry as a research chemist with Shell, he earned his M.S. in
1971 from Princeton University and his Ph.D. in 1973. During a postdoctoral period with Lennard
Wharton and Donald Levy at the University of Chicago, Smalley pioneered what has become one of
the most powerful techniques in chemical physics: supersonic beam laser spectroscopy. After coming
to Rice University in 1976 he was named to the Gene and Norman Hackerman Chair in Chemistry in
1982. He was a founder of the Rice Quantum Institute in 1979 and served as the Chairman from
1986 to 1996. In 1990 he became a professor in the Department of Physics and was appointed
University Professor in 2002. He was the founding director of the Center for Nanoscale Science and
Technology at Rice from 1996 to 2002, and is now Director of the new Carbon Nanotechnology
Laboratory at Rice.

In 1990 he was elected to the National Academy of Sciences, and in 1991 to the American Academy
of Arts and Sciences. He is the recipient of the 1991 Irving Langmuir Prize in Chemical Physics, the
1992 International Prize for New Materials, the 1992 E.O. Lawrence Award of the U.S. Department
of Energy, the 1992 Robert A. Welch Award in Chemistry, the 1993 William H. Nichols Medal of the
American Chemical Society, the 1993 John Scott Award of the City of Philadelphia, the 1994
Europhysics Prize, the 1994 Harrison Howe Award, the 1995 Madison Marshall Award, the 1996
Franklin Medal, the 1996 Nobel Prize in Chemistry, the Distinguished Public Service Medal awarded
by the U.S. Department of the Navy in 1997, the 2002 Glenn T. Seaborg Medal, and the 2003
Lifetime Achievement Award of Small Times magazine. He received three honorary degrees in 2004:
an Honorary Doctorate from the University of Richmond; a Doctor Scientiarum Honoris Causa from
Technion Israel Institute of Technology, and a Doctor of Science from Tuskegee University.

Smalley is widely known for the discovery and characterization of C60 (Buckminsterfullerene, aka
the "buckyball"), a soccer ballshaped molecule that, together with other fullerenes such as C70, now
constitutes the third elemental form of carbon (after graphite and diamond). His current research is
on buckytubes: elongated fullerenes that are essentially a new high-tech polymer, following on from
nylon, polypropylene, and Kevlar. But unlike any of these previous wonder polymers, these new
buckytubes conduct electricity. They are likely to find applications in nearly every technology where
electrons flow. In February 2000 this research led to the start up of a new company, Carbon
Nanotechnologies, Inc., which is now developing large-scale production and applications of these
miraculous buckytubes.
Peter Coffee
Peter Coffee is Technology Editor of eWEEK, Ziff Davis Media's national news magazine of enterprise
infrastructure. He has twenty years' experience in evaluating information technologies and practices
as a developer, consultant, educator, and internationally published author and industry analyst.

Coffee writes product reviews, technical analyses, and his weekly "Epicenters" column on disruptive
forces in IT tools and practices; he has appeared on CBS, NBC, CNN, Fox, and PBS newscasts
addressing Internet security, the Microsoft antitrust case, wireless telecom policies, and other e-
business issues. He chaired the four-day Web Security Summit conference in Boston during the
summer of 2000 and has been a keynote speaker or moderator at technical conferences throughout
the United States and in England. His most recent book is Peter Coffee Teaches PCs, published in
1998 by Que; he previously authored Que's ZD Press tutorial, "How to Program Java." He played a
lead role in developing eWEEK Labs' 2001 series of special reports titled "Five Steps to Enterprise
Security." His current eWEEK beats include development tools and business intelligence products.

Before joining eWEEK (then called PC Week) full time in 1989, Coffee held technical and
management positions at Exxon and The Aerospace Corporation, dealing with chemical facility
project control, Arctic project development, strategic defense analysis, end-user computing planning
and support, and artificial intelligence applications research. He has been one of eWEEK's lead
analysts throughout the life cycles of technologies, including x86 and RISC microprocessors;
Windows, OS/2, and Mac OS; object technologies, including Smalltalk, C++, and Java; and security
technologies including strong encryption. He holds an engineering degree from MIT and an M.B.A.
from Pepperdine University and has taught classes in the Department of Computer Science at UCLA
and at Pepperdine's Graziadio School of Business and Management and the Chapman College School
of Business. His weekly newsletter, Peter Coffee's Enterprise IT Advantage, and his other writings
are available at www.eweek.com/petercoffee.
Steve Jurvetson
Steve Jurvetson is a Managing Director of Draper Fisher Jurvetson (DFJ.com). He was the founding
VC investor in Hotmail (MSFT), Interwoven (IWOV), and Kana (KANA). He also led the firm's
investments in Tradex and Cyras (acquired by Ariba and Ciena for $8 billion) and, most recently, in
pioneering companies in nanotechnology and molecular electronics. Previously, Jurvetson was an
R&D Engineer at Hewlett-Packard, where seven of his communications chip designs were fabricated.
His prior technical experience also includes programming, materials science research (TEM atomic
imaging of GaAs) and computer design at HP's PC Division, the Center for Materials Research, and
Mostek. He has also worked in product marketing at Apple and NeXT Software.

At Stanford University, he finished his B.S.E.E. in two and a half years and graduated first in his
class, as the Henry Ford Scholar. Jurvetson also holds an M.S. in electrical engineering from
Stanford. He received his M.B.A. from the Stanford Business School, where he was an Arjay Miller
Scholar. Jurvetson also serves on the Merrill Lynch and STVP advisory boards and is Cochair of the
NanoBusiness Alliance. He was honored as "The Valley's Sharpest VC" on the cover of Business 2.0
and was chosen by the San Francisco Chronicle and San Francisco Examiner as one of "the ten
people expected to have the greatest impact on the Bay Area in the early part of the 21st Century."
He was profiled in the New York Times Magazine and featured on the cover of Worth and Fortune
magazines. He was chosen by Forbes as one of "Tech's Best Venture Investors," by the VC Journal as
one of the "Ten Most Influential VCs," and by Fortune as part of its "Brain Trust of Top Ten Minds."
Daniel V. Leff
Prior to joining Harris & Harris Group, Leff was a Senior Associate with Sevin Rosen Funds in the
firm's Dallas, Texas, office, where he focused on early-stage investment opportunities in
semiconductors, components, and various emerging technology areas. While at Sevin Rosen Funds,
he played an integral role in the funding of Nanomix, InnovaLight, Sana Security, and D2Audio. Leff
has also worked for Redpoint Ventures in the firm's Los Angeles office. In addition, he previously
held engineering, marketing, and strategic investment positions with Intel Corporation.

Leff received his Ph.D. in physical chemistry from UCLA's Department of Chemistry and
Biochemistry, where his thesis adviser was Professor James R. Heath (recipient of the 2000 Feynman
Prize in Nanotechnology). Leff also received a B.S. in chemistry from the University of California,
Berkeley, and an M.B.A. from The Anderson School at UCLA, where he was an Anderson Venture
Fellow. Leff has published several articles in peer-reviewed scientific journals and has been awarded
two patents in the field of nanotechnology. He is also a member of the business advisory boards of
the NanoBusiness Alliance and the California NanoSystems Institute (CNSI).
R. Douglas Moffat
R. Douglas Moffat, CFA, is President of Moffat Capital, LLC, and Nanotech Financing Solutions, LLC.
Moffat Capital, LLC, is a broker/dealer experienced in raising private capital, and Nanotech Financing
Solutions, LLC, is a leading consultancy in this emerging field.

Moffat has 30 years' experience as a research analyst at leading Wall Street brokerage firms and has
broad experience in industrial markets. He published research on the metals and steel industries,
diversified industrial companies, automotive suppliers, defense, engineering, industrial service,
industrial technology sectors, and nanotechnology. An electrical engineer and M.B.A. by education,
Moffat brings a critical technical viewpoint to identifying business models with merit.

Moffat is a Chartered Financial Analyst (CFA) and was selected five times a Wall Street Journal All-
Star Analyst. He published on more than 110 public companies, with competency in the
nanoscience, industrial, metals, power technology, and real estate sectors. He is a leading industry
consultant in nanotechnology. Moffat is also a director of Astec Industries, Inc., a public company
producing asphalt, road building, and construction aggregate equipment.
Geoffrey M. Holdridge
Geoffrey M. Holdridge is currently Vice President for Government Services at WTEC, Inc., a nonprofit
corporation that provides on-site contract staff services for various U.S. government agencies as
well as an ongoing series of international technology assessment studies for the government,
comparing the status and trends in research and development in specific science and technology
research areas overseas relative to the United States (see http://www.wtec.org). Holdridge's
primary assignment for WTEC currently is to serve as Policy Analyst and Contract Staff Manager at
the National Nanotechnology Coordination Office, which provides technical and administrative
support to the Nanoscale Science, Engineering, and Technology (NSET) Subcommittee of the
President's National Science and Technology Council (NSTC). NSET is the interagency body charged
with coordinating, planning, and implementing the U.S. National Nanotechnology Initiative (see
http://www.nano.gov). Holdridge also plays a similar role in providing staff support for NSTC's
Multi-Agency Tissue Engineering Science (MATES) Working Group, which coordinates tissue science
and engineering (also known as regenerative medicine) research across several federal agencies
(http://www.tissueengineering.gov). Previous assignments for WTEC include Vice President for
Operations, where he coordinated worldwide activities for WTEC mostly related to its series of
international technology assessment studies, and Director of the Japanese Technology Evaluation
Center (JTEC), with responsibility for studies assessing Japanese research and development relative
to the United States. In the course of these assignments, Holdridge has supervised editing staff at
WTEC and NNCO and has performed final editing passes on more than 70 WTEC and NNCO reports,
including several that were formerly cleared for publication by NSTC under the seal of the President
of the United States.

Prior to coming to WTEC, Holdridge served in several capacities at the National Science Foundation
(NSF), in the Division of Policy Research and Analysis, the Division of Electrical and Communications
Systems, and the Division of Emerging Engineering Technologies, where he was involved in helping
organize NSF's Emerging Engineering Technologies Initiative. In the Division of Policy Research and
Analysis he conducted internal studies at the request of the Office of Management and Budget and
the Office of Science and Technology Policy and supervised extramural NSF funding for policy
research on environmental, energy, and resources issues, with particular focus on renewable energy
and energy conservation research. In the Division of Electrical and Communications Systems he
served as an NSF representative to an interagency committee that helped coordinate federal R&D
policy related to the semiconductor agency.

Holdridge also has held positions at the National Research Council of the National Academies and at
the University of Virginia. He holds a bachelor's degree from Yale University in history.
Julie Chen
Julie Chen is currently the Director of the Nanomanufacturing Center of Excellence at the University
of Massachusetts Lowell, where she is a professor of mechanical engineering and is also co-Director
of the Advanced Composite Materials and Textile Research Laboratory. Chen was the Program
Director of the Materials Processing and Manufacturing and the Nanomanufacturing Programs in the
Division of Design, Manufacture, and Industrial Innovation at the National Science Foundation from
2002 to 2004.

She received her Ph.D., M.S., and B.S. in mechanical engineering from MIT. Chen has been on the
faculty at Boston University, a NASA-Langley Summer Faculty Fellow, a visiting researcher at the
University of Orleans and Ecole Nationale Superieure d'Arts & Metiers (ENSAM-Paris), and an invited
participant in the National Academy of Engineering, Frontiers of Engineering Program. In addition to
co-organizing several national and international symposia and workshops on nanomanufacturing
and composites manufacturing for NSF, ASME, ASC, and ESAFORM, Chen has served on editorial
boards, advisory committees, and review panels for several journals and federal agencies. Her
research interests are in the mechanical behavior and deformation of fiber structures, fiber
assemblies, and composite materials, with an emphasis on nanomanufacturing and composites
processing. Examples include analytical modeling and novel experimental approaches to electro-
spinning of nanofibers, and forming of textile reinforcements for structural (biomedical to
automotive) applications.
Larry Gilbert
Lawrence Gilbert is the Senior Director of Technology Transfer of Caltech, the California Institute of
Technology. The Office of Technology Transfer (OTT) provides a service to Caltech faculty members,
other Caltech researchers, and Jet Propulsion Laboratory (JPL) technologists by protecting the
intellectual property developed in their Caltech and JPL labs. The OTT fosters the commercial
development of Caltech technologies in companies ranging from local start-ups to large,
multinational firms. Gilbert has been responsible for the formation of more than 60 start-ups based
upon or associated with university research. Several have gone public or have been acquired, and
many have products in the marketplace. He acts primarily as a catalyst in putting the deal together,
linking faculty, technology, and venture capital.

Gilbert was formerly the Director of Patent Licensing for Massachusetts Institute of Technology
(MIT). Prior experience includes Patent Consultant to various universities, including Boston
University, Brandeis, Tufts, and the University of Massachusetts Medical Center and as the Director
of Patent and Technology Administration of Boston University. Gilbert is a member of the Licensing
Executive Society (LES) and a former Chairman of its Committee on Technology Transfer, and is a
Founder of the former Society of University Patent Administrators, now known as the Association of
University Technology Managers (AUTM). He is a member of the Executive Committee of the
MIT/Caltech Enterprise Forum and formerly a member of the Board of Directors of the Southern
California Biomedical Council and a former member of the Advisory Committee of the Business
Technology Center, a high-tech incubator sponsored by the Los Angeles County Community
Development Commission.

Gilbert received his B.A. from Brandeis University; an M.I.M. degree from the American Graduate
School of International Management (Thunderbird); and a J.D. from Suffolk University; he is
registered to practice before the U.S. Patent and Trademark Office (USPTO). Gilbert has been a
frequent lecturer on patent and licensing matters and has written several articles in the field.
Michael Krieger
Michael Krieger is a Los Angeles attorney with Willenken Wilson Loh & Stris. He has practiced high-
technology business and intellectual property law for more than 20 years, focusing on strategic
counseling, litigation strategy, and preventive methods to both secure and exploit clients' key IP
assets. This includes both patent, trademark, and other litigation and associated transactions for
development, acquisition, licensing, and services. His clients have ranged from start-ups to industry
leaders, the United Nations, and international Web-based initiatives. He also has been an expert in
technology litigation.

With degrees in mathematics (B.S., Caltech; Ph.D., UCLA) and law (UCLA), Krieger was on the MIT
Mathematics and UCLA Computer Science faculties as well as a Fulbright Scholar prior to practicing
law. Combining knowledge of both law and new technology, he was involved early on with emerging
issues such as public key encryption (1978 tutorial for the Computer Law Association), domain
name/trademark conflicts, open source software, and Internet governance (for example, personal
adviser to Internet pioneer Jon Postel as he oversaw privatization of Internet administration).

Krieger serves on several boards supporting new venture development, including the Caltech/MIT
Enterprise Forum. In 1997 he developed and continues to teach a graduate seminar on
entrepreneurial business, IP, and litigation issues for the Computer Science Department in UCLA's
engineering school. He has served on the Executive Committee of the Intellectual Property Section of
the California Bar, was Editor-in-Chief of its journal New Matter, and currently chairs its Computer
Law Committee.
Chinh H. Pham
Chinh H. Pham practices law at Greenberg Traurig, LLP (www.gtlaw.com), and heads the firm's
nanotechnology practice. He is a registered patent attorney with particular experience in the
strategic creation, implementation, and protection of intellectual property rights for high-technology
and life science clients.

Chinh represents and counsels start-ups as well as established companies, including those in the
areas of nanotechnologies, medical devices, electro-mechanical devices, telecommunications, data
mining, electronic commerce, and life sciences. In connection with his practice, Chinh advises clients
on the creation and development of patent portfolios through the preparation and filing of patent
applications, the acquisition and exploitation of intellectual property rights through licensing and
strategic collaboration agreements, and the preparation of invalidity, noninfringement, and
freedom-to-operate opinions. Chinh also counsels clients on IP due diligence through the evaluation
of client and competitor portfolios.

For his start-up clients, Chinh assists with strategies for leveraging their IP portfolio for high-value
commercial opportunities, introducing them to funding sources, either through the venture
community or the government, as well as identifying and establishing for these clients strategic
alliances with industry leaders. Chinh is the founder of the NanoTechnology and Business Forum, a
monthly forum dedicated to the business of nanotechnology. He is also the Secretary of ASTM
International Nanotechnology Committee. Chinh is a frequent speaker and writer on the intersection
between nanotechnology, intellectual property, and business.

Prior to practicing law, Chinh worked in the biotechnology industry, focusing on the genetic
transformation of plants. Chinh received his B.A. in genetics from the University of California,
Berkeley, and his J.D. from the University of San Francisco.
Charles Berman
Charles Berman is a principal shareholder with the law firm Greenberg Traurig, LLP, in Santa
Monica, California, and he is Co-Chair of the national patent prosecution practice of the firm. He has
been active in all areas of intellectual property law for more than 35 years. He has been practicing in
Los Angeles since 1978, and practiced in South Africa prior to that time. He has also worked with
European patent attorneys.

Berman has extensive IP experience in the United States and foreign countries and has been
involved in the U.S. and international licensing of technology. Berman has represented large
corporations in actions before the U.S. Patent Office, the European Patent Office, and the German,
Japanese, and other major patent offices. He has engaged in major international patent and
trademark procurement programs for leading corporations.

Berman currently serves as Chair of Fellows of the American Intellectual Property Law Association
(AIPLA), where he was a founding fellow, and has also served on the board of directors. He has held
several prominent positions over the past several years in the AIPLA, including being a
representative for international meetings. He has been President of the Los Angeles Intellectual
Property Law Association.

He is a frequently invited speaker, has written numerous articles on the topic of intellectual
property, and has been on the editorial boards of different intellectual property publications. Berman
was educated at the University of Witwatersrand in South Africa.
Jeff Lawrence
Jeff Lawrence is President & CEO of Clivia Systems (www.cliviasystems.com), former CTO of Intel's
Network Communications Group, and co-founder and former President and CEO of Trillium Digital
Systems. Trillium was a leading provider of communications software solutions to communications
equipment manufacturers building the converged wireless, Internet, broadband, and telephone
infrastructure. Trillium licensed its source code software solutions to more than 300 companies
throughout the world for use in a wide range of telecommunications products. Trillium's solutions
consisted of software products and services for data, voice, and high availability. Lawrence, along
with his team, built Trillium from two people, zero products, zero revenue, and $1,000 initially
invested capital at its founding in February 1988 to more than 250 people, more than 100 products
consisting of millions of lines of source code, $30 million annual revenue, and acquisition by Intel in
August 2000 for $300 million. Jeff led, built, motivated, and grew a team having a unique and deep
understanding of the communications software industry and having a culture and commitment to the
customer and success during a period of continual and rapid change in the technology, market,
competitive, and financial environment.

Lawrence is also Trustee of The Lawrence Foundation (www.thelawrencefoundation.org), a family

foundation focused on grant making to environmental, education, health, and human services
causes. He has a B.S.E.E. from UCLA, was co-recipient of the Greater Los Angeles Entrepreneur of
the Year award, and recipient of the UCLA School of Engineering's Professional Achievement award.
Jeff also writes and speaks on technology, entrepreneurship, philanthropy, economics, and ethics.
Larry Bock
Larry Bock is the Founder and Executive Chairman of Nanosys Inc. He is a General Partner of CW
Ventures, a life sciences venture capital fund, and a Special Advisor to Lux Capital, a
nanotechnology-focused venture capital fund. He is a member of the board of directors of FEI
Corporation, the leading supplier of tools for nanotechnology research.

Bock was the Founder and initial CEO of Neurocrine Biosciences, Pharmacopeia, GenPharm
International, Caliper Technologies, Illumina Technologies, IDUN Pharmaceuticals, Metra
Biosystems, and FASTTRACK Systems. Bock was a co-founder of Argonaut Technologies, ARIAD
Pharmaceuticals, Athena Neurosciences, Vertex Pharmaceuticals, and Onyx Pharmaceuticals. He also
helped found and is on the scientific advisory board of Conforma Therapeutics.

Bock started his career as a Researcher at Genentech, Inc., in the field of infectious diseases, where
he was on the team that received the AAAS Newcomb Cleveland Prize for demonstrating the first
recombinant DNA vaccine.

He has received several awards and honors. He was selected by Venture Capital Journal as one of
the "Ten Most Influential Venture Capitalists," by Red Herring as one of the "Top Ten Innovators," by
Forbes-Wolfe NanoReport as the "Number One Powerbroker in Nanotechnology," by Ernst & Young
as a finalist for "Entrepreneur of the Year," and by Small Times as "Innovator of the Year" and one of
"Top 3 Business Leaders of the Year." He received the Einstein Award from the Jerusalem Foundation
for lifetime contributions in the field of life sciences.

Bock and his wife, Diane, founded Community Cousins, a nonprofit foundation focused on breaking
down racial barriers, which was selected by former Vice President Al Gore as one of ten outstanding
grassroots efforts nationally. Bock received his B.A. in biochemistry from Bowdoin College and his
M.B.A. from the Anderson School at UCLA.
Jim Duncan
Jim Duncan is the Group Director of Business Development for Meggitt Aerospace Equipment (MAE)
Group, a strategic business unit of Meggitt PLC. MAE companies specialize in products and services
around the following technologies: thermal management systems, fluid dynamics, engineered
materials, extreme environment cabling, and sensors and subsystems.

Duncan is a Partner and Co-founder of Blue Sky Management and Consultants, Ltd. Blue Sky was
organized to develop investment, technology transfer, strategic business development, and
manufacturing opportunities for technology-oriented companies. Duncan was the Executive Vice
President for Business Development of Zone5 Wireless Systems Inc., a Rockwell Science Center
(RSC) spin-off company. He was a co-founder of the venture-capital-backed start-up business for
wireless ad hoc data network products.

Prior to joining Zone5, Duncan was the Director, Business Development & Commercialization at
Rockwell Science Center (RSC). He led the commercialization of RSC's wireless integrated network
sensor technologythe technology licensed to Zone5. The product, HIDRA, won industry recognition,
receiving Product of the Year awards in 2000 and 2001. The technology addressed the convergence
of processing, radio frequency, ad hoc networks, and sensor technologies.

Before joining the Science Center, Duncan co-founded and directed an international (operations on
Taiwan and North America) start-up company that designed, produced, marketed, and distributed
wireless consumer productsstereo speakers and audio/video surveillance systems. Duncan has held
major business development and marketing positions with technology-based companies over the
past 20 years: Research (Rockwell Scientific), Antenna and Radar Subsystems (Teledyne Ryan
Electronics), Systems Integration (Teledyne Electronic Systems), Aircraft Prime manufacturer
(Kaman), Consumer electronics (Paradox), Commercial (Zone5), and consulting (Blue Sky).

Duncan is a former U.S. Naval aviator. While a commissioned officer he flew missions in the Kaman
H-2 and Sikorsky SH-60B antisubmarine warfare helicopters. He graduated from the U.S. Naval
Academy with a B.S. in physical science.
Meyya Meyyappan
Meyya Meyyappan is Director of the Center for Nanotechnology as well as Senior Scientist at NASA
Ames Research Center in Moffett Field, CA (http://www.ipt.arc.nasa.gov). He is one of the founding
members of the Interagency Working Group on Nanotechnology (IWGN) established by the Office of
Science and Technology Policy (OSTP). The IWGN is responsible for putting together the National
Nanotechnology Initiative.

Meyyappan is a Fellow of the Institute of Electrical and Electronics Engineers (IEEE). He is Fellow of
the Electrochemical Society (ECS). In addition, he is a member of American Society of Mechanical
Engineers (ASME), Materials Research Society, American Vacuum Society, and American Institute of
Chemical Engineers. He is the IEEE Distinguished Lecturer on Nanotechnology and ASME's
Distinguished Lecturer on Nanotechnology. He is the President-elect of the IEEE's Nanotechnology
Council.

For his work and leadership in nanotechnology, he was awarded NASA's Outstanding Leadership
Medal and received the Arthur Flemming Award from the Arthur Flemming Foundation and George
Washington University. For his contributions to nanotechnology education and training, he received
the 20032004 Engineer of the Year award from the San Francisco section of the AIAA (American
Institute of Aeronautics and Astronautics). In 2004, he was honored with the President's Meritorious
Award for his contributions to nanotechnology.
Mark Reed
Mark A. Reed received his Ph.D. in physics from Syracuse University in 1983, after which he joined
Texas Instruments, where he co-founded the nanoelectronics research program. In 1990 Reed left TI
to join the faculty at Yale University, where he presently holds a joint appointment as Professor in
the Electrical Engineering and Applied Physics departments, and is the Harold Hodgkinson Chair of
Engineering and Applied Science. His research activities have included the investigation of electronic
transport in nanoscale and mesoscopic systems, artificially structured materials and devices, and
molecular-scale electronic transport. Reed is the author of more than 150 professional publications
and 6 books, has given 15 plenary and more than 240 invited talks, and holds 24 U.S. and foreign
patents on quantum effect, heterojunction, and molecular devices. He has been elected to the
Connecticut Academy of Science and Engineering and Who's Who in the World. His awards include
Fortune magazine's "Most Promising Young Scientist" (1990), the Kilby Young Innovator Award
(1994), the DARPA ULTRA Most Significant Achievement Award (1997), the Syracuse University
Distinguished Alumni award (2000), the Fujitsu ISCS Quantum Device Award (2001), and the Yale
Science and Engineering Association Award for Advancement of Basic and Applied Science (2002). In
2003 he was elected a fellow of the American Physical Society.
Sheryl Ehrman
Sheryl Ehrman received her B.S. in chemical engineering from the University of California, Santa
Barbara, in 1991, and her Ph.D. in chemical engineering from the University of California, Los
Angeles, in 1997. She has worked as a Visiting Scientist in the Process Measurements Division of the
National Institute of Standards and Technology site in Gaithersburg, Maryland. She has also worked
as a Post Doctoral Fellow in the Laboratory for Radio and Environmental Chemistry at the Paul
Scherrer Institute in Villigen, Switzerland, studying the interactions between ambient particulate
matter and ice crystals.

She currently is employed as an associate professor in the Department of Chemical and

Biomolecular Engineering and as a participating faculty in both the Bioengineering and the Chemical
Physics Programs at the University of Maryland, College Park. Her research interests include the
study of nanoparticle formation and processing and bioengineering applications of nanoparticles, as
well as the transport and fate of particulate air pollution. She teaches courses in particle technology,
transport phenomena, thermodynamics, and introductory engineering design.
Brent Segal
Brent Segal is a member of Echelon Ventures of Burlington, Massachusetts, where he focuses on
investments involving combinations of disciplines leading to explosive growth potential. Some of his
primary areas of expertise include chemistry, biochemistry, biology, semiconductors, and
nanotechnology. He is a Co-founder and part-time Chief Operating Officer of Nantero, a leading
nanotechnology company, where he oversees operations roles focusing on partnerships, involving
companies such as LSI Logic, BAE Systems, and ASM Lithography. He continues to assist Nantero
with intellectual property management and government programs involving the Navy and various
agencies.

Segal is an active member of the steering committee of the Massachusetts Nanotechnology Initiative
(MNI), executive member of the Massachusetts NanoExchange (MNE), a member of the New
England Nanomanufacturing Center for Enabling Tools (NENCET) Industrial Advisory Board, and a
member of the planning board for Nanotech 2006. He sits on the board of directors of Coretomic, of
Burlington, Vermont, and ENS Biopolymer, Inc., of Cambridge, Massachusetts.

He is an active fund-raiser, helping Nantero to raise more than $36 million in three private equity
rounds and government programs. He previously ran laboratory operations at Metaprobe LLC, where
he also assisted in raising more than $5 million in private equity financing. He was a Research
Associate at Nycomed Salutar, Inc., where he secured several new patents involving novel X-ray
contrast agents for medical imaging.

He received his Ph.D. in chemistry from Harvard University in 2000 and has published frequently in
journals, including Journal of the American Chemical Society, Inorganic Chemistry, and various IEEE
publications, including one in which Nantero was named one of the top ten companies for the next
ten years. Segal is co-author of more than 50 patents and has worked extensively on intellectual
property creation and protection issues at both Nycomed and Metaprobe. He is a graduate of Reed
College, with a degree in biochemistry.
Zhong Lin (ZL) Wang
Zhong Lin (ZL) Wang is a Regents' Professor and Director, Center for Nanostructure Characterization
and Fabrication, at Georgia Tech. He has authored and co-authored 4 scientific reference books and
textbooks, more than 400 peer-reviewed journal articles, and 45 review papers and book chapters;
has edited and co-edited 14 books on nanotechnology; and has held 12 patents and provisional
patents. Wang is among the world's top 25 most cited authors in nanotechnology from 1992 to 2002
(ISI, Science Watch). He contributed 38 percent of the total citations of Georgia Tech papers in
nanotechnology in the past decade, which places Tech number 12 worldwide. His publications have
been cited more than 9,000 times.

Wang discovered the nanobelt in 2001, which is considered to be a groundbreaking work. His paper
on nanobelts was the second most cited paper in chemistry in 2001 and 2003 worldwide. His paper
on piezoelectric nanosprings was one of the most cited papers in materials science in 2004
worldwide. In 1999, he and his colleagues discovered the world's smallest balance, nanobalance,
which was selected as the breakthrough in nanotechnology by the American Physical Society. He
was elected to the European Academy of Science (www.eurasc.org) in 2002 and made a fellow of
the World Innovation Foundation (www.thewif.org.uk) in 2004. Wang received the 2001 S.T. Li prize
for Outstanding Contribution in Nanoscience and Nanotechnology, the 2000 and 2005 Georgia Tech
Outstanding Faculty Research Author Awards, Sigma Xi 2005 sustaining research awards, Sigma Xi
1998 and 2002 best paper awards, the 1999 Burton Medal from Microscopy Society of America, the
1998 U.S. NSF CAREER award, and the 1998 China-NSF Overseas Outstanding Young Scientists
Award. A symposium in honor of Wang was organized by L'Institut Universitaire de France (IUF) on
May 7, 2003. He is a member of the editorial boards of 12 journals. His most recent research focuses
on oxide nanobelts and nanowires, in-situ techniques for nanoscale measurements, self-assembly
nanostructures, and fabrication of nanodevices and nanosensors for biomedical applications. Details
can be found at http://www.nanoscience.gatech.edu/zlwang.
Fiona Case
Fiona Case has more than 15 years' experience in the industrial applications of polymer and
surfactant science. Her introduction to industrial polymer science was in the late 1980s at Courtaulds
Research in the U.K., where she worked as part of the team developing Tencel, a new
environmentally friendly solvent-spun cellulose fiber. She also investigated the effects of
polyacrylonitrile microstructure on carbon fiber performance using early molecular and quantum
mechanics computer modeling techniques. Case's involvement as a founding member of the
Biosym/Molecular Simulations Inc. (MSI) Polymer Consortium, one of the earliest materials
simulation efforts, meant frequent trips to sunny San Diego, California. In 1991 she moved to
California to join Biosym. Case spent nine years at Biosym/MSI (now Accelrys). She carried out
contract research for some of the top U.S. and European companies. As manager of the MSI training
group, she prepared and presented more than 30 workshops worldwide on polymer science and
molecular modeling. She also worked in marketing and technical sales support.

In 1999 she was hired into a central research group at Colgate Palmolive. This presented challenges,
including materials structure and property prediction for toothpaste, detergent, hard surface care
and personal care products, and packaging and fragrance technology. In 2003 Case left Colgate
Palmolive to move to beautiful Vermont with her husband, Martin Case, and to found Case Scientific
(www.casescientific.com), offering consultancy and contract research in soft nanotechnology,
computational chemistry, and polymer and surfactant science. Case is a Chartered Chemist and a
member of the Royal Society of Chemistry, the ACS, the American Oil Chemists Society, and the
National Association of Science Writers.
David J. Nagel
David Nagel started school at an early age and completed it shortly before turning 40, apparently a
slow learner. Unable to decide on what to do, he studied three majors and wound up with a Ph.D. in
materials engineering from the University of Maryland. After four years of active duty and 26 years
in the Naval Reserve, he became an expired captain in 1990. He worked at the Naval Research
Laboratory for 36 years, apparently unable to find a job elsewhere. While there, he had an accident
and turned into a division head for 13 years. His careers in the Navy and in R&D were concurrent,
not consecutive. For the past six years, he has been a research professor at The George Washington
University. This means that he is neither a real doctor nor a real professor. Currently, Nagel, still
unable to focus, performs studies on a wide variety of topics. He teaches a course on applications of
micromachines, which is his chance to retaliate for suffering inflicted by teachers during his long
academic career. His primary products are hot air and marks on otherwise clean papers.

(Editor's meddling: Nagel was Superintendent of the Condensed Matter and Radiation Sciences
Division at the Naval Research Laboratory and has written or co-authored more than 150 technical
articles, reports, book chapters, and encyclopedia articles primarily on the applications of MEMS and
nanotechnology.)
Sharon Smith
Sharon Smith is a Corporate Executive at Lockheed Martin's headquarters in Bethesda, Maryland. As
Director, Advanced Technology, she is responsible for research and technology initiatives, including
independent research and development projects, university involvement, and various other R&D
activities. She is the prior chair of the Lockheed Martin Steering Group on Microsystems/MEMS and
is currently the chair of the corporation's Steering Group on Nanotechnology.

Smith has 25 years of experience in management, program management, engineering, and research
and development at Eli Lilly and Company, IBM Corporation, Loral, and Lockheed Martin
Corporation. She has more than 25 technical publications and has given numerous technical
presentations in the United States and Europe. She serves on the Nanotechnology Committee for
JCOTS (Joint Committee On Technology and Science) for the state of Virginia and is also a member
of the National Academies' National Materials Advisory Board.

Smith has a Ph.D. in analytical chemistry from Indiana University, an M.S. in physical chemistry
from Purdue University, and a B.S. in chemistry from Indiana University.
George Thompson
George Thompson is currently in Intel's Technology Strategy Group. Previously, he has managed
projects for new product launches and pathfinding, enterprise platform enabling, materials
development, and high-volume manufacturing. His main interests in silicon processing were etch
process development and diagnosis, process integration, and yield analysis. His past research
interests include applied optics, solid-state laser development, solar energy research, precision
frequency control, and molecular spectroscopy. He has a Ph.D. in physical chemistry.
Stephen Goodnick
Stephen Goodnick received his Ph.D. in electrical engineering from Colorado State University in
1983. He is currently Interim Deputy Dean and Director of Nanotechnology for the Ira A. Fulton
School of Engineering at Arizona State University. He joined ASU in fall 1996 as Department Chair of
Electrical Engineering. Prior to that, he was professor of electrical and computer engineering at
Oregon State University from 1986 to 1996. He has also been a visiting scientist at the Solar Energy
Research Institute and Sandia National Laboratories and a visiting faculty member at the Walter
Schottky Institute, Munich, Germany; the University of Modena, Italy; the University of Notre Dame;
and Osaka University, Japan. He served as President (20032004) of the Electrical and Computer
Engineering Department Heads Association (ECEDHA), and as Program Chair of the Fourth IEEE
Conference on Nanotechnology in 2004.

Goodnick has published more than 150 refereed journal articles, books, and book chapters related to
transport in semiconductor devices, computational electronics, quantum and nanostructured devices
and device technology, and high-frequency and optical devices. He is co-author of the textbook
Transport in Nanostructures with David K. Ferry (Cambridge University Press, 1997). He is a Fellow
of the IEEE (2004), and an Alexander von Humboldt Research Fellow in Germany.
Axel Scherer
Axel Scherer is Professor of Electrical Engineering, Applied Physics, and Physics at the California
Institute of Technology, specializing in device microfabrication and packaging. He graduated from
New Mexico Institute of Mining and Technology in 1985 and worked in the Quantum Device
Fabrication group at Bellcore for the following eight years. In the past, Scherer specialized in
improving the state of the art of semiconductor microfabrication, which resulted in the development
of the smallest vertical cavity lasers (400nm wide) and some of the world's smallest etched
structures (6nm wide), as well as ultranarrow gratings (30nm pitch). He has also been working on
reducing the sizes of microlasers and changing their emission wavelengths. Scherer's research
laboratory is built around producing nanostructures and applying them to new optoelectonic,
magnetooptic, and high-speed electronic devices. The aim of his research group is to develop
functional devices that use their reduced geometries to obtain higher speed and greater efficiencies,
and can be integrated into systems in large numbers.
Suzie Hwang Pun
Suzie Pun is an assistant professor in the Department of Bioengineering at the University of
Washington. Her research focuses on synthetic gene and drug delivery systems. She received her
B.S. in chemical engineering at Stanford University. For her graduate work, she developed polymeric
materials for drug delivery and obtained her Ph.D. in chemical engineering from the California
Institute of Technology under the guidance of Mark E. Davis in 2000. She then worked at Insert
Therapeutics as a Senior Scientist, pioneering the use of cyclodextrin-containing polymer delivery
systems for nucleic acids. She joined the faculty at University of Washington in 2003 and has
published 16 papers in the field of drug delivery. In addition, she has 8 granted or pending patent
applications.

Pun has been recognized by MIT Technology Review magazine as one of 2002's "Top 100 Young
Innovators" in its TR100 Awards. She is the recipient of a Career Development Award from the
National Hemophilia Foundation (2004), a Young Investigator Award from the Alliance for Cancer
Gene Therapy (2005), and a Faculty Early Career Development (CAREER) award from the NSF
(2005).
Jianjun (JJ) Cheng
Jianjun Cheng is an Assistant Professor in the Department of Materials Science and Engineering of
the University of Illinois at Urbana-Champaign. Cheng received his B.S. in chemistry at Nankai
University and his M.S. in chemistry from Southern Illinois University. He then received his Ph.D. in
materials science from the University of California, Santa Barbara. His industry experience includes
working as a Senior Scientist and Project Leader for Insert Therapeutics, Inc., where he developed
Cyclodextrin-based polymers for systemic delivery of camptothecin and the modification of
polycations for systemic gene delivery and targeting. He has also done postdoctoral research at the
Massachusetts Institute of Technology with Robert Langer, an MIT Institute professor who has
written more than 840 articles, has more than 500 issued or pending patents, and has received the
Charles Stark Draper Prize, considered the equivalent of the Nobel Prize for engineers. In this
position Cheng researched magnetic nanoparticles for oral protein delivery and Aptamer-
nanoparticles for in vivo targeted prostate cancer therapy and diagnosis. Cheng has more than 20
peer-reviewed publications and patent applications.
Dan Garcia
Dan Garcia is currently a Ph.D. student in the Department of Bioengineering at UCLA. He works in
the laboratory of Dr. Chih-Ming Ho, where he is using NEMS and nanofluidic technology to develop
the actin muscle protein for a bottom-up/top-down hybrid nanofabrication process to construct two-
and three-dimensional nanostructures. This will ultimately facilitate the generation of actin filaments
according to a two- or three-dimensional, predesigned layout.

Prior to joining Dr. Ho's group, Garcia conducted immunology research in the laboratory of Dr.
Genhong Cheng. Garcia's work helped clarify the interaction between a novel protein, TRAF3-
interacting JunN-terminal kinase (JNK)-activating modulator (T3JAM), and tumor necrosis factor
receptor (TNFR)-associated factor 3 (TRAF3), two proteins that play important roles in the CD40
signal transduction pathway. The CD40 signaling pathway plays a role in the adaptive immune
response, atherosclerosis, and the body's response to transplants.
Dean Ho
Dean Ho received his B.S. in physiological science from UCLA in 2001, and his Ph.D. in 2005 from
the UCLA Department of Bioengineering. He is currently a Hewlett-Packard Fellow in the Department
of Mechanical and Aerospace Engineering at UCLA. His research has covered emerging areas in
bionanotechnology to interface membrane-bound proteins with block copolymeric biomimetic
membranes to fabricate biomolecular hybrids. Ho has been among the first to demonstrate the
coupling of protein function and the potential of using biostructures as energy conversion systems.
This work is the subject of a featured article in Nanotechnology that was downloaded more than
1,000 times, which was among the top 10 percent of all downloaded Institute of Physics (IOP)
publications, as well as a feature article in Advanced Functional Materials. He has published more
than 20 peer-reviewed papers and several book chapters in the areas of biochemical energetics and
biotic-abiotic interfacing, as well as developing biologically active devices based on the harnessing of
protein functionality. Ho's research achievements have garnered news coverage in Nature,
MICRO/NANO, and BBC Radio, where Ho was interviewed on the subject of the societal impacts of
bionanotechnology. He has presented several invited talks at internationally renowned institutions,
including the California Nanosystems Institute (CNSI), Academia Sinica, and the Bionanotechnology:
Academic and Industrial Partnerships in the U.K. and U.S. conference held at the University of
Southern California. Ho is a member of Sigma Xi, the Biomedical Engineering Society, Materials
Research Society, IEEE, AAAS, ASME, and American Academy of Nanomedicine. In addition, he
currently serves on the editorial board of the Journal of Nanotechnology Law and Business and
previously served as the Editor-in-Chief of the CESASC Technical Symposium Proceedings and as an
Editor of the UCLA Graduate Scientific Review.

In addition to his academic accomplishments, Ho has made extensive contributions to the UCLA
community, having previously served as a Trustee-at-Large of the Unicamp Board of Trustees, the
body that oversees the official philanthropy of UCLA that is currently in its 70th year of activity. For
his service and leadership to the UCLA and greater Los Angeles community, Ho was presented with
the UCLA Chancellor's Service Award in 2001.
Chih-Ming Ho
Chih-Ming Ho is the Ben Rich-Lockheed Martin Chair Professor at the UCLA School of Engineering
and the Director of the Institute for Cell Mimetic Space Exploration (CMISE). He graduated from the
Mechanical Engineering Department of the National Taiwan University. After receiving his Ph.D. from
The Johns Hopkins University, Ho started his career at the University of Southern California and rose
to the rank of Full Professor. In 1991, he moved to the University of California, Los Angeles, to lead
the establishment of the microelectromechanical system (MEMS) field in UCLA and served as the
founding Director of the Center for Micro Systems. The UCLA MEMS research has been recognized as
one of the best in the world. He served as UCLA Associate Vice Chancellor for Research from 2001 to
2005.

He is an internationally renowned scientist in micro- and nanofluidics, bio-nano technology, and

turbulence. He was ranked by ISI as one of the top 250 most cited researchers in all engineering
categories around the world, and by ECI as number 7 in the field of MEMS. In 1997, Ho was
inducted as a member of the National Academy of Engineering. In the next year, he was elected as
an Academician of Academia Sinica, which honors scholars of Chinese origin with exceptional
achievements in liberal arts and the sciences. Ho holds five honorary professorships. He has
published 220 papers and 7 patents. He has presented more than 100 keynote talks in international
conferences. Ho was elected fellow of the American Physical Society as well as American Institute of
Aeronautics and Astronautics for his contributions in a wide spectrum of technical areas.

In addition to his academic accomplishments, he has made extensive contributions to professional

societies around the world. He has chaired the Division of Fluid Dynamics (DFD) of the American
Physical Society, which is the leading platform in the United States for scientists interested in
fundamental fluid dynamics. He is on the advisory board for AIAA Journal and is a member of the
IEEE/ASME JMEMS coordinating committee. He was an Associate Editor of the ASME Journal of Fluids
Engineering and an Associate Editor of the AIAA Journal. He also has served as a Guest Editor for
Annual Review of Fluid Dynamics.

On the international level, Ho has served on advisory panels to provide assistance to many countries
and regionsFrance, China, United Kingdom, Israel, Taiwan, and Japanon the development of nano-
and microtechnologies. Ho also has chaired or served on numerous organizing committees of
international conferences on high-technology topics.
Mihail C. Roco
Mihail Roco is Co-Chair of the U.S. National Science and Technology Council's Subcommittee on
Nanoscale Science, Engineering and Technology (NSET), and is Senior Advisor for Nanotechnology
at the National Science Foundation. He also coordinates NSF's Grant Opportunities for Liaison with
Industry program. Previously he was Professor of Mechanical Engineering at the University of
Kentucky (19811995) and held visiting professorships at the California Institute of Technology
(19881989), Johns Hopkins University (19931995), Tohoku University (1989), and Delft University
of Technology (19971998).

Roco is credited with 13 inventions. He has authored or co-authored numerous archival articles and
twelve books, including Particulate Two-phase Flow (Butterworth, 1993), Nanostructure Science and
Technology (Kluwer Acad., 1999), Societal Implications of Nanoscience and Nanotechnology (Kluwer
Acad., 2001), Converging Technologies for Improving Human Performance (Kluwer Acad., 2003) and
The Coevolution of Human Potential and Converging Technologies (N.Y. Acad. of Sciences, 2004).
Roco was a researcher in multiphase systems, visualization techniques, computer simulations,
nanoparticles, and nanosystems in 1980s as Professor, and in 1991 initiated the first federal
government program that focused on nanoscale science and engineering (on Synthesis and
Processing of Nanoparticles at NSF). He formally proposed NNI in a presentation at White
House/OSTP, Committee on Technology, on March 11, 1999. Roco is a key architect of the National
Nanotechnology Initiative and coordinated the preparation of the U.S. National Science and
Technology Council reports "Nanotechnology Research Directions" (NSTC, 1999) and "National
Nanotechnology Initiative" (NSTC, 2000).

Roco is a Correspondent Member of the Swiss Academy of Engineering Sciences, a Fellow of the
American Society of Mechanical Engineers, a Fellow of the Institute of Physics, and a Fellow of the
American Institute of Chemical Engineers. He is Editor-in-chief of the Journal of Nanoparticle
Research and has served as Editor for the Journal of Fluids Engineering and the Journal of
Measurement Science and Technology. He is a member of the Executive Governance Board for
Sandia and Los Alamos National Laboratories, the Review Board for National Research Council
Institute (Canada), International Risk Governance Council, and other boards in Europe and Asia.

Roco was selected as "Engineer of the Year" by NSF and the U.S. National Society of Professional
Engineers in 1999 and again in 2004. Among his other honors are Germany's Carl Duisberg Award,
a Burgers Professorship Award in Netherlands, the U.S. University Research Professorship award,
and a 2002 Best of Small Tech Award as "Leader of the American Nanotechnology Revolution."
Forbes magazine recognized him in 2003 as first among "Nanotechnology's Power Brokers," and
Scientific American named him one of 2004's "Top 50 Technology Leaders."
William Sims Bainbridge
William Sims Bainbridge earned his doctorate in sociology from Harvard University. He is the author
of 11 books, 4 textbook-software packages, and about 180 shorter publications in information
science, social science of technology, and the sociology of religion. Most recently, he is the Editor of
the Berkshire Encyclopedia of Human-Computer Interaction and author of the forthcoming God from
the Machine, a study using artificial intelligence techniques to understand religious belief. With
Mihail Roco, he co-edited Societal Implications of Nanoscience and Nanotechnology (2001), Societal
Implications of Nanoscience and Nanotechnology II (2005), Converging Technologies for Improving
Human Performance (2003), and Converging Technologies in Society (2005). At the National Science
Foundation since 1992, Bainbridge represented the social and behavioral sciences on five advanced
technology initiativesHigh Performance Computing and Communications, Knowledge and Distributed
Intelligence, Digital Libraries, Information Technology Research, and Nanotechnologybefore joining
the staff of the Directorate for Computer and Information Science and Engineering. More recently he
has represented computer science on the Nanotechnology initiative and the Human and Social
Dynamics initiative. Currently, he is Program Director for Social Informatics, after having directed
the Sociology, Human Computer Interaction, Science and Engineering Informatics, and Artificial
Intelligence programs.
Section One: Development Drivers
Chapter 1. Lessons in Innovation and Commercialization from the Biotechnology Revolution

Chapter 2. Nanotechnology and Our Energy Challenge

Chapter 3. Fads and Hype in Technology: The Sargasso Sea of "Some Day Soon"
Chapter 1. Lessons in Innovation and
Commercialization from the Biotechnology
Revolution
Gerald Gallwas

"We shape our tools and forever after, they shape us."

Marshall McLuhan

Chemistry in many forms is a major force shaping the modern world. It is the fundamental science
of materials, providing everything from the tools we use to the medicines we take. Silicon and
germanium enabled integrated circuits, hydrogen and oxygen propelled us into space, and
recombinant DNA brought new drugs and pest-resistant crops.

Yet for all these benefits, chemistry is both a misunderstood, and in many ways an unappreciated,
science. Rather than praise its benefits, our attention is repeatedly focused on chemistry's perils,
such as its potential to pollute. Nevertheless, we have at our disposal a great abundance of chemical
technology that is changing our lives without our even knowing it. An ancient Chinese proverb
reminds us that "only a fool would predict the future." As we contemplate that future, the wiser
question to ask is, what did we learn from chemistry in the twentieth century? The story of
biotechnology offers many contemporary lessons, especially in innovation and the commercialization
of new technologies.
The Story of Biotechnology
Although the story of biotechnology began much earlier, it was Jim Watson and Francis Crick's 1953
announcement of the structure of DNA that made the new biology a public issue.[1] The double-helix
model they described was simple and eloquent. It provided an explanation for the replication of life
at the molecular level.

An avalanche of research followed, but it was not until 1972 that Paul Berg and colleagues at
Stanford University developed techniques to "cut and paste" DNA, creating the first recombinant
DNA molecule containing DNA from two different species.[2] As an analogy, think of editing an
audiotape. Suppose you cut the tape with a pair of scissors at a point between two songs, insert a
new piece of tape with a new song at the cut, and use an adhesive to join the ends together. If you
insert the spliced tape into a tape recorder, you'll hear a different sequence of songs.

Even at this early stage, Berg postulated that recombinant DNA technology could provide a pathway
to gene therapy. Berg shared the 1980 Nobel Prize in chemistry for this pioneering work. In 1973,
Herbert Boyer (of the University of California, San Francisco) and Stanley Cohen (of Stanford
University) were credited with being the first "genetic engineers"; they used restriction enzymes to
selectively cut and paste DNA and then inserted the new DNA into bacteria, which, by reproducing,
made millions of copies of the new DNA. In effect, this was the creation of a DNA factory.[3]

The news spread. Advances in recombinant DNA were exciting and yet frightening. Scientists, then
the news media, and finally Congress became concerned about the implications of gene
manipulation. Would it create a modern Frankenstein's monster? What controls should be imposed?
In early 1975, more than 100 interested parties from around the world, guided by the leadership of
Paul Berg, met at the Asilomar Conference Center in California to debate the promise and pitfalls of
recombinant DNA.[4] The recommendations of the meeting were sent to the National Institutes of
Health (NIH) and served as the basis for the official guidelines for the technology, published in
1976.[5]

Boyer and Cohen's success in inserting a gene into bacteria aroused the interest of a young venture
capitalist, Robert Swanson, from San Francisco.[6] In 1976, Swanson's question was, how could the
Boyer-Cohen technology be used to produce a marketable protein product, perhaps a therapeutic
product such as human insulin? In April of that year, Swanson and Boyer each invested $500 to
create Genentech, the world's first biotechnology company. Competition quickly followed, with the
formation of Biogen. The flag of the biotech industry had been planted, and the first goal was to
create human insulin.

Genentech and Biogen chose different technical paths to this common goal. Genentech focused on
chemically synthesizing the human insulin gene, whereas Biogen relied on cloning techniques. The
chemically synthesized gene would escape the NIH safety regulations, but the cloning of the human
gene would be subject to the NIH controls.

At the time, Genentech was a company in name only. It had no staff, no facilities, and no money.
Boyer turned to Arthur Riggs and Keiichi Itakuratwo colleagues at the City of Hope National Medical
Centerand asked whether they would accept a contract to synthesize the human insulin gene. Riggs
and Itakura were in the process of writing a grant proposal to the NIH for the synthesis of the
human hormone somatostatina simpler task, but one that would demonstrate the pathway to the
synthesis of insulin.

Riggs answered Boyer's question with a question: Would Genentech be willing to sponsor the
somatostatin project first? The answer was yes, and the Genentech and City of Hope teams joined
forces. Soon thereafter, Riggs and Itakura inserted a 21-nucleotide-long strand of DNA into E. coli
bacteria, and with the collaboration of Herb Heyneker, a young chemist from Boyer's lab, they
demonstrated for the first time that man-made DNA would function in a living cell.

Sixteen months later, the combined team successfully synthesized a gene for somatostatin, cloned
it, and expressed the somatostatin protein hormone in bacteria.[7] This was the first time anyone
had successfully expressed a protein of any kind in genetically engineered bacteria. The race for
human insulin accelerated.

The Riggs-Itakura technology was remarkable because it was a general technique, one that could be
used to manufacture most proteins in a bacterial host. It resulted in numerous U.S. and foreign
patents, from which billions of dollars' worth of pharmaceutical products have been developed. In
the meantime, the NIH turned down Riggs and Itakura's grant proposal on the grounds that it was
too ambitious and without practical purpose!

With the somatostatin success, Swanson began to raise funds in earnest, holding out the real
promise of human insulin to investors. By June 1978, Genentech was hiring scientists and had built
a laboratory facility near the San Francisco airport. Three months later, near the end of August, the
combined City of Hope and Genentech team had produced human insulin from a synthesized gene.
The improbable had become reality.

The story of Genentech and the launch of the biotech industry is well told in histories by Hall and by
Evans.[8], [9] It is the story of basic science from an academic environment turned into a
phenomenal business success. It is the story of an industry starting from scratch, not a spin-off from
a mature business sector, as with pharmaceuticals.

Today, nearly thirty years later, biotechnology is on its way to being a trillion-dollar industry
producing hundreds of therapeutic and biological products.[10] As we anticipate the future
development of nanotechnology, lessons from the biotechnology revolution can offer a useful
perspective, particularly with respect to two concepts fundamental to an understanding of
technology innovation and commercialization.
Concept 1: Lessons From the S-Curve
The first concept is that of the S-curve. Introduced by Richard Foster, the S-curve describes the
relationship between the investment of resources in a technology or process and the resulting
performance produced by that investment (Figure 1-1).[11] It is referred to as an S-curve because
when the results are plotted, the resulting figure typically takes the shape of the letter S.

Figure 1-1. An example of an S-curve.

In an early stage, as effort is ramping up on a technology or process, there is little return on

investment while basic knowledge is slowly gained. As the knowledge base increases, the investment
passes a tipping point; after that point, progress accelerates rapidly and then begins to slow as the
technology reaches maturity. Beyond a certain point, no amount of additional investment will
markedly improve the performance.

The single-engine propeller aircraft serves as an excellent example (Figure 1-2).[12] The Wright
brothers' first flight in 1903 was at a speed of about 35 mph. Seven years later, in 1910, the Gordon
Bennett air race at Belmont Park, New York, was won at 60 mph. As the fundamentals of aircraft
design became widely understood, speeds increased to 139.66 mph in 1914 and then to 145.7 mph
in 1922. In 1925, Lieutenant James Doolittle, in a Curtiss R3C-2, flew at 232.57 mph. By 1939, the
record stood at 463.9 mph, and the S-curve began to flatten. In 1966, some 27 years later, a new
record for a single-engine piston aircraft was set at the Reno (Nevada) Air Races at 520 mph. By
1989, that number had improved by less than 9 mph. Somewhere in the vicinity of 525 mph, the
limits of single-engine propeller technology were reached. No amount of investment will return
significantly more performance.

Figure 1-2. S-curve, single-engine propeller aircraft example.

[View full size image]

Jet aircraft engine technology offered the next step in performance and, as you might suspect,
defined a new S-curve in air speed. The gap between the two curves is referred to as the
discontinuity between the two technologies (Figure 1-3).

Figure 1-3. S-curves often come in pairs.

The example of the single-engine propeller-driven aircraft offers two lessons that are characteristic
of innovation and commercialization: the lessons of limits and of discontinuity. Low on the curve
there is high risk, great uncertainty, and high potential for growth. High on the curve there is
performance certainty, giving rise to a false sense of security and yet little opportunity for growth.
The only pathway to significantly greater performance is to jump to a new S-curvefrom propeller to
jet, from vacuum tube to transistor, from the horse-drawn vehicle to the automobile. These are the
lessons of limits and discontinuities.

In the case of biotechnology, the original S-curve might be characterized as the technology for
commercialization of animal proteins for human use, as in the case of insulin. Bovine and porcine
insulin were extracted from slaughterhouse animals and then purified and sold. The discontinuity
created by the second S-curve involved the use of the synthesized insulin gene inserted into bacteria
for the production of human insulin. This innovation provided the basis for an entirely new industry.
Concept 2: Lessons From Commercial Innovation
The second concept that is useful in understanding the commercialization of innovative technology
relates to the basic drivers of successful new product or process innovation. Simplistically,
innovation has been described as a function of creativity and implementation. But it is more than
that. The biotechnology experience, among other examples, shows that innovation should be viewed
more comprehensively as a function of

Creativity

Management

Team

Investment

Demand

It required creative people with innovative ideas, strong, focused management, a multidisciplinary
team, significant investment of capital, and the promise of return on investment to bring
biotechnology from the research laboratory to the marketplace.

Innovative Product Commercialization, a function of:

(Creativity x Management x Team)(Investment)(Demand)

As an analogy, consider a musical concert. Creativity is contributed by the composer, management

by the music director, and the team by the performing artists and members of the orchestra.
Investment in the concert is a matter of the sponsor's belief that the musical experience will attract
attendance (demand) and that box office receipts will supply the expected revenue and return on
investment. All are required for success.

In the insulin example, the Boyer-Cohen technology clearly provided the creative catalyst that
inspired Robert Swanson to lead and manage the commercial development of chemically
synthesized insulin. But without the combined team at the City of Hope and Genentech, the race for
genetically engineered insulin would not have been a West Coast victory. Swanson's ability to both
manage the start-up of Genentech and raise investment capital based on the promise (demand
attraction) of insulin was remarkable. But it was the combined multifunctional team of Genentech
and the City of Hope, with leverage from the Riggs-Itakura technology, that turned the game
entirely in the favor of the Genentech success.
The S-Curve Summarized
Here is the concept of the S-curve in a nutshell:

New technology is a slow process, requiring years of incubation. Often, new technologies
appear to be solutions looking for problems. Some 22 years elapsed between the invention of
powered flight and Doolittle's flight at 232 mph. Similarly, 24 years elapsed between Watson
and Crick's DNA announcement in 1953 and development of the general technique to
manufacture proteins in bacterial hosts based on the somatostatin model created by Riggs and
Itakura in 1977. Typically, 20 or more years are required for a new technology to mature to
the point of an accelerating S-curve. The knowledge base and tools must be put into place.
Eventually, limits are reached; but biotechnology is still relatively low on the S-curve, with
hundreds of new products in the development process.

Every technology has limits. The process of insulin production based on animal source
materials was inadequate to meet rising future demand.

When new technology is introduced, there is skepticism from all quarters, including other
scientists, the news media, Congress, government agencies, and the investment community.
The discontinuity between the two S-curves means leaving the security of the old for the
uncertain promise of the newa required step to reach new heights of performance.
Commercial Innovation Summarized
The commercial application of innovation can be summarized as follows:

New technology requires creative thinking and innovative action. The creative discovery or
invention is essential, but it is the implementation through strong management and
multidisciplinary team performance that enables commercial success.

The value of new technology often goes unrecognized and unfunded until the potential is put
into perspective. The Riggs-Itakura somatostatin grant request to NIH was rejected as too
ambitious and impractical. However, with the announcement of the success of somatostatin
and the publicity that followed, the scientific community, the news media, and even Congress
took notice.

Early visionary champions drive the diffusion of new technology. In the case of biotechnology,
Robert Swanson was the visionary and champion who inspired Boyer and the multibillion-dollar
industry that followed.

To attract capital for products and processes that are low on the S-curve, investor knowledge
and education are required. Somatostatin drew little investment interest until its value was
clearly demonstrated by way of a process to create human insulin. It was that promise that
drove investment.
The Future of Nanotechnology
Only a fool would predict the future.Ancient Chinese Proverb

Predicting the future is a hazardous task. What we need is a tool chest of relevant experience and
intuition, one that enables us to move from today's paradigm to a vision of tomorrow's potential.
These tools are needed because the rules of the physical world change when technology moves to
the atomic level. Our everyday understanding of mass and inertia, which govern actions such as
driving an automobile, no longer apply at the nanoscale.

For example, think of inserting a straw into a glass of water. Based on what we have been taught in
the macro world, water seeks its own level. Thus, we would expect the water inside the straw to
remain at the same level as the water on the outside of the straw, and that is the case. Yet if you
were to dip a capillary tube into the same glass of water, the water would rapidly rise in the
capillary far above the level of water in the glass. The rules change as we cross from our world of
macro reality into the dimension of the capillary, and so it will be with nanotechnology.

Only scientists armed with a sound understanding of the fundamental principles are likely to explore,
discover, and invent. They will be questioned and challenged every step of the way. Such was the
case with Riggs, Itakura, and Boyer in the example of synthetic insulin. Somatostatin was an
experiment of high potential and promise to the City of Hope scientists, and yet even the expert
reviewers at the National Institutes of Health failed to recognize the value of the Riggs-Itakura grant
proposal. Boyer, well versed in the science, understood the logic and so was able to sell the idea to
Swanson. This secured financial support for the somatostatin experiment based on the promise that
it provided the pathway to insulin. And so it did.

In the brief history and concepts offered in this chapter, a greatly simplified view has been taken.
Fundamental to any view of technological innovation is the discontinuity between two S-curvesin this
case, the step from biotechnology to nanotechnology. In the biotechnology example, we relied on
natureenzymesto do the molecular manipulation of cutting and pasting DNA molecules, and we
relied on bacteria to provide the factories for creation of new sources of materials. As we move into
the nanotechnology era, all the experience and tools of chemistry and biology in general and
recombinant DNA in particular are at our disposal. But rather than rely on enzymes and bacteria, we
must now create new nanoscale tools and processes, and it will take time. The ensuing
commercialization pathway requires a number of well-defined elements. After discovery come the
requirements of demand, investment, and implementation.

By way of example, William Coblentz of the National Bureau of Standards in Washington, D.C., first
examined and documented the relationship between the chemical structure of molecules and
infrared absorption spectra in 1905.[13] Yet even with the substantial knowledge base that grew
from this original work, the first commercial infrared spectrophotometer (an instrument that
measures light absorption as a function of wavelength) was not produced until 1942, when it was
driven by demand: the urgent need during World War II to produce synthetic rubber. Commercial
progress follows as technology evolves from the science to fulfill unmet needs in the marketplace. In
the case of nanotechnology it will be evolutionary and ubiquitous, and not revolutionary and
spontaneous.

Predicting the future is a hazardous task, but you can try it by conducting this thought experiment.
Consider the world before synthetic fibers, such as nylon; then jump back to the earlier S-curve of
natural fibers: hemp, silk, and cotton. With your feet planted in that earlier S-curve, use your tool
chest of relevant experience and "enlightened" intuition to envision the world of synthetic fibers.
Describe their characteristics; envision the ubiquitous applications that these new materials would
enable. You have just experienced the S-curve discontinuity. Now consider the drivers required for
the new synthetic technology to become commercial reality.

You have just forecast the future of nanotechnology. Read on.

References
1. J. D. Watson and F. H. C. Crick, Nature 171 (April 25, 1953): 737.
2. D. A. Jackson, R. H. Symons, and P. Berg, Proc. Nat. Acad. Sci. USA 69 (1972): 29042909.
3. Stanley N. Cohen, Annie C. Y. Chang, Herbert W. Boyer, and Robert B. Helling, "Construction
of Biologically Functional Bacterial Plasmids In Vitro," Proceedings of the National Academy of
Sciences (1973).

4. P. Berg et al., "Potential Biohazards of Recombinant DNA Molecules," letter, Science 185
(1974): 303.

5. Federal Register 41, no. 131 (1976), 2791127943.

6. S. S. Hughes, Isis 92 (2001): 541575.
7. K. Itakura et al., Science 198 (1977): 10561063.
8. S. S. Hall, Invisible Frontiers: The Race to Synthesize a Human Gene (Oxford: Oxford
University Press, 2002)

9. H. Evans, They Made America (New York: Little, Brown, 2004).

10. J. D. Watson, DNA, The Secret of Life (New York: Alfred A. Knopf, 2004).
11. R. Foster, Innovation: The Attacker's Advantage (New York: Summit Books, 1986).
12. M. W. Bowman, The World's Fastest Aircraft (Wellingborough, UK: Patrick Stephens Limited,
1990).

13. W. Coblentz, Investigations of Infrared Spectra (Washington, DC: National Bureau of

Standards, 1905).
Chapter 2. Nanotechnology and Our Energy
Challenge
Richard Smalley

I've increasingly begun to believe that a grand challenge before usthe world and humanityis what I
call "the terawatt challenge." I've been looking into the energy issue and I've been on a quest for
terawatts, or trillions of watts of electricity. What I'm looking for is to solve what I believe is the
most important problem facing humanity, the problem of generating energy of the magnitude that
we will need in this century for what could very well turn out to be ten billion people on the planet.

Energy is the single most important challenge facing humanity today. As we peak in oil production
and worry about how long natural gas will last, life must go on. Somehow we must find the basis for
energy prosperity for the twenty-first century. We should assume that by the middle of this century
we will need to at least double world energy production from its current level, with most of this
coming from some clean, sustainable, carbon dioxidefree source. For worldwide peace and
prosperity, it must be cheap.

Energy is a $3 trillion a year enterprise, by far the biggest enterprise of humankind. The second
most important is agriculture. It used to be that agriculture was almost everything, but agriculture
is now only half of energy. All of Defense, both in the United States and around the planet, is only
$0.7 trillion. I want to find a new oil, an energy source that will do for this century what oil did in
the last century.

I have asked audiences across the country, "What do you think deserves to be on the list of world
problems?" My hypothesis is that if you gather any group of people together the word energy will
always appear on this list. I've done this with fourteen independent audiences, and energy, phrased
in one way or another, is one of the first problems suggested.

World Problems

1. Energy

2. Water

3. Food

4. Environment

5. Poverty

6. Terrorism and war

7. Disease

8. Education

9. Democracy

10.
 8.

9.

10. Population

My second hypothesis is that if you solve the energy problem you will find that at least five of the
remaining nine problems on the list now have a path to an answer that's acceptable, whereas in the
absence of solving the energy problem, it is difficult, if not impossible in most cases, to have
imagined an answer.

Water is a very brutal problem. Either you've got it or you don't. Luckily, on our planet, there's
plenty of water. In fact, we probably have more water than anything else. But it has salt in it, and
it's often thousands of miles away from where we need it. We need it in vast amounts, hundreds of
millions of gallons a day. We can take the salt out of the water. There's no doubt some
nanotechnology that will do it at 100 percent efficiency or close to it, or you can just boil the water.
You can do it if you find the energy. And you've got to put it in a pipe and pump it to where you
need it, which might be thousands of miles away. We can make pipes and we know how to pump
them, but it costs energy to make them, it costs energy to maintain them, and energy to pump the
water from here to there. We can do it. If we have the energy, we can solve the water problem. Just
solve it, for ten billion people everywhere in the planet. If you haven't got the energy, you can't
solve the problem.

The third one on the list is food, which is going to be an increasing problem on our planet. We need
agriculture and we need water. So if you solve the water problem, you've gone a long way to solving
the food problem. In addition to food and water, you need fertilizers. You need energy for that. We
need to have a structure where we harvest food and move it around. We need energy for that also.
If you've got energy, you can hack this problem. If you don't have cheap, fast energy, I don't see
how you can solve the problem.

Virtually every aspect of our fourth problem, the environment, has directly to do with either the way
we generate energy, where we get it, how we store it, or what happens when we generate it. I don't
know of any other single thing, if you care about the environment, that would have a bigger positive
effect than to solve the energy problem. I don't know of anything else you could do for the
environment that would be more effective.

Energy would have a tremendous impact if you could solve itmake it cheap, make it abundant, find a
new oil. Miracles of science and technology in the physical sciences are primarily what enables this.

My third hypothesis is that no matter what you suggest as being items that deserve to be on this list
of the top ten, if you take something other than energy and move it to the top, you will not find
anywhere near the same cooperative, positive effect on the other ones as energy.

So you look at where the power is available, the true energy source that's available to generate
terawatts. It turns out it's very simple. The big place where we can get the terawatts we need is in
the place where there might as well be nothing right now. The technology that enables that has to
happen a lot sooner than 2050, because of the huge size of the population. So this is what I call the
terawatt challenge: to find a way of changing the energy source so that we can still be prosperous.

It's actually not clear that there is enough coal that's really efficiently, cheaply producible. It's
interesting that when you look for terawatts, all the other answers are nuclear. Solar energy is a
nuclear energy source, of course. Thus if you like nuclear and if you like nuclear fusion, you'll love
the sun. Every day, even though vast amounts of the solar energy go someplace else, 165,000
terawatts hit the Earth. We need only 20 terawatts to completely solve the world's energy needs.
This is a vast energy source. We just don't know how to get it cheaply yet.
Transport and Storage
I've done a lot of thinking about this, trying to think of some scheme for energy around the planet
that actually makes sense, technologically and economically, that's up to this terawatt challenge we
have. I call this idea the distributive storage grid. In the year 2050, instead of transporting energy
by moving masses of coal or oil, you transport energy as energy. You do that with a grid of electrical
connections, an interconnected grid of hundreds of millions of local sites.

Consider, for example, a vast interconnected electrical energy grid for the North American continent
from above the Arctic Circle to below the Panama Canal. By 2050 this grid will interconnect several
hundred million local sites. There are two key aspects of this future grid that will make a huge
difference: (1) massive long-distance electrical power transmission and (2) local storage of electrical
power with real-time pricing.

Storage of electrical power is critical for the stability and robustness of the electrical grid, and it is
essential if we are ever to use solar and wind as our dominant primary power sources. The best
place to provide this storage is locally, near the point of use. Imagine that by 2050 every house,
every business, every building has its own local electrical storage device, an uninterruptible power
supply capable of handling the entire needs of the owner for 24 hours. Because the devices are,
ideally, small and relatively inexpensive, the owners can replace them with new models every five
years or so as worldwide technological innovation and free enterprise continuously and rapidly
develop improvements in this most critical of all aspects of the electrical energy grid.

Today, using lead-acid storage batteries, such a unit for a typical house to store 100 kilowatt hours
of electrical energy would take up a small room and cost more than $10,000. Through revolutionary
advances in nanotechnology, it may be possible to shrink an equivalent unit to the size of a washing
machine and drop the cost to less than $1,000. With these advances the electrical grid can become
exceedingly robust, because local storage protects customers from power fluctuations and outages.
Most importantly, it permits some or all of the primary electrical power on the grid to come from
solar and wind.

The other critical innovation needed is massive electrical power transmission over continental
distances, permitting, for example, hundreds of gigawatts of electrical power to be transported from
solar farms in New Mexico to markets in New England. Then all primary power producers can
compete, with little concern for the actual distance to market. Clean coal plants in Wyoming,
stranded gas in Alaska, wind farms in North Dakota, hydroelectric power from northern British
Columbia, biomass energy from Mississippi, nuclear power from Hanford, Washington, and solar
power from the vast western deserts. Remote power plants from all over the continent contribute
power to consumers thousands of miles away on the grid. Nanotechnology in the form of single-
walled carbon nanotubes (aka "buckytubes"), forming what we call the "Armchair Quantum Wire,"
may play a big role in this new electrical transmission system.

Such innovationsin power transmission, power storage, and the massive primary power-generation
technologies themselvescan come only from miraculous discoveries in science, together with free
enterprise in open competition for huge worldwide markets.

The key is not only an energy source but also energy storage and energy transport. If you can solve
the problem of local storage, you've basically solved the whole problem. That's because, by
definition, the storage you need is local. You've got terawatts of power moving into the grid. The
biggest problem with renewable energies in general, and solar and wind in particular, is that they're
episodic and not dispatchable. You've got to have storage. Storing energy in batteries, capacitors,
fuel cells, and some chemical systems like hydrogen depends on nanoscale interactions. It depends
on charge transfer reactions that take place over the span of a few atoms on their surface. The next
generation of storage devices are all optimized by nanoengineered advances and the use of
nanoscale catalyst particles. Nanotechnology is where the action is in energy storage.
Energy for Everyone
So in summary I believe that if you had to pick one issue that's more important than any other
single issue, it is energy. You could have picked any issue, but energy is something we can do
something about, and if we do it, we can affect positively most of the other problems facing us.

The task would be supplying energy for ten billion people, and let's get it clean, cheap, and
continually available. If there's an answer, it will be some manipulation of matter on the nanoscale
that will give it to ussomething I like to call nanotechnology.
Chapter 3. Fads and Hype in Technology:
The Sargasso Sea of "Some Day Soon"
Peter Coffee

Is nanotechnology a fad? Prospective investors, or prospective research sponsors, want to knowand

it's not too early in the life cycle of the field to ask, and answer, this question. First, though, let's be
a little more specific about the ways that nanotechnology might disappoint us.

It could be another cold fusion, with its germ of potential utility vastly outweighed by its
hypeand with fractious scientific infighting scaring capital away to pursue more plausible
pathways.

It could be another synthetic-fuels or bubble-memory scenario, backed by valid science but not
economically competitive with established approachesor with their surprisingly long-lived
processes of continuing improvement.

It could be another artificial intelligence, a label that's reasonably defined as what we haven't
figured out how to dobecause once we can do it, it's assimilated into computer science,
operations research, game theory, or some other respectable discipline.

It's reasonable to wonder whether the concepts that sail together under the "nanotechnology" label
are heading for a new world of efficient use of energy and massor whether they're destined to circle
indefinitely around a Sargasso Sea of "some day soon."
Knowing Success When We See It
In this chapter we look at some fundamental reasons nanotechnology represents a virtuous circle, in
which every development enables additional progress, rather than sending us down a long and
costly road with no real destination.

But just as fad is too general a word for how things might go wrong, nanotechnology is also so big
an umbrella that it's bound to harbor both realities and fantasies beneath it. The signal-to-noise
ratiothe proportion of reliable information to badmay always be less than we'd like, because the
upper bound on what nanotechnology could someday mean is a compelling vision.

Moreover, as we learn to do specific things, and as that knowledge makes the move from concept to
practice, it will be natural for people to devise more specific labels for what they're doing
successfully. When people are trying to attract resources to present-day efforts, they want to
distance themselves from speculative visions of what nanotechnology might someday enable.
Paradoxically, this need of researchers to define their own niches could make it seem as if the term
nanotechnology has vanished from practical discussions.

The more ways that nanotechnology succeeds, the sooner this could happen.

Disappearance of the word would not mean, though, that nanotechnology was a fad. We can't
equate the success of a technology with the ubiquity or the longevity of its label. Some technology
labels come and go, whereas others survive for decades: We do well to recognize that a label
sometimes disappears through success rather than failure.

The labels that hang around forever may describe what we merely wish we could inventfor example,
"perpetual motion." Other labels fade from use, though, precisely because the thing they describe
has become the mainstream. We can already see, for example, the beginnings of the disappearance
of the adjectives in cellular phone, digital camera, and perhaps, in a few more years, hybrid car.

To today's teenagers, the first item is just a phone; to their younger brothers and sisters, the second
is just a camera. And by the time a child born tomorrow has learned to drive, the third will just be a
car. Will it seem quaint, in 2020 or perhaps as soon as 2010, to say that a product incorporates
nanotechnology components or that it's built using nanotechnology methods? Will this term seem as
dated as a label on a 1960s or 1970s radio that proudly proclaims it to be "solid state," trumpeting
its use of transistors rather than tubes?

Yes, in all likelihood it will.

Nanotechnology is not a fad, because it is a trend: It's being adopted, not defensively by firms afraid
of being left behind, but aggressively by companies that see what it can doand by communities of
research and application that are meeting long-felt needs through nanoscale control of ingredients
and processes.

Even if nanotechnology does have its roots in the singular vision of a Richard Feynman or a K. Eric
Drexler, that tree quickly leafs out into branches that extend into every industry. One recalls the
conversation from the 1967 movie The Graduate, in which an adult counsels a newly minted college
graduate that the one word that matters is plastics: Those who saw the new things that plastics
enabled, and did them, have most likely outperformed those who merely focused on the materials
themselves. So it will be with nanotechnology: Those who apply it will achieve greater returns than
those who merely enable and deliver it.
The nanotechnology components of finished products such as flat-panel displays will represent a
fraction of the product's value; far more significant will be the radical reduction of the up-front
capital cost of manufacturing such devices, lowering barriers to entry and thus changing the entire
landscape of that marketplace.
The Nature of Hype
The flip side of a fad, though, is the problem of hype: excessive chatter about a technology that
generates unreasonable expectations. It would be one thing if hype were merely a disconnected
phenomenon, like an instrument that gives wildly inaccurate readings without any possibility of
actually changing what it purports to measure. In the realms of research and finance, though, hype
can actually drive the best teams away from a field.

Why? A pragmatic researcher may choose to avoid the no-win proposition of either failing, on the
one hand, or succeeding only to find that people are unimpressed with what they had been falsely
told was sure to happen sooner or later. Computer recognition of unconstrained human speech is a
good example: Even the best actual products are simply no match for what people have been seeing
on science-fiction TV shows for decades.

Similarly, a finance team may want to avoid being tarred with the brush of only going after the
obvious opportunities, even when it takes real talent to see the genuine prospects through the
smoke of popular misperceptions.

Researchers from Gartner, an analysis and research company specializing in the information
technology industry, have even defined a "hype cycle," which begins with a "technology trigger" that
creates significant interest. One might pick any of several such triggers for the nanotech
manifestation of this cycle, but K. Eric Drexler's 1986 novel Engines of Creation is probably a
document that can be cast in this role.

Today's environment of commercial technology reporting and forecasting, venture capital (VC)
looking for opportunity, and the conference and lecture circuit creates a volatile mix: A small
injection of the fuel of technical potential is finding a vast oxidizing atmosphere of those who have
an interest in anointing The Next Big Thing. The result is a hot but short-lived explosion of inflated
expectations.

Investors may almost throw money at start-ups whose success in attracting capital may have little
to do with their founders' actual skills as developers and implementers. People in the venture capital
industry, observes David Eastman, General Partner at Prospector Equity Capital, have "the bad habit
of sometimes jumping into and out of the latest fad together. You've seen it happen with disk drives,
optical networking and network storage." Eastman has warned, "VCs will fund three or four times as
many players as can possibly survive in a hot sector; when the hockey stick projections don't
develop in the expected time frame, many will abandon the sector, often just as it's starting to
develop into a real business."

The subsequent disillusionment may last much longer than the initial flush of interest, as those who
expected too much seek to wind up with at least an aura of hard-earned wisdom by narrating their
lessons learned. This is when good technologies may find themselves starved of needed resources
for legitimate, moderately paced refinement, and this is what nanotechnology proponents might
justifiably have feared only a few years ago.

What keeps a technology out of that pit, though, is the combined effects of many different players
finding many different applications of the kinds described here and in other chapters. The need is for
applications in which fundamental barriers of physical possibility, or thickets of diminishing returns
on increasing investments, make it clear that something better is needed. The present ferment of
nanoscale technologies is being driven by such applications, and therefore by actual science rather
than mere marketing. Capital and talent are being pulled into play by the opportunity that exists to
develop products that have solid advantages to offer. This is quite different from the dot-com boom,
in which success was measured by hits on unprofitable Web sites.

The resulting "slope of enlightenment," as Gartner puts it, is gradual but important: It leads to an
even less dramatic, but ultimately more valuable, "plateau of productivity" on which most of the
money is madeeven while the chattering techorati lament the imminent end of the era. Silicon-based
semiconductors come to mind: Their displacement by gallium arsenide has been confidently
predicted as both necessary and imminent for at least a decade, but it seems very little closer now
than it did in the early 1990s.

Given the fundamental nature of atoms, perhaps the end of the nanotechnology era will not be
chatted up so prematurelysince it's hard to imagine what will succeed it.
Clouding the Picture
It can be hard, though, to see a clear picture of nanotechnology's bright future through the haze of
arguments over terminology. Arguably, for example, current semiconductor manufacturing
techniques operate at the nanoscale in that they meet the simple test of working with dimensions on
the order of nanometers.

In the same way that a circuit designer needs an oscilloscope that has at least a 10-GHz bandwidth
to accurately characterize a 1-GHz signal, a semiconductor fabrication line needs nanometer (or
even subnanometer) accuracy to fabricate devices with feature sizes on the order of 20 nanometers
thick, or about one thousandth the width of a human hair. That is the announced goal of Intel, for
example, which hopes to produce flash memory chips on that scale around 2012.[1]

Others, though, insist that "real" nanotechnology is the building of devices that give users
molecular-level control of the content and arrangement of the components of the device, as opposed
to merely working with bulk materials at nanometer scale. Consider the building of carbon
nanotubes, which are cylinders made up of pentagonal rings about a nanometer in diameter.
Building carbon nanotubes is a molecule-by-molecule processone that has yet to achieve the
simplicity and consistency, and therefore the economy, of growing a monolithic semiconductor-
grade silicon crystal.

It's certain that key nanotechnology goals depend on achieving this level of control, but progress is
being made along these lines. Work published in November 2004, for example, has described the
use of artificially constructed DNA molecules to orient and place carbon nanotubes between
electrode pairs to create transistors.[2]

This kind of synergythat is, the use of one kind of molecular engineering to carry out another kind of
molecular construction processseems likely to be a common theme of successful nanotechnology
developments.

Moreover, mass-market manufacturers such as South Korea's Samsung are already applying the
properties of nanoscale materials such as carbon nanotubes to their next-generation products.
Already working in prototype form, for example, are flat-panel TV screens, known as "field emission
displays," that are on track for mass-market availability by the end of 2006.[3] Functioning as an
array of precise and compact electron guns bombarding a phosphor screen, a nanotube backplane
allows a display designer to combine superior brightness, sharpness, and power consumption
characteristics with the convenient flat-panel form.

Any consumer electronics maker that does not match Samsung's aggressive investment in this
technology is rehearsing for a replay of the fate that befell competitors of Sony and Panasonic in the
1960s, when those companies essentially created the pocket-sized transistor radio as the icon of the
solid-state revolution.[4] Note well that although Sony was not the first to offer an all-transistor
radio, its 1955 product was the first to come from a company that made its own transistors.
Subsequent innovations, such as Sony's use of vertical-field-effect devices in FM-stereo receivers
came from the same focus on core technology. Samsung's Advanced Institute of Technology (south
of Seoul) represents a similar commitment of energy and resources.

It's also vital to recognize that nanomaterial applications stem from the many different
characteristics of these unfamiliar substances. The electrical properties of carbon nanotubes are one
thing; their thermal propertiesspecifically, the high thermal conductivity that could make them a
useful addition to the heat-transferring "thermal grease" that's applied between computer
microprocessors and their heat sinksare another.[5]
Difficulties in fabrication consistency that might cripple one applicationfor example, one that
depends on a consistent nanotube lengthcould be irrelevant in a task, such as heat conduction, that
depends only on aggregate properties. Other such aggregate-property impacts of nanomaterials
include improved air retention in tennis balls, better stain resistance in fabrics, longer shelf life and
better skin-penetration characteristics for cosmetic and physical-therapy products, and reduced
degradation of meat and cheese products prior to sale.[6] These are not merely potential
applications, but are actual uses of mass-produced nanomaterials that are now being incorporated
into consumer products. For example, nearly half of Dockers clothing uses nanotechnology-based
fabric treatments that resist stains or improve perspiration handling.

It's also important to note that nanomaterials are interesting, not merely for their size and their
average properties, but for their potential of achieving unprecedented levels of consistency in many
physical characteristics that were previously far below the "noise floor" of conventional manufacture.
In the same way that lasers enabled new processes by offering a coherent source of perfectly
monochromatic light, a nanotechnological process can deliver what we might call coherent objectsfor
example, the so-called nanoshell spheres that can be precisely tailored to convert a particular
wavelength of light into heat. When coated with a material that preferentially bonds to cancerous
tumor cells, this property of nanoshells paves the way to a highly specific tumor-killing technique
(described in Cancer Letters in June 2004) that has far fewer detrimental side effects than other
cancer treatments.[7]

Even for those who insist on infinitesimally small mechanisms, built to order from molecular-scale
building blocks, the nanotechnology practitioners are ready to deliver. Prototypes of 35-nanometer
mechanical valves, potentially suited to applications such as ink delivery in ink-jet printers, were
constructed in 2004 from assemblies of roughly 75,000 atoms: Components derived from this work
could be seen in printers by 2008, and perhaps in drug-delivery systems before 2015, according to
researchers at California Institute of Technology, who demonstrated the use of a silicon beam to
pinch closed a carbon nanotube.[8]
A Virtuous Circle
Technologies can succeed only when they combine appropriate control of energy, materials, design,
measurement, fabrication, and marketing. Absent any of these, one has at best a laboratory
demonstration; at worst, a costly or even fraudulent disappointment.

Nanotechnology, though, has all these elements at the ready. What's more, nanotechnology
represents a practical solution to fundamental limits being encountered in all these areas by existing
approaches.

Nanotechnology therefore has vastly more friends than enemies: There is really no industry that's
likely to perceive nanotechnology as a threat. Rather, it represents the prospect of offering many
industries their next generation of improved products that deliver more capabilityor novel,
previously unobtainable capabilityat a quite attractive price.

A virtuous circle can be kinked or broken, though, if those who offer a supposed technology
improvement fail to understand the environment in which it will be used. On a much larger scale
than the nanometer, it might look as if buttons (which can be lost) or zippers or drawstrings (which
can break or jam) might be better replaced by Velcro fasteners on soldiers' battle uniforms, but a
soldier's first reaction to a Velcro-flapped pocket might well be, "This makes way too much noise!"

Before manufacturers develop nanotechnology products based on what the developers think are
superior features or properties, it's essential to study the ways that existing products are actually
usedand the features or properties of those products that users never think to mention when asked
what they like or dislike, because it's never occurred to them that things could be otherwise.

At the same time, those who bring new products to market must anticipate and address prospective
buyers' objectionseven when those objections arise from a buyer's combining past experience with
inadequate understanding of future benefits. When vacuum tubes were being replaced by transistors
in field communications equipment, one experienced technician complained to an engineer that a
failed transistor needed a piece of test gear to identify it, unlike a blown tube, which could easily be
recognized on sight. That's perfectly accurate, but it failed to appreciate the enormous reduction in
the actual number of device failures that would be encountered in the field with solid-state devices.

Bringing nanoscale processes and products to market may depend on overcoming similarly
incomplete understanding of their impact.

Technologies fail to gain traction in the marketplace when they require too great a discontinuous
leap from existing modes of design and production. Nanotechnology has already succeeded, though,
in building on existing manufacturing foundations; one example is the May 2004 production of
carbonnanotube computer memory cells on a high-volume semiconductor production line by LSI
Logic, working with nanotechnology semiconductor pioneer Nantero Inc. in Woburn,
Massaschusetts.[9]

Perhaps equally important is that nanotechnology semiconductors don't depend on one single
approach, such as Nantero's. Another company, Zettacore Inc., of Englewood, Colorado, is
developing memory chips that use a chlorophyll-derived molecule having the ability to act as an
electron-storage site. Still another approach has been demonstrated at Boston University, where a
microscopic mechanical beamin late-2004 tests, 8,000 nanometers longcan be made to flex in either
of two directions, thereby storing a binary 1 or 0, the form in which computer data is stored and
manipulated. When scaled down to 1,000-nanometer length, the resulting computer memory device
is expected to store 100 gigabytes per square inch while operating at frequencies exceeding 1
GigaHertz, surpassing semiconductor memory in both respects.

These three approachesone based on an engineered molecule, another on a biologically derived

molecule, and yet another on a nanoscale implementation of a familiar physical
behaviordemonstrate how broad the nanotechnology field really is.

Putting aside the nano- prefix, let's look for a moment at the many aspects that make up a
technology. The technology of firearms is a well-studied example. Its foundations include the
packaging and control of energy on the proper scale and in a convenient and reliable form. Without
gunpowder that's stable enough to store but prompt and vigorous in detonating when desired,
nothing else could happen.

Nanotechnology has that control of energy at its disposalwhether in the form of electrons, photons,
or mechanical storage methods.

Firearms also depend on materials science: Simple materials could be used to construct bulky,
failure-prone cannons, but a practical portable firearm demanded more sophisticated knowledge of
materials behavior. Applications of nanomaterials that are already in the marketplace display this
knowledge.

Finally, and most often noted when firearms are used as an example, there is the need for precise
and reproducible methods of manufacture. This implies tools and techniques of measurement and
fabrication. Nanoscale manufacture, in the purists' sense of controlling the arrangements of
individual molecules or even atoms, implies at the very least the ability to resolve images of
structures on this scale. It's one thing to measure bulk properties of materials and to estimate the
degree of molecular order and purity that's been attained; it's another to observe, let alone
manipulate, material fragments at this level of precision.

Progress in this area has been notable, though, and promising. FEI Co., in Hillsboro, Oregon,
announced in 2004 its achievement of image resolution below the threshold of one Angstrom unit
(0.1 nanometers)that is, about the size of a single hydrogen atom.[10] The U.S. Department of
Energy began work in 2000 on a microscope with half-Angstrom resolution, using an aberration-
correcting assembly of multiple magnetic-field "lens" elements: As of the end of 2004, the first such
unit at Lawrence Berkeley National Laboratory, in Berkeley, California, was expected to be
operational by 2008.
When Science Gets Down to Business
If adolescence must come between infancy and maturity, then nanotechnology's maturity is perhaps
on the waybecause adolescent behavior is already starting to emerge. Scamsters and rip-off artists
may already be entering the nanomaterials marketplace: Anecdotal reports have described, for
example, the shipment of ordinary carbon soot to buyers who thought they were getting nanotubes,
or the receipt of high-priced nanotube shipments containing tube-growth catalyst making up as
much as one-third of the volume.

There are indications that the materials most prone to customer complaint are those, such as carbon
nanotubes and fullerenes, in which precise molecular structure is everything. Other items, such as
nanoporous materials, whose value is better approximated by statistically measurable behaviors,
appear to be less of a problem. This suggests that precise measurements, standardized and reliable
tests, and mutually agreed-upon standards for characterizing and verifying nanomaterial quality will
be needed to make nanomaterials ready for full-time employment.

Another adolescent aspect of nanotechnology is the question of product safety. Nanoscale particles
may be able to bypass many of the human body's long-standing defenses, such as the skin and the
circulatory vessels' walls; toxicity issues may therefore arise. Car exhaust, toner particles from
xerographic copiers, and drug molecules are already produced and used in many environments
without dramatic ill effects being observed, but nanotechnology adopters must exercise
responsibility and manage public relations to address both legitimate and exaggerated concerns.[11]
Far From a Fad
We asked at the beginning of this chapter whether nanotechnology might be a kernel of utility
buried in a heap of hype. It's clear that this is not the case. The problems that nanotechnology is
already solving are fundamental; their solution is clearly valuable.

We asked whether the continued evolution of other approaches might make nanotechnology always
interesting, but never attractive in the mass market. That scenario has already been left behind.
Nanomaterials are not merely competitive, but are poised on the threshold of becoming the
dominant choice for many tasks.

We asked whether nanotechnology would remain forever a theoretical or philosophical possibility,

but always blocked from widespread use in practical manufacturing or other mainstream situations.
Again, that question has already been answered by existing uses, such as fabric treatments and
drug-delivery tools, with additional answers in the successful prototyping of new types of nanoscale
mechanical component or full-scale consumer electronics devices.

Not a fad, but a trend; not a field in itself, but a transformation in nearly every field of technology. If
there's bad news, it's that nanotechnology may be the next commodity: The mere ability to fabricate
and produce basic materials at the nanoscale may command unexciting profit margins beyond the
time frame of the 2010s, or at latest the 2020s.

The good news, though, is that the resulting new technology foundations will enable explosions of
new value on the upper levels of industry, medicine, and lifestyle.
References
1.
http://www.reed-electronics.com/eb-mag/article/CA475441?industryid=2116 .

2.
http://www.technologyreview.com/articles/04/12/rnb_120304.asp?p=1 .

3.
http://www.technologyreview.com//articles/04/11/mann1104.asp .

4.
http://eetimes.com/special/special_issues/millennium/companies/sony.html .

5.
http://news.com.com/Can+nanotubes+keep+PCs+cool/2100-7337_3-5166111.html?tag=nl .

6.
http://www.usatoday.com/tech/news/nano/2004-11-08-nano-on-the-move_x.htm .

7.
http://sciencentral.com/articles/view.php3?article_id=218392390 .

8.
http://www.trnmag.com/Stories/2004/102004/Mechanical_valve_design_goes_nano_Brief_102004.html
.

9.
http://www.trnmag.com/Stories/2004/111704/Nanomechanical_memory_demoed_111704.html .

10.
http://news.com.com/Superpowered+micro-scope+could+help+focus+nanotech+dream/2100-
7337_3-5471939.html .

11.
http://www.dailycal.org/article.php?id=17119 .
Section Two: The Players
Chapter 4. Nanotechnology Commercialization: Transcending Moore's Law with Molecular
Electronics and Nanotechnology

Chapter 5. Investment in Nanotechnology

Chapter 6. The Role of the U.S. Government in Nanoscale Science and Technology

Chapter 7. Overview of U.S. Academic Research

Chapter 8. Understanding University Technology Transfer for Nanotechnology

Chapter 9. Intellectual Property Policy and Impact

Chapter 10. Entrepreneurs in the Technological Ecosystem

Chapter 11. Major Corporations: Technology, Business, and the Culture of Opportunity

Chapter 12. Nanotechnology in Federal Labs

Chapter 4. Nanotechnology
Commercialization: Transcending Moore's
Law with Molecular Electronics and
Nanotechnology
Steve Jurvetson

The history of technology is one of disruption and exponential growth, epitomized in Moore's Law
and generalized to many basic technological capabilities that are compounding independently from
the economy. More than a niche subject of interest only to computer chip designers, the continued
march of Moore's Law will affect all sciences, just as nanotech will affect all industries. (We define
Moore's Law in some detail a bit later in this chapter.)

Thinking about Moore's Law in the abstract provides a framework for predicting the future of
computation and the transition to a new substrate: molecular electronics. An analysis of progress in
molecular electronics provides a detailed example of the commercialization challenges and
opportunities common to many nanotechnologies.
Technology Exponentials
Despite a natural human tendency to presume linearity, accelerating change from positive feedback
is a common pattern in technology and evolution. We are now crossing a threshold where the pace
of disruptive shifts is no longer intergenerational; instead, it begins to have a meaningful impact
over the span of careers and eventually over product cycles.

As early-stage venture capitalists (VCs), we look for disruptive businesses run by entrepreneurs who
want to change the world. To be successful, we must identify technology waves early and act upon
those beliefs. At Draper Fisher Jurvetson (DFJ), we believe that nanotech is the next great
technology wave, the nexus of scientific innovation that revolutionizes most industries and indirectly
affects the fabric of society. Historians will look back on the upcoming epoch as having no less
portent than the Industrial Revolution.

The aforementioned are some long-term trends. Today, from a seed-stage VC perspective (with a
broad sampling of the entrepreneurial pool), we are seeing more innovation than ever before. And
we are investing in more new companies than ever before.

In the medium term, disruptive technological progress is relatively decoupled from economic cycles.
For example, for the past 40 years in the semiconductor industry, Moore's Law has not wavered in
the face of dramatic economic cycles. Ray Kurzweil's abstraction of Moore's Law (from its focus on
transistors to a broader focus on computational capability and storage capacity) shows an
uninterrupted exponential curve for more than 100 years, again without perturbation during the
Great Depression or the world wars. Similar exponentials can be seen in Internet connectivity,
medical imaging resolution, genes mapped, and solved 3-D protein structures. In each case, the
level of analysis is not products or companies, but basic technological capabilities.

Kurzweil has summarized the exponentiation of our technological capabilities, and our evolution,
with this near-term shorthand: The next 20 years of technological progress will be equivalent to that
of the entire twentieth century. For most of us, who do not recall what life was like 100 years ago,
the metaphor is a bit abstract. In the early 1900s, in the United States, there were only 144 miles of
paved road, and most Americans (more than 94%) were born at home, without a telephone, and
never graduated from high school. Most (more than 86%) did not have a bathtub at home nor
reliable access to electricity. Consider how much technology-driven change has compounded over
the past century, and consider that an equivalent amount of progress will occur in one human
generation, by 2020. It boggles the mind, until one dwells on genetics, nanotechnology, and their
intersection. Exponential progress perpetually pierces the linear presumptions of our intuition.
"Future shock" is no longer on an intergenerational time scale.

The history of humanity is that we use our knowledge and technical expertise to build better tools
and expand the bounds of our learning. We are entering an era of exponential growth in our
capabilities in biotech, molecular engineering, and computing. The cross-fertilization of these
formerly discrete domains compounds our rate of learning and our engineering capabilities across
the spectrum. With the digitization of biology and matter, technologists from myriad backgrounds
can decode and engage the information systems of biology as never before. This inspires new
approaches to bottom-up manufacturing, self-assembly, and the development of layered, complex
systems.
Moore's Law
Moore's Law is commonly reported as a doubling of transistor density every 18 months. But this is
not something that Gordon Moore, co-founder of Intel, has ever said. It is a nice blending of his two
predictions; in 1965, he predicted an annual doubling of transistor counts in the most cost-effective
chip, and he revised it in 1975 to every 24 months. With a little hand waving, most reports attribute
18 months to Moore's Law, but there is quite a bit of variability.

The popular perception of Moore's Law is that computer chips are compounding in their complexity
at a nearly constant per-unit cost. This is one of the many abstractions of Moore's Law, and it relates
to the compounding of transistor density in two dimensions. Others relate to speed (the signals have
less distance to travel) and to computational power (speed x density).

So as not to miss the long-term trend while sorting out the details, we will focus on the 100-year
abstraction of Moore's Law. But we should digress for a moment to underscore the importance of
continued progress in Moore's Law to a broad set of industries.

The Importance of Moore's Law

Moore's Law drives chips, communications, and computers and has become the primary driver in
drug discovery and bioinformatics, medical imaging and diagnostics. Over time, the lab sciences
become information sciences, modeled on a computer rather than trial-and-error experimentation.

The NASA Ames Research Center shut down its wind tunnels this year. Because Moore's Law
provided enough computational power to model turbulence and airflow, there was no longer a need
to test iterative physical design variations of aircraft in the wind tunnels, and the pace of innovative
design exploration dramatically accelerated.

Pharmaceutical giant Eli Lilly processed 100 times fewer molecules this year than it did 15 years
ago, but its annual productivity in drug discovery did not drop proportionately; it went up over the
same period. "Fewer atoms and more bits" is Lilly's coda.

Accurate simulation demands computational power, and once a sufficient threshold has been
crossed, simulation acts as an innovation accelerant compared with physical experimentation. Many
more questions can be answered per day.

Recent accuracy thresholds have been crossed in diverse areas, such as modeling the weather
(predicting a thunderstorm six hours in advance) and automobile collisions (a relief for the crash
test dummies), and the thresholds have yet to be crossed for many areas, such as protein folding
dynamics.

Unless you work for a chip company and focus on fab-yield optimization, you do not care about
transistor counts. Integrated circuit customers do not buy transistors. Consumers of technology
purchase computational speed and data storage density. When recast in these terms, Moore's Law is
no longer a transistor-centered metric, and this abstraction allows for longer-term analysis.

The exponential curve of Moore's Law extends smoothly back in time for more than 100 years, long
before the invention of the semiconductor. Through five paradigm shiftssuch as electromechanical
calculators and vacuum tube computersthe computational power that $1,000 buys has doubled
every two years. For the past 30 years, it has been doubling every year.
Each horizontal line on the logarithmic graph given in Figure 4-1 represents a 100 times
improvement. A straight diagonal line would be an exponential, or geometrically compounding,
curve of progress. Kurzweil plots a slightly upward curving linea double exponential.

Figure 4-1. One-hundred-year version of Moore's Law. Each dot is a

computing machine. (Source: Ray Kurzweil.)

[View full size image]

Each dot represents a human drama, although the humans did not realize that they were on a
predictive curve. Each dot represents an attempt to build the best computer using the tools of the
day. Of course, we use these computers to make better design software and algorithms (formulas)
for controlling manufacturing processes. And so the progress continues.

One machine was used in the 1890 census; another one cracked the Nazi Enigma cipher in World
War II; still another one predicted Eisenhower's win in the presidential election. And there is the
Apple II, and the Cray 1, and just to make sure the curve had not petered out recently, I looked up
the cheapest PC available for sale on Wal-Mart.com, and that is the gray dot that I have added to
the upper-right corner of the graph.

And notice the relative immunity to economic cycles. The Great Depression and the world wars and
various recessions do not introduce a meaningful delay in the progress of Moore's Law. Certainly,
the adoption rates, revenue, profits, and inventory levels of the computer companies behind the
various dots on the graph may go through wild oscillations, but the long-term trend emerges
nevertheless.

Any one technology, such as the complementary metal oxide semiconductor (CMOS) transistor,
follows an elongated S-curve of slow progress during initial development, upward progress during a
rapid adoption phase, and then slower growth from market saturation over time. But a more
generalized capability, such as computation, storage, or bandwidth, tends to follow a pure
exponentialbridging a variety of technologies and their cascade of S-curves.

If history is any guide, Moore's Law will continue and will jump to a different substrate than CMOS
silicon. It has done so five times in the past and will need to again in the future.

Problems with the Current Paradigm

Gordon Moore has chuckled at those in past decades who predicted the imminent demise of Moore's
Law. But the traditional semiconductor chip is finally approaching some fundamental physical limits.
Moore recently admitted that Moore's Law, in its current form, with CMOS silicon, will reach its limit
in 2017.

One of the problems is that the chips are operating at very high temperatures. This provides the
impetus for chip-cooling companies to provide a breakthrough solution for removing 100 watts per
square centimeter. In the long term, the paradigm must change.

Another physical limit is the atomic limitthe indivisibility of atoms. Intel's current gate oxide is
1.2nm thick. Intel's 45nm process is expected to have a gate oxide that is only three atoms thick. It
is hard to imagine many more doublings from there, even with further innovation in insulating
materials. Intel has recently announced a breakthrough in a nanostructured gate oxide (high-k
dielectric) and metal contact materials that should enable the 45nm node to come online in 2007.
None of the industry participants has a CMOS road map for the next 50 years.

A major issue with thin gate oxides, and one that will also come to the fore with high-k dielectrics, is
quantum mechanical tunneling. As the oxide becomes thinner, the gate current can approach and
even exceed the channel current to the point that the transistor cannot be controlled by the gate.

Another problem is the escalating cost of a semiconductor fabrication plant (called a fab), a cost that
is doubling every three years, a phenomenon dubbed Moore's Second Law. Human ingenuity keeps
shrinking the CMOS transistor, but with increasingly expensive manufacturing facilitiescurrently $3
billion per fab.

A large component of fab cost is the lithography equipment that is used to pattern the wafers with
successive submicron layers. Nanoimprint lithography can dramatically lower cost and leave room
for further improvement from the field of molecular electronics.

We have been investing in a variety of companies that are working on the next paradigm shift to
extend Moore's Law beyond 2017. One near-term extension to Moore's Law focuses on the cost side
of the equation. Imagine rolls of wallpaper embedded with inexpensive transistors. One of our
companies deposits traditional transistors at room temperature on plastic, a much cheaper bulk
process than growing and cutting crystalline silicon ingots.
Molecular Electronics
The primary contender for the post-silicon computation paradigm is molecular electronics, a
nanoscale alternative to the CMOS transistor. Eventually, molecular switches will revolutionize
computation by scaling into the third dimensionovercoming the planar deposition limitations of
CMOS. Initially, these switches will substitute for the transistor bottleneck that results from a
standard silicon process using standard external input/output interfaces.

For example, Nantero, a nanotech firm based in Woburn, Massachusetts, employs carbon nanotubes
suspended above metal electrodes on silicon to create high-density nonvolatile memory chips (the
weak Van der Waals bond can hold a deflected tube in place indefinitely with no power drain).
Carbon nanotubes are small (approximately 10 atoms wide), 30 times as strong as steel at one-
sixth the weight, and they perform the functions of wires, capacitors, and transistors with better
speed, power, density, and cost. Cheap nonvolatile memory enables important advances, such as
"instant-on" PCs.

Other companies, such as Hewlett-Packard and ZettaCore, are combining organic chemistry with a
silicon substrate to create memory elements that self-assemble using chemical bonds that form
along prepatterned regions of exposed silicon.

There are several reasons molecular electronics is the next paradigm for Moore's Law:

Size: Molecular electronics has the potential to dramatically extend the miniaturization that
has driven the density and speed advantages of the integrated circuit (IC) phase of Moore's
Law. In 2002, using a scanning tunneling microscope (STM) to manipulate individual carbon
monoxide molecules, IBM built a three-input sorter by arranging those molecules precisely on a
copper surface. It is 260,000 times as small as the equivalent circuit built in the most modern
chip plant. For a memorable sense of the difference in scale, consider a single drop of water.
There are more molecules in a single drop of water than in all the transistors ever built. Think
of the transistors in every memory chip and every processor ever built; there are about 100
times as many molecules in a drop of water. Certainly, water molecules are small, but an
important part of the comparison depends on the 3-D volume of a drop. Every IC, in contrast,
is a thin veneer of computation on a thick and inert substrate.

Power: One of the reasons that transistors are not stacked into 3-D volumes today is that the
silicon would melt. The inefficiency of the modern transistor is staggering. It is much less
efficient at its task than the internal combustion engine. The brain provides an existing proof of
what is possible; it is 100 million times as efficient in power and calculation as our best
processors. Sure, it is slow (less than 1 kHz), but it is massively interconnected (with 100
trillion synapses between 60 billion neurons), and it is folded into a 3-D volume. Power per
calculation will dominate clock speed as the metric of merit for the future of computation.

Manufacturing cost: Many of the molecular electronics designs use simple spin coating or
molecular self-assembly of organic compounds. The process complexity is embodied in the
synthesized molecular structures, and so they can literally be splashed on to a prepared silicon
wafer. The complexity is not in the deposition nor the manufacturing process nor the systems
engineering. Much of the conceptual difference of nanotech products derives from a biological
metaphor: Complexity builds from the bottom up and pivots about conformational changes,
weak bonds, and surfaces. It is not engineered from the top down with precise manipulation
and static placement.
 Low-temperature manufacturing: Biology does not tend to assemble complexity at 1,000
degrees in a high vacuum. It tends to work at room temperature or body temperature. In a
manufacturing domain, this opens the possibility of using cheap plastic substrates instead of
expensive silicon ingots.

Elegance: In addition to these advantages, some of the molecular electronics approaches offer
elegant solutions to nonvolatile and inherently digital storage. We go through unnatural acts
with CMOS silicon to get an inherently analog and leaky medium to approximate a digital and
nonvolatile abstraction that we depend on for our design methodology. Many of the molecular
electronic approaches are inherently digital, and some are inherently nonvolatile.

Other research projects, from quantum computing to using DNA as a structural material for directed
assembly of carbon nanotubes, have one thing in common: They are all nanotechnology.
The Commercialization of Nanotechnology
Nanotech is often defined as the manipulation and control of matter at the nanometer scale (critical
dimensions of 1 to 100nm). It is a bit unusual to describe a technology by a length scale. We
certainly didn't get very excited by "inch-o technology." As venture capitalists, we start to get
interested when there are unique properties of matter that emerge at the nanoscale and that cannot
be exploited at the macroscale world of today's engineered products. We like to ask the start-ups
that we are investing in, "Why now? Why couldn't you have started this business ten years ago?"
The responses of our nanotech start-ups have a common thread: Recent developments in the
capacity to understand and engineer nanoscale materials have enabled new products that could not
have been developed at larger scale.

Various unique properties of matter are expressed at the nanoscale and are quite foreign to our
"bulk statistical" senses (we do not see single photons or quanta of electric charge; we feel bulk
phenomena, like friction, at the statistical or emergent macroscale). At the nanoscale, the bulk
approximations of Newtonian physics are revealed for their inaccuracy and give way to quantum
physics. Nanotechnology is more than a linear improvement with scale; everything changes.
Quantum entanglement, tunneling, ballistic transport, frictionless rotation of superfluids, and several
other phenomena have been regarded as "spooky" by many of the smartest scientists, even Einstein,
upon first exposure.

For a simple example of nanotech's discontinuous divergence from the "bulk" sciences, consider the
simple aluminum soda can. If you take the inert aluminum metal in that can and grind it down into a
powder of 2030nm particles, it will spontaneously explode in air. It becomes a rocket fuel catalyst.
In other words, the energetic properties of matter change at that scale. The surface-area-to-volume
ratios become relevant, and even the distances between the atoms in a metal lattice change from
surface effects.

Innovation from the Edge

Disruptive innovation, the driver of growth and renewal, occurs at the edge. In start-ups, innovation
occurs out of the mainstream, away from the warmth of the herd. In biological evolution, innovative
mutations take hold at the physical edge of the population, at the edge of survival. In complexity
theory, structure and complexity emerge at the edge of chaosthe dividing line between predictable
regularity and chaotic indeterminacy. And in science, meaningful disruptive innovation occurs at the
interdisciplinary interstices between formal academic disciplines.

Herein lies much of the excitement about nanotechnology: in the richness of human communication
about science. Nanotech exposes the core areas of overlap in the fundamental sciences, the place
where quantum physics and quantum chemistry can cross-pollinate with ideas from the life sciences.

Over time, each of the academic disciplines develops its own proprietary systems vernacular that
isolates it from neighboring disciplines. Nanoscale science requires scientists to cut across the
scientific languages to unite the isolated islands of innovation. As illustrated in Figure 4-2, nanotech
is the nexus of the sciences.

Figure 4-2. Nanotech is the nexus of the sciences.

In academic centers and government laboratories, nanotech is fostering new discussions. At
Stanford, UCLA, Duke, and many other schools, the new nanotech buildings are physically located at
the symbolic hub of the schools of engineering, computer science, and medicine.

Nanotech is the nexus of the sciences, but outside the sciences and research itself, the nanotech
umbrella conveys no business synergy whatsoever. The marketing, distribution, and sales of a
nanotech solar cell, memory chip, or drug delivery capsule will be completely different from each
other and will present few opportunities for common learning or synergy.

Market Timing
As an umbrella term for a myriad of technologies spanning multiple industries, nanotech will
eventually disrupt these industries over different time framesbut most are long-term opportunities.
Electronics, energy, drug delivery, and materials are areas of active nanotech research today.
Medicine and bulk manufacturing are future opportunities. The National Science Foundation predicts
that nanotech will have a trillion-dollar impact on various industries within 15 years.

Of course, if one thinks far enough in the future, every industry eventually will be revolutionized by
a fundamental capability for molecular manufacturingfrom the inorganic structures to the organic
and even the biological. Analog manufacturing will become digital, engendering a profound
restructuring of the substrate of the physical world.

Futuristic predictions of potential nanotech products have a near-term benefit. They help attract
some of the best and brightest scientists to work on hard problems that are stepping-stones to the
future vision. Scientists relish exploring the frontier of the unknown, and nanotech embodies the
tangible metaphor of the inner frontier.

Given that much of the abstract potential of nanotech is a question of "when" and not "if," the
challenge for the venture capitalist is one of market timing. When should we be investing, and in
which subsectors? It is as if we need to pull the sea of possibilities through an intellectual filter to
tease apart the various segments into a time line of probable progression. That is an ongoing
process of data collection (for example, the growing pool of business plan submissions), business
and technology analysis, and intuition.

Two touchstone events for the scientific enthusiasm for the timing of nanotech were the decoding of
the human genome and the dazzling visual images output by the scanning tunneling microscope
(such as the arrangement of individual xenon atoms into the IBM logo). These events represent the
digitization of biology and mattersymbolic milestones for accelerated learning and simulation-driven
innovation.

More recently, nanotech publication has proliferated, as in the early days of the Internet. In addition
to the popular press, the number of scientific publications on nanotech has grown by a factor of 10
in the past ten years. According to the U.S. Patent and Trademark Office (USPTO), the number of
nanotech patents granted each year has skyrocketed by a factor of 3 in the past seven years. Ripe
with symbolism, IBM has more lawyers working on nanotech than engineers.

With the recent codification of the National Nanotech Initiative into law, federal funding will continue
to fill the pipeline of nanotech research. With $847 million earmarked for 2004, nanotech was a
rarity in the tight budget process; it received more funding than was requested. Now nanotech is
second only to the space race for federal funding of science. And the United States is not alone in
funding nanotechnology. Unlike many previous technological areas, we aren't even in the lead;
Japan outspends the United States each year on nanotech research. In 2003, the U.S. government
spending was one-fourth of the world total.

Federal funding is the seed corn for nanotech entrepreneurship. All of our nanotech portfolio
companies are spin-offs (with negotiated intellectual property [IP] transfers) from universities or
government labs, and all got their start with federal funding. Often these companies need
specialized equipment and expensive laboratories to do the early tinkering that will germinate a new
breakthrough. These are typically lacking in the proverbial entrepreneur's garage.

Corporate investors have discovered a keen interest in nanotechnology, with internal R&D, external
investments in start-ups, and acquisitions of promising companies, such as chipmaker AMD's recent
acquisition of Coatue, a molecular electronics company.

Despite all this excitement, there are a fair number of investment dead ends, and so we continue to
refine the filters we use in selecting companies to back. All entrepreneurs want to present their
businesses as fitting an appropriate time line to commercialization. How can we guide our intuition
to determine which of these entrepreneurs are right?

The Question of Vertical Integration

Nanotech involves the reengineering of the lowest-level physical layer of a system, and so a natural
business question arises: How far forward do you need to vertically integrate before you can sell a
product on the open market? For example, in molecular electronics, if you can ship a DRAM-
compatible chip, you have found a horizontal layer of standardization, and further vertical
integration is not necessary. If you have an incompatible 3-D memory block, you may have to
vertically integrate to the storage subsystem level, or farther, to bring a product to market. That
may require that you form industry partnerships, and it will, in general, take more time and money
as change is introduced farther up the product stack. Three-dimensional logic with massive
interconnectivity may require a new computer design and a new form of software; this would take
the longest to commercialize. And most start-ups on this end of the spectrum would seek
partnerships to bring their vision to market. The success and timeliness of that endeavor will depend
on many factors, including IP protection, the magnitude of improvement, the vertical tier at which
that value is recognized, the number of potential partners, and the needed degree of tooling and
other industry accommodations.

Product development time lines are impacted by the cycle time of the R&D feedback loop. For
example, outdoor lifetime testing for organic light-emitting diodes (LEDs) will take longer than in
silicon simulation spins of digital products. If the product requires partners in the R&D loop or
multiple nested tiers of testing, it will take longer to commercialize.

The Interface Problem

As we think about the start-up opportunities in nanotechnology, an uncertain financial environment
underscores the importance of market timing and revenue opportunities over the next five years. Of
the various paths to nanotech, which of them are 20-year quests in search of a government grant,
and which are market-driven businesses that will attract venture capital? Are there co-factors of
production that require a whole industry to be in place before a company ships products?

As a thought experiment, imagine that I could hand you today any nanotech marvel of your designa
molecular machine as advanced as you would like. What would it be? A supercomputer? A
bloodstream submarine? A matter compiler capable of producing diamond rods or arbitrary physical
objects? Pick something.

Now imagine some of the complexities: Did it blow off my hand as I offered it to you? Can it
autonomously move to its intended destination? What is its energy source? How do you
communicate with it?

These questions draw the interface problem into sharp focus: Does your design require an entire
nanotech industry to support, power, and interface to your molecular machine? As an analogy,
imagine that you have one of the latest Intel Pentium processors. How would you make use of the
Pentium chip? You then need to wire-bond the chip to a larger lead frame in a package that connects
to a larger printed circuit board, fed by a bulky power supply that connects to the electrical power
grid. Each of these successive layers relies on its larger-scale precursors (which were developed in
reverse chronological order), and the entire hierarchy is needed to access the potential of the
microchip.

Where Is the Scaling Hierarchy for Molecular Nanotech?

To cross the interface chasm, today's business-driven paths to nanotech diverge into two strategies:
the biologically inspired bottom-up path, and the top-down approach of the semiconductor industry.
The developers of nonbiological micro-electromechanical systems (MEMS) are addressing current
markets in the micro world while pursuing an ever-shrinking spiral of miniaturization that builds the
relevant infrastructure tiers along the way. Not surprisingly, this path is very similar to the one that
has been followed in the semiconductor industry, and many of its adherents see nanotech as
inevitable but in the distant future.

On the other hand, biological manipulation presents numerous opportunities to effect great change
in the near term. Drug development, tissue engineering, and genetic engineering are all powerfully
impacted by the molecular manipulation capabilities available to us today. And genetically modified
microbes, whether by artificial evolution or directed gene splicing, give researchers the ability to
build structures from the bottom up.

The Top-Down "Chip Path"

This path is consonant with the original vision of physicist Richard Feynman (in a 1959 lecture at
Caltech) of the iterative miniaturization of our tools down to the nanoscale. Some companies are
pursuing the gradual shrinking of semiconductor manufacturing technology from the MEMS of today
into the nanometer domain of nanoelectromechanical systems (NEMS).

MEMS technologies have already revolutionized the automotive industry with air-bag sensors, and
the printing sector with ink-jet nozzles, and they are on track to do the same in medical devices and
photonic switches for communications and mobile phones. In-StatJMDR forecasts that the $4.7
billion in MEMS revenue in 2003 will grow to $8.3 billion by 2007. But progress is constrained by the
pace (and cost) of the semiconductor equipment industry, and by the long turnaround time for fab
runs.

Many of the nanotech advances in storage, semiconductors, and molecular electronics can be
improved, or in some cases enabled, by tools that allow for the manipulation of matter at the
nanoscale. Here are three examples:

Nanolithography: Molecular Imprints is commercializing a unique imprint lithographic

technology developed at the University of Texas at Austin. The technology uses photo-curable
liquids and etched quartz plates to dramatically reduce the cost of nanoscale lithography. This
lithography approach, recently added to the ITRS Roadmap, has special advantages for
applications in the areas of nanodevices, MEMS, microfluidics, and optical components and
devices, as well as molecular electronics.

Optical traps: Arryx has developed a breakthrough in nanomaterial manipulation. Optical

traps generate hundreds of independently controllable laser tweezers that can manipulate
molecular objects in 3-D (move, rotate, cut, place), all from one laser source passing through
an adaptive hologram. The applications span from cell sorting, to carbon nanotube placement,
to continuous material handling. They can even manipulate the organelles inside an unruptured
living cell (and weigh the DNA in the nucleus).

Metrology: Imago's LEAP atom probe microscope is being used by the chip and disk drive
industries to produce 3-D pictures that depict both the chemistry and the structure of items on
an atom-by-atom basis. Unlike traditional microscopes, which zoom in to see an item on a
microscopic level, Imago's nanoscope analyzes structures, one atom at a time, and "zooms
out" as it digitally reconstructs the item of interest at a rate of millions of atoms per minute.
This creates an unprecedented level of visibility and information at the atomic level.

Advances in nanoscale tools help us control and analyze matter more precisely, which in turn allows
us to produce better tools. To summarize, the top-down path is designed and engineered with the
following:

Semiconductor industry adjacencies (with the benefits of market extensions and revenue along
the way and the limitation of planar manufacturing techniques)

Interfaces of scale inherited from the top

The Biological, Bottom-Up Path

In contrast to the top-down path, the biological bottom-up archetype is

Grown via replication, evolution, and self-assembly in a 3-D, fluid medium

Constrained at interfaces to the inorganic world

 Limited by gaps in learning and theory (in systems biology, complexity theory, and the pruning
rules of emergence)

Bootstrapped by a powerful preexisting hierarchy of interpreters of digital molecular code

To elaborate on this last point, a ribosome takes digital instructions in the form of mRNA and
manufactures almost everything we care about in our bodies from a sequential concatenation of
amino acids into proteins. The ribosome is a wonderful existence proof of the power and robustness
of a molecular machine. It is roughly 20nm on a side and consists of only 99,000 atoms. Biological
systems are replicating machines that parse molecular code (DNA) and a variety of feedback to grow
macroscale beings. These highly evolved systems can be hijacked and reprogrammed to great effect.

So how does this help with the development of molecular electronics or nanotech manufacturing?
The biological bootstrap provides a more immediate path to nanotech futures. Biology provides us
with a library of prebuilt components and subsystems that can be repurposed and reused, and
research in various labs is well under way in reengineering the information systems of biology.

For example, researchers at NASA's Ames Research Center are taking self-assembling heat shock
proteins from thermophiles and genetically modifying them so that they will deposit a regular array
of electrodes with a 17nm spacing. This could be useful for making patterned magnetic media in the
disk drive industry or electrodes in a polymer solar cell.

At MIT, researchers are using accelerated artificial evolution to rapidly breed an Ml3 bacteriophage
to infect bacteria in such a way that they bind and organize semiconducting materials with molecular
precision.

At the Institute for Biological Energy Alternatives (IBEA), Craig Venter and Hamilton Smith are
leading the Minimal Genome Project. They take Mycoplasma genitalium from the human urogenital
tract and strip out 200 unnecessary genes, thereby creating the simplest organism that can self-
replicate. Then they plan to layer new functionality onto this artificial genome, such as the ability to
generate hydrogen from water using the sun's energy for photonic hydrolysis.

The limiting factor is our understanding of these complex systems, but our pace of learning has been
compounding exponentially. We will learn more about genetics and the origins of disease in the next
ten years than we have in all of human history. And for the minimal genome microbes, the
possibility of understanding the entire proteome and metabolic pathways seems tantalizingly close
to achievable. These simpler organisms have a simple "one gene, one protein" mapping and lack the
nested loops of feedback that make the human genetic code so rich.

An Example: Hybrid Molecular Electronics

In the near term, a variety of companies are leveraging the power of organic self-assembly (bottom-
up) and the market interface advantages of top-down design. The top-down substrate constrains the
domain of self-assembly.

Based in Denver, ZettaCore builds molecular memories from energetically elegant molecules that
are similar to chlorophyll. ZettaCore's synthetic organic porphyrin molecule self-assembles on
exposed silicon. These molecules, called multiporphyrin nanostructures, can be oxidized and reduced
(their electrons removed or replaced) in a way that is stable, reproducible, and reversible. In this
way, the molecules can be used as a reliable storage medium for electronic devices.

Furthermore, the molecules can be engineered to store multiple bits of information and to maintain
that information for relatively long periods before needing to be refreshed. Recall the water-drop-to-
transistor-count comparison, and add to that the fact that these multiporphyrins have already
demonstrated as many as eight stable digital states per molecule.
The technology has future potential to scale to 3-D circuits with minimal power dissipation, but
initially it will enhance the weakest element of an otherwise standard 2-D memory chip. To end
customers, the ZettaCore memory chip looks like a standard memory chip; nobody needs to know
that it has "nano inside." The input/output pads, sense amps, row decoders, and wiring interconnect
are produced via a standard semiconductor process. As a final manufacturing step, the molecules
are splashed on the wafer, where they self-assemble in the predefined regions of exposed metal.

From a business perspective, this hybrid product design allows an immediate market entry because
the memory chip defines a standard product feature set, and the molecular electronics
manufacturing process need not change any of the prior manufacturing steps. Any
interdependencies with the standard silicon manufacturing steps are also avoided, thanks to this late
coupling; the fab can process wafers as it does now before spin-coating the molecules. In contrast,
new materials for gate oxides or metal interconnects can have a number of effects on other
processing steps, and these effects need to be tested. That introduces delay (as with copper
interconnects).

Generalizing from the ZettaCore experience, the early revenue in molecular electronics will likely
come from simple 1-D structures such as chemical sensors and self-assembled 2-D arrays on
standard substrates, such as memory chips, sensor arrays, displays, CCDs for cameras, and solar
cells.

IP and Business Model

Beyond product development time lines, the path to commercialization is dramatically impacted by
the cost and scale of the manufacturing ramp. Partnerships with industry incumbents can be an
accelerant or an albatross for market entry.

The strength of the IP protection for nanotech relates to the business models that can be safely
pursued. For example, if the composition of matter patents afford the nanotech start-up the same
degree of protection as for a biotech start-up, then a "biotech licensing model" may be possible in
nanotech. A molecular electronics company could partner with a large semiconductor company for
manufacturing, sales, and marketing, just as a biotech company partners with a big pharmaceutical
partner for clinical trials, marketing, sales, and distribution. In both cases, the cost to the big
partner is on the order of $100 million, and the start-up earns a royalty on future product sales.

Notice how the transaction costs and viability of this business model option pivot on the strength of
IP protection. A software business, on the other end of the IP spectrum, would be very cautious
about sharing its source code with Microsoft in the hopes of forming a partnership based on
royalties.

Manufacturing partnerships are common in the semiconductor industry, with the "fabless" business
model. This layering of the value chain separates the formerly integrated functions of product
conceptualization, design, manufacturing, testing, and packaging. This has happened in the
semiconductor industry because the capital cost of manufacturing is so large. The fabless model is a
useful way for a small company with a good idea to bring its own product to market, but the
company then must face the issue of gaining access to its market and funding the development of
marketing, distribution, and sales.

Having looked at the molecular electronics example in some depth, we can now move up the
abstraction ladder to aggregates, complex systems, and the potential to advance the capabilities of
Moore's Law in software.
Systems, Software, and Other Abstractions
Unlike memory chips, which have a regular array of elements, processors and logic chips are limited
by the rat's nest of wires that span the chip on multiple layers. The bottleneck in logic chip design is
not raw numbers of transistors but the lack of a design approach that can use all that capability in a
timely fashion. For a solution, several next-generation processor companies have redesigned
"systems on silicon" with a distributed computing bent; wiring bottlenecks are localized, and chip
designers can be more productive by using a high-level programming language instead of wiring
diagrams and logic gates. Chip design benefits from the abstraction hierarchy of computer science.

Compared with the relentless march of Moore's Law, the cognitive capability of humans is relatively
fixed. We have relied on the compounding power of our tools to achieve exponential progress. To
take advantage of accelerating hardware power, we must further develop layers of abstraction in
software to manage the underlying complexity. For the next thousandfold improvement in
computing, the imperative will shift to the growth of distributed complex systems. Our inspiration
will likely come from biology.

As we race to interpret the now complete map of the human genome and embark upon deciphering
the proteome, the accelerating pace of learning is not only opening doors to the better diagnosis and
treatment of disease but is also a source of inspiration for much more powerful models of computer
programming and complex systems development.

The Biological Muse

Many of the interesting software challenges relate to growing complex systems or have other
biological metaphors as inspiration. Some of the interesting areas include Biomimetics, Artificial
Evolution, Genetic Algorithms, A-life, Emergence, IBM's Autonomic Computing initiative, Viral
Marketing, Mesh, Hives, Neural Networks, and the Subsumption architecture in robotics. The Santa
Fe Institute just launched a BioComp research initiative.

In short, biology inspires IT, and IT drives biology. But how inspirational are the information
systems of biology? If we took your entire genetic codethe entire biological program that resulted in
your cells, organs, body, and mindand burned it into a CD, it would be smaller than Microsoft Office.
Just as images and text can be stored digitally, two digital bits can encode the four DNA bases (A, T,
C, and G), resulting in a 750MB file that can be compressed for the preponderance of structural filler
in the DNA chain.

If, as many scientists believe, most of the human genome consists of vestigial evolutionary
remnants that serve no useful purpose, then we could compress it to 60MB of concentrated
information. Having recently reinstalled Office, I am humbled by the comparison between its
relatively simple capabilities and the wonder of human life. Much of the power in bioprocessing
comes from the use of nonlinear fuzzy logic and feedback in the electrical, physical, and chemical
domains.

For example, in a fetus, the initial interneuronal connections, or "wiring," of the brain follow
chemical gradients. The massive number of interneuron connections in an adult brain could not be
simply encoded in our DNA, even if the entire DNA sequence were dedicated to this one task. Your
brain has on the order of 100 trillion synaptic connections between 60 billion neurons.

This highly complex system is not "installed," like Microsoft Office, from your DNA. Rather, it is
grown, first through widespread connectivity sprouting from "static storms" of positive
electrochemical feedback, and then through the pruning of many underused connections through
continuous usage-based feedback. In fact, human brains hit their peak at the age of two to three
years, with a quadrillion synaptic connections and twice the energy burn of an adult brain.

The brain has already served as an inspirational model for artificial intelligence (AI) programmers.
The neural network approach to AI involves the fully interconnected wiring of nodes, followed by the
iterative adjustment of the strength of these connections through numerous training exercises and
the back-propagation of feedback through the system.

Moving beyond rule-based AI systems, these artificial neural networks are capable of many
humanlike tasks, such as speech and visual pattern recognition, with a tolerance for noise and other
errors. These systems shine precisely in the areas where traditional programming approaches fail.

The coding efficiency of our DNA extends beyond the leverage of numerous feedback loops to the
complex interactions between genes. The regulatory genes produce proteins that respond to external
or internal signals to regulate the activity of previously produced proteins or other genes. The result
is a complex mesh of direct and indirect controls.

This nested complexity implies that genetic reengineering can be a very tricky endeavor if we have
partial knowledge about the systemwide side effects of tweaking any one gene. For example, recent
experiments show that genetically enhanced memory comes at the expense of enhanced sensitivity
to pain.

By analogy, our genetic code is a dense network of nested hyperlinks, much like the evolving Web.
Computer programmers already tap into the power and efficiency of indirect pointers and recursive
loops. More recently, biological systems have inspired research in evolutionary programming, where
computer programs are competitively grown in a simulated environment of natural selection and
mutation. These efforts could transcend the local optimization inherent in natural evolution.

But therein lies great complexity. We have little experience with the long-term effects of the artificial
evolution of complex systems. Early subsystem work can be deterministic of emergent and higher-
level capabilities, as with the neuron. (Witness the Cambrian explosion of structural complexity and
intelligence in biological systems once the neuron enabled something other than nearest-neighbor
intercellular communication. Prior to the neuron, most multicellular organisms were small blobs.)

Recent breakthroughs in robotics were inspired by the "subsumption architecture" of biological

evolutionusing a layered approach to assemble reactive rules into complete control systems from the
bottom up. The low-level reflexes are developed early and remain unchanged as complexity builds.
Early subsystem work in any subsumptive system can have profound effects on its higher-order
constructs. We may not have a predictive model of these downstream effects as we are developing
the architectural equivalent of the neuron.

The Web is the first distributed experiment in biological growth in technological systems. Peer-to-
peer software development and the rise of low-cost Web-connected embedded systems raise the
possibility that complex artificial systems will arise on the Internet, rather than on one
programmer's desktop. We already use biological metaphors, such as "viral" marketing, to describe
the network economy.

Nanotech Accelerants: Quantum Simulation and High-Throughput

Experimentation
We have discussed the migration of the lab sciences to the innovation cycles of the information
sciences and Moore's Law. Advances in multi-scale molecular modeling are helping some companies
design complex molecular systems in silicon. But the quantum effects that underlie the unique
properties of nanoscale systems are a double-edged sword. Although scientists have known for
nearly 100 years how to write down the equations that an engineer needs to solve in order to
understand any quantum system, no computer has ever been built that is powerful enough to solve
them. Even today's most powerful supercomputers choke on systems bigger than a single water
molecule.

This means that the behavior of nanoscale systems can be reliably studied only by empirical
methodsbuilding something in a lab and then poking and prodding it to see what happens.

This observation is distressing on several counts. We would like to design and visualize nanoscale
products in the tradition of mechanical engineering, using CAD-like (Computer Aided Design)
programs. Unfortunately this future can never be accurately realized using traditional computer
architectures. The structures of interest to nanoscale scientists present intractable computational
challenges to traditional computers.

The shortfall in our ability to use computers to shorten and reduce the cost of the design cycles of
nanoscale products has serious business ramifications. If the development of all nanoscale products
fundamentally requires long R&D cycles and significant investment, the nascent nanotechnology
industry will face many of the difficulties that the biotechnology industry faces, without having a
parallel to the pharmaceutical industry to shepherd products to market.

In a wonderful turn of poetic elegance, quantum mechanics itself turns out to be the solution to this
quandary. Machines known as quantum computers, built to harness some simple properties of
quantum systems, can perform accurate simulations of any nanoscale system of comparable
complexity. The type of simulation conducted by a quantum computer results in an exact prediction
of how a system will behave in naturesomething that is literally impossible for any traditional
computer, no matter how powerful.

Once quantum computers become available, engineers working at the nanoscale will be able to use
them to model and design nanoscale systems, just as today's aerospace engineers model and design
airplanescompletely virtuallywith no wind tunnels (or their chemical analogs).

This may seem strange, but really it's not. Think of it this way: Conventional computers are really
good at modeling conventional (that is, nonquantum) stuff, such as automobiles and airplanes.
Quantum computers are really good at modeling quantum stuff. Each type of computer speaks a
different language.

One of our companies is building a quantum computer using aluminum-based circuits. The company
projects that by 2008 it will be building thumbnailsized chips that will have more computing power
than the aggregate total of all computers on the planet today and ever built in history, when applied
to simulating the behavior and predicting the properties of nanoscale systemsthereby highlighting
the vast difference between the capabilities of quantum computers and those of conventional
computers. This would be of great value to the development of the nanotechnology industry. And it's
a jaw-dropping claim. Professor David Deutsch of Oxford summarized it this way: "Quantum
computers have the potential to solve problems that would take a classical computer longer than the
age of the universe."

Although any physical experiment can be regarded as a complex computation, we will need quantum
computers to transcend Moore's Law into the quantum domain to make this equivalence realizable.
In the meantime, scientists will perform experiments. Until recently, the methods used for the
discovery of new functional materials differed little from those used by scientists and engineers a
hundred years ago. It was very much a manual, skilled-labor-intensive process. One sample was
prepared from millions of possibilities, then it was tested, and then the results were recorded and
the process repeated. Discoveries routinely took years.

Companies like Affymetrix, Intematix, and Symyx have made major improvements in a new
methodology: high-throughput experimentation. For example, Intematix performs high-throughput
synthesis and screening of materials to produce and characterize these materials for a wide range of
technology applications. This technology platform enables the company to discover compound
materials solutions more than 100 times as fast as with conventional methods. Initial materials have
been developed that have applications in wireless communications, fuel cells, batteries, x-ray
imaging, semiconductors, LEDs, and phosphors.

Combinatorial materials discovery replaces the old traditional method by simultaneously generating
a multitude of combinationspossibly all feasible combinationsof a set of raw materials. This
"materials library" contains all combinations of a set of materials, and they can be quickly tested in
parallel by automated methods similar to those used in combinatorial chemistry and the
pharmaceutical industry. What used to take years to develop now takes only months.
Time Line
Given our discussion of the various factors affecting the commercialization of nanotechnologies, how
do we see them sequencing?

Early Revenue

Tools and bulk materials (powders, composites). Several revenue-stage and public companies
already exist in this category.

One-dimensional chemical and biological sensors, out-of-body medical sensors and diagnostics.

Larger MEMS-scale devices.

Medium Term

Two-dimensional nanoelectronics: memory, displays, solar cells.

Hierarchically structured nanomaterials and bionano assembly.

Efficient energy storage and conversion.

Passive drug delivery and diagnostics, improved implantable medical devices.

Long Term

Three-dimensional nanoelectronics.

Nanomedicine, therapeutics, and artificial chromosomes.

Quantum computers used in small-molecule design.

Machine-phase manufacturing.

The safest long-term prediction is that the most important nanotech developments will be the
unforeseen opportunities, something that we cannot predict.

In the long term, nanotechnology research might ultimately enable miniaturization to a magnitude
never before seen and might restructure and digitize the basis of manufacturingsuch that matter
becomes code. As with the digitization of music, the importance of this development is not only in
the fidelity of reproduction but also in the decoupling of content from distribution. Once a product is
digitized, new opportunities arise, such as online music swappingtransforming an industry.

With replicating molecular machines, physical production itself migrates to the rapid innovation
cycle of information technology. With physical goods, the basis of manufacturing governs inventory
planning and logistics, and the optimal distribution and retail supply chain has undergone little
radical change for many decades. Flexible, low-cost manufacturing near the point of consumption
could transform the physical goods economy and even change our notion of ownershipespecially for
infrequently used objects.

These are profound changes in the manufacturing of everything, changes that will ripple through the
fabric of society. The science futurists have pondered the implications of being able to manufacture
anything for $1 per pound. And as some of these technologies couple tightly to our biology, it will
bring into question the nature and extensibility of our humanity.
The Ethical Debate: Genes, Memes, and Digital
Expression
These changes may not be welcomed smoothly, especially with regard to reengineering the human
germ line. At the societal level, we will likely try to curtail the evolution of evolvability and "genetic
free speech." Larry Lessig predicts that we will recapitulate the 200-year debate about the first
amendment to the Constitution. Pressures to curtail free genetic expression will focus on the dangers
of "bad speech"; others will argue that good genetic expression will crowd out the bad, as it did with
mimetic evolution (in the scientific method and the free exchange of ideas). Artificial chromosomes
with adult-trigger events can decouple the agency debate about parental control. And, with a touch
of irony, China may lead the charge.

We subconsciously cling to the selfish notion that humanity is the end point of evolution. In the
debates about machine intelligence and genetic enhancements, there is a common and deeply
rooted fear of being surpassedin our lifetime. When the question is framed as a matter of
parenthood (would you want your great-grandchild to be smarter and healthier than you?), the
emotion often shifts from a selfish sense of supremacy to a universal human search for symbolic
immortality.
Conclusion
Although predicting the future is becoming more difficult with each passing year, we should expect
an accelerating pace of technological change. We conclude that nanotechnology is the next great
technology wave and the next phase of Moore's Law. Nanotech innovations enable an array of
disruptive businesses, driven by entrepreneurship, that were not possible before.

Much of our future context will be defined by the accelerating proliferation of information
technologyas it innervates society and begins to subsume matter into code. It will be a period of
exponential growth in the impact of the learning-doing cycle, where the power of biology, IT, and
nanotech compounds the advances in each formerly discrete domain.

At DFJ, we conclude that it is a great time to invest in start-ups. As in evolution and the Cambrian
explosion, many will become extinct. But some will change the world. So we pursue the strategy of a
diversified portfolio, or, in other words, we try to make a broad bet on mammals.
Chapter 5. Investment in Nanotechnology
Investment decisions will be a major force in shaping how and where nanotechnology develops.
Nanotechnology investments will largely be handled through partnership and technology licensing
between companies rather than by young companies experiencing explosive growth.

The perspective of venture capitalists (VCs) is an excellent one for instruction, even though only a
small percentage (less than 5 percent) of companies fit the profile of a company that merits venture
capital investment. Serving to quarterback the technology economy through investment decisions, a
VC makes investments in those companies that, although they are risky, hold the most promise for
the future. This chapter outlines both venture and public funding decisions.
Venture Capital Investing
Daniel V. Leff

Venture capital is money that is typically invested in young, unproven companies with the potential
to develop into multibillion-dollar industry leaders, and it has been an increasingly important source
of funds for high-technology start-up companies in the last several years. Venture capitalists are the
agents that provide these financial resources as well as business guidance in exchange for ownership
in a new business venture. VCs typically hope to garner returns in excess of 3050 percent per year
on their investments. They expect to do so over a four- to seven-year time horizon, which is the
period of time, on average, that it takes a start-up company to reach a liquidity event (a merger,
acquisition, or initial public offering).

Very few high-tech start-up companies are attractive candidates for VC investment. This is especially
true for nanotechnology start-ups, because the commercialization of nanoscience is still in its
nascent stages. Companies that are appropriate for VC investment generally have some combination
of the following five characteristics: (1) an innovative (or disruptive) product idea based on
defensible intellectual property that gives the company a sustainable competitive advantage; (2) a
large and growing market opportunity that is greater than $1 billion and is growing at more than
2030 percent per year; (3) reasonable time to market (one to three years) for the first product to be
introduced; (4) a strong management team of seasoned executives; and (5) early customers and
relationships with strategic partners, with a strong likelihood of significant revenue.

An early-stage start-up company rarely possesses all of these characteristics and often does not
need to in order to attract venture financing. Indeed, early-stage start-ups are often funded without
complete management teams, strategic partners, or customers. Absent these characteristics,
however, there should be, at a minimum, a passionate, visionary entrepreneur who helped develop
the core technology and wants to play an integral role in building the company.
Nanotechnology Venture Capital Investment
Nanotechnology is not a single market but rather a set of enabling (and potentially groundbreaking)
technologies that can be applied to solve high-value problems in almost every industry. This
includes industries as disparate as telecommunications, biotechnology, microelectronics, textiles,
and energy. Many investors refer to nanotechnology investing as if it were its own investment
category, because nanotechnology can add unique and specific value to a product that results in
greatly enhanced performance attributes or cost advantages (or both). But customers purchasing
nanotechnology products are buying these products, not because they are based on nanotechnology,
but because they are characterized by specific performance enhancements, reduced costs, or both.

Almost every product application of nanotechnology is based either on a material characterized by

nanoscale dimensions or on a process technology conducted at the nanometer scale. Nanomaterials
possess unique propertiesincluding optical, electronic, magnetic, physical, and chemical reactivity
propertiesthat, when harnessed appropriately, can lead to entirely new, high-performance
technologies and products. Changing a material's size, rather than its chemical composition, enables
the control of that material's fundamental properties.
Nanotechnology Start-up Companies
Nanotechnology start-up companies should not expect to defy fundamental business principles, as
did the Internet companies of the mid- to late 1990s, if only for a brief period. Nanotechnology
companies should expect to be measured by standard metrics and to confront the same industry
dynamics and fundamental business issues (for example, personnel choices, sales strategy, high-
volume manufacturing, efficient allocation of capital, marketing, execution of their business model,
time-to-market challenges, and so on) that face the other companies in their relevant industry
category.

Certain key characteristics often differentiate nanotechnology start-up companies. They possess a
technology platform with a body of intellectual property and a team of scientists, but no formal
business plan, product strategy, well-defined market opportunity, or management team. Second,
they are founded by (or are associated with) leading researchers at top-tier academic institutions.
They employ a financing approach that highly leverages equity financing with the application of
grant funding, and they need to have a more scientifically diverse workforce than other start-up
companies.

It is common for these companies to employ chemists, physicists, engineers, biologists, computer
scientists, and materials scientists because of the interdisciplinary nature of nanotechnology and the
unique skills and knowledge that are required for product commercialization. Moreover, nanotech
companies tend to sign up development partners (usually larger, more established companies) early
in their maturation to provide technology validation and additional resources in the form of
development funds, access to technology, sales and distribution channels, and manufacturing
expertise.

Nanotechnology start-up companies can best be classified into six primary categories: nanomaterials
and nanomaterials processing; nanobiotechnology; nanosoftware; nanophotonics; nanoelectronics,
and nanoinstrumentation. Many companies in the nanomaterials category are developing methods
and processes to manufacture a range of nanomaterials in large quantities as well as developing
techniques to functionalize, solubilize, and integrate these materials into unique formulations. A
variety of nanomaterials will ultimately be integrated into a host of end products (several are on the
market) that will provide unique properties, such as scratch resistance, increased stiffness and
strength, reduced friction and wear, greater electrical and thermal conductivity, and so on.

The three areas that have received the most funding based on dollars invested are nanoelectronics,
nanophotonics, and nanoinstrumentation. However, in terms of the absolute number of companies
that have been funded, nanomaterials companies are the clear leader.

Nanobiotechnology is the application of nanotechnology to biological systems. Applications exist in

all of the traditional areas of biotechnology, such as therapeutics discovery and production, drug-
delivery systems technologies, diagnostics, and so on. Incorporating nanotechnology into
biotechnology will lead to the enhanced ability to label, detect, and study biological systems (such
as genes, proteins, DNA fragments, single molecules, and so on) with great precision as well as to
develop unique drug targets and therapies.

Nanoelectronics is based upon individual or ordered assemblies of nanometer-scale device

components. These building blocks could lead to devices with significant cost advantages and
performance attributes, such as extremely low power operation (~nanoWatt), ultra-high device
densities (~1 trillion elements/cm2), and blazing speed (~1 Terahertz switching rates). In addition,
the possibility exists of enabling a new class of devices with unique functionality. Examples include,
but are not limited to, multi-state logic elements; high-quantum-efficiency, low-power, tunable,
multicolor light-emitting diodes (LEDs); low-power, high-density nonvolatile random access memory
(RAM); quantum dot-based lasers; universal analyte sensors; low-impedance, high-speed
interconnects, and so on.

Nanophotonics companies are developing highly integrated, subwavelength optical communications

components using a combination of proprietary nanomaterials and nanotech manufacturing
technologies, along with standard complementary metal oxide semiconductor (CMOS) processing.
This provides for the low-cost integration of electronic and photonic components on a single chip.
Products in this category include low-cost, high-performance devices for high-speed optical
communications, such as wavelength converters, tunable filters, polarization combiners,
reconfigurable optical add/drop multiplexers (ROADMs), optical transceivers, and so on.

Nanoinstrumentation is based on tools that manipulate, image, chemically profile, and write matter
on a nanometer-length scale (far less than 100nm). These tools include the well-known microscopy
techniques such as transmission electron microscopy (TEM), scanning electron microscopy (SEM),
and atomic force microscopy (AFM), as well as newer techniques such as dip-pen nanolithography
(DPN), nanoimprint lithography (NIL), and atom probe microscopes for elucidating three-
dimensional atomic composition and structure of solid materials and thin films. These are the basic
tools that enable scientists and engineers to perform nanoscale science and to develop
nanotechnology products.

Nanosoftware is based on modeling and simulation tools for research in advanced materials
(cheminformatics) and the design, development, and testing of drugs in the biotechnology industry
(bioinformatics). This category also includes electronic and photonic architecture, structure, and
device modeling tools such as specific incarnations of electronic design automation (EDA) software
or quantum simulations, and so on. In addition, one might further include proprietary software
packages developed to operate nanoinstrumentation-based tools or interpret data collected from
such instruments.
Public Markets and Nanotechnology Companies
R. Douglas Moffat

Historically, public equity markets have provided capital for rapidly expanding firms having
established products and seeking growth capital. Periodically, new technology or corporate growth
models, combined with unusually heavy money flows into the stock market, fuel speculative demand
for shares in new companies. Biotechnology investing has run in such cycles for more than 20 years.
The Internet boom of the late 1990s reached unprecedented levels of irrational expectations and
speculation. Other examples include the fuel cell boom of 20002001.

The public market's appetite for initial public offerings (IPOs) in a sector also is heavily influenced by
the business model characteristics and the track record of the model for success. Biotech has
achieved success in part because of the appetite for these firms by big pharmaceutical firms.
Software stocks have proven to be fast growers without heavy capital investment.

Nanotech probably will be a big hit on Wall Street, but the timing will depend on progress achieved
in moving products closer to market acceptance. Many of the nanoscience-enabled products being
commercialized now are coming out of large companies. Examples include nanotube-based plasma
televisions and personal care products. A limited number of smaller firms are introducing nanotech
products in the short term. Most companies, however, are still refining the science behind paradigm-
shifting technologies having massive potential. Commercialization issues include interfacing
nanodevices with the macro environment, scalable manufacturing, and, in the health-care world,
long FDA approval cycles.

Wall Street investors typically have preferred focused business models concentrated on growth from
a narrowly defined technology or product group. Management focus historically has produced better
execution and shareholder returns.

At this stage of nanotechnology development, however, intellectual property platforms based on

broad patents (often coming from academia) are the main assets behind many companies. The
applicability of this IP could cut across many markets and applications. Some firms have amassed
broad IP by taking a portfolio approach to early-stage commercialization, an approach most stock
investors do not favor. Such diversification, however, makes sense not only from a scientific point of
view but also to lessen risks associated with potential patent litigation. The patent landscape in
nanotech might be likened to the gold rush days, with overlapping claims.

Nanotechnology is different from other tech waves. First, the technology is often paradigm shifting,
either creating new markets or providing quantum improvement in performance at a low cost. The
enabling science probably is applicable to a wide variety of applications. In time, stock market
investors may come to appreciate the power of a new nanotech business model, one with core IP at
its center and with the prospects to spin off many companies with varied new products. The
evolution of acceptable nanotech business models in public markets will depend in part on VC
investors' willingness to extend funding horizons to allow firms to develop products.

There is significant buzz on Wall Street around nanotechnology. Leading Wall Street firms are
beginning to commit resources to research and fund nanotechnology. A favorable environment is
emerging for a successful nanotech début on the street.

Since the Internet bubble deflation in 2000, public equity markets have taken on a more risk-averse
character. IPO investors have preferred to fund companies with established products, revenues, and
profits as well as large companies restructured by private equity firms. A limited number of
nanotechnology-enabled firms have been able to tap public equity markets. Public equity access
likely will improve as nanotechnology firms move closer to the introduction of novel products having
a clear path to revenue and profits. Equity issuance by nanotech firms likely will grow slowly over
the next five years, gathering potentially explosive momentum thereafter.
Chapter 6. The Role of the U.S. Government
in Nanoscale Science and Technology
Geoffrey M. Holdridge

One of the cornerstone principles of the United States, and of the free market system that has
helped to make the United States one of the world's richest countries, is that the central government
should play only those roles that are both critical to the nation's welfare and that private citizens,
private industry, or state and local governments are either unable or unwilling to undertake. One
role for the federal government that was envisioned from the start of the Republic by the framers of
the U.S. Constitution was to "promote the Progress of Science and useful Arts."[1] This role was
originally intended only for the protection of intellectual property and was the basis for the
establishment of the U.S. Patent and Trademark Office (USPTO).

However, as science and technology have become ever more critical to the fate of nations and the
well-being of their citizens, the U.S. government has taken on additional corollaries to this role
outlined in the Constitution, including funding research and development, education, and critical
research infrastructure, as well as measures to more effectively promote the transfer of "Science"
into "useful Arts" for exploitation by private industry. This chapter outlines and explains the
sometimes unique roles that the U.S. federal government plays in the development of nanoscale
science and technology. These roles can be expected to be similar in other countries as well.

The most fundamental government role in nanoscale science and technology, or nanotechnology, is
to support research and developmentlong-term basic research as well as development of
applications relevant to specific national priorities (such as defense). Another key government role is
developing educational resources, a skilled workforce, and the supporting infrastructure and tools
(for example, laboratory facilities and instrumentation) needed to advance nanotechnology. The
government has an important role to play in facilitating transfer of new technologies developed in
university and government laboratories to the private sector, where the real benefits of
nanotechnology (such as new and improved products, jobs, and sustainable economic growth) can
be pursued.

Finally, the government has a responsibility for encouraging the responsible development of
nanotechnology, by supporting research on the potential impacts (both positive and negative) of
nanotechnologies and by creating a regulatory environment that protects public health and safety
while providing a clear path in which industry can pursue development of novel products and
services based on nanotechnology.

These roles are not unique to nanotechnology but rather reflect the roles that the U.S. government
and many other governments around the world have played in the development and exploitation of
science and technology at least since World War II. What is perhaps unique about the case of
nanoscale science and technology is its accelerated pace of development, the broad spectrum of its
potential benefits, and hence its potential to have a rapid and revolutionary impact on industry and
society.

Another unique aspect is the extent to which progress in nanotechnology stems from a confluence of
developments in different fields of science and technology (for example, biology and physics),
presenting new challenges and opportunities for researchers and educators working across
traditional disciplinary boundaries. Government plays an important role in helping to foster
interdisciplinary research and education in three ways: (1) by supporting the development of and
making available facilities and research instruments that allow researchers from all disciplines to
visualize and manipulate matter at the nanometer scale, (2) by establishing research centers and
groups with the explicit goal of bringing together researchers from previously divergent fields, and
(3) by promulgating policies to encourage the education of a new generation of multidisciplinary
researchers.
The National Nanotechnology Initiative and the 21st
Century Nanotechnology Research and Development Act
The U.S. National Nanotechnology Initiative (NNI) was proposed in 2000 following the realization
that the ability to understand and control matter on the nanometer scale was creating a revolution
in science, technology, and industry, and with the vision of accelerating and guiding that revolution
for the benefit of society. Because of the breadth of nanotechnology's disciplinary roots and of its
potential applications, it relates to the missions of an extraordinary number of U.S. government
agencies.

At its outset the NNI involved eight agencies. As of this writing, eleven agencies have specific
funding under the NNI, and an additional eleven participate as partners and in-kind contributors
because the development of nanotechnology is relevant to their missions or regulatory roles. To
coordinate this broad interagency effort, the President's National Science and Technology Council
has established a Subcommittee on Nanoscale Science, Engineering, and Technology (NSET), with
representatives from all twenty-two NNI participating agencies. NSET in turn has established a
National Nanotechnology Coordination Office (NNCO), with a small full-time staff to provide
technical and administrative support to NSET, to serve as the point of contact on federal
nanotechnology activities, to conduct public outreach, and to promote technology transfer.

Another somewhat extraordinary aspect of nanotechnology is that it is the subject of an act of

Congress. Of the thousands of bills that are proposed in Congress each year, few are ever signed
into law, and even fewer of those (other than routine annual appropriations bills) concern science
and technology. But in 2003 Congress passed the 21st Century Nanotechnology Research and
Development Act, which was signed into law by President George W. Bush on December 3, 2003, as
Public Law 108-153.[2] This act calls for the establishment of a National Nanotechnology Program,
with the following mission:

(1) establish the goals, priorities, and metrics for evaluation for Federal nanotechnology
research, development, and other activities; (2) invest in Federal research and development
programs in nanotechnology and related sciences to achieve those goals; and (3) provide for
interagency coordination of Federal nanotechnology research, development, and other
activities undertaken pursuant to the Program.

The NNI continues as the primary means by which the Executive Branch implements the National
Nanotechnology Program, and for carrying out the many roles that it stipulates for the federal
government in promoting the development and commercialization of nanotechnology.

In December 2004, in keeping with the provisions of PL 108-153, the NNI released a Strategic Plan
that sets out its vision, goals, and strategies for achieving those goals.[3] The NNI's goals closely
align with the government roles just discussed. The following sections briefly review each of those
roles.
Research and Development
Prior to World War II the U.S. government played only a minor role in R&D funding. Private
foundations, corporations, and internal university funds provided the bulk of support. The U.S.
military funded some advanced development of technologies for deployment in Army and Navy
equipment, but it did not provide significant support for basic research. The National Advisory
Committee for Aeronautics (NACA, precursor to NASA) played an important role in developing and
testing new airfoil designs in the 1930s. The Department of Agriculture, through the Hatch Act of
1887, supported agricultural research at the land grant colleges. Federal support for basic research
in the health sciences, and hence in biology, dates to the latter part of the nineteenth century but
began as a major funding activity in the 1930s with the establishment of the National Institutes of
Health. Except for these and a few other isolated examples, however, there was no systematic
federal support for scientific research.

The obvious importance of science and technology to the war effort during World War II led to a new
role for the U.S. government in supporting not only applied research for immediate military
applications but also basic research. The August 1939 letter from Albert Einstein to President
Roosevelt ultimately led to an understanding during and after WWII of the need for federal support
for basic research in fields such as nuclear physics. The federal government has been the mainstay
of funding for basic research in the physical sciences and engineering ever since, through agencies
such as the Office of Naval Research, the Atomic Energy Commission, and the National Science
Foundation, all of which trace their origins to the aftermath of World War II and the early days of
the cold war.

Federal support for R&D increased steadily through the 1950s and early 1960s, including
considerable funding for basic research in particle physics, electronics, and materials science needed
for the space program and the military. This research in turn led to major benefits for the civilian
economy, including civilian nuclear power, inexpensive and ubiquitous integrated circuits, the
widespread use of computers in the banking industry, and dramatic advances in air travel. All these
advances stemmed in part from increased understanding and control of the properties of matter at
the atomic and molecular scale.

Federal R&D funding leveled off and even declined somewhat in real dollars starting in the late
1960s, but it increased from the late 1970s through the mid-1980s, with increases in federal support
for energy and military research.[4] The National Institutes of Health also received sustained funding
increases, notably with the advent of Richard Nixon's war on cancer and more recently with the
bipartisan pledge to double the overall NIH budget in the first few years of the twenty-first century.

Throughout this period the federal investment in research continued to return significant dividends
for military security, the civilian economy, and health carewith advances in military electronics that
dramatically improved the performance of U.S. forces, novel treatments for many diseases, and the
development of the Internet. The U.S. standard of living and life expectancy grew dramatically
during the entire postWorld War II period, fueled to a large extent by advances in science and
technology funded by the U.S. government.

In fact, basic research in particle physics and materials science conducted in the national laboratory
system during the latter half of the twentieth century greatly enhanced our understanding of the
properties of matter on the atomic and molecular scales, developing along the way novel methods of
measuring, visualizing, and controlling these properties. Research funded by the National Institutes
of Health improved our understanding of the basic operating principles of life itself. Much of this
basic and applied research funded by the federal government in the latter half of the twentieth
century provided the foundation on which the nanotechnology revolution of the twenty-first century
will be constructed.

The Federal Role in Nanoscale Research and Development: Basic and

Applied
Although political parties have debated the role of the federal government in applied research over
the last several decades, there has been largely unanimous support across a wide expanse of the
political spectrum for basic research funding. That's because private corporations cannot justify
large investments in basic science that, as important as they are to our future, may take decades to
provide reasonable returns on the investments, and it may be difficult for private corporations to
capture such returns. In recent years, this federal role has been even more important as large
corporations such as AT&T and RCA have scaled down or eliminated the investments they had been
making in basic research during the mid-twentieth century. NNI participating agencies such as the
National Science Foundation (NSF) and the Office of Science at the Department of Energy (DOE)
provide a key role in supporting basic nanoscale science and engineering research.

The appropriate federal role in supporting applied research has been debated publicly in recent
years. The mission agenciessuch as the Department of Defense (DoD), the National Aeronautics and
Space Administration (NASA), and the National Institutes of Health (NIH)have an agreed role in
supporting applied research and even product development that will directly contribute to their
respective missions. These agencies have identified numerous opportunities where applied research
in nanotechnology can make important contributions to their missions. Examples include DoD
support for development of nanotechnology-enabled sensors to detect chemical, biological,
radiological, and explosives agents; NASA support for development of flexible, lightweight, and
superstrong materials for future spacecraft; and NIH support for development of nanostructures that
can be used to selectively target tumor cells with either radiation or chemotherapy.

Research at the intersection of traditional scientific and engineering disciplines is a requirement if we

are to make rapid progress in nanoscale science, technology, and applications. The agencies
participating in the NNI encourage such interdisciplinary research through several mechanisms,
including funding of small multidisciplinary teams as well as large research centers involving faculty
from many different disciplinary departments, and ultimately promoting the development of a new
generation of young researchers not bound by the traditional disciplinary divisions.
Education and Workforce Development
Support for the education of the next generation of nanoscale science and engineering researchers is
key to continued progress in nanotechnology, and thus it represents another key federal role. The
NNI provides support for hands-on training of undergraduates, graduate students, and postdoctoral
researchers at universities, federal laboratories, and other research institutions. Participating
agencies award funding directly to students for fellowships and traineeships.

NNI agencies also encourage the development of new curricula at various educational levels,
curricula designed to nurture the new generation of interdisciplinary researchers. A variety of
programs are targeted at bringing the concepts of nanoscale science and technology into classrooms
for high school and even middle school students. The exciting opportunities offered by
nanotechnology are providing a new incentive for students to take an early and continuing interest
in pursuing careers in science and technology generally.

Equally important is the need for a workforce familiar with the concepts of nanoscale science and
technology and equipped with the skills that will be needed in the nanotechnology-enabled
industries of the future. NNI participating agencies support development of educational programs
that have the objective of training technicians to meet the growing demand from industry, as
nanotechnology applications move into more products and services. Such programs are targeted to
community colleges and other institutions that emphasize development of job-related skills and
knowledge.

It also is vital for the general population to be informed about nanotechnology. A profusion of
science-fiction literature and video, as well as various Web sites, promulgates information and
conjecture that may mislead some people into thinking of nanotechnology as either a panacea or a
reason for panic. It is, of course, impossible to accurately foretell the future, especially to predict the
long-term implications of nanotechnology on society. But in the near term, nanotechnology will not
solve all the world's problems, nor will it dissolve the human race into blobs of "gray goo."

The NNI supports various efforts to communicate to the general populace the real promise of
nanotechnology through venues such as science museum exhibits and outreach from NNI-funded
research centers to elementary schools. NNI also is working to provide information on the real
hazards that some aspects of nanotechnology may pose (such as the possible inhalation of certain
types of nanoparticles) and to explain what the federal government is doing to clarify and address
those issues (for example, information on environmental health and safety research found on the
NNI Web site).[5]
Facilities and Instrumentation
Nanoscale science and technology R&D often requires the use of complex and expensive facilities
and instrumentation. In fact, it was the development of tools such as the scanning tunneling
microscope (STM) at IBM/Zurich in the 1980s that many experts point to as among the key events
that enabled the dawn of this new era of nanoscale science and technology. Tools like the STM are
what make it possible to "image, measure, model, and manipulate matter on the nanoscale."[6]
Effective use of such tools also can require specialized facilities to house them, including dedicated
buildings designed to eliminate the vibration, particulate contamination, noise, and temperature
variations typical of conventional research facilities. Without this vital infrastructure it would be
impossible to realize the true promise of nanotechnology.

The NNI provides access to such facilities and instrumentation through a variety of means. Some
large NNI-funded research centers can include funding for such infrastructure in their budgets.
However, breakthroughs in science and technology often come from unexpected quarters. In
particular, some of the most creative work often is conducted by individual investigators or small
teams, which may or may not be affiliated with large universities housing NNI-funded research
centers. Even more importantly, for the fruits of basic research to be developed into useful products,
researchers in industry also require access to the essential tools of nanotechnology R&D. Only a few
very large corporations can afford to purchase such infrastructure for their own exclusive use,
whereas small start-up high-technology companies are often the source of some of the most
important commercial innovations, and they are well known to be the engine of new job creation in
the U.S. economy.

Therefore, a critical role for the government is to provide access to nanotechnology facilities and
instrumentation for a wide spectrum of researchers, both in academia and in industry. Accordingly,
a large component of the NNI funding is dedicated to the development and operation of user
facilities, open to any qualified researchers on a merit-review basis. Two of the most significant NNI
user facility programs are (1) the five DOE Nanoscale Science Research Centers (NSRCs) now under
construction, each with a specific focus and associated with existing large-scale research facilities
and competencies at DOE laboratories across the country; and (2) the NSF's National
Nanotechnology Infrastructure Network, with existing and new facilities available at thirteen
universities.[7] NSF also supports a seven-university network of specialized user facilities for
research on modeling and simulation of nanostructures and related systems.[8]

Another related government role is support for development of new types of instrumentation for
nanoscale science and technology. Just as the development of the AFM and other probe microscopes
opened up whole new worlds for research and application in recent years, future progress likely will
be enabled by new instrumentation breakthroughs. The National Institute of Standards and
Technology (NIST) plays a key role in conducting research on novel instrumentation. NSF also funds
university research on new instrumentation concepts.
Technology Transfer
The NNI vision is that nanoscale science and technology will lead to "a revolution in technology and
industry."[9] To realize that vision, the results of NNIfunded R&D must be effectively transferred to
private industry, where technologies are incorporated into new and improved products and services.
Although the government role stops short of directly commercializing nanotechnology per sebecause
this role is most appropriately carried out in the private sectorit is not surprising that technology
transfer of NNI-funded research to the private sector is among the four principal goals of the NNI.
This transfer can occur via various pathways, such as publication of the results of federally funded
research, hiring by industry of recent graduates of NNI-funded educational programs, and licensing
of intellectual property resulting from federally funded research.

The traditional role of the USPTO is critical to the latter example. USPTO has undertaken a number
of activities to enhance its ability to address the intellectual property issues associated with
nanotechnology. Examples include training programs for its patent examiners, networking with its
European and Japanese counterparts, and efforts to identify and classify nanotechnology-related
patents, thus improving its ability to search nanotechnology-related prior art.

A primary aspect of all technology transfer is interaction among those who are performing R&D and
those who manufacture and sell goods and services. NSET has established liaisons with various
commercial sectors to promote the exchange of information on NNI research programs and industry
needs that relate to nanotechnology. Such activities are under way with the semiconductor,
electronics, and chemical industries and are in development with the biotechnology, aerospace, and
automotive industries.

The NNI agencies also support meetings at which researchers from academia, government, and
industry exchange information on results and possible applications. The NNI-funded user facilities
help to foster interaction among industry, academic, and government researchers who use the
facilities. The NSF-funded research centers include industry partners, allowing industry to
communicate its needs at an early stage and increasing the likelihood that new ideas will ultimately
be developed and commercialized. The government-wide Small Business Innovation Research
(SBIR) and Small Business Technology Transfer (STTR) programs support the early-stage
development of many nanotechnology-based small start-up companies, frequently spun off from
NNI-supported university research.

The government also plays a key role in supporting standards development, another activity
important to successful commercialization of nanotechnology. The American National Standards
Institute (ANSI) established the Nanotechnology Standards Panel (NSP) in September 2004. The
present director of the NNCO is the government co-chair of the NSP. The National Institute of
Standards and Technology (NIST) also plays a central role for the government in standards
development for nanotechnology.
Responsible Development
Given the breadth of the expected applications of nanotechnology and their likely revolutionary
impact on industry and society, another important role for the Government is to support research
and other activities that address the broad social implications of nanotechnology, including benefits
and risks. Responsible development of nanotechnology comprises one of the four principal goals
outlined in the 2004 NNI Strategic Plan, and it is also one of the principal components of the NNI
research and education program. Activities supported by the NNI consistent with this role include
support for research on the environmental, health, and safety impacts of nanotechnology,
education-related activities, and research directed at identifying and quantifying the broad
implications of nanotechnology for society, including social, economic, workforce, educational,
ethical, and legal implications.

Perhaps the most pervasive concern that has been raised in the popular press about potential
negative impacts of nanotechnology relates to its potential for adverse environmental, health, or
safety implications. The NSET Subcommittee has formed a formal interagency working group to
exchange information among regulatory and R&D agencies on this subject, including participation by
several agencies within the Executive Office of the President.[10] This group also seeks to help
prioritize and implement research required for the responsible development and oversight of
nanotechnology, and to promote communication of information related to the responsible handling
and use of nanotechnology-enabled products. Some industry groups have expressed the view that
the government needs to provide a clear regulatory path for industry to follow for the safe and
responsible commercialization of nanotechnology, as a key government role necessary to successful
industrial development.

Existing Laws and Regulations and the Responsible Development of

Nanotechnology
Some people have asked whether there is a need for new regulations or even statutes governing the
development of nanotechnology to avoid any possible adverse consequences to the environment,
public health, worker safety, or even economic stability. Although research on the environmental,
health, safety, and societal impacts of nanotechnology is in its infancy, this may remain an open
question. However, with the information available to date, it is difficult to imagine a scenario in
which the existing legal and regulatory framework that has evolved over the past century to address
such concerns would need to be changed significantly.

The following discussion outlines some of the existing laws, regulations, and procedures that are in
place to protect public health and safety that might apply to nanotechnology. These should obviate
the need for any major legal or regulatory changes.

Research Agencies
The U.S. government agencies that fund scientific research already have in place various policies to
address ethical, health, and safety considerations related to the research they are funding or
performing in their laboratories. Applicants for NSF research funding are required to certify in
writing that they are in compliance with various NSF policies and relevant sections of the U.S. Code
of Federal Regulations with respect to, for example, recombinant DNA, human subjects, and the use
of animals in research. NSF has broad authority to suspend or terminate ongoing research grants if
grantees fail to comply with grant regulations, or for "other reasonable cause."[11] NSF program
officers conduct regular site visits to review ongoing research, where they have an opportunity to
see whether there are any problems that might justify such actions. Other research agencies have
comparable mechanisms.

Regulatory Agencies
For research and product development not funded by the government, other statutory and practical
controls apply. The many existing statutes and regulations addressing commercial products also
apply to nanotechnology-based products and materials. For example, the Consumer Products Safety
Act of 1972 (administered by the Consumer Products Safety Commission) requires that
manufacturers of consumer products ensure that their products are safe and holds them liable if
they are not; CPSC can require the recall of products in cases where it has evidence that they are
not safe.[12] The Occupational Safety and Health Act of 1970 (administered by the Occupational
Safety and Health Administration, or OSHA, within the Department of Labor) provides for federal
regulation of safety in the workplace, including public as well as private research laboratories.[13]

The National Institute of Occupational Safety and Health (NIOSH), within the Centers for Disease
Control, conducts research and training to inform OSHA regulatory decisions.[14] NIOSH is leading
an effort within the government to develop a set of recommended safe handling practices for
nanomaterials, for research as well as commercial production facilities.

The Toxic Substances Control Act of 1976 (administered by the Environmental Protection Agency)
regulates the manufacture, importation, and use of new and existing chemical substances.[15]
Several other statutes administered by the EPA (such as the Clean Air Act and the Clean Water Act)
also may come into play with respect to nanotechnology. The National Institute of Environmental
Health Sciences, within the National Institutes of Health, also conducts health-related research that
informs regulatory decisions by other agencies.[16] The Federal Food, Drug and Cosmetic Act
(originally enacted as the Pure Food and Drug Act in 1906 and administered by the Food and Drug
Administration within the Department of Health and Human Services) requires prior testing and
review of pharmaceutical and medical products under strictly controlled conditions. [17]

Under most of these statutes, any adverse effects of new products or processes that are uncovered
as a result of privately funded research must be reported to the government. These and many other
statutes and accompanying regulations provide an ample basis for both criminal and civil legal
action against any private organizations that produce or import products or services that may be
deemed hazardous to the public. All of the agencies and institutes listed here are coordinating their
nanotechnology-related activities through their participation in the NSET Subcommittee and its NEHI
Working Group.

To clarify how these existing statutes and regulatory structures apply to nanotechnology, scientific
as well as legal research efforts are under way. For example, NSET member agencies are working
with universities, industry, and standards organizations to develop a clear system of nomenclature
for classifying new nanomaterials. This nomenclature standard is needed to facilitate both
appropriate regulation of nanotechnology and its commercial development. In another example, EPA
will be holding a public hearing in 2005 to inform discussion of how the Toxic Substances Control Act
should be applied to nanomaterials, starting with a voluntary pilot program.[18]

For nanotechnology R&D specifically, the 21st Century Nanotechnology Research and Development
Act includes a number of additional measures to ensure adequate oversight of the interagency NNI
activity. One of the stated purposes of the Act is to ensure that "ethical, legal, environmental, and
other appropriate societal concerns" are properly addressed. Specific measures include oversight of
the NNI by the President's National Science and Technology Council, a separate National
Nanotechnology Advisory Panel, and a triennial review of the NNI by the National Academy of
Sciences. All three of these oversight bodies are charged with addressing the responsible
development of nanotechnology. The NNCO and the Office of Science and Technology Policy (part of
the Executive Office of the President) also play coordinating and oversight roles, respectively, in the
responsible management of the NNI research portfolio.

In short, within the United States, not only are the mechanisms for minimizing any misuses of
nanotechnology in place, but also they are working to ensure the responsible and safe development
of nanotechnology.

Geoffrey M. Holdridge is Vice President for Government Services, WTEC, Inc.

(http://www.wtec.org), currently on assignment as Policy Analyst at the U.S. National
Nanotechnology Coordination Office (http://www.nano.gov/html/about/nnco.html). Any
opinions, conclusions, or recommendations expressed in this material are those of the author
and do not necessarily reflect the views of the United States government or of WTEC, Inc.
Portions of text extracted from the National Nanotechnology Initiative Strategic Plan,
http://www.nano.gov/NNI_Strategic_Plan_2004.pdf.
References
1. U.S. Constitution, Article 1, Section 8. See
http://www.house.gov/Constitution/Constitution.html.

2. 15 USC 7501, Page 117 STAT. 1923. See

http://www.nano.gov/html/news/PresSignsNanoBill.htm for a press release and a pointer to
the text of the law.

3. http://www.nano.gov/NNI_Strategic_Plan_2004.pdf.
4. http://www.aaas.org/spp/rd/rddis06b.pdf.
5. http://www.nano.gov/html/society/EHS.htm. See also the nanotechnology Web sites at the
Food and Drug Administration (http://www.fda.gov/nanotechnology/), the Environmental
Protection Agency
(http://www.epa.gov/ordntrnt/ORD/accomplishments/nanotechnology.html), and the
National Institute for Occupational Safety and Health
(http://www.cdc.gov/niosh/topics/nanotech/).

6. NNI Strategic Plan, http://www.nano.gov/NNI_Strategic_Plan_2004.pdf, Preface, p. iii.

7. See http://nnin.org/.
8. Network for Computational Nanotechnology, http://ncn.purdue.edu/.
9. NNI Strategic Plan, http://www.nano.gov/NNI_Strategic_Plan_2004.pdf, Executive
Summary, p. i.

10. Interagency Working Group on Nanotechnology Environmental and Health Implications

(NEHI). See http://www.nano.gov/html/society/EHS.htm.

11. See the NSF Grant Policy Manual, http://www.nsf.gov/pubs/2002/nsf02151/, in particular

Chapter VII, "Other Grant Requirements," and the sections in Chapter IX on research
misconduct and on termination policies and procedures.

12. http://www.cpsc.gov.
13. http://www.osha.gov.
14. http://www.cdc.gov/niosh/.
15. http://www.epa.gov.
16. http://www.niehs.nih.gov.
17. http://www.fda.gov.
18. See U.S. Federal Register notice, volume 70, number 89 (May 10, 2005): 2457424576
(http://www.gpoaccess.gov/fr/index.html).
Chapter 7. Overview of U.S. Academic
Research
Julie Chen

A large portion of current research in nanotechnology is done by academic researchers, and

understanding nanoscale behavior falls naturally within their sphere. The National Science
Foundation (NSF) has the largest role in funding such research within the National Nanotechnology
Initiative (NNI), with additional academic research being supported by the Department of Defense,
Department of Energy, National Institutes of Health, National Aeronautics and Space Administration,
Department of Agriculture, and Environmental Protection Agency.

The National Science Foundation is an independent federal agency that provides research funding for
colleges and universities in many fields, such as mathematics, computer science, and the social
sciences. By definition, nanotechnology represents a significant shift in the behavior of materials,
devices, structures, and systems because of the nanoscale dimension. This fundamental research
also extends to research in manufacturing science, because the assembly of nanoelements is a
critical scientific barrier to moving nanotechnology toward application in commercial products.

Every university with a research program in science and engineering has some activity in
nanotechnology, and a basic search of these programs is likely to provide a limited view.
Recognizing that the majority of academic researchers rely on federal funding to pay for graduate
students, equipment, and supplies, we can gain a better understanding of the multitude of research
activities by understanding what types of research and education outcomes are most likely for the
various federal funding mechanisms. As an example, this chapter provides basic information on
some of the NSF funding structure, research focus areas, and resources for more information.
National Science Foundation Funding Mechanisms
NSF has developed a multilevel approach to funding research in nanotechnology. The Nanoscale
Science and Engineering (NSE) program has been funded for five years now. The funding structure
ranges from small, one-year, exploratory grants to large five- to ten-year center awards. Each type
of grant provides a different opportunity for researchers and a different level of technological
maturity for companies that may be looking for new technology and partners in academia. NSF also
has primary programs (not specifically related to nanotechnology) in the Directorates for
Engineering, Math and Physical Sciences, and Biological Sciences; these programs fund substantial
levels of research related to nanotechnology. Abstracts of funded research projects can be found at
the NSF Web site (www.fastlane.nsf.gov).

Nanoscale Science and Engineering Centers (NSECs)

NSEC awards are typically for five years and are renewable for another five years. Although the
actual funding for individual research projects within a center is not large, a key mission of these
centers is to address interdisciplinary, systems-level research, as well as to build an infrastructure
for both education and research. Each NSEC is also meant to be a focal point and portal for a specific
research vision, leading advances in a specific theme while retaining knowledge about what others
are doing in related areas. Currently fourteen NSECs have been established, with two others
anticipated to be funded in the fiscal year 2005 competition (see Table 7-1).

Table 7-1. NSF-funded Nanoscale Science and Engineering Centers

(NSECs)

Institution Center Established

Northwestern University Integrated Nanopatterning and Detection Sept. 2001
Technologies (www.nsec.northwestern.edu)
Cornell University Nanoscale Systems in Information Technologies Sept. 2001
(www.cns.cornell.edu)
Harvard University Science of Nanoscale Systems and Their Device Sept. 2001
Applications (www.nsec.harvard.edu)
Columbia University Electronic Transport in Molecular Nanostructures Sept. 2001
(www.cise.columbia.edu/nsec)
Rice University Nanoscience in Biological and Environmental Sept. 2001
Engineering (www.cben.rice.edu)
Rensselaer Polytechnic Directed Assembly of Nanostructures Sept. 2001
Institute, University of (www.rpi.edu/dept/nsec)
Illinois
Institution Center Established

UCLA, UC Berkeley, UC San Center for Scalable and Integrated Sept. 2003
Diego, Stanford, UNC Nanomanufacturing (www.sinam.org)
Charlotte
University of Illinois Urbana- Center for Nanoscale Chemical-Electrical- Sept. 2003
Champaign Mechanical-Manufacturing Systems (www.nano-
cemms.uiuc.edu)
Northeastern University, Center for High-rate Nanomanufacturing Sept. 2004
University of Massachusetts (www.nano.neu.edu)
Lowell, University of New
Hampshire

University of California Center for Integrated Nanomechanical Sept. 2004

Berkeley Systems(nano.berkeley.edu/coins)

Ohio State University Center for Affordable Nanoengineering of Sept. 2004

Polymer Biomedical Devices (www.nsec.ohio-
state.edu)
University of Pennsylvania Center for Molecular Function at the Nano/Bio Sept. 2004
Interface (www.nanotech.upenn.edu)

University of Wisconsin Templated Synthesis and Assembly at the Sept. 2004

Madison Nanoscale (www.nsec.wisc.edu)
Stanford University Center for Probing the Nanoscale Sept. 2004

Nanoscale Interdisciplinary Research Teams (NIRTs)

NIRT awards are typically for four years and must involve a minimum of three principal
investigators. These awards typically fund research for which promising preliminary results have
already been obtained and where joining researchers having different expertise will boost the rate of
progress and degree of impact. For industry researchers looking at cutting-edge projects with
shorter time horizons, NIRTs are a good resource. Typically about 50 to 70 awards are funded each
year.

Nanoscale Exploratory Research (NER)

NER awards are typically for one year only. As suggested by the name, these grants are meant for
high-risk, high-impact projects at a very early research stage. About 50 to 70 are funded each year.

In addition, NSF has funded two user networks. These networks are meant to provide access for
both industrial and academic researchers to instrumentation, tools, and computational resources.

National Nanotechnology Infrastructure Network (NNIN)

The NNIN (www.nnin.org), funded at a level of $14 million per year for five years and renewable for
another five years, was completed in 2004 after conclusion of the National Nanofabrication Users
Network (NNUN). Led by Cornell, the initial network includes Georgia Institute of Technology,
Harvard University, Howard University, North Carolina State University, Pennsylvania State
University, Stanford University, the University of California at Santa Barbara, the University of
Michigan, the University of Minnesota, the University of New Mexico, the University of Texas at
Austin, and the University of Washington, with the potential of adding new nodes. The mission of the
NNIN is to provide access to nanotechnology-relevant infrastructure for synthesis, characterization,
fabrication, and integration.

Network for Computational Nanotechnology (NCN)

Initially funded in 2002 and led by Purdue, the NCN (ncn.purdue.edu and www.nanohub.org) has a
number of participants, including Northwestern University, University of Illinois, University of
Florida, Morgan State University, University of Texas at El Paso, and Stanford University. The
mission of the NCN is to create and provide access to new algorithms, modeling approaches,
software, and computational tools.

Education and Workforce Development

In the 2003 NSF solicitation, a new component in Nanotechnology Undergraduate Education (NUE)
was added, followed by a separate solicitation on Nanoscale Science and Engineering Education
(NSEE) in 2004. In addition to the funding provided by the NUE, the NSEE included funding for
Centers for Learning and Teaching (NCLT), Informal Science Education (NISE), and Instructional
Materials Development (NIMD). These efforts are focused primarily on expanding nanotechnology
knowledge and generating excitement in K12 and undergraduate students.
NNI and NSF Research Focus Areas
One of the strengths of nanotechnology is its potential to impact a wide range of technology areas,
but it is often easier to understand and foresee probable areas of scientific advancement by
recognizing the organization of the funding initiatives. For example, the following represent various
sets of R&D focus areas that have been identified over the past five years.

The original National Nanotechnology Initiative plan identified nine "grand challenges."[1] Significant
emphasis was placed on connections to the interests of the participating federal agencies, to
establish major, long-term objectives in nanotechnology in these areas:

1. Nanostructured Materials by Design

2. Nano-Electronics, Optoelectronics, and Magnetics

3. Advanced Healthcare, Therapeutics, and Diagnostics

4. Nanoscale Processes for Environmental Improvement

5. Efficient Energy Conversion and Storage

6. Microspacecraft exploration and Industrialization

7. Bio-nanosensors for Communicable Disease and Biological Threat Detection

8. Economic and Safe Transportation

9. National Security

Later modifications to the list included two additional grand challenge areas: Manufacturing at the
Nanoscale and Nanoscale Instrumentation and Metrology. In addition, grand challenges 79 were
combined into one category: Chemical-Biological-Radiological-Explosive Detection, and Protection.
The most recent strategic plan, "The National Nanotechnology Initiative: Strategic Plan" (December
2004), identified a slightly different organization of seven program component areas for investment:

1. Fundamental nanoscale phenomena and processes

2. Nanomaterials

3. Nanoscale devices and systems

4. Instrumentation research, metrology, and standards for nanotechnology

5. Nanomanufacturing

6. Major research facilities and instrument acquisition

7. Societal dimensions

These were based on the stated NNI goals of (1) maintaining worldclass R&D; (2) facilitating
 7.

transfer of new technologies into products for economic growth, jobs, and other public benefits; (3)
developing educational resources, a skilled workforce, and the supporting infrastructure and tools;
and (4) supporting responsible development of nanotechnology. [2]

The effect of these identified focus areas can be seen in the research themes of the NSF Nanoscale
Science and Engineering (NSE) solicitations, the most recent of which identified the following
research and education themes:

Biosystems at the Nanoscale

Nanoscale Structures, Novel Phenomena, and Quantum Control

Nanoscale Devices and System Architecture

Nanoscale Processes in the Environment

Multi-scale, Multi-phenomena Theory, Modeling and Simulation at the Nanoscale

Manufacturing Processes at the Nanoscale

Societal and Educational Implications of Scientific and Technological Advances on the

Nanoscale

On a broad scale, the NSF research themes represent the interests of the NSF and its program
directors as well as input from the technical community through strategic workshops and submitted
proposals. Thus, large groupings of research discoveries are likely to be organized under these
themes. Therefore, if a decision maker in, say, a biomedical sensor company wanted to find out
what discoveries might be applicable to its products, the decision maker would not only want to look
at awards under the Biosystems at the Nanoscale theme area, but also Nanoscale Devices and
Manufacturing at the Nanoscale. Many of the research projects may have a particular "test bed"
application in mind, but with nanotechnology, as with other research, some of the critical
developments are actually applications of technology from one field to a different field.

Following are brief descriptions of the theme areas excerpted from a NSF solicitation.[3]

Biosystems at the Nanoscale. This theme addresses the fundamental understanding of

nanobiostructures and processes, nanobiotechnology, biosynthesis and bioprocessing, and
techniques for a broad range of applications in biomaterials, biosystem-based electronics,
agriculture, energy, and health. Of particular interest are the relationships among chemical
composition, single-molecule behavior, and physical shape at the nanoscale and biological
function level. Examples include the study of organelles and subcellular complexes such as
ribosomes and molecular motors; construction of nanometer-scale probes and devices for
research in genomics, proteomics, cell biology, and nanostructured tissues; and synthesis of
nanoscale materials based on the principles of biological self-assembly.

Nanoscale Structures, Novel Phenomena, and Quantum Control. Research in this area
explores the novel phenomena and material structures that appear at the nanoscale, including
fundamental physics and chemistry aspects, development of the experimental tools necessary
to characterize and measure nanostructures and phenomena, and development of techniques
for synthesis and design. This research is critical to overcoming obstacles to miniaturization as
feature sizes in devices reach the nanoscale. Examples of possible benefits include molecular
electronics, nanostructured catalysts, advanced drugs, quantum computing, DNA computing,
the development of high-capacity computer memory chips, production of two- and three-
dimensional nanostructures "by design," nanoscale fluidics, biophotonics, control of surface
processes, and lubrication.
Nanoscale Devices and System Architecture. Research in this area includes development
of new tools for sensing, assembling, processing, manipulating, manufacturing, and integration
along scales; controlling and testing nanostructure devices; design and architecture of
concepts; software specialized for nanosystems; and design automation tools for assembling
systems of large numbers of heterogeneous nanocomponents. One can envision "smart"
systems that sense and gather information and analyze and respond to that information; more
powerful computing systems and architectures; and novel separation systems that provide
molecular resolution.

Nanoscale Processes in the Environment. Research in this area will focus on probing
nanostructures and processes of relevance in the environment from the Earth's core to the
upper atmosphere and beyond. Emphasis will be on understanding the distribution,
composition, origin, and behavior of nanoscale structures under a wide variety of naturally
occurring physical and chemical conditions, including nanoscale interactions at the interface
between organic and inorganic solids, between liquids and gases, and between living and
nonliving systems. Examples are biomineralization of nanoscale structures, molecular studies
of mineral surfaces, study of the transport of ultrafine colloidal particles and aerosols, and
study of interplanetary dust particles. Possible benefits include gaining a better understanding
of molecular processes in the environment, developing manufacturing processes that reduce
pollution, creating new water purification techniques, composing artificial photosynthetic
processes for clean energy, developing environmental biotechnology, and understanding the
role of surface microbiota in regulating chemical exchanges between mineral surfaces and
water or air.

Multi-scale, Multi-phenomena Theory, Modeling and Simulation at the Nanoscale. The

emergence of new behaviors and processes in nanostructures, nanodevices, and nanosystems
creates an urgent need for theory, modeling, large-scale computer simulation, and new design
tools in order for researchers to understand, control, and accelerate development in new
nanoscale regimes and systems. Approaches will likely include and integrate techniques such
as quantum mechanics and quantum chemistry, multiparticle simulation, molecular simulation,
grain-and continuum-based models, stochastic methods, and nanomechanics. Of particular
interest is the interplay of coupled, time-dependent, and multi-scale phenomena and processes
in large atomistic and molecular systems to make connections between structures, properties,
and functions. Examples of possible benefits include the realization of functional nanostructures
and architectures by design, such as new chemicals, multifunctional materials, bioagents, and
electronic devices.

Manufacturing Processes at the Nanoscale. Research in this area will focus on creating
nanostructures and assembling them into nanosystems and then into larger-scale structures.
This research should address these areas: understanding nanoscale processes; developing
novel tools for measurement and manufacturing at the nanoscale; developing novel concepts
for high-rate synthesis and processing of nanostructures and nanosystems; and scale-up of
nanoscale synthesis and processing methods. Examples are synthesis of nanostructures for
various functions, fabrication methods for devices and nanosystems, design concepts for
manufacturing, simulation of the manufacturing methods at the nanoscale, and evaluation of
the economic and environmental implications of manufacturing at the nanoscale. Possible
benefits include improving understanding of manufacturing processes in the precompetitive
environment, generating a new group of nanoscale manufacturing methods, increasing the
performance and scale-up of promising techniques, and establishing the physical and human
infrastructure for measurements and manufacturing capabilities.

Societal and Educational Implications of Scientific and Technological Advances on the

Nanoscale. Innovations in science and technology require societal support and also influence
social structures and processes, sometimes in unexpected ways. We need to examine the
ethical and other social implications of these societal interactions to understand their scope and
influence and to anticipate and respond effectively to them. Support for nanoscience and
 nanotechnology is likely to enhance understanding of fundamental natural processes, from
living systems to astronomy, and to change the production and use of many goods and
services. Studies of the varied social interactions that involve these new scientific and
technological endeavors can improve our understanding of, for example, the economic
implications of innovation; barriers to adoption of nanotechnology in commerce, health care, or
environmental protection; educational and workforce needs; ethical issues in the selection of
research priorities and applications and in the potential to enhance human intelligence and
develop artificial intelligence; society's reaction to both newly created nanoparticles and
nanoparticles that newly developed techniques permit us to recognize, detect, characterize,
and relate to health and environmental issues; implications of the converging interests of
different fields of science and engineering in the nanoscale; risk perception, communication,
and management; and public participation and involvement in scientific and technological
development and use. This theme aims to develop a long-term vision for addressing societal,
ethical, environmental, and educational concerns.

Along with these themes, a Memorandum of Agreement with SRC (Semiconductor Research
Corporation, which sponsors university research on behalf of its member companies) led to the
addition of a seventh theme area: Silicon Nanoelectronics and Beyond. This research, which
represents an example of a joint collaboration between NSF and industry, encourages proposals of
interest to a particular industry sector through its inclusion as a theme area in the NSF solicitation,
while providing additional funding opportunities from SRC funds. Similar joint solicitations have
been arranged between NSF and other federal agencies, such as DoD, DOE, and EPA. Many of these
funding agencies have searchable databases that identify funded research in specified theme areas.
Future Directions
The nature of federal funding of academic research can be envisioned as tossing pebbles into a lake.
Major research program solicitations tend to run for about five years, providing only the initial
impact of the pebble on the water, with the expectation that the spreading rings will last much
longer and spread much farther. The next pebble can fall in a completely different part of the lake,
or it can fall in an overlapping area of the spreading rings, leading to interaction between rings in a
region. Because of its impact, nanotechnology has already been given more pebbles to work with;
nanotechnology support was extended beyond five years and further supported by Congress in
December 2003 with the enactment of the 21st Century Nanotechnology Research and Development
Act. [4]

Although the funding for nanotechnology will logically continue to shift from its current form,
industrial interests are more likely to focus on the subsequent outcomes of earlier funded research.
The hope, with concurrent funding in Manufacturing at the Nanoscale, is that the typical period that
elapses between initial discovery and widespread commercializationsome 20 to 30 yearscan be
shortened for nanotechnology.[5]

In the next few years, as commercial products and processes become more viable and more visible
to the general public, the emphasis on environmental and health implications will grow. Already,
federal agencies such as NIH, National Institute of Environmental Health Studies (NIEHS), NIOSH,
and the EPA are establishing new multimillion-dollar initiatives in exposure, transport, detection,
and toxicity of nanoparticles and other nanomaterials.[6]

Many of the initial discoveries were rooted in the extension of the quantum and molecular scales of
physics and chemistry and the reduction of the microscales of microelectronics, but the most exciting
future discoveries lie in the intersection and integration of several technologies and scales.
Introduced even in the earliest NNI literature, this convergence of nanotechnology with
biotechnology, information technology, and cognitive sciences is anticipated to lead to significant
advances in human health, human performance, human productivity, and quality of life.

Such grand challenges are important because they ensure coordination among researchers from a
wide range of backgrounds. Perhaps one of the most far-reaching benefits of the NNI has been its
effectiveness in encouraging scientists, engineers, and social scientists to learn how to communicate
with each other.
Research Focus Areas of Other NNI Agencies
Many other agencies involved in the NNI are active in supporting academic research in nanoscale
science and technology.

The Department of Defense has funded research in nanoscale materials and applications that would
meet the operation needs of the U.S. Armed Forces. These include developing nanostructures for
revolutionary catalysts and sensors as well as developing nanoscale applications in areas such as
solar cells, solid-state power generation, and decontamination from chemical, biological, or
radiological attacks. DoD also funds a substantial share of the NNI investment in nanoelectronics,
nanophotonics, and nanomagnetics research, in particular research on spin electronics and quantum
information science. The U.S. Army's Institute for Soldier Nanotechnologies at MIT provides a vital
conduit for the transition of academic innovations in nanoscale science and engineering into
applications for the benefit of warfighters in the field. DoD agencies have also funded a number of
Multi-University Research Initiative (MURI) topics in nanotechnology-related areas.

The Department of Energy has funded a wide variety of research efforts in nanotechnology. These
include fundamental research into the unique properties and phenomena that matter exhibits at the
nanoscale. DOE research interests include catalysis by nanoscale materials, the use of interfaces to
manipulate energy carriers, nanoscale assembly and architecture, and scalable methods for
synthesis of nanomaterials.[7] DOE has also funded extensive research into modeling and simulation
of nanoscale materials and processes, as well as advanced computing to enable large-scale
modeling and simulation.

DOE's network of five NSRCs will play a key role in providing access to large-scale research facilities
and equipment needed by academic nanotechnology researchers. Small universities in particular do
not always have the resources to purchase the latest nanotechnology research instruments, and
even large institutions may find it prohibitive to buy specialized light sources and other large-scale
instruments that are needed for some experiments. These resources will be available at the NSRCs,
which are user facilities available to the entire R&D community, with time and staff support allocated
on the basis of merit-reviewed proposals. The centers are under construction as of this writing, and
are co-located with complementary light sources and other facilities at Oak Ridge National
Laboratory, Argonne National Laboratory, Brookhaven National Laboratory, Lawrence Berkeley
National Laboratory, and a combined center at Sandia National Laboratory and Los Alamos National
Laboratory. Time, materials, and technical assistance are provided free of charge for researchers
who are willing to publish the results of their work in the open literature, and on a cost-recovery
basis when used for proprietary purposes. These DOE centers complement NSF's National
Nanotechnology Infrastructure Network and the Network for Computational Nanotechnology, NNIN's
network of user facilities devoted to computational modeling of nanomaterials.

The National Institutes of Health has many Institutes that are funding research into nanotechnology-
based disease detection, prevention, and therapeutics, as well as tools that will allow greater
understanding of the biological processes that influence our health. Nanotechnology research can
develop unique capabilities to measure and manipulate on the size scale of individual cells. Efforts
have already been funded to develop new tools that gather information on macromolecular systems
in living cells or organisms. Other funding is targeted to detection and treatment of specific
diseasesfor example, research into targeted imaging contrast agents for detecting very small
numbers of cancer cells at the earliest stages of the disease, and even nanoparticles that can
selectively deliver chemotherapy drugs only to tumors without damaging normal tissues. The
National Institutes of Health, like most federal agencies, funds considerable other basic nanoscale
research that it does not formally classify as nanotechnology.
The Environmental Protection Agency is funding research in nanotechnology applications that protect
the environment by sensing and removing pollutants as well as research in more environmentally
friendly manufacturing technologies. EPA also is supporting extensive research studies on how
nanoscale materials might impact human health and the environment. In particular, in 2004 EPA
took the lead in organizing (with NSF and the National Institute for Occupational Safety and Health,
or NIOSH) an interagency program for environmental and human health effects of manufactured
nanomaterials. This project is likely to be expanded in future years, possibly to include funding
agencies in other countries.

NASA sponsors a wide variety of research on the fusion of nanotechnology, biotechnology, and
information technology to study and mimic the organizational structures found in nature. Other
research funded by NASA supports space exploration in areas such as sensors for extraterrestrial
materials and applications that monitor human health. NASA researchers have collaborated with
universities in a number of nanotechnology-related areas, including some leading-edge research in
carbon nanotube fabrication and applications. In 2003 and 2004 NASA funded four University
Research, Engineering and Technology (URETI) centers devoted to promoting interdisciplinary
academic research in a variety of nanotechnology-related topics. These are located at UCLA, Texas
A&M University, Princeton University, and Purdue University. The initial awards were for five years,
with options to extend NASA's support for an additional five years.
Summary
The ability to take advantage of the products of academic research lies in understanding the
structure of academic research funding. Depending on whether the goal is to obtain a general
introduction to a new technical area, to identify technologies that are close to commercialization, or
to keep up with revolutionary new ideas, one can narrow the starting point for a search by
identifying appropriate centers, groups, or individual investigators through award databases.

In a more active mode, industry can have a guiding and accelerating influence on the progress of
academic research, either through participation in workshops and conferences that identify the
critical barriers or through true research partnerships with academia, supporting not only the
research but also the development of the students who will constitute the future workforce.
References
1. "National Nanotechnology Initiative: The Initiative and Its Implementation Plan," NSTC/NSET
report, July 2000.

2. The National Nanotechnology Initiative Strategic Plan, December 2004.

3. http://www.nsf.gov/pubs/2004/nsf04043/nsf04043.htm.
4. http://www.nano.gov/html/about/history.html.
5. http://www.nsf.gov/crssprgm/nano/.
6. http://www.nano.gov/html/facts/EHS.htm.
7. http://nano.gov/nni_energy_rpt.pdf.
Chapter 8. Understanding University
Technology Transfer for Nanotechnology
Larry Gilbert and Michael Krieger

At first blush a straightforward process, commercializing the results of university research depends
on many factors coming together "just right," and in a hospitable environment. Because the
variability of the actors and elements in the process tends to dominate any idealized model of
successful technology transfer, this article focuses the unique features of the components rather than
the process per se.

Universities are a wellspring of nanotechnology discovery, with the dominant portion supported by
the federal government as it puts ever-increasing public funding into nanotechnology grant and
contracts programs.[1] In contrast, corporate and other private developments are just thatprivate
and substantially unavailable to entrepreneurs, investors, or others in the public. Combining this
dichotomy with the fact that pursuing most nanotechnology ideas requires a level of capital
investment and a team of scientific talent rarely assembled by the lone inventor, the research fruits
of universities (which typically are mandated by federal funding to be made available for
commercialization) present a central opportunity to entrepreneurs and investors for involvement in
nanotechnologyto find discoveries to turn into viable commercial products.

The lab-to-market journeywhether involving nanotech or another technologyis generally referred to

as technology transfer and is initially shepherded by a university's office of technology transfer
(OTT) or licensing office.[2] Idealized, that process is often characterized in terms of these major
steps:

1. A research discovery or technology advance is made by a professor or other senior researcher

(the "invention").

2. The invention is disclosed to the university's technology transfer office.

3. That office files a provisional patent to protect associated intellectual property (IP).

4. The office "markets" the invention to or responds to commercial interest from potential
licensees that are willing to bear the cost of patenting the invention, developing the technology
to commercial viability, and taking it to market.

Three caveats are in order lest this process seem overly straightforward and easy to execute.

First, the sequence requires that all the actors involvedthe people, companies, and institutionspull
together, that is, cooperate to a considerable degree to make the deal, as well as the technical
development, commercially viable. Any significant aberration, such as unreasonable licensing terms,
stands to break the chain of steps needed to bring the discovery to market, or perhaps even prevent
making it to the patent office. Second, discoveries also advance from lab bench to market shelf in
other ways, several of which are described later in this chapter.

Finally, and most fundamentally, we put "markets" in quotation marks because it implies and
represents the common belief that an OTT's market push creates technology awareness, interest,
and ultimately license deals. In our view, this almost universal faith is misplaced: Although "push"
marketing is done almost universally by tech transfer offices nationwide, we believe its effectiveness
for sophisticated technologies is minimal, if not mythical, when compared with the "pull" of
awareness created by a researcher's publications, professional presentations, former students, Web
sites, and so on.[3]

This chapter describes key facets, dimensions, and pitfalls of technology transfer that need to be
understood by anyone hoping to participate in moving an attractive scientific or technology
discovery into the commercial world.
Unique Rather than Common Elements Characterize Tech
Transfer Deals
As already suggested, our present focus is not the process per se but rather its components. The
reason is fundamental yet perhaps too little appreciated: Although each tech transfer
commercialization certainly reflects and results from an identifiable process, it is decidedly not
manageable as such. That is, the word process suggests that one can delineate a set of steps,
criteria, measures, inputs, outputs, and so on and then hand them, as if a recipe, to someone of
reasonable skill to manage for a variety of situations and technologies.

That would be true if the commonalities existing among the various successes dominated the story.
Nothing could be further from the truth. Rather, the unique differences in the constituents must be
dealt with. Each deal must be handled with its own particular emphasis on the blend of ingredients,
from human factors to royalty rates.

Indeed the misconception of emphasizing tech transfer as a process has seriously undercut the
potential success of many tech transfer efforts; unfortunately, emphasizing commonalities of process
from deal to deal diverts attention from the unique, vital, and critical deal-dependent differences of
the components. These include faculty personalities, the nature of the technology, the time and
capital required to advance from laboratory discovery to proof of concept, the nature of the market,
and other factors.

Ultimately determinative of success are the motivations and relationships of those involved. We thus
look at the researchers, their relationships with their institutions and administrators, and the types
of arrangements they have with commercial entities. Subsequent sections treat those components
and their special elements that affect the success of transferring an invention and technology.
Why Does a University Transfer Technology?
This question is underscored if one looks at the statistics: Few university OTTs generate enough
income to justify themselves when measured strictly by revenue. But many other reasons exist:

Federal Mandate. U.S. government funding may require the university to at least make the
resulting discoveries available to those who might commercialize them.

Equity. A share in an early-stage company that succeeds can eventually be very valuable.

Faculty recruitment. A significant number of faculty members want to see their results
commercialized, for reasons that range from the greater social good, to the opportunity to
interact with industry, to the hope of enhanced income from sharing in royalties resulting from
the invention's commercialization.

Goodwill. Faculty and alumni who become business successes, and others in the business
world, are more likely to become donors if they recall and see an environment that encourages
technology entrepreneurship and business development.[4]
How is Technology Transferred?
Technology can pass from a university into the commercial world in many ways; five are discussed
in more detail later in the section "Types of Business Relationships." Typically, the discovery or
result of interest centers on a patentable invention by a professor for which the university will file a
provisional if not full utility patent. The simple process model sketched earlier then posits that a
commercial entity learns of the invention, desires to exploit the technology, and thus executes a
licensing arrangement with the university. The licensee may be an established company or a start-
up formed by entrepreneurial researchers from the university. Depending on the type of licensee,
the agreement may provide for some up-front payment or equity in the licensee in addition to
royalties on sales when the technology enters the market.

In reality this simple picture is incomplete or masks many potentially distorting elements. Most
fundamentally, successful development of a technology usually requiresin addition to rights in the
relevant patentsthe know-how of the discoverer and his or her graduate students and other lab
personnel. This in turn means that the licensee's commercial venture likely requires the professor's
cooperation, typically in the form of a consulting arrangement or employment of (former) students.
It is essential to appreciate that absent such know-how a patent may well be worthless.

With this in mind, we now look at the sources of technology, the effects of academic culture, and the
types of business relationships that provide vehicles for technology transfer.

Sources of Technology
Implicit in the preceding section is a licensable or otherwise transferable technology, that is, one
that has come to the attention of the university and is being protected by the patent system.[5]
Indeed, by virtue of faculty, grad student, and staff employment agreements, as well as the Bayh-
Dole Act requirements for federal funding, ownership in any inventionand typically in any
discoveryvests in the university (unless it disclaims the invention).[6]

How does the university administration learn of the invention? It finds out in the same way
corporate administrations do: by the inventor submitting an invention disclosure form. Of course,
that depends upon whether the inventors submit the disclosures.

Indeed, to the extent that faculty fail to disclose technology so that patent protection can be
invoked, the technology may become part of the public domain and fair game for all, especially if it
is disclosed at a professional conference. Although this may at first seem socially desirable, the lack
of a patent-conferred monopoly may hinder or effectively prevent commercial development should
the technology require a deep investment to render it viable.

What Are the Incentives for the Discloser?

In enlightened companies there are educational programs to help researchers realize that what their
deep familiarity with the technology makes "obvious" may not be and could well be patentable.
Moreover, many companies conspicuously display their patents and reward their inventors with
payments upon invention disclosure, patent filing, and patent issue.

In contrast, few universities have effective IP education programs, and virtually none has an
immediate cash award. But in contrast to private industry, university inventors typically receive a
substantial share of the royalty stream, commonly 2550 percent (an arrangement very rare in the
private sector).

Faculty Trust
Although such a high royalty percentage might seem to be a strong incentive for invention
disclosure, faculty generally recognize that the tech transfer policies and practices of their
institutions are a gateway to achieving royalties. Thus their confidenceor lack of itin their tech
transfer offices is a key determinant of their willingness to file the disclosure statements that trigger
the OTT's involvement and IP protection. After all, why bother if nothing will come of it?

More broadly, lack of trust may arise for various not entirely independent reasons:

Distrust of institutional administrators generally

The belief that tech transfer officers are looking out for the university and might at some level
be disingenuous with the faculty member

Doubt about the OTT's ability to market (find licensees for) the invention (for researchers who
believe this to be the OTT's role)

Doubt that the OTT has the business sophistication and nimbleness to make contract
arrangements that investors or industry will accept

An OTT's reputation (whether or not justified) for being difficult, unresponsive, or unsuccessful

It should be recognized that a certain amount of tech transfer will take place in every major
research institution, even those saddled with these liabilities. Some technologies speak for
themselves, some researchers have enormous entrepreneurial and business skills, and some
individual technology transfer officers have the interpersonal skills to overcome a general distrust of
their offices or their histories.

But in the institutions that have had truly successful programs, the researchers trust the OTT (and
conversely the office trusts them). Not only does this encourage formal disclosure of inventions, but
also it means, among other things, that the OTT is likely to be privy to research developments early
on, is welcome in the lab, meets the graduate students who may be the ones to carry the start-up
ball or to go to work for a licensee, and so on. Furthermore, it means that when the OTT wants to
show or explain the technology to a potential licensee or partner, the researcher is likely to
cooperate and spend the time it may take.

Academic Culture Issues

A potential licensee, especially a corporate entity, may have to make considerable adjustment in
dealing with a university compared to the familiar styles of commercial suppliers and partners. This
can manifest itself, for example, in problems with maintaining the secrecy it may usually take for
granted and in the slow pace of negotiation. In the following sections we delineate key factors
affecting the perspectives of university personnel.

Faculty Publication
"Publish or perish" remains alive and well. A professor's publication record is central to salary and
position within the university. Similarly, any researcher's bibliography is a critical qualification for
external funding. In parallel, reputation among peersarising from activities such as research
collaboration and conference presentationsis requisite for the professor to get the favorable letters of
support solicited by outside funding sources (such as federal agencies) and by campus promotion
committees. All this puts a premium on early dissemination of research. Closely allied is the spirit of
academic freedomthe belief that on campus almost any topic of discussion is acceptable and
available to be discussed and shared freelyand its corollary: Restraints on sharing information are
unacceptable.

What does this culture imply? First, it implies that commercially valuable ideas may be released into
the public domain, that potential patents may be barred by early disclosure, or that an existing
licensable patent (or application) may be subject to invalidation. Second, if an acquirer of
technology is considering a partnering arrangement there will need to be a mutual assessment of
what level of research secrecy is really needed and how it fits the personnel and institution involved;
for example, it must be determined that no insurmountable conflict exists with the views of
academic freedom held by the campus personnel, with university policy, or with obligations under
government funding.

Practical needs for publication and presentation must be taken into account when a commercial
entity negotiates consulting services, whether they are made directly with a faculty member or as
part of licensing a patent. To this end, for example, confidentiality provisions may need to be
customized in lieu of using nondisclosure agreement (NDA) forms. More generally, to the extent that
key faculty are necessary to exploit a technology, personality issues come into play; some university
faculty are resistant to being told what to do; others are quite naive about business practices, and
still others are most cooperative. The main issue is to be prepared so that, for example, cooperative
but less worldly faculty can be coached to appreciate corporate business practices, to understand
that some of their work for the company cannot be immediately shared at conferences or in
publications or that turning research into a marketable product takes many times the cost of the
underlying discovery and will take time.

Technology Transfer Offices and University Administration

To a significant degree, the nature of a university or other research center as a large organization is
antithetical to developing a successful technology transfer program. In large measure the conflict is
one of having a short- versus a long-term view in establishing goals and evaluating results.
Although many of the reasons for technology transfer are intangible benefits, an OTT nonetheless
costs money, so licensing revenue becomes the most natural measure of its success.

To a start-up, licensing means little or no initial royalty payment and a long window until sales yield
royalties. And even if an established corporation is the licensee, it is likely to require some years
before profitable, royalty-generating sales occur. Meanwhile the costs of filing and maintaining a
patent portfolio as well as the OTT staff and overhead costs appear every year in the university
budget. This may lead to tension between the OTT staff and university administration as to whether
or not to patent an invention; for example, the admin may want to patent only the "viable"
technologies (somehow expecting technology transfer personnel to bat 1000 at picking the winners).
Yet picking a commercial success at such an early stage is simply not possible. To underscore the
point, venture capitalistswho invest in technology at a much later stagethemselves end up funding
far more losers than successes.

On the other side of the coin, many researchers will believe their discoveries are unquestionably
worth patenting, and then they will become disenchanted with the OTT should it fail to recommend
patenting their discoveries.

Another organizational factor running counter to tech transfer effectiveness is that OTT personnel
may feel pressure to perform in a shorter time frame than is realistic; in other words, annual
reviews do not comport with the three to five years it may take to know whether the deals done by
the OTT member were good. This can cause turnover of tech transfer staff and the attendant failure
to build the faculty relationships and develop the trust that is requisite to motivating invention
disclosures and post-disclosure cooperation.

Types of Business Relationships

Although licensing a patentable technology to a commercial entity is the most visible mode of
transferring technology, it is only one of a variety of arrangements that are commonly done.
Valuable IP is typically acquired through one of the following forms of relationship with research
institutions.

Licensing

In this first method, the university grants certain rights in intellectual property to a third party, the
licensee. Licensees are typically one of two types: an existing company interested in some
technology the university holds, or a new start-up company. Licenses can be exclusive or
nonexclusive and usually involve patents, although some occasionally include software.[7]

The university will try to limit the field of use for the license, and the company will often want to
negotiate a more expansive field because it may be unclear at the time the license is granted which
fields or applications best suit commercial application of the invention. The university will generally
require, in the case of exclusive licenses, evidence of diligence in exploiting the technology.
Generally the lack of such diligence will cause the license to become nonexclusive or the field of use
to be reduced.

Even when granting an exclusive license, the university may retain certain rights, including the right
to use its invention for research and development. The federal government also retains rights under
the Bayh-Dole Act, and there may also be third-party rights.

Failure to investigate and to keep these rights in mind can lead to later disappointments.

Faculty Consulting

As the leadersand frequently the definersof cutting-edge scientific breakthroughs and technology
advances, university faculty can be uniquely valuable consultants to a corporate R&D effort.

For the most part, patented technology is best developed and exploited with the help of its inventor,
because there is usually extensive, valuable know-how that is not necessarily disclosed in the formal
patent. To this end, part of a licensing arrangement will involve participation by the faculty members
whose research led to the patent.

As with any other outside contractor to the company, faculty consulting may also be arranged
independently, in which case there may be no specific university involvement. In this case, particular
care must be taken to set out the parties' expectations and ground rules for the scope of the
engagement. This is because faculty members almost surely have obligations to the university
regarding ownership of IP related to their funded research. If the consulting yields, for example,
patentable inventions closely aligned with the university-based efforts, disputes over ownership
could arise, especially were the consulting to lead to a corporate product with visible financial
success.
Strategic Partnering with University Spin-Offs

Promising, innovative university technologies are often best developed under the mantle of a
separate company. The transformation from lab bench discovery to economically viable technology
may require resources not found in or not appropriate to the university setting; conversely, the
intense and autonomous work needed to prove the technology may not fit under the corporate wing.
Such a start-up may be initiated by a faculty member and graduate students, or it may be explicitly
contemplated by a licensing arrangement. In either case, a technology license and corporate
investment in the company will likely go hand in hand. Often, the relationship will have been
initiated by corporate R&D personnel, who learn of the technology from conferences and
publications. Other times university "show and tell" events give rise to the relationship.

Special Funding of Faculty Research

Once they are aware of faculty working in areas of corporate interest, some companies have found it
useful to cultivate a link with the faculty member through research grants. Typically such grants do
not have a specific mission but rather simply contemplate work within a specific area. In significant
measure, the main function of such grants is to establish a channel of communication with the
faculty member so that the company has an early awareness of the research or ready access to
consulting time of the professor and employment of advanced and knowledgeable students.

Major and Ongoing Research Partnering

Continuing relationships between a corporation and a university may take many forms. Specific
departments and schools often have industrial affiliate programs in which a company makes an
annual contribution and, in turn, gains advanced access to university research through special
programs, meetings, and the like. At the other end of the spectrum, a company may fund a major
research facility on an ongoing basis in exchange for a right of first refusal and certain exclusive
rights to the fruits of discovery from the funded research.

Risks
Perhaps the biggest risk in acquiring technology from a university is to be sure that the ownership of
the IP is clear. Although this is not as likely to be a problem in pure licensing arrangements, it can
become murky in consulting and partnering unless one is alert to potential pitfalls. Indeed
litigationalthough relatively uncommonhas been rising in the tech transfer context, no doubt
because of the increased frequency of technology being transferred without a corresponding gain in
sophistication about tech transfer and intellectual property. Considered here are the most common
litigation risks and what a business can do to prevent getting embroiled.

University Licensing Litigation Risks

Inadequate attention to detail when licensing university technology can result in a host of problems.
First, a company should require that the university represent and warrant that it owns the
technology that it is transferring. There have been cases in which non-university entities have
claimed they developed the same technology the university has licensed. Second, make sure that
the university is clear about the scope of the technology's application or market. Litigation has
arisen over the proper scope of the university's license to an outside company. Third, inquire
whether the university has offered other licenses on the technology, to guard against errors in the
university's licensing program. On occasion, universities have been known to unwittingly offer
overlapping "exclusive" licenses. Similarly, a "favored-nation" clause in a non-exclusive agreement
with an initial licensee may be overlooked in deals with later licenses.

Professor Consulting Relationships

Hiring a professor who is an expert in a company's research and development field is a popular and
effective way to bring cutting-edge academic knowledge to the corporate setting. Unfortunately,
there are litigation risks. First, and foremost, the corporation must assure itself that the professor is
not taking university-owned technology off campus. This can be a tricky inquiry. The best place to
start is to obtain a copy of the university's patent policies. This will give the corporation a checklist
of the do's and don'ts for its consultant professor.

Typically, a university's patent policy is part of its professors' binding employment contracts. The
corporation should ask professors to represent and warrant that none of the work that they will be
doing for the corporation would represent a violation of their obligation under the patent policy. A
recommended precaution is to be sure that professors in fact understand the policy by, for example,
having corporate counsel review that policy with them.

Second, the corporation should make sure that professors have not entered into any joint venture
with any other person (such as an agreement with a former graduate student to develop the same
technology with which the professor is now helping the corporation). Again, the best way to protect
against this litigation risk is to have professors represent and warrant that the technology that they
are consulting about has not been developed in conjunction with (or with the assistance of) any third
party.

Finally, a consulting professor can cause problems when the corporation is making a bid for
university technology. Although it is true that a university in a technology licensing bidding process
may well favor a company that has hired one of its faculty members, the professor (and his or her
corporation) must be careful not to corrupt the bidding process. Professors should not use their
position at the university to influence the bidding on a university patent license beyond the channels
available and known to every bidder. For example, professors should not use the faculty dining room
as an opportunity to politic the head of the licensing office for the company to get the technology
when other bidders cannot engage in the same sort of lobbying. Such activity could, in some
jurisdictions, subject both the professor and the company to legal liability.

Other Litigation Risks

Because universities are increasingly attempting to market their technology, a corporate researcher
may be shown technology under circumstances that suggest confidentiality or other obligation, and
thus the researcher needs to be careful about how information gleaned from visiting university
facilities is used. Overzealous corporate researchers could create significant exposure to liability if
they misuse university technology learned about while chatting with university faculty.

In sum, as with all corporate dealings, the basic rules of the road are the same for avoiding litigation
in technology transfer licensing: (1) Get it in writing, (2) make sure somebody else's intellectual
property rights are not being violated, and (3) make sure that deal terms are clear and state exactly
who bears the risk.
Final Words
At the heart of a successful tech transfer program is the trust between the faculty and the university
personnel shepherding the invention toward viability and the commercial world. Without that trust,
far less technology will be disclosed by researchers, faculty will be less willing to cooperate with the
OTT, and unseen "leakage" of inventions into the private sector will be more common. Although our
setting is academic and not corporate, it is appropriate to recall the words attributed to John
Patterson, founder of NCR Corporation, who said nearly a hundred years ago that the only assets a
company really has are people, ideas, and relationships.
Notes
1. Because universities are the dominant component of the nation's public research enterprise,
we use the terms university and academic as a collective that also includes noncommercial
academic and think-tank research centers and certain nonprofit centers formed by industry
consortia, to which most of the observations in this chapter also apply.

2. The term technology transfer is sometimes used more broadly to embrace most any licensing
of technology between entities, such as a catalytic process licensed by a major chemical
corporation to a major refiner. We use it here in the narrower sense described earlier.

3. Caltech's OTT does no traditional technology marketing and yet is widely acknowledged to
have among the country's most fertile tech transfer programs, despite the institute's small
faculty.

4. Indeed, very large donations exceed amounts that any successful technology ever can be
expected to yield directly. For example, Broadcom co-founder Henry Samueli contributed $30
million to the UCLA Engineering School, and venture capitalist Mark Stevens gave $22 million
to USC for an Institute of Technology Commercialization. Inventor and businessman Arnold
Beckman has contributed in excess of $100 million to Caltech and large sums to other schools
as well, and Gordon Moore's commitments to Caltech exceed $500 million.

5. In the commercial world, patents are typically born as trade secrets by virtue of the implicit
status of private information held by a company's researchers. In the academic world, one
rarely counts on such protection for two intertwined reasons: The spirit of the academy has a
big component of sharing knowledge, and so any initial discovery is soon out of the bagfor
example, by disclosure at scientific symposia or by exchange between colleagues far and wide;
moreover, participation in a lab and its discussions can be very fluid, so not only the number
but also the diversity of people involved (students, visitors from other universities, lab techs)
makes keeping secrets problematic. By contrast, effective legal enforcement of trade secret
protection requires that the owner have treated the subject matter as a trade secret, which
means, at least in court, a showing of reasonable security procedures and signed NDAs with all
who have had access to the information. Relatively few university research facilities are likely
to withstand the scrutiny of such a review.

6. The bulk of research funding for universities comes from the U.S. government and is subject to
the 1980 Bayh-Dole Act (35 U.S.C. §§ 200-212). If a university does not want to carry the
burden of prosecuting the patents associated with a discovery, it must timely so inform the
U.S. government, which may choose to patent the invention.

7. Under the Bayh-Dole Act, where the research was at least partially supported by federal
funding, the U.S. government retains significant usage rights even if the license agreement
from the university to a third party is for exclusive rights.
Chapter 9. Intellectual Property Policy and
Impact
Chinh H. Pham and Charles Berman

Over the past two decades, the ability to manipulate, control, and measure matter at the atomic
scale has led to interesting discovery of novel materials and phenomena, discovery that underlies
the multidisciplinary areas of research and development known today as nanotechnology.
Nanotechnology, simply put, involves the working and manipulating of matter on a scale that is one
billionth of a meter in size.[1] The field spans the spectrum of research and development across
many disciplines, including physics, engineering, electronics, materials, molecular biology, and
chemistry.

Because the market for nanotechnology-related products and services promises to increase
significantly, and with more companies trying to stake out territories while grabbing as much of the
intellectual property pie as they can, the value and strategic importance of protecting intellectual
property have become crucial in the quest to capture valuable opportunities.

According to the ISI Science Citation Index, in 1987 there were only 237 scientific articles published
with the prefix nano- in the title. By 2002, the number had risen to about 10,000. In addition,
between 1999 and 2002, according to the Derwent Patents Index, the number of U.S. patents
published for nanotechnology almost doubled. A quick search of the U.S. Patent and Trademark
database shows that at the end of 2004, there are about 7,780 issued patents and about 9,060
pending applications containing the prefix nano-.

To the extent that many companies are now placing a priority on intellectual property (IP), the
building of a strong IP portfolio for strategic and economic purposes will therefore play an important
role in whether these companies can create for themselves commercially viable opportunities.
Types of IP Protection
The U.S. Constitution, statutes, and common law provide protection for intellectual property rights
through patent, trademark, copyright, and trade secret law. For many early-stage companies,
patents and trade secrets will be predominantly used in the protection of their IP assets. However, in
many instances, and depending on the circumstance, trademarks and copyrights can also act to
enhance the value of the IP assets.

Patents
In the United States, patents (that is, utility patents) offer protection for inventions that are directed
to an apparatus, a concept, or a method or process that is novel, useful, and nonobvious. It is a
contract between the inventor and the government (the U.S. Patent and Trademark Office, or
USPTO, also called the Patent Office), whereby the inventor agrees to disclose the invention to the
public, and in return, the USPTO grants exclusivity in the invention to the inventor if the invention is
deemed new, useful, and not obvious. This exchange is seen as helpful in developing the
technological knowledge base that is available to the public, while promoting the sciences and
technologies.

In general, a patent does not grant to the owner the right to practice the invention. Rather, a patent
provides negative rights, in that it grants to the patent owner the right to exclude others from
making, using, selling, offering for sale, or importing the invention. With the recent change in U.S.
patent law, the enforceable term of a patent now expires 20 years from the priority date of the
patent application from which the patent issues.

Often, after one obtains patents in any technological field, it is essential to then engineer and tune
the patents to create a substantially strong and solid portfolio to maximize the return from the
patent assets. In other words, the portfolio should minimize the gaps that competitors can design
around. The challenge of creating a strong and solid portfolio is equally applicable in the field of
nanotechnology.

Protecting a new nanotechnology-related invention can be a difficult process, especially when the
resources are simply not available at the early stages to pursue patent protection. Moreover,
because nanotechnology is an emerging field, protecting the invention requires a level of knowledge
and technical expertise that may be lacking.

Furthermore, some new ideas simply cannot be patented because they do not rise to the level of
being novel or being nonobvious. For nanotechnology-related inventions, there can be substantial
overlap with existing technology except that the nanotechnology-related inventions involve subject
matter on a substantially smaller scale. Other nanotechnology-related ideas may be eligible only for
narrow or partial protection from potential competition and imitation. Even if minimal protection can
be obtained, such pursuit can often be expensive and time-consuming, with the ultimate result
remaining uncertain.

A decision to seek protection for a new nanotechnology-related product or process should therefore
be approached with the careful consideration that one brings to other commercial transactions. Just
because a new nanotechnologyrelated product or process may be eligible for patent protection does
not necessarily mean that the cost of obtaining and preserving such protection is justified from a
business viewpoint. Patent protection is viewed as one part of the successful marketing equation.
Before pursuing patent protection, one should consider a few statutory requirements and strategic
points.

Trade Secrets
In addition to patents, a nanotechnology company can also use trade secrets to protect its
proprietary information and intellectual property. A trade secret, in general, is confidential business,
technical, or other information that gives a company a competitive advantage over its rivals. A trade
secret need not be novel and requires no formal filing procedure for protection. Its duration can be
indefinite, as long as reasonable efforts are made to keep the information secret. If, however, the
trade secret is publicly disclosed or is reverse-engineered by a competitor, legal protection of the
trade secret is destroyed.

For a nanotechnology-related invention, because of the nature, science, and scale of the technology
at issue, it may be difficult to reverse-engineer the nanoscale technology when compared with
traditional technology. To ensure maintenance of the trade secret, a company should pay close
attention to its activities externally as well as internally. For example, companies should consider
using a nondisclosure agreement (NDA) when exploring a potential partnership, collaboration, or
investment opportunity.

In addition, because of the potential for high employee movement in this field, a nanotechnology
company should consider instituting a companywide protocol for maintaining the confidentiality of
proprietary information. For example, a nanotechnology company can educate its employees on the
importance of maintaining confidentiality, can mark proprietary or appropriate information
"Confidential," and can inform departing employees of their obligation to keep such information
confidential.

Trademarks
Another strategy for protecting intellectual property rights is through the use of trademarks.
Generally, trademark rights protect the name or symbol associated with the company in relation to
its commercial products or services. The rights afforded to a trademark prevent others from using
similar, confusing names or symbols that may take advantage of the goodwill and quality associated
with the protected names and symbols. Trademarks can have unlimited duration, as long as the
mark is renewed at the appropriate time and is commercially used continuously.

As more companies begin to position themselves to take advantage of the opportunities in the field
of nanotechnology, there has been an increasing trend to register, as a trademark, names that
include the word nano. A brief check of the trademark database at the U.S. Patent and Trademark
Office reveals that, at the end of 2004, there are more than 1,600 such registered and pending
marks.

Copyrights
Copyrights protect the original expression of an idea, as opposed to patents, which protect the idea.
Protection under copyrights attaches immediately when the idea is fixed in a tangible medium, such
as paper, compact disc, or hard drive. Copyrights can offer protection for as long as 75 to 100 years
for work made for hire, which is generally the case in the field of nanotechnology.
Statutory Requirements
In the United States, there are several major hurdles that an inventor must overcome before patent
protection can be obtained. Specifically, an inventor must be able to demonstrate that the invention
is new, useful, and nonobvious. A patent cannot be obtained unless the invention is new. In
addition, the invention must not have been known or used by others in the United States, or
patented or described in a publication in the United States or any foreign country, before the
applicant made the invention. Moreover, if the invention was patented or described in a publication
anywhere in the world or in public use or sale in the United States more than one year prior to the
date the application is filed, a patent will be denied.

In connection with this last point, it is critical that a patent application be filed with the U.S. Patent
Office prior to the one-year anniversary of the public disclosure, use, or sale of the invention.
However, unlike the United States, most countries do not allow this one-year grace period. "Absolute
novelty" is typically the requirement. Thus, any public disclosure, use, or sale of the invention will
foreclose the right of the applicant to pursue patent protection in these countries. Public disclosure
includes presentations, printed and online publications, public meetings, offers for sale, and
discussions with someone not under a confidentiality agreement. Accordingly, because
nanotechnologyrelated inventions have far-reaching benefits beyond the borders of the United
States, it is imperative that an application be filed prior to any public disclosure, use, or sale.

To determine whether an invention is novel (i.e., new), an application is examined by a patent

examiner skilled in the technology of the invention and is compared against the available prior art.
The examiner makes a thorough study of the application and all the available public information
pertaining to its claims. Currently, much of this examination is conducted electronically, and the
examiner has access to databases of the USPTO, European Patent Office, and Japanese Patent Office.
The examiner also has access to other non-patent literature; however, in practice this is more
limited.

Given the interdisciplinary nature of nanotechnology-related inventions, as well as the potential for
these inventions to have application in multiple industries, examiners may have a difficult time
performing adequate searches. For example, an invention directed to the manufacture of
nanoparticles might involve materials science, chemistry, and physics. Furthermore, if the invention
involves the use of the nanoparticles for drug delivery or imaging purposes, additional consideration
must be given to the fields of molecular biology and optoelectronics.

Moreover, there is no specific examination group within the U.S. Patent Office dedicated to
nanotechnology. Consequently, the search process currently falls to other existing art units, many of
which are overburdened with the number of applications to be examined. As a result, it is important
that the application be provided with an adequate and thorough search of the prior art to ensure
that the invention at issue is novel.

The invention must also be nonobvious. It is common for the U.S. Patent Office to reject a patent
application as being obvious. In certain instances, it may well be that the invention is something
that has never before existed. However, if the Patent Office determines that a hypothetical person
having access to the available information concerning that particular field of technology would have
"known" how to make the invention (or modify a previous invention to make it), it may reject the
patent as being obvious.

The claimed invention must also be useful. This utility requirement is seldom a hurdle encountered
by the established disciplines. However, it can be an issue for nanotechnology-related inventions. By
way of example, as a nanotechnology start-up tries to fortify the landscape around its core
technology, it may file additional patents that recite multiple commercial uses for the invention in a
variety of industries without clearly knowing whether such uses may work. In doing so, the company
may encounter a risk that the invention lacks utility and the patent application may be denied.

Inventions also must be fully described in an enabling manner. The requirements for an enabling
disclosure can provide a unique challenge and must be carefully addressed. The nanotechnology-
related invention being disclosed might involve not yet clearly understood phenomena or might be
addressed by technology that is being disclosed for the first time in the application. Accordingly, for
nanotechnology-related patent applications it is imperative to use an interdisciplinary team
approach. A team of experts will be much better able to address and provide solutions across
various nanotechnology platforms.

Having a team of experts, all of whom understand the various aspects of the invention, can lead to
an efficiently generated work product without any compromise in quality.

The USPTO evaluates its patent examiners primarily according to the number of applications they
process. Examiners therefore have no incentive to spend very much time on any one application; it
is to their benefit to process applications as quickly as possible.

The examiner typically does not take the time to read and study an application at length. An
examiner usually does a quick search to discover all the relevant patents and other public
information pertaining to the claims in an application. The examiner sends the applicant an "Office
Action" explaining the examination. Invariably this includes a rejection of at least some of the claims
as being obvious in view of the material the examiner located when conducting the review. The
applicant then responds by explaining and distinguishing each cited reference, thereby
demonstrating to the examiner that a patent should be issued. This routine saves the examiner time
because the applicant has spent his or her own time figuring out why the references cited by the
examiner are not particularly relevant. Claims that were originally rejected by an examiner are
frequently later allowed after the examiner has had the opportunity to read the applicant's response
distinguishing the invention from the cited references.

The applicant is also obliged essentially to assist the examiner in the examination. That is, the
applicant needs to advise the examiner of prior art of which the applicant is aware. This serves at
least two purposes. First, the applicant obtains a patent knowing that because the examiner has
considered the prior art there will be a presumption of validity of the patent at a later time. This
means that the patent can be enforced or licensed with more confidence. A second reason for
advising the Patent Office of the prior art is the requirement that if an applicant intentionally
withholds prior art from the examiner during examination of the patent, the patent can later be
unenforceable.

Enforcing a Patent
By bringing a court action against an infringernamely, a person who intentionally or unintentionally
copies the inventionthe patent owner may seek both an injunction against the infringer and the
recovery of monetary damages. The scope of the injunction, as well as damages, will be determined
on a case-by-case basis and should be adequate to compensate the patent owner for the acts of
infringement. In no event should the damages be less than a reasonable royalty for the use made of
the invention by the infringer.

An alternative is to offer the infringer a license to make the patented invention. Such a license may
include an initial base payment, as well as a royalty for each unit of the patented invention that the
licensee would make, use, or sell.

The USPTO is responsible for examining and issuing patents to eligible inventors. For all practical
purposes the role of the USPTO ceases upon issuance of the patent. The USPTO does not monitor
commercial transactions for the presence of potential infringement, nor does it enforce patent rights
against potential infringers once their presence is made known. It is the duty of the owners of the
patent to protect their patent rights at their own expense. Moreover, the USPTO does not guarantee
the validity of a patent. At any time during its lifetime, a patent may be found by a court to be
invalid and hence unenforceable.

The financial cost of enforcing a patent against a potential infringer is highly dependent upon the
complexity of the case, but legal expenses alone can easily reach several hundred thousand dollars
and often reach millions of dollars. A few attorneys are willing to litigate such cases for a fee
contingent upon winning the case. It may be possible to recoup some of the legal costs should the
patent holder win, but this prospect is never certain in advance of the court action.

The patent owner may gain economic benefit from the patent by selling it, exclusively or
nonexclusively licensing it, or by commercially exploiting the patented invention. For an independent
inventor to attempt either the sale or licensing of the patent, the inventor must first identify the
potential buyers or licensees. Once a potential buyer is located, the inventor must then place a value
on the patent. If the product covered by the patent has not yet been commercially produced, it may
be quite difficult to determine accurately the value of the patent. Therefore, the patent owner may
wish to license the patent and obtain a royalty on the future commercial exploitation of the patent.
The specific terms of each individual license would have to be negotiated with the licensee.

Provisional Application Versus Regular Application

For many nanotechnology start-ups, the availability of capital resources is often a critical issue in
their pursuit of patent applications. In the course of managing this limited capital resource, there
may be a constant battle between the need to use the capital to hit predetermined milestones and
the need to spend it to strategically build and protect the intellectual property assets.

Because it can be costly to pursue patent protection through the filing of a regular utility application,
many nanotechnology start-ups have opted to pursue an alternative strategy of filing a less costly
provisional patent application as a way to initially protect their intellectual property.

Unlike a regular utility application, a provisional application does not have any formal requirements,
and thus it can be quickly prepared and filed relatively inexpensively. Once filed with the Patent
Office, however, the provisional application does not get examined; instead, it provides an applicant
a way to establish an early U.S. filing date. The provisional application will also preserve the right to
foreign filings.

Often, the provisional application is a technical disclosure from the inventor. Thus, care needs to be
taken when preparing the provisional application. In particular, the more details put into the
provisional application, the better, because the benefit of the provisional filing will extend only to
subject matter disclosed in the provisional application. This can be particularly important for a
nanotechnology-related invention, because the multidisciplinary nature of the invention may require
an additional focus on disclosures that may not otherwise have been initially anticipated. A
provisional application, by its nature, is often not as robust as a regular utility application. Thus, the
provisional filing procedure should be followed only in cases of emergency (for example, when a
deadline is fast approaching or public disclosure is imminent), or when there is a financial
restriction. Otherwise, a complete and well-prepared regular utility application should be filed.

The life of a provisional application is one year from the date of filing and cannot be extended.
During this period, the invention can be referred to as "patent pending." As indicated earlier, it is
not examined. Still, the "pending" status can be advantageously used to deter potential competition.
In addition, when a company is seeking an investment or a strategic partnership, the "pending"
status can assure the potential investor or partner who is about to take a step toward a risky
investment that patent protection has been pursued.

The U.S. patent system is based on a "first to invent" standard, whereas most other countries award
patents based on "first to file." This is a unique characteristic of U.S. patent practice and does not
exist in other jurisdictions. The U.S. patent system is concerned with granting the patent to the first
inventor and not the applicant that is the first to file. There is therefore periodically an evaluation of
which of two or more applicants first conceived and diligently reduced an invention to practice (that
is, interference process). This evaluation is extremely complicated, costly, and time-consuming.
Nonetheless, interferences may arise in highly competitive emerging technologies.

IP Challenges and Impact: Restriction on Innovation

The pace of technology adoption in nanotechnology will follow patterns similar to that of other fields.
If the USPTO were to allow broad patent claims it would restrict innovation by allowing a few major
players to control a large share of the field and crowd out small, innovative players. Conversely,
patent claims that are not granted or that are too narrow will hinder progress by failing to protect
innovation and will also hinder investment in the new innovations. The first scenario is more likely in
the nanotechnology field, and in some areas a restriction on innovation may soon be created. This
can be especially true for inventions involving carbon nanotubes. There are currently an abundance
of issued patents, many of which may be overlapping in scope.

The patent system can provide insight into the landscape of innovation. For example, the number of
patents that have been issued or the number of applications that have been filed in a particular area
of nanotechnology can provide insight into a particular trend or focus, as well as insight into
potential areas that may be commercially exploited by owners of those patents. The number of
patents or applications, alternatively, can help determine the risks associated with entering such a
market in light of the particular patent landscape. Ownership information of patents can also help to
determine whether there will be risks within a particular area or application based on the number of
potential competitors and the relative positions of intellectual property.

Citation of patents may also be a useful indicator. When a patent has been repeatedly cited by
others, such information can determine the licensing potential of that patent. Accordingly, if a
company is looking to establish a dominant position in a particular area of nanotechnology, it may
look to enhance its portfolio by acquiring those patents that have been repeatedly cited by others.

Alternatively, repeated citations of certain patents by others can be indicative of potential roadblocks
to be overcome when a company is looking to expand its technology outward. In such a scenario,
the company may want to determine whether there is an opportunity to create a "picket fence"
around the cited patents. In other words, the company may want to file its own patent applications
around the cited patents; these new applications would be directed to potentially valuable areas that
the cited patents may have missed, so as to create a potential cross-licensing relationship with the
owners of the cited patents.

Patent claim scope can also be used as an indicator of available opportunities. To the extent that the
patent provides broad scope of protection, the number of competitors entering that market can be
minimized.

Litigation
Nanotechnology companies will need to address patent litigation issues from the perspective of
enforcing their own patents against a competing product or from the perspective of answering a
claim that their product has infringed a competing patent. There has been little or no activity to date
in nanotechnology-related patent litigation. It is expected that within the next few years there may
be a significant increase in the amount of patent litigation as more nanotechnology-related products
become commercialized and nanotechnology companies begin to assert their patents.

Note that in contrast to the rise of other new technologies, such as biotechnology, it is not expected
that a new body of law will be developed specifically for nanotechnology. Rather, it is expected that
certain facets of existing law will ultimately develop to take into account the special nature of
nanotechnology-related inventions.

Funded Research
Although plentiful funds have been awarded by the federal government through the various
governmental agencies that are part of the National Nanotechnology Initiative, a company should
consider the impact of pursuing government grants to further its nanotechnology-related research.
Under the Bayh-Dole Act, universities and small business entities can retain intellectual property
ownership rights in federally funded research. The government retains a royalty-free license to any
patented technology that is federally funded, although this has very rarely (if ever) been used. Any
transfer or acquisition of these patent rights requires compliance with certain formalities and can
impact or interfere with the growth of a company or its exit strategy.
Conclusion
Implementation of at least some of the processes suggested in this chapter can assist in improving
business and increasing the value of the intellectual property portfolio. Different industries, including
those based on nanotechnology, will have short-, mid-, and long-term technology and business
objectives. Accordingly, the patenting objectives for different aspects of nanotechnology can differ
for different industry uses. Every business can extract extra revenue from its business knowledge
base by strengthening and building on its patentable assets. It is difficult to act on all of these
criteria to define a patenting policy, but implementation of at least some of these processes can
assist in improving business and increasing the value of your patents.
Reference
1. http://www.nano.gov/html/facts/whatIsNano.html.
Chapter 10. Entrepreneurs in the
Technological Ecosystem
Jeff Lawrence and Larry Bock

There are thousands of people with ideas. There are thousands of people who can lead and manage.
There are thousands of people who can get things done. There are far fewer people with the unique
combination of these qualities that can be labeled as entrepreneurs.

Entrepreneurs aren't satisfied when they can see a vision and express it; they will be satisfied only
when that vision becomes real. Entrepreneurs exist in all areas and at all scales of human endeavora
local business on a street corner, a large technology business spread across the world, or an
organization trying to bring about social, political, or economic change. Entrepreneurs become
possessed by their vision and will persevere in developing, refining, and spreading that vision until it
has changed the world in some way, large or small.

There are many theories, stories, and how-to descriptions of entrepreneurship. This chapter briefly
discusses a framework for thinking about entrepreneurship, the role of entrepreneurs, who they are,
what they do, what they can expect, and why they do what they do.
Lions, Tigers, and Bears: What is the Role of an
Entrepreneur?
Human and technological progress is both the cause and the effect of a rich and complex set of
interlocking relationships and cycles that is similar to many aspects of natural ecosystems. Natural
ecosystems consist of small and large thermodynamic, chemical, and biological loops that are
necessary to sustain, proliferate, and advance life. By the time an ecosystem matures, either on a
local, regional, or even global scale, there are diverse species, stable populations, and complex
interdependencies among the members of the ecosystem's communities.

The technology ecosystem is very similar. The loops necessary to sustain an ecosystem consist of
people, information, technology, and capital. Capital (that is, money), although very real, is also an
abstract method for transferring energy (in the form of work and labor) within and between
communities. The food chain (also known as the food web because of a potentially large number of
interconnections) describes the various populations and their relationships to each other. In
nanotechnology the food chain consists of users, businesses (vendors of technology, products, and
information), investors, government, academia, industry forums, and standards organizations.

Each population is trying to sustain itself and proliferate in the context of the development stage and
available resources of its community and ecosystem. Ecosystems develop and become populated
over time by different populations. Some ecosystem populations reach maturity, but others never
fully develop or fail. Occasionally populations fail because of natural disasters or severe disruptions
(a meteorite, a forest fire, a stock market crash).

Businesses' and industries' development progress along the population curve is also typically
affected by their movement along the hype curve. The vertical axis of the hype curve is visibility,
and the horizontal axis is time, divided into periods including the start, the peak of inflated
expectations, the trough of disillusionment, the slope of enlightenment, and the plateau of
productivity. To some extent, how well businesses and industries negotiate the hype curve will
determine whether the population of the ecosystem follows an S-curve to maturity or a J-curve to
failure and removal from the gene pool. The early stages of a developing ecosystem are sparsely
populated and typically have low species diversity, low inertia (resistance to change), and high
resilience (the ability to restore itself after a disturbance). As an ecosystem develops, species
diversity and inertia increase and resilience decreases.

Interestingly, some people don't consider nanotechnology an industry per se but rather a series of
technologies and products that are applied to solve a wide and possibly unrelated range of
problems. In many cases it is unclear whether business synergies can be developed between the
disparate uses of the technologies and products. Some of these technologies and products include
materials, medical devices, other devices, and processes and tools.

Materials take a long time to get to the market and replace or supplement existing industrial process
flows. Planning, procurement, and testing cycles can be very long and are usually tied to capital
budgets. Medical devices are expensive and take a long time to get to market because of scientific
peer review, government testing, and the need to resolve potential reimbursement issues. Other
devices may be less expensive or quicker to get to market, but the value proposition may be more
difficult to define.

In all cases, success will depend on having a clear value proposition (in the form of lives saved,
quality of life improved, costs or expenses saved, or markets opened) and having sufficient capital
available to ensure survival until product sales can scale up. In the early stages of the ecosystem,
the development of infrastructure and tools to support the rest of the ecosystem may offer the best
possibilities for success.

Nanotechnology resides primarily in academic institutions, federal laboratories, large corporations,

and to a lesser extent in small entrepreneurial businesses. There is significant research and some
development going on. Nanotechnology is people- and capital-intensive. The tools, processes, and
techniques to monitor and control the structural, electronic, optical, and magnetic properties on the
atomic scale are expensive. Capital to fund these activities is coming from taxpayers in the form of
federal research grants and to a lesser extent from large corporation research and development
budgets.

There is some private equity available. The private equity market, in the form of angel investors or
venture capitalists, has fairly high expectations that must be met to engage its interest:

A strong, transparent, predictable, and ethical management team

A large, identifiable, addressable market

Good product or service value and a strong, defensible market position

Strong, growing, and consistent revenue and earnings performance

An understandable story and strategy, leading to a future liquidity event (in the form of
acquisition, buyout, or public financing)

There is still disagreement about whether the prodigious sums of capital that were available for the
Internet, telecommunications, and pharmaceutical industries will become available for the
nanotechnology industry. Many investors feel that public equity funding will become available as
privately or self-funded companies mature and show the predictability and financial performance the
public markets expect.

Private equity is not the only way to fund a start-up. Self-funding is possible, but very difficult,
because of the capital-intensive requirements of nanotechnology. It can take millions of dollars to
perform nanotechnology research and development, although it may not be as capital-intensive as
the semiconductor industry on the back end. Licensing or using open source technology or products,
rather than creating them from scratch, and using shared labs, facilities, and tools can make self-
funding more viable.

The nanotechnology ecosystem has analogous models in the information technology,

pharmaceutical, and energy industry ecosystems. These industries can be looked to as examples of
how nanotechnology might evolve over time in terms of the landscape, the food chain, the ways
they operate in regulated or unregulated environments, capital requirements, infrastructure
requirements, innovation and development models, and paths to liquidity. Survival and proliferation
through all the stages of nanotechnology ecosystem development will depend on the entrepreneur's
ability to create or fill a niche that provides a unique value and becomes an integral part of the
relationships and loops of the ecosystem.

As the ecosystem develops, as it has in analogous industries, adaptability and flexibility will be
essential for proliferation and advancement. Interestingly, there is a fundamental difference in the
ways adaptability and flexibility are realized in nature and in industry. In nature, members of the
food chain "float" around, but in industry, entrepreneurs can make deliberate choices of how to
adapt, stay flexible, and innovate. The ability to make choices and innovate is important because in
the early days of most ecosystem (industry) development, the fast rate of change disfavors large,
slow-moving organisms (organizations) and favors organisms (organizations) that are smaller, more
adaptable, and responsive. Large organizations in general don't innovate as well as small ones
donot necessarily because they lack the vision, but because risk taking is judged and supported
differently than in small organizations.
The Power of an Idea: What is a Good Idea?
All organizations, institutions, and creations of humans have started with an idea. The power of a
good idea cannot be underestimated. An idea by itself is a necessary, but not sufficient, condition to
successfully effect change, develop a technology or product, or start a business. Many ideas have
not gone beyond the stage of being only ideas.

To have an impact, the idea must be wrapped in a vision and an understanding of whom the vision
serves. This is where entrepreneurs enter the picture. They work with an idea, either their own or
somebody else's, and mold it into a vision that is part possibility (what can be) and part reality
(what needs to be). Entrepreneurs power the vision into reality by spending their time and energy
and, most importantly, by maintaining their belief about the importance of the vision. Entrepreneurs
may find it challenging to keep people focused on the entrepreneurial vision over the long time
horizons of nanotechnology.

For many entrepreneurs, ideas come from methodical thinking and planning. Others may stumble
upon ideas or find ideas thrust upon them by a life event or epiphany. Good ideas address a real
problem or need for change, are realizable, are easy to communicate, and provide understandable
value. In many cases, good ideas (such as sticky notes and penicillin) have come from what were
perceived as problems by some but were seen as solutions by others.

Ideas can be sustaining or disruptive. Sustaining ideas improve the performance or capabilities of
existing technologies or products along dimensions that have been previously valued by customers.
They tend to be cumulative in their effect. Disruptive technologies bring to market a different value
proposition than was previously available. They tend to be revolutionary and, at least initially, must
be sufficiently resilient and flexible to survive ambiguity, incoherence, and uncertainty as the
relationships and loops of the ecosystem rearrange themselves to support the new value
proposition. In the beginning, successful disruptive ideas are embraced by a few but, as their value
proposition becomes obvious, are adopted by many.

Importantly, even if an idea is good, to be successful its timing must also be good. Many ideas
coming from academics must be tempered by the realities of business. Educating others about new
ideas may take significant time and effort. Nanotechnology as an industry is still fairly new, and
although many are interested in its possibilities, as yet few totally understand the technology, its
application, and its value in the ecosystem. Some ideas may simply occur too early in the
ecosystem's development to be successful. It is up to the entrepreneur to be keenly aware of the
state of the ecosystem and to know whether or not it is ready to accept and embrace the idea. If the
ecosystem is not ready for the idea, either the idea must be shelved or the ecosystem must be
prepared for its adoption.

Entrepreneurs are generally not ideologists; they are pragmatists and innovators at heart. They
enjoy seeing their technology, product, or service established in the ecosystem, and they understand
that the value of their vision must be unique, real, and understood if it is to be adopted.
A Single Person can Change the World: What is an
Entrepreneur?
A vision doesn't exist by itself. It is a highly personal view of a possible future (what can be). The
literature is filled with stories of successful entrepreneurs. Every vision, and the story behind it, is as
unique as the individual entrepreneur. Stories serve to show possibilities and to focus and inspire.
Although each story is unique, the commonalities in the motivations, risks, and challenges are
many.

Entrepreneurs are not born, they are madesometimes consciously and many times unconsciously.
Their path to success tends to go through three phases: learning, epiphany, and doing. The learning
phase is usually a lifelong process. A college degree in business may be helpful, but history shows
that it is not necessarily required for someone to be successful. Knowing the theories and practices
of business, technology, and other disciplines is important, but a would-be entrepreneur may need
to develop and refine many other skillssuch as listening, learning, judging, deciding, and
communicatingthrough personal experience. Entrepreneurs, more or less intuitively, put themselves
through a long apprenticeship during which they develop the knowledge, experience, and skills they
will need in the future. To some extent, entrepreneurship is about constantly preparing yourself to
deal with the opportunities and challenges that may cross your path in the future.

During the learning phase, entrepreneurs may be building toward an epiphany or may experience a
jolt from a completely unexpected source or direction that pushes them out of their comfort zone.
The epiphany may be incremental or dramatic. The epiphany is the defining moment, when a new
idea or a life event forces a change or rethinking of the entrepreneur's path in life. It is a
crystallization of the inklings, intuitions, desires, beliefs, and learning leading up to that moment.

Put simply, from the epiphany forward, entrepreneurs feel and believe that they must pursue the
path they have seen for their vision and themselves. They are driven to have an impact on
technology, industry, society, or individuals; to gain new knowledge and skills; to make money; to
control their own destiny; to prove they can do it; or to gain recognitionor all of these.

Having an epiphany is one thing; making it real is something else. Getting from the first point to the
second requires extraordinary persistence and entails numerous risks and uncertainties.
Entrepreneurs generally see opportunity where others might see risk or uncertainty. There is usually
greater opportunity associated with greater risk and uncertainty.

Risk is relative to the person judging the risk, the situation itself, and whether the person is looking
forward or backward in time. Entrepreneurs manage risk and uncertainty by understanding their
goals, the environment, and the players, as well as the worldviews, languages, perspectives,
intentions, and motivations of possibly affected parties. Entrepreneurs recognize what they don't
understand and their ability or inability to position, influence, or control the situation. They judge
the alternatives and scenarios against their own and others' experience, knowledge, information,
principles, and goals, and they decide on action or inaction and adapt as necessary.

Engineers and scientists are often given to amassing data before making a decision. Entrepreneurs
realize that it can be dangerous to avoid making a decision because of a lack of information.
Sometimes the information is simply not available or nonexistent, and they learn to work with what
information, opinions, and views are available at the time to reach decisions and take actions.
Look Forward, Think Backward: What Does an
Entrepreneur Do?
To be realized, a vision requires time, energy, capital, belief, and drive. It is not enough to talk; it is
as important to lead and do. Some people look at where they are and what they have in order to see
where they can go (that is, they look forward and think forward). Others see where they want to go
and look at what they need to get there (they look forward and think backward).

The two approaches sound similar but in fact are very different. The former is limited to using
whatever resources and information are available, whereas the latter doesn't accept this limitation
and determines what needs to become available (that is, enabling) to realize the vision. The practice
of looking forward and thinking backward will identify the enablers and changes needed for future
success. Once identified, these enablers and changes must be encouraged and developed.

Incremental visions can be realized with either approach, but more disruptive visions usually are
realized by looking forward and thinking backward. Disruptive visions may require significant
changes to the ecosystem before they can be realized. A handful of individual grains of sand will
have very little impact when it is thrown against something. But when that same handful of sand is
molded into a ball, it will have a much greater impact. Entrepreneurial leadership is about molding
the individual grains of sand into a coherent whole. Entrepreneurs lead by

Giving a voice to the vision and ideas

Building and inculturating a team or organization and giving it purpose

Identifying and acquiring resources (people, capital, information)

Removing obstacles and solving problems

These activities should be performed in the context of a set of values and principles that guide the
entrepreneur's behavior. The values and principles vary from entrepreneur to entrepreneur and
should represent his or her views about how to develop, manage, and value relationships with
employees, customers, investors, and others, as well as the entrepreneur's views about what
success is and how to create the conditions necessary for success. These values and principles do not
necessarily have to be articulated in detail, but at a minimum they should show themselves
consistently in the everyday actions and behaviors of the entrepreneur. Transparency and
consistency will allow others to understand the motivations and expectations as well as the likely
directions and actions of the entrepreneur, which in turn will allow them to act in concert and
contribute to the entrepreneur's vision.

The entrepreneur must understand and carefully consider all aspects of the vision and the steps it
must be moved through to become real. Entrepreneurs must constantly deal with and move back
and forth between broad, general issues and mundane, detailed issues. Building a company has
many challenges, including these:

Creating value through technologies, products, services, or content

Measuring value in its tangible, intangible, financial, and strategic forms

 Protecting value using trade secrets, copyrights, patents, trademarks, agreements, and
contracts

Positioning the products, services, content, and company in the ecosystem

Building and managing relationships with customers, employees, shareholders, advisers,

media, analysts, and suppliers

The day-to-day activities of addressing these challenges consist of listening, learning, judging,
deciding, and communicating. Entrepreneurs are judged by their ability to meet these challenges,
their own expectations, and the expectations of others.
The Good, Bad, and Ugly: What Should an Entrepreneur
Expect?
Entrepreneurs generally commit themselves full-time to realizing their vision. If they are unwilling to
make this commitment, then they probably haven't developed the vision to the point where they are
confident that it will be realizedor else they are not entrepreneurs. True entrepreneurs cannot rest
until their ideas have succeeded.

During the journey from idea to success, entrepreneurs will experience many feelings and emotions.
The hours are long and the personal commitment is usually complete, especially in the early stages
of the vision's development. It is not unusual for the entire journey to take many years.
Entrepreneurs wake up in the morning thinking about their vision and go to sleep at night thinking
about their vision. Work, play, and family blur together. The single-mindedness of purpose an
entrepreneur feels is hard to explain to others. A supportive, patient, and understanding family and
social network are helpful. Finding somebody to talk to who is familiar with the entrepreneur's
vision, but without a personal stake in it, is also helpful as a means to test, practice, and refine
thinking and communications skills.

The best idea and vision in the world will not be realized if others can't understand it and can't
become excited by it. Sometimes the vision is too complicated to explain easily, sometimes the
markets do not exist or are not fully developed, and sometimes institutions and organizations are
not ready for the changes that are necessary for the vision to be realized.

It is important for entrepreneurs to understand the worldview and language of the audience they are
trying to influence. Scientists, engineers, finance people, salespeople, and marketing people all have
very different mental models and views of how the world operates and behaves. These differences
manifest themselves in many forms, particularly in language. Entrepreneurs must use this
knowledge and make an effort to communicate using the target audience's own worldview and
language, which are not necessarily the entrepreneur's own, to influence those things that need to
be influenced. Indeed, an entrepreneur must be prepared, especially at the leading edge, to create
and teach a new vocabulary so that the vision can be understood and embraced by the target
audience.

Entrepreneurs generally lack some or all of the information, knowledge, experience, and skills they
need to realize their vision. Entrepreneurs learn very quicklyif they don't know it alreadythat they
can't do everything by themselves. A large part of entrepreneurship consists of on-the-job training
and building a team to do the things entrepreneurs can't do themselves.

As they build their team, an interesting question entrepreneurs in nanotechnology must consider is
whether they should use proven experts from other fields or novices from nanotechnology itself. The
former may bring experience to the challenge, but the latter may bring energy. Time and windows of
opportunity are usually short and moving targets, so points of view must be established and
decisions usually must be made under uncertain and ambiguous circumstances. There are high
degrees of uncertainty, risk, and ambiguity in trying to realize a vision, and it is important to
recognize and accept that mistakes will be made. If they aren't made, there won't be progress.
Sometimes taking an informed, calculated risk is the best thing an entrepreneur can do. It is also
important not to take false comfort in numbers, because they can be manipulated to represent or
support almost any point of view.

The world of large companies is very different from the world of small companies. Resources
(people, capital, and support), systems, awareness, and reputation can vary dramatically. The
transition between these worlds, although not impossible, can be difficult. Large companies offer an
opportunity to learn and make mistakes in a relatively safe environment. They have already
established themselves as part of the ecosystem, and their survival is usually not an immediate
concern. Small companies, on the other hand, tend to be focused on their survival and on
establishing a niche in the ecosystem. This means that day-to-day operational issues take priority
over more strategic or long-range issues. Small companies have the advantage that their small size
and organizational looseness provide them with adaptability and flexibility to move through the
ecosystem in ways a large company cannot.

As a practical matter, whether self-financed or investor-financed, entrepreneurs can expect, at best,

to sustain their existing lifestyle. The financial rewards of pursuing your vision, if they are ever
realized, probably won't come for many years in the future through some form of liquidity event
such as an acquisition, public financing, or buyout.

At its heart, any successful business depends on its people. People and their behaviors are not
always logical or predictable. Engineers and scientists sometimes have a difficult time dealing with
this. During the development of a business an entrepreneur will experience the full breadth of
human behavior. Small organizations tend to be self-selecting and usually don't represent the entire
range of human behavior. As an organization grows, the odds are that a broader range of human
behaviors will be encountered and in some instances will be surprising and challenging.

Delegating responsibility and authority and letting others do things their own way is also a difficult
transition for many entrepreneurs. Once they get through this transition it can be liberating, because
they are able to give up tasks to others and free themselves to do new and interesting things. They
must understand their own and evolving value and niche within the ecosystem of their organization
and anticipate how it will change over time.

Moving a vision forward is fraught with skepticism, criticism, conflict, surprises, and mistakes.
Entrepreneurs must listen to skepticism or criticism openly and not take it personally, and they must
understand, accept, and deal with any truths that may have been expressed, no matter how ugly
they might be. It is important to learn from adversity and delight in the surprises. Confidence in
your ability will develop over time.

Leadership in its simplest form is about getting people somewhere they don't know they need to be.
Inertia will be a strong counterforce to change, and the act of overcoming it may take large amounts
of time and energy. There will be a constant need and opportunity to change and adapt to new
situations.
Is It Worth It?
Many people start down the path of entrepreneurship, but only a few are successful at fully realizing
their vision and other aspirations. Entrepreneurs are driven by the chance to make an impact, to
learn, to prove something to themselves or others, or to make money. All entrepreneurs have a
unique definition of success and a list of expectations for themselves and others.

Successful entrepreneurs have a vision, understand whom they serve, understand the vision's place
in the ecosystem, and give purpose to the organization they build. They must throw themselves
wholeheartedly into realizing their vision and must be comfortable with risk, uncertainty, and
ambiguity; must be good listeners and learners and strong communicators; and must be adaptable
and flexible and pragmatic problem solvers. The necessary experience and skills can be developed
on the job and by learning from others.

Even though entrepreneurs can control and influence many things, a certain amount of good luck is
also required to be successful. One cannot underestimate the importance of being at the right place
at the right time or meeting the right person. An entrepreneur's days can be long, stressful, and
tiring, but they can also be exhilarating and joyful. The team building and the shared struggle of
trying to realize a vision can be intense and satisfying. The potential rewards can be huge.

Entrepreneurship is a unique and privileged opportunity to pursue a vision. Even though the
challenges are daunting at times, true entrepreneurs would say that their experience, whether or not
they were successful, was worth it, and in fact it would be hard for them to imagine having done
anything else in their lives.
Chapter 11. Major Corporations:
Technology, Business, and the Culture of
Opportunity
Jim Duncan

Your interest in this book is likely based on one of two reasons: You are a technologist looking for
insight in how to build a business, or you are from the business side and are trying to grow a
company from the technology.

This is the usual paradox of any technology-based venture and doubtless an extreme challenge
when nanotechnology is involved. As this book is being composed, the first of a new generation of
nanotechnology-enabled products are finding their way to the market, and plenty more are being
developed. Perhaps an even greater effort is being made to develop the tools and processes that
many future generations of products will be based on.

Although it may be impossible to address the specific issues in the evolution from nanoscience to
nanoproducts, we can address some of the classic issues surrounding technology-based
opportunities.
Culture, Models, and Cycles
There is enormous variety in the attempts to manage these opportunities from both a technology
and a business perspective. Each has its strengths and weaknesses. The prospects of success are
better with an integrated approach, with success more probable when an integrated team addresses
development issues.

It is also crucial to use management processes that are appropriate for the technology. Processes
developed for mature products are rarely effective for emerging and new technologies. Despite the
definition and control the scientific method brings, innovation remains a creative process. Outside of
independent government-funded research centers and fewer still commercial centers, research
centers strive to make their technology relevant to present and future problems.

On the one hand, few research and development organizations can afford to explore science and
technology without an eye to its commercial potential. The potentially huge return on investment
creates the business motivation to provide the resources for the exploration. The "best" of these
ideas are those that are thought to have the best commercial potential. In theory, the best ideas get
the necessary resources. On the other hand, not many businesses can afford the sustained
investment required to examine the science and explore the technology that results in a successful
product and the protective set of enabling intellectual property.

Accordingly, the business needs and the state of the technology have an entwined relationship.

In the technology-based community, conversation often centers on the technology, its promises, and
its challenges. We often include the myriad possible applications as a validation of the effort. More
often than not, the applications and eventual product are our dreams. We quietly acknowledge that
these pursuits require different skills. The possibilities are, however, the stuff that fuels our
imagination and motivates our investigations of science and new technology.

In parallel, the business community hopes to have the technology that will give it a sustainable,
ethical advantage for its product in the marketplace. As business executives look toward the
research and development community, while managing the profit and loss expectations of investors
and owners, it is a challenge for them to nurture the technology, apply it, develop a product, and
market it. Anyone that has managed or led technology from its R&D origins to a fully developed
product knows that the process has a staggering amount and variety of variables.

The process can be reduced to two major stages: research and development and commercial
enterprise.

The research and development stage has two major subcategories: science and technology. Science
is the way we learn about the physical universe by applying the principles of the scientific method:
observation, hypothesis, and testing. Technology is the application of the science to develop tools,
techniques, materials, and systems.

The commercial enterprise stage has three major subcategories: application, product, and market.
In the application phase, the technology is brought to bear to solve a customer problem. Product is
the commodity that is for sale, and marketing identifies customers for those commodities.

The two major areasresearch and development and commercial enterpriseare cultures apart. They
are separated by a gulf.

The gulf is the boundary for the two points of view: technology and business. The technical mind is
trained to believe and follow the scientific method, and scientific truths and laws govern the process.
The business mind is not very different, but there are vast market forces that cannot be controlled or
isolated and can be serendipitous. It is those forces that determine the market value of an
opportunity.

More often than not, the research and commercial enterprises exist as separate organizations. Only
a few of the largest companies have resident R&D staff. Small, medium, and even some large
companies often rely on outside sources for technology. Whether resident or not, they are separated
by the gulf of cultural differences. Language barriers, differing goals, and differing metrics for
success define the gulf. The challenges of the commercial enterprise deserve as much consideration
as those of the research enterprise. Therefore, we are addressing the approach to the gulf from the
technology side.

Bridging the gulf is the challenge of developing technology into real products. In other words, the
opportunity cannot be only about the technology, nor can it be only about the business. The
technology must serve the business, and the business must respect and nurture the technology.
Commercial enterprises are concerned about the role technology plays in their competitive position.
A general assumption is that a strong intellectual property position is a tool to protect profit margin.
Profit margin is only one of the important business metrics of a flourishing commercial enterprise.

Both technology and business enterprises must stretch across their boundaries and reach for
inspiration and guidance.
The Holy Grail
The greatest discovery of them all may be the process that guides us through the evolution of
science to product, especially one that is capable of taking advantage of a great business
opportunity. Our hopes in this regard form on two points of view: the science and the business.

From the technology point of view there is a tendency to hope that after the application of the
technology to an existing problem, a business will pull the technology forward through the
remaining commercialization steps. From the business point of view there is a hope that the
technology will present itself as a product and will need only to be marketed and sold. Neither
eventuality is likely.

The chances of success are increased when you have an appreciation of the difference and culture of
each of the environments. The technology needs to be mentored by an understanding of the
anticipated needs of the business, and the business must be vigilant of opportunities presented by
emerging technology.

The ultimate process is more of an approach. The approach is both flexible and adaptive. The effort
involves multidisciplinary teams of creative, success-driven professionals who have entrepreneurial
talent. It's obvious when one is in the presence of a process that is working to take the technology
out of the lab environment and into the marketplace. It's evident in the team members' relationships
among themselves and their relationship with organizational management. The evidence is a mutual
respect and appreciation for each of the necessary contributions to the opportunity.

The process is the development of a culture of innovation, irrespective of whether the parent
organization is a commercial or a research enterprise.

The challenge in either situation centers on a single core concept: The opportunity must be managed
by using processes that are appropriate for the maturity level of the technology. For emerging
technology there must be room for error, failure, reevaluation, rehabilitation, and even
abandonment. However, being afforded the opportunity to take the challenge should be seen as a
high compliment.

The professionals involved and leading these efforts must exhibit a number of special attributes.
Look for the presence of most of the following eight points in every member involved in the effort to
bring the technology forward:

Confidence. Confidence leverages training, qualifications, and experience for the individual to
take calculated but not reckless risks.

Focus. Participants must be outcome oriented.

Self-sufficiency. The ability to operate and thrive independent of broad and deep
organizational infrastructure stimulates creative problem solving and obstacle removal.

Adaptability. Adaptability is active learning: analyzing, solving, and adjusting.

Emotional stability. The desired team member balances the range of emotions (fear, anger,
frustration, excitement) and does not reject the extremes for the median.

Insightful. Being insightful in this case is the ability to know what is important in a given
 situation, to know what it takes to get a task done, and to filter distractions.

Courage. Life and entrepreneurial ventures are not without their obstacles of all natures. The
team member must be able to face these challenges.

Motivation. The team wants its members to be appropriately inspired to start the journey and
continue on the path.

The culture of opportunity balances soft and hard points. The culture addresses the needs and
characteristics of the people, the technology, and the business. The balancing starts at the gulf
where research and commercial enterprises meet.
Chapter 12. Nanotechnology in Federal
Labs
Meyya Meyyappan

Federal laboratories play a major role in the development of nanotechnology. Some of the key
players include NASA's Ames Research Center, U.S. Naval Research Laboratory, Army Research
Laboratories, the National Institute of Standards and Technology (NIST), and the various
Department of Energy (DOE) national laboratories around the country. The focus of the efforts in
these laboratories is technology development for the needs of the parent organization.

For example, the impetus for nanotechnology research at NASA labs is the development of advanced
miniaturization of sensors and instrumentation for science missions to meet the need for smaller
mass, volume, and power consumption. Some of the mission needs expected to benefit from
nanotechnology include the development of radiation-hardened electronics and communication
devices, microcraft (weighing only 10kg or less), high-strength but low-weight composites for future
spacecraft, and a sensor network consisting of thousands of physical, chemical, and biosensors for
planetary exploration.

Federal laboratories in the Department of Defense are focused on developing ultrasensitive and
highly discriminating sensors for chemical, biological, and nuclear threats. Revolutions in
electronics, optoelectronics, and photonics devices for gathering, protection, and transmission of
information are critical for DoD's missions. The goal of Army Research Lab in its nanotechnology
efforts is to reduce the weight carried by individual soldiers without losing any functionality. DOE
national laboratories serve the agency's missions related to both basic and applied energy research
as well as national security. The DOE national laboratories also include the nation's largest network
of user facilities, open to all researchers on a peer-review basis, including five Nanoscale Science
Research Centers.
The Role of Federal Research Laboratories
As research and development components of participating agencies of the National Nanotechnology
Initiative (NNI), the federal laboratories address various grand challenges in nanotechnology,
including nanomaterials for energy needs, metrology, nanoelectronics, materials for chemical
industries, health-care needs, and space exploration.

The broader goals of many federal agencies are also addressed by academic universities through
contracts and grants, and by small businesses through research contracts from the Small Business
Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. All these
augment the in-house efforts within the federal laboratories.

In addition to serving the needs of the federal labs' parent organizations, the devices, processes,
and technologies developed at federal labs often have commercial applications. Federal laboratories
have historically been a rich source of new commercial products, with hundreds of successful stories
of tech transfer to the private sector over the past forty years. Products such as cordless drills
emerged from the Apollo program because of the need for astronauts to drill down beneath the
moon's surface and use compact, battery-powered tools. Wilson Sporting Goods Company used
technology developed for the Space Shuttle's tanks to create a more symmetrical golf ball surface.
The resulting selection and placement of dimples on the surface of the golf ball help the ball travel
longer distances. The Space Shuttle's thermal protection technology is now used to insulate race
cars from sweltering interior temperatures. Technology originally developed for NASA's Skylab led to
the home smoke detectors commonly used today. Research at DOE national laboratories has
contributed to the development of an artificial retina that uses a nanocrystalline diamond film and
spun out a company that is one of the leading producers of specialized nanoscale materials.

These are only a few examples of commercial products that can trace their origin to one of the
federal labs. One can expect this trend to continue with nanotechnology as well in the coming years.
There is a well-established mechanism for technology transfer to the commercial sector. In the case
of NASA, there is the Office of Technology Partnerships, which works on all the technology licensing
programs. NASA Tech Briefs magazine, a monthly publication, lists and describes NASA innovations
that are ready for the marketplace.

In addition, NASA has regional tech transfer offices that focus on matching a particular innovation
with the needs of the industry in the region. Regular tech transfer conferences are also organized by
the field centers, and regional tech transfer offices bring together NASA innovators and industrial
participants. All possible avenues are used to get the word out about the availability of technologies
for commercial licensing.

As an example of federal laboratory activities, consider technology transfer efforts at one of the
leading nanotechnology laboratories at NASA Ames Research Center. The research focus at NASA
Ames is on nanomaterials such as carbon nanotubes, inorganic nanowires, conducting organic
molecules, and protein nanotubes. The applications focus for these nanomaterials is diverse:
nanoelectronics, computing, data storage, nanoscale lasers, chemical sensors and biosensors,
ultraviolet and infrared detectors, and advanced life-support systems that address waste
remediation, air purification, and water purification as well as instrumentation for planetary
exploration and astronaut health monitoring devices.
Transferring Technology
NASA Ames has developed a substantial intellectual property portfolio in these areas. Some of the
technologies have been licensed to private companies. For example, the use of carbon nanotubes in
computer chip cooling and associated processing techniques have been licensed to a start-up
company in the Bay Area. Similar efforts are ongoing for licensing biosensors, genechips, and
chemical sensors. Another avenue of tech transfer has been companies founded by employees of the
NASA Ames Center for Nanotechnology.

NASA Ames Office of Technology Partnerships routinely organizes one-day workshops to showcase
the Ames-developed technologies. To meet entrepreneurs and members of the industrial community,
this office also participates in such workshops organized by other NASA centers and regional tech
transfer centers, as well as other conferences and symposia.

In addition to working on tech transfer to industry, this office facilitates joint research between NASA
Ames and interested companies through an arrangement called the Space Act Agreement (SAA). The
SAA is a type of cooperative research and development agreement that enables the two parties to
jointly develop a process or product, with each contributing to certain aspects of the development.
The rights of each party for commercialization and marketing are clearly spelled out in the SAA
document as negotiated by the two parties. NASA Ames currently has several SAAs in place with a
number of industrial partners.

Technology transfer in Department of Defense labs takes place in a variety of ways. The primary
focus of DoD labs is not to develop commercial products but to develop solutions to the problems of
military services such as the Army, Navy, and so on. These services communicate problems, issues,
and limitations they experience in the conduct of their operations, and priorities are developed by
the DoD labs to resolve these problems. Solutions are proposed by the labs through written and oral
proposals to meet specific needs, with funding provided (when available) to those of the highest
priority.

For additional research and scientific validation, labs may also partner with an outside company or
university through a Cooperative Research and Development Agreement (CRADA). This can leverage
both the funding and the expertise of the laboratory to greater meet the needs of the military
services. When a project has reached this point and is close to developing a prototype, funding may
be obtained from DoD sources outside the lab, such as a branch's Scientific Office of Research or
funding from an applied program (for example, the F-22 aircraft or global positioning satellites).
Defense labs rarely directly spin out commercial companies, but they have extensive
commercialization and licensing programs similar to those of other agencies.

DOE's Nanoscale Science Research Centers convene regular meetings to provide a forum for
exchange of ideas among researchers from many institutions, as well as a means to educate users
on the capabilities that exist and are being developed at these unique national facilities. The facilities
are available for use on a peer-reviewed basis. Time, materials, and technical assistance are
provided free of charge for researchers who are willing to publish the results of their work in the
open literature, and on a cost-recovery basis when used for proprietary purposes.
Summary
There are active nanotechnology programs with a substantial investment of personnel at many
federal laboratories. These mission-driven labs explore specific technologies, seeking solutions to
urgent and long-standing problems in their road maps. Invariably the developments have
commercial possibilities, and each lab has a commercialization office and well-established
procedures to transfer technology to industry. In addition to the nation's universities, the federal
labs are anticipated to be a key source for intellectual property in nanotechnology.
Section Three: Materials and Industries
Chapter 13. Nanoscale Materials

Chapter 14. Nanotechnology-Enabled Sensors: Possibilities, Realities, and Diverse Applications

Chapter 15. Microelectronics

Chapter 16. Drug Delivery

Chapter 17. Bio-Nano-Information Fusion

Chapter 13. Nanoscale Materials
Overview

Nanoparticles

References

Carbon Nanotubes

References

Nanowires

Soft Nanotechnology
Overview
Mark Reed

Materials form the basic underlying building block of nearly every advanced technology, and
nanotechnology is no exception. Most technologies have various levels of differentiation, which can
be broken down roughly into (1) materials, (2) design and fabrication, and (3) integration. In the
case of some conceptual nanotechnologies, the path to achieve the last two levels is not at all clear.
However, the science and technology of nanomaterials are both vibrant fields, with breathtaking
advances on a daily basis. In many ways contemporary nanoscience is essentially the study of
nanomaterials.

What differentiates nanomaterials from classical materials science, chemistry, and the like is the
degree of control. Whereas many scientific disciplines have for more than a century dealt with
phenomena and understanding on the atomic scale, the emerging field of nanomaterials strives to
achieve control on that level beyond stochastic processes. One might view this field as a variant of
engineering; instead of studying what is, we try to create what never wasand now on an
unprecedented level.

One of the original areas of nanosciencethe production of nanometer-scale particles of various

materialsis nearly as old as human civilization. Not until the past few decades have researchers
begun to appreciate the unique properties of nanoparticles. With the understanding of structure and
synthesis, researchers worldwide have gained nearly atomistic control over size and properties,
creating such intriguing structures as "core-shell" quantum dots. Nanoparticles are finding
applications in a number of diagnostic and biomedical uses and will become widespread when
toxicity and functionalization issues are solved.

The unarguable poster child of nanoscience is the carbon nanotube (CNT), which are graphene
sheets rolled into a perfect cylinder with mind-bending aspect ratios, often being only a nanometer
in diameter but many micrometers in length. More interestingly, their electronic structure is
dramatically dependent on dimension and twistan exciting advantage if these parameters can be
controlled, but generally viewed as a limitation until these problems can be solved. Nonetheless,
fascinating electrical, thermal, and structural properties of single-walled nanotubes (SWNTs) have
been measured. The scaling of this understanding to large-scale synthesis and the use of these
properties on a macroscopic scale remain challenges.

More recently, inorganic semiconducting nanowires have begun to attract attention as an alternative
to nanotubes because their electronic properties are easier to control. First explored in the early
1990s, these single-crystal nanowhiskers, with dimensions of only tens of nanometers, have seen a
resurgence in the past few years because of the development of a wide variety of synthesis methods.
In addition, the range of materials that can be fabricated into nanowires is impressive, giving a
large design space for property control. Although the exploration of these systems is still in its
infancy, this field represents a rapidly expanding frontier of functional nanomaterials.

Finally, the interface between nanomaterials and numerous applications, such as biomedical,
requires nonstandard materials. Whereas soft and polymeric materials are not nanomaterials, these
materials produce critical fabrication and interface implementations, and an understanding of their
properties is essential to modern nanomaterials applications. An extension of this field is to integrate
polymeric and single-molecule structures into other nanostructures and complex hybrid materials.
These represent the most challenging nanostructures investigated to date.

The field of nanomaterials has a long way to go to reach an understanding and control on the truly
atomic scale. A combination of innovative synthesis approaches and new characterization
techniques, and an understanding of fluctuations and control at this new length scale, is needed, and
it will lead to revolutionary advances in nanomaterials and eventually in nanoscience.
Nanoparticles
Sheryl Ehrman

Sometimes called the building blocks of nanotechnology, nanoparticles (particles with diameters less
than 100nm) constitute a commercially important sector of the nanotechnology market. Unlike many
speculative applications of nanotechnology, nanoparticles have been with us for a while. Nanoscale
gold clusters have been used to color ancient glass as far back as Roman civilization.[1] More
recently, in the twentieth century, carbon blacka material composed of nanoparticles of high-grade
carbon "soot"was incorporated into tires, resulting in greatly improved durability. By the year 2000,
carbon black for tires was a 6-million-tons-per-year global market.[2] Nanoparticles are useful when
their properties at the nanoscale (mechanical, optical, magnetic, and so on) are different from those
at the bulk in some beneficial way and also when their size enables interactions with biological
systems.

An example nanoparticle is shown in Figure 13-1.

Figure 13-1. TiO2 particles (micron scale formed from nanoscale particles,
used for clarity). (Courtesy of Altair Nanotechnologies, Inc.)

Applications of Nanoparticles
Remember white, pasty sunscreen? It is now transparent because the key ingredient, zinc oxide,
which absorbs ultraviolet light, is transparent if it is made of nanoparticles but white when made of
larger, micron-sized particles. The same holds for titanium dioxidewhich is a white paint pigment
and an additive to improve opacity in colored paintsif the particles are hundreds of nanometers in
diameter or greater. Now, these transparent nanoparticles, which still absorb in the UV range, are
finding their way into modern, transparent, and highly effective sunscreens.[3]

Nanoparticles of titania are also a key ingredient in dye-sensitized solar cells. The efficiency of these
cells is boosted by incorporating nanoparticles that increase the total surface area for harvesting
light by a factor of a thousand as compared with a single crystal of titania.[4] Compared with silicon-
based photovoltaic materials, dye-sensitized solar cells are much less expensive to produce, and in
2001 a manufacturing plant opened in Australia.[5]

Another significant market for nanoparticles is in the semiconductor industry, in a process known as
chemical mechanical planarization (CMP). In the manufacturing of computer chips, the component
materials must be coated onto wafers, and at several points in the process, the coatings must be
rendered nearly atomically smooth across the entire wafer. For 300-mm wafers, this is no small
challenge! In CMP, slurries of nanoparticles are used. In this process, a combination of chemical
removal and mechanical abrasion acts to accomplish this atomic-level polishing task. Silica,
alumina, and ceria nanoparticles, the most common materials, are very effective. As a result, the
global market for CMP has grown rapidly, from $250 million in 1996 to more than $1 billion in 2000,
with the market for CMP consumables alone (slurries and polishing pads) expected to hit $800
million by 2005.[6] With ever-increasing miniaturization in device features, resulting in a need for
increasing precision in manufacturing, the CMP market will surely continue to grow.

In addition to these existing large-scale applications for nanoparticles, many more products have
been recently commercialized or are in development. Professors Paul Alivisatos of the University of
California, Berkeley, and Moungi Bawendi of MIT developed processes for making semiconducting
nanoparticles out of materials including cadmium selenide (CdS) and cadmium telluride (CdTe).
These particles, coated with zinc sulfide, absorb light in the UV range, and then because of size-
dependent quantum confinement effects, they emit light in the visible range, at a wavelength
dependent on the particle size. Their stability and brightness are much better than those of
conventional fluorescent chemical dyes, and when they are functionalized with proteins,
oligonucleotides, or smaller molecules of interest, they can be used for fluorescent labeling
applications in biotechnology.[7] Silicon nanocrystals less than 4nm in diameter also emit light in the
visible range, with the wavelength depending on particle size. These nanoparticles are of interest for
solid-state lighting applications and promise much higher efficiency as well as longer lifetimes
compared with current incandescent and fluorescent lighting technology.[8]

As well as these optical properties of nanoparticles, chemical propertiesin particular, catalytic

activitycan be greatly improved at the nanoscale. One important example is gold. In bulk form, gold
is relatively inert. However, when deposited at very low concentrations (0.2 to 0.9 atomic %) in a
nonmetallic form onto nanoparticles of cerium dioxide, it becomes very active for the watergas shift
reaction.[9] In this reaction, carbon monoxide and water are converted to carbon dioxide and
hydrogen. For fuel cells that are powered by hydrocarbon fuels, converted first to hydrogen and
carbon-containing by-products, the watergas shift reaction is key for maximizing the amount of
hydrogen while minimizing the amount of carbon monoxide, a molecule that poisons the
electrocatalysts in the fuel cell itself. Because of the small amount of precious metal used in this
material, the economics are favorable compared with catalysts that contain precious metals at up to
10% atomic percent concentration.

Magnetic properties of nanoparticles can also be exploitedfor example, the tendency of small
magnetic nanoparticles to be superparamagnetic. Superparamagnetic nanoparticles, in the absence
of a magnetic field, have random magnetic moments at temperatures above their Curie
temperature, but in the presence of an external magnetic field, they align with the field, producing a
high magnetic moment. One application of this phenomenon is in magnetic resonance imaging
(MRI). MRI contrast is aided in the body by the presence of naturally occurring materials such as
deoxyhemoglobin but can be greatly enhanced by introduction of superparamagnetic iron oxide
nanoparticles (SPIONs). These particles have cores consisting of magnetite (Fe3O4), maghemite
(gamma Fe2O3), or some combination of both, and are coated to enhance colloidal stability and
biocompatibility. The type of contrast enhancement enhanced by SPION is useful in the imaging of
features that contain large amounts of fluid, such as internal injuries or cancerous lesions. These
nanoparticles are commercially available from several sources.[10] The surface of the SPION can be
further functionalized to engineer interactions between the contrast agents and specific tissue and
cell types, and this is an active area of research.[11]

Production of Nanoparticles
Production methods for nanoparticles can be loosely classified into three general categories: wet
synthesis, dry synthesis, and milling. In both wet and dry synthesis, nanoparticles are generally
produced in a bottom-up way from atomic precursors, whereas in the milling approach,
nanoparticles are produced from the top down by mechanically breaking down larger particles. Wet
approaches include sol-gel and precipitation methods, whereas dry approaches encompass
combustion, furnace, and plasma synthesis of nanoparticles.

In all cases, there are concerns about the narrowness of the size distribution of the nanoparticles,
and concern about the degree of agglomeration. All processes for making nanoparticles lead to some
spread in the particle size. The size distribution can be modified somewhat by adjusting the process
parameters, or the size distribution can be tailored by removing the tails of the distribution through
additional separation steps. This typically leads to lower process yield. With respect to
agglomeration, nanoparticles have a high ratio of surface area to volume, and it is much more
energetically favorable for them to reduce their surface area by coalescing together. Thus, materials
that melt at high temperatures if they are in bulk form may fuse together at much lower
temperatures if they are nanoparticles.

Some applications, such as the fluorescing quantum dots mentioned earlier, have very tight
requirements for particle size and aggregation. Other applications, such as CMP slurries, may not
have such narrow constraints. There is no one perfect process. Milling is very energy-intensive, and
it may not work at all for some materials, such as pure metals, that are malleable. Precipitation
methods may require the addition of capping ligands to the nanoparticle suspension, to stop particle
growth and to prevent the particles from agglomerating together. These ligands bind to the surface
of the particles, and if they do not impart the desired functionality to the particles, they must be
displaced in a separate processing step.

In high-temperature synthesis of nanoparticles, agglomeration can be avoided for some materials by

simultaneously quenching and diluting, but this presents a challenge when the process is scaled up.
If the nanoparticles suspended in the gas are more dilute, more energy is required to recover them.
For some materials that are viscous glasses at high temperature, such as silica, diluting and
quenching may not help. Some processes, such as electro-spray or plasma-based syntheses,
produce particles that are highly charged, and this aids in reducing agglomeration.

Outlook for Nanoparticles

Before a process can be considered commercially viable, there are additional economic concerns.
Many processes for nanoparticles have been developed at the laboratory scale, but they are not yet
commercialized because of constraints, including scalability considerations and precursor costs.
Aerosol pyrolysisthe process used to make nanoparticles of silica, alumina, and titania by companies
such as Cabot, Degussa, and DuPonthas long been in existence. Plasma-based processes, because of
their potential for high-throughput reduced agglomeration, have been more recently scaled up in
industry.[12] Many other processes could perhaps be scaled up, but there is a catch-22 involved:
Without a sufficient commercial market for the nanoparticles, there are insufficient resources
available for process development. Without sufficient quantities of nanoparticles available, it is
difficult to conduct product development research.

In the past several years, there has been increasing public concern about the occupational and
environmental risks associated with nanoparticles.[13] The correlation between particle phase air
pollution and adverse health effects has been noted for some time.[14] There is now concern that
nanoparticles may also threaten human health and ecosystems. It is important to consider that
materials that may not pose health risks in bulk may become toxic in nanoparticle form because of
their small size. Safety precautions that are appropriate for materials in bulk form may prove
insufficient for nanoparticles. As a result, research into potential health risks associated with these
new materials, supported by U.S. government agencies such as the Environmental Protection
Agency and the National Science Foundation, is actively under way.
References
1. J. S. Murday, "The Coming Revolution: Science and Technology of Nanoscale Structures,"
The AMPTIAC Newsletter 6 (2002): 510.

2. A. M. Thayer, "Nanomaterials," Chemical and Engineering News 81 (2003): 1522.

3. M. Oswald and K. Deller, "Nanotechnology in Large Scale: Pyrogenic OxidesReady for New,"
Elements, Degussa Science Newsletter 9 (2004): 1620.

4. B. O'Regan and M. Grätzel, "A Low-Cost, High-Efficiency Solar-Cell Based on Dye-Sensitized

Colloidal TiO2 Films," Nature 353 (1991): 737740.

5. http://www.sta.com.au/index.htm.
6. R. K. Singh and R. Bajaj, "Advances in Chemical Mechanical Planarization," MRS Bulletin 27
(2002): 743751.

7. A. P. Alivisatos, "The Use of Nanocrystals in Biological Detection," Nature Biotech 22 (2004):

4752.

8. http://www.innovalight.com/.
9. Q. Fu, H. Saltsburg, and M. Flytzani-Stephanopoulos, "Active nonmetallic Au and Pt species
on ceria-based water-gas shift catalysts," Science 301 (2003): 935938; and Q. Fu, W. L.
Deng, H. Saltsburg, and M. Flytzani-Stephanopoulos, "Activity and stability of low-content
gold-cerium oxide catalysts for the water-gas shift reaction," Applied Catalysis
BEnvironmental 56 (2005): 5768.

10. S. Mornet, S. Vasseur, F. Grasset, and E. Duguet, "Magnetic nanoparticle design for medical
diagnosis and therapy," Journal of Materials Chemistry 14 (2004): 21612174.

11. A. M. Morawski, G. A. Lanza, and S. A. Wickline, "Targeted contrast agents for magnetic
resonance imaging and ultrasound," Current Opinion in Biotechnology 16 (2005): 8992.

12. http://www.nanophase.com/technology/family.asp.
13. R. Weiss, "For Science, Nanotech Poses Big Unknowns," Washington Post, February 1, 2004.
14. D. W. Dockery, C. A. Pope, X. P. Xu, J. D. Spengler, J. H. Ware, M. E. Fay, B. G. Ferris, and
F. E. Speizer, "An Association between Air-Pollution and Mortality in 6 United States Cities,"
New England Journal of Medicine 329 (1993): 17531759.
Carbon Nanotubes
Brent Segal

Since their discovery in 1991 by Sumio Iijima, carbon nanotubes have fascinated scientists with
their extraordinary properties. [1] Carbon nanotubes are often described as a graphene sheet rolled
up into the shape of cylinder. To be precise, they are graphene cylinders about 12nm in diameter
and capped with end-containing pentagonal rings. One would imagine that a new chemical such as
this would be discovered by a chemist, slaving away in front of a series of Bunsen burners and
highly reactive chemicals, with a sudden epiphany being revealed in a flurry of smoke or
precipitation from a bubbling flask. However, carbon nanotubes were discovered by an electron
microscopist while examining deposits on the surface of a cathode; he was performing experiments
involving the production of fullerenes, or buckyballs.

This discovery presents one of the key tenets of nanotechnology. Novel tools allow researchers to
observe materials and properties at the nanoscale that often have existed for hundreds or thousands
of years and to exploit the properties of such materials.

After Iijima's fantastic discovery, various methods were exploited to produce carbon nanotubes in
sufficient quantities to be further studied. Some of the methods included arc discharge, laser
ablation, and chemical vapor deposition (CVD). [2] The general principle of nanotube growth involves
producing reactive carbon atoms at a very high temperature; these atoms then accumulate in
regular patterns on the surface of metal particles that stabilize the formation of the fullerenes,
resulting in a long chain of assembled carbon atoms.

The arc-discharge methodology produced large quantities of multiwalled nanotubes (MWNTs),

typically greater than 5nm in diameter, which have multiple carbon shells in a structure resembling
that of a Russian doll. In recent years, single-walled nanotubes (SWNTs) using this method also
have been grown and have become available in large quantities. The laser ablation method of
carbon nanotube growth produced SWNTs of excellent quality but requires high-powered lasers
while producing small quantities of material. The CVD method was pioneered by Nobel Laureate
Richard Smalley and colleagues at Rice University, whose experience with fullerenes is nothing short
of legendary. This growth technique is aided by a wealth of well-known inorganic chemicals
specifically involving the formation of highly efficient catalysts of transition metals to produce
primarily single-walled nanotubes.

Figure 13-2 shows a simple carbon nanotube.

Figure 13-2. A simple example of a carbon nanotube. (Courtesy of Dr.

Peter Burke, University of California, Irvine.)
Novel Properties
Although carbon nanotubes have a suitably interesting structure, there are a multitude of important
properties that impart the potential for novel applications of significant commercial value.
Multiwalled and single-walled nanotubes have similar properties, and for illustration, focusing on
single-walled nanotubes provides a reasonable primer of the primary features.

Some of these properties include remarkable strength, high elasticity, and large thermal
conductivity and current density. Several reports have determined that SWNTs have a strength of
between 50 and 100 times that of steel.[3] The elasticity of SWNT is 11.2 terrapascal (TPa), a
measure of the ability of a material to return to its original form after being deformed. Imagine a
molecule that, on the atomic scale, is as strong as steel but flexible like a rubber band!

Despite these structural properties, SWNTs have a thermal conductivity almost as great as twice
that of diamond, which is known to be one of the best conductors of heat. Perhaps one of the most
impressive properties of SWNTs involves their electrical conductivity, which is reported to be 10 9
Amps per square centimeter, which is about 100 times that reported in copper, the conductor of
choice for nearly every electrical device in common use today.

SWNTs have two types of structural forms, which impart an additional set of electrical
characteristics. Depending upon the alignment of the carbon atoms in the cylindrical form, SWNTs
can be either achiral (having atomic uniformity along its axis) or chiral (having a twisted alignment
from the uniform case). Achiral and chiral forms can act as metals or semiconductors and yet retain
the same basic nanotube structural motif.

In addition to these well-known properties, SWNTs have other features that make them attractive
beyond their scientific novelty. SWNTs have a density approximately half that of aluminum, making
them an extremely light material. SWNTs are stable at temperatures up to 2700°C under vacuum.
This is truly impressive considering the melting point of Ruthenium, Iridium, and Niobium metals are
about the same temperature.[4] Although nanotubes have structural uniformity, the carbon atoms
within them have the same precise features as a typical graphene sheet. These atoms can be
derivitized to alter the structure of the SWNTs, allowing their properties to be tailored. This allows
nanotubes to be subject to literally hundreds of years of rich organic chemistry.

Carbon nanotubes not only can be functionalized to change their structure but also can interact
beneficially with organic chemicals that have biological usefulness. Fullerene materials have been
explored for use as antioxidants, drug-delivery agents, and amino acid replacements; the latter
could lead to new drug candidates. Reports have been published of their benefits in enhancing virus-
specific antibody responses or as a scaffold for growing retinal epithelial cells to be transplanted into
the retina to treat macular degeneration.[5]

Manufacturing and Scaling Issues

Carbon nanotube synthesis in recent years has been driven by yields and cost. To move nanotubes
from scientific curiosity to practicality, they must be available in sufficient quantities at a reasonable
cost with high uniformity and reproducibility. In the case of MWNTs, the arc-discharge method
provides a good alternative, yielding large quantities of material at a good cost. In the case of
SWNTs, while generating large quantities of material, the purity is often unacceptable for a subset of
applications because of excessive carbonaceous contamination. Instead, the CVD method and a
recent alternative, plasma-enhanced chemical vapor deposition (PECVD), have burst onto the scene
as the methods of choice for producing large quantities of SWNTs with micron lengths, purity, and
reliability within specifications for certain applications. Figure 13-3 shows an example of PECVD
nanotubes.
 Figure 13-3. Array of carbon nanotubes grown by plasma-enhanced
chemical vapor deposition.

PECVD has been reported to lower the temperature of nanotube growth significantly by using a
plasma to generate the reactive carbon atoms instead of very high temperatures, as in standard
CVD growth. In the case of nanoelectronicsperhaps one of the early applications for which SWNTs
will be adoptedextremely high purity nanotubes are required, and only a few providers have
managed to generate such materials at a reasonable cost.

The key issue with respect to commercial use of nanotubes for most applications comes in placing
wafers on silicon or silicon on insulators, which are typical substrates for making circuits or devices.
To the extent that alignment or specific orientation is required, applicability has been limited. Two
general methodologies exist for proceeding toward manufacturability of devices: specific growth
using prepatterned catalysts (Figure 13-4), or patterning of nonoriented fabrics using application of
solutions. In the former case catalysts are placed in specific regions of a substrate onto which
nanotubes grow in either a vertical or a horizontal direction.

Figure 13-4. Patterned growth of multiwalled carbon nanotubes by

chemical vapor deposition.

Vertically oriented growth has been demonstrated by several groups and is especially valuable for
field emitting devices. Many potential CNT device approaches using CVD growth of SWNTs suffer
from manufacturability and scalability issues, primarily because typical CVD temperatures are
>800°C for SWNTs. At such high temperatures, other steps in a fabrication process can be adversely
affected, causing the yields of working devices to be lower. Indeed this a serious limitation if the
underlying substrate or control electronics cannot withstand such temperatures. Some reports have
presented data on lower-temperature methods of growing SWNTs using techniques such as PECVD.
These techniques are still in their infancy but could represent a reasonable pathway for certain types
of devices or applications.

Horizontal fabrics have been applied to substrates whose thickness can be controlled by solution
concentration and application procedure. Such methods have conquered the issues of purification of
nanotube solutions, distribution of networks of nanotubes of uniform density over large substrates,
and patterning of traces of conductive nanotubes into shapes that can be further integrated into
complicated process flows.

SWNTs can be obtained in bulk from various suppliers, which have exploited advanced CVD
techniques to grow SWNTs in large scale of excellent quality. These nanotubes can then be purified
to remove metallic contaminants (for example, Group IA and IIA elements) used in the growth
process and carbonaceous species that serve as a potential source of contamination. The processed
SWNTs are solubilized and can then be applied to device substrates for further processing.

Potential Applications
A variety of potential applications exist for carbon nanotubes. MWNTs have been reported for use
primarily as a composite for batteries and as field emitters for television monitors.[6] As the price for
these materials continues to drop, other potential applications, especially as additives in composites,
are likely.

The molecular nature of carbon nanotube fabrics allows various CNT physical properties, including
electromagnetic, mechanical, chemical, and optical behaviors, to be exploited to create integrated
electronic devices (including nonvolatile memory devices); chemical, biological, and radiation
sensors; passive low-resistance, low-capacitance conformal interconnects; and electromagnetic field
emission devices, scaffolds for cell growth, antioxidants, and near infrared imaging tags for
biological samples and cells, to name a few. Table 13-1 summarizes a number of proposed
applications that could use SWNT fabrics as an enabling component.[7]

Table 13-1. Sample applications of single-walled carbon nanotube

fabrics.

Semiconductors Life Sciences Instrumentation

Nonvolatile and volatile Membranes Mechanical relays and switches
memory

Programmable logic Chemical absorption Thermal sensors and actuators

devices
Global and local Valves Acceleration sensors
interconnects
Inductors Nanomixers Bolometers
Radio frequency (RF) Heat exchangers Gyroscopes
components
Semiconductors Life Sciences Instrumentation

Micromirrors Nanochannels Field emission tips displays

Chip-to-chip Reaction chambers Acoustic/Pressure sensors
interconnects

Transistors Nanofluidics devices Radiation detectors

One existing application for which SWNTs are particularly useful is in the arena of electronics,
specifically to create nonvolatile memory.[8] In the case of nonvolatile memory applications,
significant progress has been made in using fabrics, or assemblages of SWNTs, as electrical traces
within integrated circuits.[9] These fabrics retain their molecular-level properties while eliminating
the need for nanoscale physical control. These monolayers are created by room-temperature spin-
coating of a solution of SWNTs in a semiconductor-grade solvent. After evaporation of the solvent,
the resulting monolayer fabric is lithographically patterned and etched in an oxygen plasma. The
process of spin-coating SWNT solutions can be used to produce monolayer fabric of very steep
aspect ratios, which allows coverage of fabrics over sharp edges or tall structures. Such diversity in
the coating of nanotube fabrics on three-dimensional structures has the potential to support
traditional horizontal integration schemes in electronics as well as a novel set of devices oriented in
a vertical fashion that could lead to significantly more dense electronics.

The combination of patterned nanotube fabrics and the use of fabricated sacrificial layers around the
fabric allows the formation of an open cavity, in which a suspended patch of fabric can be
mechanically drawn into electrical contact with an electrode. These devices, called molecular
microswitches (MMSs), can be used as storage elements for memory or logic applications.

The SWNT fabric approach uses a 12-nm thick patterned SWNT fabric and can be interconnected
monolithically with additional standard semiconductor (for example, CMOS) circuitry above or
below, providing buffering and drive circuitry to address and control the MMS devices. When this
technique is used, the limit to the scalability of the hybrid nanotube/ CMOS system depends only on
the available photolithographic node. Hence, the CMOS fabrication, and not the inclusion of
nanotubes, remains the limiting factor in scaling. Indeed, the ultimate physical limit to the
integration density of this approach scales down to two individual metallic nanotubes and their
electromechanical interaction.
References
1. S. Iijima, Nature 354, (1991): 56.
2. C. Journet et al., Nature 388 (1997): 756; A. Thess et al., Science 273 (1996): 483; and A. M.
Cassell, J. A. Raymakers, J. Kong, and H. Dai, J. Phys. Chem. B 103 (1999): 6484.

3. T. W. Ebbesen et al., Nature 382 (1996): 54; M. M. J. Treacy, T. W. Ebbesen, and J. M.

Gibson, Nature 381 (1996): 678; and J. W. Mintmire, B. I. Dunlap, and C. T. White, Phys Rev
Lett 68 (1992): 631.

4. http://www.lenntech.com/Periodic-chart-elements/melting-point.htm.
5. D. Pantarotto et al., Chem Biol. 10 (2003): 961.
6. Y. Chen et al., Appl. Phys. Lett. 78 (2001): 2128; and D. Qian et al., Appl. Phys. Lett. 76
(2000): 2868.

7. R. H. Baughman, A. A. Zakhidov, and W. A. de Heer, Science 297 (2002): 787.

8. T. Rueckes et al., Science 298 (2000): 94.
9. D. K. Brock et al., Proc. 2005 IEEE Aero. Conf. (2005).
Nanowires
Zhong Lin Wang

Semiconductor nanowires (NWs) are wires only a few nanometers in size that do not occur naturally.
They represent an important broad class of nanometer-scale wire structures, which can be rationally
and predictably synthesized in single-crystal form with all their key parameters controlled during
growth: chemical composition, diameter, length, doping, and so on. Semiconductor NWs thus
represent one of best-defined and best-controlled classes of nanoscale building blocks, which
correspondingly have enabled a wide range of devices and integration strategies (Figure 13-5). For
example, semiconductor NWs have been assembled into nanometer-scale field effect transistors
(FETs), p-n diodes, light-emitting diodes (LEDs), bipolar junction transistors, complementary
inverters, complex logic gates, and even computational circuits that have been used to carry out
basic digital calculations. It is possible to combine distinct NW building blocks in ways not possible in
conventional electronics. Leveraging the knowledge base of chemical modifications of inorganic
surfaces can produce semiconductor NW devices that achieve new functions and produce novel
device concepts.

Figure 13-5. Aligned semiconducting ZnO nanowire arrays. These wires

are grown uniformly from a solid substrate, and their location and density
can be defined by the deposited catalyst of gold.

Semiconducting oxide nanobelts (NBs) are another unique group of quasi-one-dimensional

nanomaterials with well-defined side surfaces, which have been systematically studied for a wide
range of materials having distinct chemical compositions and crystallographic structures. Beltlike,
nanobelts (also called nanoribbons) have been synthesized for semiconducting oxides of zinc (Figure
13-6), tin, indium, cadmium, and gallium by simply evaporating the desired commercial metal oxide
powders at high temperatures. These oxide nanobelts are pure, structurally uniform, single-
crystalline, and largely free of imperfections; they have a rectangularlike cross section with
controllable dimension. Field effect transistors and ultrasensitive nanosize gas sensors,
nanoresonators, and nanocantilevers have also been fabricated based on individual nanobelts.
Thermal transport along the nanobelt has also been measured. Nanobelts, nanosprings, and
nanorings that exhibit piezoelectric properties have been synthesized that could eventually be used
to make nanoscale traducers, actuators, and sensors.

Figure 13-6. Nanobelt of ZnO synthesized by a vapor-solid process. The

nanobelt has a well-defined side surface, and it usually has a rectangular
cross section.

Applications

Biological Sensors Based on Individual Nanowires

Because many biological molecules, such as proteins and DNA, are charged under physiological
conditions, it is also possible to detect the binding of these macromolecules to the surface of
nanowires. Protein detection by SiNW nanosensors has been demonstrated for the well-
characterized ligand-receptor binding of biotin-streptavidin (Figure 13-7) using biotin-modified NW
surfaces.

Figure 13-7. Detection of protein binding. The schematic illustrates a

biotin-modified SiNW (left) and subsequent binding of streptavidin to the
SiNW surface (right). The SiNW and streptavidin are drawn approximately
to scale.
Crossed p-n Junction Light-Emitting Diodes

In direct band gap semiconductors like InP, the p-n junction also forms the basis for critical
optoelectronic devices, including LEDs and lasers (see Figure 13-8). To assess whether our crossed
NW devices might behave similarly, the photoluminescence (PL) and electroluminescence (EL) from
crossed NW p-n junctions can provide a means for controlling the color of the LEDs in a well-defined
way. The ability to tune color with size in these nanoLEDs might be especially useful in future
nanophotonic applications.

Figure 13-8. Three-dimensional plot of light intensity of the

electroluminescence from a crossed NW LED.

Integrated Nanowire Logic Devices

The controlled high-yield assembly of crossed NW p-n diodes and crossed-nanowire field effect
transmitters with attractive device characteristics, such as high gain, enable the bottom-up
approach to be used for assembly of more complex and functional electronic circuits such as logic
gates. Logic gates are critical blocks of the hardware in current computing systems that produce a
logic-1 and logic-0 output when the input logic requirements are satisfied.

Diodes and transistors represent two basic device elements in logic gates. Transistors are more
typically used in current computing systems because they can exhibit voltage gain. Diodes do not
usually exhibit voltage gain, although they may also be desirable in some cases. For example, the
architecture and constraints on the assembly of nanoelectronics might be simplified using diodes
because they are two-terminal rather than three-terminal transistors. In addition, by combining the
diodes and transistors in logic circuits, it is possible to achieve high voltage gain while
simultaneously maintaining a simplified device architecture. The flexibility of these NW device
elements for both diode- and FET-based logic has been demonstrated in the creation of AND, OR,
NOR gates that have been used to implement simple basic computation (Figure 13-9).

Figure 13-9. Logic NOR gate. Schematic of logic NOR gate constructed
from a 1x3 crossed NW junction array. The insets show a sample scanning
electron microscope image (bar is 1 m) and symbolic electronic circuit.

Polar-Surface Dominated Novel Nanostructures

For applications in nanotechnology, ZnO has three key advantages. First, it is a semiconductor that
has a direct wide-band gap and significant excitation-binding energy. It is an important functional
oxide, exhibiting near-UV emission and transparent conductivity at room temperature and higher. It
is also piezoelectric because of its noncentral symmetry. This is a key phenomenon in building
electromechanical coupled sensors and transducers at nanoscale. The piezoelectric coefficient of a
polar nanobelt is about three times that of bulk material, and this makes it a candidate for nanoscale
electromechanical coupling devices. Finally, ZnO may be biosafe and biocompatible, so it can be
used for biomedical applications without coating. With these three unique characteristics, ZnO could
be one of the most important nanomaterials in future research and applications. The diversity of
nanostructures presented here for ZnO should open many fields of research in nanotechnology.

The synthesis of various nanostructures is based on a solid-state thermal sublimation process, in

which a pile of source materials, typically the powder form of oxides, is placed at the center of a
tube furnace. The source materials are sublimated by raising the temperature of the furnace; a
redeposit ion of the vapor phase at a lower temperature zone produces novel nanostructures. By
controlling the growth kinetics, the local growth temperature, and the chemical composition of the
source materials, researchers have synthesized a wide range of polar-surface dominated
nanostructures of ZnO under well-controlled conditions at high yield (Figure 13-10).
 Figure 13-10. A collection of polar-surface induced/dominated
nanostructures of ZnO, synthesized under controlled conditions by
thermal evaporation of solid powders unless specified otherwise: (a)
nanocombs induced by asymmetric growth on the Zn-(0001) surface; (b)
tetraleg structure due to catalytically active Zn-(0001) surfaces; (c)
hexagonal disks or rings synthesized by solution-based chemical
synthesis; (d) nanopropellers created by fast growth; (e) deformation-
free nanohelixes as a result of block-by-block self-assembly; (f) spiral of a
nanobelt with increased thickness along the length; (g) nanosprings; (h)
single-crystal seamless nanoring formed by loop-by-loop coiling of a polar
nanobelt; (i) a nanoarchitecture composed of a nanorod, nanobow, and
nanoring. The percentage in each figure indicates the purity of the as-
synthesized sample for the specific nanostructure in a specific local
temperature region.

Zinc oxide (ZnO) is a material that has key applications in catalysts, sensors, lasering, piezoelectric
transducers, transparent conductors, and surface acoustic wave devices. This chapter focuses on the
formation of various nanostructures of ZnO, showing their structures, growth mechanisms, and
potential applications in optoelectronics, sensors, transducers, and biomedical science. For the
nonpolar surfaces of ZnO, various forms of nanostructures have been synthesized for ZnO (Figure
13-11). These structures were realized by controlling growth kinetics.

Figure 13-11. A collection of nonpolar-surface dominated nanostructures

of ZnO, synthesized under controlled conditions by thermal evaporation of
solid powders by controlling source materials, growth temperature,
 temperature gradient, and substrate. (a) Nanobelt; (b) aligned nanowire
arrays; (c) nanotubes; (d) array of propellers; (e) mesoporous nanowires;
(f) cages and shell structures; and (g) hierarchical shell and propeller
structure. The percentage in each figure indicates the purity of the as-
synthesized sample for the specific nanostructure in a specific local
temperature region.
Soft Nanotechnology
Fiona Case

Many soft or fluid consumer productssuch as foods, paint, detergents, personal care products, and
cosmeticscontain nanometer- to micrometer-scale structures. These structures are formed by the
spontaneous self-assembly of natural or synthetic surfactants or block copolymers. In many cases,
to create the desired structure and performance, complex mixtures of different surfactants and
polymers are required.

Figure 13-12 shows an example of a simple, nonionic surfactant. Figure 13-13 illustrates some of the
soft nanoscale structures that form spontaneously in surfactant or block copolymer solution. The
particular structure that is formed depends on the relative sizes of the head and tail and their
chemical character. For example, surfactants that have ionic (charged) head groups often form
spherical micelles, whereas non-ionic (uncharged) surfactants are more likely to form rodlike
structures, and surfactants that have more than one tail are more likely to form vesicles or lamella
(almost flat sheets). The soft nanoscale structure can also be influenced by the order of addition of
the different ingredients.

Figure 13-12. A simple example of a surfactant, in this case a non-ionic

ethoxylate surfactant, shown as the chemical structure (top), as a space-
filling molecular model (bottom left), and as a cartoon representation
(bottom right).

Figure 13-13. Cartoon representations of different surfactants forming a

spherical micelle (top), a rodlike micelle (middle), and a vesicle (bottom)
in water. A slice through each of the nanostructures is shown; in the
complete structures, the hydrophilic head groups surround the
hydrophobic tails, shielding them from unfavorable interactions with
water.
These soft nanostructures do work on demand. When you add dish liquid to hot water in a dishpan
full of dirty pots and pans, the nanoscale structure of the surfactant micelles change as they migrate
to the oily surfaces, encapsulate the grease, and carry it into solution. When you paint a wall with a
good-quality emulsion-based paint, the brush moves easily as you spread the paint on the wall, but
as soon as you finish brushing an area, the structure changes and the viscosity of the paint increases
to reduce the occurrence of drips. Soft nanotechnology is also at work when you mix up a cake or
even enjoy the taste and texture of chocolate, ice cream, or yogurt.

Designing these complex materials is difficult, and characterizing them is challenging. Until recently,
most soft nanostructured products were created by experienced formulators, using empirical rules
that were passed down through generations of product developers. Although ideas of self-assembly
were invoked to explain behavior, it was almost impossible to predict what structure would be
created from a particular mixture of ingredients. And because it was extremely difficult to
characterize products that were known to be successful, it was hard to know what structure was
desirable for a particular application.

Today, new methods of characterization are providing insight into soft nanostructured materialsfor
example, dynamic light scattering, NMR diffusion experiments, X-ray and neutron scattering, and
electron microscopy. New robotics techniques are allowing developers to explore many more
formulas than was possible when each candidate formula had to be created by hand. New theories
and computer simulation methods are enabling researchers to construct realistic models of soft
nanostructured materials. Taken together, these developments have the potential to revolutionize
consumer product development.

Other members of the nanotechnology community are also becoming interested in self-assembly and
nanostructured fluids, which indeed have the potential to provide robust and inexpensive strategies
for creating nanoscale materials. For example, IBM recently highlighted the potential for block-
copolymer self-assembly to create nanometer-size structures for electronics applications. Several
groups are exploring strategies for creating hard nanoparticles using soft self-assembled structures
as templates, and self-assembled block copolymer-stabilized emulsions and vesicles are being
proposed as drug- (and nutriceutical-) delivery devices. Moreover, various soft nanotech strategies
are being applied to stabilize colloidal systems (nanoparticle solutions and gels).
Chapter 14. Nanotechnology-Enabled
Sensors: Possibilities, Realities, and
Diverse Applications
David J. Nagel and Sharon Smith

Whether you are a producer or a user of sensors, your business will likely be impacted by current
and future developments in nanotechnology. Emerging nanotechnologies offer an unprecedented
promise for sensors: smaller size and weight, lower power requirements, more sensitivity, and more
specificity, to name a few.

This chapter surveys both the promise and the limitations of the new sensors that are enabled by
technologies on the scale of nanometers (one-thousandth of a micrometer). Nanosensors and nano-
enabled sensors have applications in a wide variety of industries, including transportation,
communications, building and facilities, medicine, safety, defense, and national security. Proposed
applications of nanoscale sensors are far reaching and include using nanowire nanosensors to detect
chemicals and biologics, putting nanosensors in blood cells to detect early radiation damage in
astronauts, and using nanoshells to detect and destroy tumors.[1] Many such applications are being
developed by start-up companies, which seek to build businesses that exploit particular nanoscale
effects or particular applications of nanotechnology.

The expected impact of nanotechnology on sensors can be understood by noting that most chemical
and biological sensors, as well as many physical sensors, depend on interactions that occur on the
scale of atoms and molecules. Nanotechnology refers to an expanding science, and a very promising
technology, that enables the creation of functional materials, devices, and systems through control
of matter at the scale of atoms and molecules, and the exploitation of novel properties and
phenomena at the same scale.[2]

Nanotechnologies can extend the long-established trend toward smaller, faster, cheaper materials
and devices. The miniaturization of macro techniques led to the now established field of
microtechnologies. For example, electronic, optical, and mechanical microtechnologies have had a
dramatic impact on the sensor industry in recent decades. Improved, new, and smart sensors are
among the many beneficial effects of integrated circuits, fiber, and other microoptics and MEMS
(microelectromechanical systems). Now, developments in nanotechnology will drive the devices into
even smaller dimensions, with significant potential advantages.

As the trend continues toward the use of smaller building blocks of atoms and molecules, there will
also tend to be convergence of technology disciplinesfor example, the merging of nanotechnology,
biotechnology, and information technology. This overlap and the resulting synergy should contribute
to the growing strength of each of these major technologies.
Possibilities
The global excitement over nanotechnology has resulted from several discoveries late in the
twentieth century. Primary among them is the ability to manipulate individual atoms in a controlled
fashion, a sort of atomic brick-laying made possible by techniques such as scanning probe
microscopy (SPM). The ability to produce significant amounts of nanoparticles, such as silver and
gold nanoparticles, has also fed the excitement. And the underlying fact that materials and devices
on the scale of atoms and molecules have new and useful propertiesdue in part to quantum and
surface effectscan also be cited. Nanoscale quantum dots with remarkable optical properties are a
prime example.

Another major contributor to the interest in nanotechnology was the discovery of carbon nanotubes
(CNTs), which are extremely narrow, hollow cylinders made up of carbon atoms. With the possibility
of single- and multiple-walled varieties, each with a myriad of potential applications, carbon
nanotubes offer many exciting prospects. The single-walled versions can have various geometries,
as shown in Figure 14-1. Depending upon the exact orientation of the carbon atoms, the nanotubes
can exhibit either conducting (metallic) or semiconducting properties. This fact, plus the ability to
grow CNTs at specific locations and to manipulate them after growth, leads to optimism that CNTs
will be important for electronics and sensors, either alone or integrated with each other.

Figure 14-1. Carbon nanotubes can exist in a variety of forms, which can
be either metallic or semiconducting in nature. (Courtesy of NASA Ames
Research Center, Moffett Field, CA.)

For these and other reasons, the funding for nanotechnology has increased more than a factor of 5
in the period 1997 to 2003, and it is still increasing.[3] With the major increase in funding and the
resulting scientific breakthroughs, there is great potential for improvements in existing sensors and
for the development of really new sensors. One market study of nanoenabled sensors predicts sales
near $0.6 billion by 2009.[4] Another is much more aggressive, saying that the nanotechnology
sensor market will generate global revenues of $2.7 billion by 2008.[5] Whatever the actual
outcome, it seems clear that the sales of nano-enabled sensors will grow significantly, and the
growth is largely a result of the research investment in nanoscience and nanotechnology.

Relentless Integration
Historically, there has been a relatively clean separation between the materials, device, and systems
levels. However, in recent decades, integration has been a major theme of technology. First,
transistors were made into integrated circuits. Then such microelectronics were integrated with
microoptics and micromechanics. The microtechnology devices were packaged individually and
mounted on printed circuit boards. The recent use of flip chipswhere the chip is the packageand the
placement of passive components within printed circuit boards are blurring the classical distinction
between devices and systems. The integration of nanomaterials into MEMS devices is now a major
research topic. Nanotechnology makes it possible to integrate the different levels to the point that
the (very smart) material essentially is the device and possibly also the system. Larry Bock, founder
of Nanosys, recently noted, "Nanotech takes the complexity out of the system and puts it in the
material." [6]

Now the vision of sensing the interaction of a small number of molecules, processing the data,
transmitting the information using a small number of electrons, and then storing information in
nanometer-scale structures can be seriously contemplated. Fluorescence and other means of single-
molecule detection are being developed. Data storage systems, which use proximal probes to make
and read indentations in polymers, are being developed by IBM and others. They promise read and
write densities near one trillion bits per square inch, far in excess of current magnetic storage
densities.[7]

The integration of such nanoscale capabilities, once they are adequately developed, is challenging,
but it would result in capable smart sensors that are small, use low power, and can be used cheaply
in large numbers. These advances will enable, for example, more in-situ sensing of structural
materials, more sensor redundancy in systems, and increased use of sensors in size-and weight-
constrained systems, such as satellites and space platforms.

The production of nano-enabled sensors depends on the availability of nanomaterials and processes
to grow them in place or else the practice of placing previously grown materials in the right positions
in the desired amounts and geometries. Hence, there is a three-dimensional space that interrelates
nanomaterials, processes for making or handling them, and specific sensors. This is sketched in
Figure 14-2. What materials are used, how they are employed, and why a particular sensor is being
produced all come into consideration. A given material might be made or handled by a variety of
processes and made into different sensors. A particular process might be germane to various
materials and sensors.

Figure 14-2. The schematic relation between nanomaterials, processes for

making or emplacing them, and the sensors that are thus enabled.
Advances in Processing
Recent progress in "top-down" manufacturing processes has helped enable microtechnologies as
well as nanotechnologies. Leading-edge integrated circuits are made by top-down processes in
which lithography, etching, and deposition techniques are used to sculpt a substrate, such as silicon,
and then build up structures on it. Using these approaches, conventional microelectronics has
approached the nanometer scale as the line widths in chips surpass the 100-nm level and are
continuing to shrink. MEMS devices are constructed in a similar top-down process. As these
processes continue to shrink to smaller and smaller dimensions, they can be used for making a
variety of nanotechnology components, much as a large lathe can be used to make small parts in a
machine shop.

In the nanotechnology arena, such processes are being joined by a collection of "bottom-up"
methods in which individual atoms and molecules are used to construct useful structures. Under the
right conditions, the atoms, molecules, and larger units can self-assemble.[8] Alternatively, directed
assembly techniques can be employed.[9]

The control of both self-assembly and directed assembly presents major technical challenges.
Processes for getting nanomaterials to grow in the right places in the desired geometries require
development. Overall, the combination of nanoscale top-down and bottom-up processes gives the
designer of materials and devices a wide variety of old and new tools. It is also possible to combine
micro- and nanotechnologies to enable the development of new sensor systems.

Diverse Nanomaterials
Nanomaterials and structures offer other possibilities for sensors. There are two often separable
functions within many sensors, especially those for chemicals and biological materials. They are
recognition of the molecule of interest, and transduction of that recognition event into a useful
signal. Nanotechnology offers new possibilities in both of these fundamental arenas in a manner that
offers benefits far beyond the advantages offered by MEMS and other microsensors.

Most of the nanomaterials that have been produced and used to date contain only one kind of
nanostructure and chemistry. There are a few exceptions, but the situation for nanomaterials is now
similar to that for macromaterials before composites, such as fiberglass, were formulated. There is
no reason that composites of two or more nanomaterials should not be made, tested, and exploited.

As with large-scale materials, the combinatorics of making composite materials results in a very
large number of potential new materials. This is illustrated in Figure 14-3 for composite materials
made of two nanomaterials. Making nanocomposites from different kinds of nanomaterials, which
can have a wide range of chemistries, presents many processing challenges. It is expected that the
production and use of composite nanomaterials for sensors and other applications will increase
steadily in the coming years.

Figure 14-3. Binary composites made of nanomaterials taken two at a

time. The top row contains zero-dimensional (0-D) materials, the second
row 1-D materials, the third row 2-D materials, and the bottom row 3-D
materials. The binaries represent 28 possible composite materials.

New Tools
Another aspect of the development of nanotechnology-based sensors deserves emphasis. Because of
experimental tools now availablenotably synchrotron X-radiation and nuclear magnetic resonancethe
atomic structures of many complex molecules are now known. But knowledge of the structure on the
nanometer scale is not enough. It is the interactions of atoms and molecules that are important in
the recognition, and sometimes the transduction, stage of sensing. The availability of powerful
computers and algorithms for the simulations of interactions on the nanoscale makes it possible to
design nano-tech-based sensors computationally, and not just experimentally. Molecular dynamics
codes and calculations are already a fundamental tool in nano-science, and they can be applied to
the development of nanotechnology-based sensors.[10]
Realities
Although the excitement about nanotechnology and its prospective uses is generally well founded,
there are many inescapable requirements that must be considered for the successful development
and integration of nanotechnology sensors. These requirements include those imposed by physics,
chemistry, biology, engineering, and commerce.

For example, as nanotechnologies are integrated into macro-sized systems, it will be necessary to
provide for and control the flow of matter, energy, and information between the nanometer-scale
and macro-scale systems. Calibration of nano-enabled sensors can be problematic if very small
amounts of analyte and reagent materials are involved. It must be remembered that the size of
most sensor systems is determined by the scale of the computer, memory, and radio chips, and
(especially!) by the batteries and antennas. This is true for both micro- and nanoscale sensors.

Intensified Design Problems

Many of the design considerations for nanoscale sensors are similar to those of microsensorsnotably,
interface requirements, heat dissipation, interferants, and noise (both electrical and mechanical).
Each interface in a microsystem is subject to unwanted transmission of electrical, mechanical,
thermal, and possibly chemical, acoustical, and optical fluxes. Dealing with unwanted molecules and
signals in very small systems often requires ancillary equipment and the use of low temperatures to
reduce noise.

Flow control is especially critical in chemical and biological sensors into which gaseous or liquid
analytes must be brought and from which they are expelled. The very sensitive, tailored surfaces in
molecular sensors, chemical as well as biological, are subject to degradation by interfering
substances, heat, and cold. One of the attractions of nanotechnology is the chance to make
hundreds of sensors in a small space so that sensors that have degraded can be ignored in favor of
fresh sensors to prolong the useful lifetime of a system containing them.

The Risks of Commercialization

The path from research to engineering to products to revenues to profits to sustained commercial
operations is difficult for technologies of any scale. It is particularly challenging for new
nanotechnologies, and not only because of the common reluctance to specify new technologies for
high-value systems. The reality is that most nanoscale materials are currently difficult to produce in
large volumes, so unit prices are high and markets limited. Costs will decrease over time, but it may
be difficult for small companies to make enough profit soon enough. A recent review has focused on
the commercialization of nanosensors.[11]
Diverse Applications
Although there are few sensors today based on pure nanoscience and it is early in the development
of nano-enabled sensors, some of the possible devices and applications are already clear. Examples
of nanotech and nano-enabled physical, chemical, and biological sensors are given in this section.
Although sensors for physical quantities were the focus of early development efforts, nanotechnology
will contribute heavily to realizing the potential of chemical and biosensors for safety, medical, and
other purposes. Vo-Dinh, Cullum, and Stokes recently provided an overview of nanosensors and
biochips for the detection of biomolecules.[12] It is anticipated that many major industries will
benefit from nanotechnology-enabled sensors.

Physical Sensors
An early example of a nanotech physical sensor is given in Figure 14-4. Researchers at the Georgia
Institute of Technology demonstrated the world's smallest balance by taking advantage of the
unique electrical and mechanical properties of carbon nanotubes.[13] They mounted a single particle
on the end of a carbon nanotube and applied an electric charge to it. The carbon nanotube acted
much like a strong, flexible spring. The nanotube oscillated without breaking, and the mass of the
particle was calculated from changes in the resonance vibrational frequency with and without the
particle. This approach may lead to a technique for the weight measurement of individual
biomolecules.

Figure 14-4. The mass of a carbon sphere shifts the resonance frequency
of the carbon nanotube to which it is attached. (Courtesy of Walter de
Heer, Georgia Institute of Technology, Atlanta, GA.)

Cleland and Roukes at the California Institute of Technology reported the fabrication and
characterization of a submicron, mechanical electrometer.[14] Shown in Figure 14-5, this device,
made possible by modern nanofabrication technology, has demonstrated charge sensitivity less than
a single electron charge per unit bandwidth (~0.1 electrons/sqrt (Hz) at 2.61MHz). This sensitivity
exceeds that of state-of-the-art semiconductor devices.

Figure 14-5. A nanometer-scale mechanical electrometer consists of a

torsional mechanical resonator, a detection electrode, and a gate
electrode used to couple charge to the mechanical element. (Reprinted
 with copyright permission from Nature Publishing Group.)

[View full size image]

Chemical Sensors
A variety of nanotube-based gas sensors have been described in the past few years. Modi et al. have
used carbon nanotubes to develop a miniaturized gas ionization detector.[15] This system could be
used as a detector for gas chromatography. Titania nanotube hydrogen sensors have been employed
in a wireless sensor network for detecting hydrogen concentrations in the atmosphere.[16] And Kong
et al. have developed a chemical sensor for gaseous molecules, such as NO 2 and NH3, based on
nanotube molecular wires.[17] In a recent study, Parikh et al. used office equipment to print carbon
nanotubes on flexible plastic to make sensors for organic vapors.[18]

Sensors based on nanocantilevers also are possible. Datskos and Thundat have fabricated
nanocantilevers using a focused ion beam (FIB) technique.[19] They developed an electron transfer
transduction approach to measure the motion of the nanocantilever. An array of such sensors is
shown in Figure 14-6. They may provide the sensitivity to detect single chemical and biological
molecules. Structurally modified semiconducting nanobelts of ZnO have also been demonstrated to
be applicable to nanocantilever sensor applications.[20][21]

Figure 14-6. This array of chemical sensors incorporates MEMS cantilevers

and the electronics for signal processing. (Courtesy of Thomas G.
Thundat, Oak Ridge National Laboratory, Oak Ridge, TN.)
Biosensors
Nanotechnology will also enable the very selective, sensitive detection of a broad range of
biomolecules. It is now possible to create cylindrical rods made up of metal sections that are
between 50nm and 5 m m long. This is done by the sequential electrochemical reduction of the metal
ions onto an alumina template. These particles, called Nanobarcodes, can be coated with analyte-
specific entities, such as antibodies, for selective detection of complex molecules, as illustrated in
Figure 14-7. DNA detection with these nanoscale coded particles has been demonstrated.

Figure 14-7. Biomolecules can be detected optically when they are

attached to antibodies affixed to particles called Nanobarcodes.

Researchers at NASA Ames Research Center have taken a different approach to DNA detection.[22]
Carbon nanotubes in the range of 3050nm in diameter are mounted vertically on a silicon chip, with
millions of nanotubes covering the surface of the chip, as shown in Figure 14-8. Probe DNA
molecules are attached to the ends of the nanotubes. When the chip is placed in a liquid containing
DNA molecules, the substrate DNA attaches to the target DNA, increasing the measured electrical
conductivity. This approach, expected to reach the sensitivity of fluorescence-based detection
systems, may find application as a portable sensor.
 Figure 14-8. Vertical carbon nanotubes are embedded in a silicon chip.
DNA molecules attached at the ends of the nanotubes detect specific
types of DNA or other substances. (Courtesy of NASA Ames Research
Center, Moffett Field, CA.)

Deployable Sensors
We are starting to see nanoscale materials and devices being integrated into real-world systems. An
example is SnifferSTAR, a lightweight and portable chemical detection system, shown in Figure 14-
9.[23] This unique system combines a nanomaterial for sample collection and concentration with a
MEMS-based chemical lab-on-a-chip detector. SnifferSTAR has defense and home-land security
applications and is ideal for deployment on unmanned systems such as micro-UAVs (unmanned
aerial vehicles).

Figure 14-9. A nano-enabled chemical sensor has been integrated into a

micro-UAV. (Courtesy of Sandia National Laboratories, Albuquerque, NM,
and Lockheed Martin Corporation.)

[View full size image]

Other areas expected to benefit from sensors based on nanotechnologies include the following:
transportation (land, sea, air, and space); communications (wired and wireless, optical and radio
frequency); buildings and facilities (homes, offices, factories, and other structures); monitoring of
humans (especially health and medical monitoring of aging baby boomers); and robotics of all
types. The integration of nano-enabled sensors into commercial and military products will be fueled
by many new companies making nanomaterials and some making sensors based on them.

Although much progress is being made, many challenges still must be met before we will see the full
impact of nanotechnology in the sensor industry. They include reducing the cost of materials and
devices, improving reliability, and the packaging of the devices into useful products. Such challenges
notwithstanding, the future of nano-enabled sensors is bright for several reasons. It may be possible
to put sensors into very small volumes, including individual cells. Nanosensors may have a
significant scientific impact by measuring molecular interactions and kinetics on very small scales at
high speeds. The practical impacts of nanosensors will include having many sensors in a single
system to improve both the range of materials that can be analyzed and the lifetime of the overall
system.

In short, nanotechnology presents a historic opportunity for the improvement of existing sensors, as
well as the development of new sensors that will have numerous new applications in many
industries.

This chapter is based on an article, "Nanotechnology-Enabled Sensors: Possibilities, Realities,

and Applications," that ran in the November 2003 issue of Sensors magazine
(www.sensorsmag.com).
References
1. Y. Cui, Q. Wei, H. Park, and C. M. Lieber, "Nanowire Nanosensors for Highly Sensitive and
Selective Detection of Biological and Chemical Species," Science 293 (August 17, 2001):
12891292; "Space Mission for Nanosensors," The FUTURIST, November/December 2002, 13;
J. A. Cassell, "DoD grants $3M to study nanoshells for early detection, treatment of breast
cancer," NanoBiotech News 1, no. 3 (August 13, 2003).

2. "Small Wonders, Endless Frontiers: A Review of the National Nanotechnology Initiative,"

National Academy Press (2002).

3. S. K. Moore, "U.S. Nanotech Funding Heads for $1 Billion Horizon," IEEE Spectrum On-line,
http://www.spectrum.ieee.org/WEBONLY/resource/jun02/nnano.html.

4. "Nanosensors," Business Communications Company, Inc., 2004,

http://www.marketresearch.com.

5. NanoMarkets LLC, "Nanosensors: A Market Opportunity Analysis," 2004,

http://www.nanomarkets.net/news/pr_detail.cfm?PRID=156.

6. L. Bock, "Nano's Veteran Entrepreneur," SMALLTIMES, July/August 2003, 2732.

7. http://www.research.ibm.com/resources/news/20020611_millipede.shtml.
8. I. Bernt et al., Molecular Self-assembly: Organic Versus Inorganic Approaches, 1st edition,
ed. M. Fujita (Berlin: Springer Verlag, 2000).

9. www.zyvex.com/Capabilities/other.html.
10. Daan Frenkel and B. Smit, Understanding Molecular Simulation, 2nd edition (New York:
Academic Press, 2001); and D. C. Rapaport, The Art of Molecular Dynamics Simulation, 2nd
edition (Cambridge: Cambridge University Press, 2004).

11. R. Chandrasekaran, J. Miller, and M. Gertner, "Detecting Molecules: The Commercialization

of Nanosensors," Nanotechnology Law and Business Journal 2, issue 1 (2005): 116.
http://pubs.nanolabweb.com/nlb/vol2/iss1/1.

12. T. Vo-Dinh, B. M. Cullum, and D. L. Stokes, "Nanosensors and biochips: Frontiers in

biomolecular diagnosis," Sensors and Actuators B 74 (2001): 211.

13. P. Poncharal, Z. L. Wang, D. Ugarte, and W. A. deHeer, "Electrostatic Deflections and

Electromechanical Resonances of Carbon Nanotubes," Science 283 (1999): 15131516; and J.
Toon, "Weighing the Very Small: 'Nanobalance' Based on Carbon Nanotubes Shows New
Application for Nanomechanics," Georgia Tech Research News, Mar. 4, 1999.

14. A. N. Cleland and M. L. Roukes, "A Nanometre-scale Mechanical Electrometer," Nature 392
(March 12, 1998).

15. A. Modi, N. Koratkar, E. Lass, B. Wei, and P. M. Ajayan, "Miniaturized Gas Ionization Sensors
using Carbon Nanotubes," Nature 424 (July 10, 2003): 171174.

16. C. A. Grimes et al., "A Sentinel Sensor Network for Hydrogen Sensing," Sensors 3 (2003):
6982.

17. J. Kong et al., "Nanotube Molecular Wires as Chemical Sensors," Science 287 (Jan. 28,
2000): 622625.
18. K. Parikh et al., "Flexible Vapor Sensors Using Single Walled Carbon Nanotubes," Sensors
and Actuators B, in press.

19. P. G. Datskos and T. Thundat, "Nanocantilever Signal Transduction by Electron Transfer," J.

Nanosci. Nanotech 2, no. 3-4 (2002): 369372.

20. W. L. Hughes and Z. L. Wang, "Nanobelts as nanocantilevers," Applied Physics Letters 82,
no. 17 (April 28, 2003): 28862888.

21. R. Nicewarner-Pena et al., "Submicrometer Metallic Barcodes," Science 294 (2001): 137; and
F. Freemantle, "Nano Bar Coding for Bioanalysis," Science 79, no. 41 (Oct. 8, 2001): 13.

22. E. Smalley, "Chip Senses Trace DNA," Technology Res. News (Jul 30/Aug. 6, 2003).
23. "Ultralight device analyzes gases immediately. Flying SnifferSTAR may aid civilians and US
military," Sandia National Laboratories, press release, January 23, 2003.
Chapter 15. Microelectronics
The microelectronics industry has steadily improved the speed and efficiency of computing while
simultaneously lowering costs in a highly predictable road map. This steady progression is popularly
known as Moore's Law, after Gordon Moore, co-founder of Intel. Moore observed in 1965 that the
number of transistors on a chip roughly doubles every two years.

Moore's Law has been the metronome of the microelectronics industry: The predictability of "faster-
better-cheaper" allows the industry to precisely plan for the future in areas from engineering to
capital expenditures to marketing. It has benefited everyone who is in the industry or purchases its
products.

However, the physical limits of the current paradigm in computing are approaching, and the S-curve
transition to the next stage is looming. The industry is driven by large companies that have a clear
corporate focus and high equipment costs. They will not experiment with innovations from
nanotechnology unless a clear, compelling case for their profitability can be made.

This chapter outlines manufacturing strategy, gives an overview of current technologies, and
examines future devices we are likely to see. It concludes by examining photonics as a candidate for
the technology that will enable continued progress at the lower limits of Moore's Law.
Nanomanufacturing Product Strategy
George Thompson

The use of nanotechnology in microelectronics is starting to take hold in the microelectronics

industry, and this chapter discusses some of the strategic reasoning for incorporating
nanotechnology into products that will be manufactured in high volume. This discussion begins with
a review of the reasons any new technology should be incorporated into a new product and then
discusses the specific case of nanotechnology.

A strategy for inserting a new technology into a product requires a clear understanding of both the
existing product and the new technology if the manufacturer is to avoid the common case of a
successful new technology becoming a commercial product failure. A clear understanding of the
reasons for a product's success in the marketplace is critical before major changes are made in the
product's base technology.

When an organization is evaluating innovations from nanotechnology and their success in the
marketplace, there are a few points to consider. A key point is that most customers want to buy a
superior product, and the technology embedded in that product is of secondary concern. Technology
by itself is of little value to the customer unless it is incorporated into a product that people will buy.

A key to developing a coherent technology strategy for a new product is to consider whether the new
technology creates a simple, one-time improvement opportunity or whether a rapidly evolving
dynamic technology, such as nanotechnology, is involved. It is critical to understand the difference
in the opportunities and the challenges. The incorporation of a static technology will be expected to
provide a one-time change in the product, whereas the incorporation of a dynamic technology will
create the possibility of improving the product in the near future as the base technology evolves.

Nanotechnology is a rapidly evolving technology. Predicting trends is difficult, and sudden major
discontinuities in the technology are expected. This greatly complicates the business strategy for
integrating nanotechnology into new products. It is helpful to consider a few simple but important
points about the introduction of a static new technology into a product, without the added
complications that exist in the case of a dynamic technology such as nanotechnology. A new
technology can be embedded at several different stages in a product's life cycle, ranging from
assumptions made in the early R&D stages up to the time when end users decide whether or not to
buy the final product. Usually a series of highly objective processes is at work, although the role of
irrational processes, such as fads, should not be ignored.

Consider the case of introducing a new technology, such as a new material, into an existing product.
This new product will have to compete with the other products that serve the same or a similar
function in the marketplace. The two most obvious factors to consider are performance and cost.
Usually the customer base will quickly notice an improvement in price or performance and will
transition to the new product if the improvement does not involve major design changes or
integration investments. A product with superior performance, at the same cost, will have a very
good chance of gaining market share over time, and in some cases will drive an increase in the total
available market.

The case of a product being characterized by only price and performance is far too simple for
practical use, although most products can be described by a reasonably small set of product
characteristicsfor example, function, features, performance, cost, reliability, delivery schedule, form
factor (size), quantity (needed to succeed in the market), and input requirements (electricity,
cooling, and so on). Other considerations include disposal costs and potential legal or ethical issues
arising from any health or safety considerations related to the use of the product.

Before planning a significant change in a technology road map, the strategist who is planning to
incorporate nanotechnology into a product line should begin by understanding the product's
characteristics. The utility of a well-defined list of product characteristics is that it provides clear
design guidance to the development team. In many cases the product characteristics are only
vaguely defined, at the level of, "Is this supposed to be a sports car or a truck?" At times, a product
is not defined even at this level, and the design team's primary goal becomes simply how to find an
application for a new technology. Without a clear definition and without mapping customer
requirements to the product's characteristics, the chance of an economically successful product
launch decrease dramatically.

A review of the product's characteristics and of customer requirementsfor example, the

characteristics and customer requirements for a sports car versus those for a truckmakes for a useful
exercise in clarifying ideas that are both simple and well known but often overlooked by designers
when they incorporate new technologies. It is critical to focus on a product as a collection of product
characteristics; a successful product is a specific collection of product characteristics that customers
value enough to buy at a price that provides the manufacturer with a reasonable return on
investment.

Considering Future Impacts

These comments on product characteristics serve to illustrate a few key ideas involved in launching
a product based on nanotechnology. It's important to note that nanotechnology is dynamic and has
an uncertain future. A critical long-term strategic concern is how nanotechnology will continue to
evolve in the future and its overall impact on the microelectronics industry. In addition, planners
must comprehend the future impacts on their products as nanotechnology continues to evolve.

A reasonable prediction of this process requires an understanding of how the specific

nanotechnology affects the final product. It is also necessary to determine in some detail which
product parameters will benefit, and which may be degraded, from the application of
nanotechnology. Of course, this must be considered in enough detail to explain the impact of
nanotechnology on competitors' products as well.

Ideally, the future evolution of nanotechnology should lead to a continuous improvement in the final
product, an improvement that the customer will value. The best example of this type of long-term
improvement is in the semiconductor industry, which has achieved unprecedented growth by
providing its customers with products that are "faster-better-cheaper." This industry mantra is the
key to creating new markets for its products and to making existing customers happy to replace old
computers with newer ones as a result of a dramatic increase in performance.

The semiconductor industry has been able to maintain this scaling of better performance and better
cost for a simple reason: Smaller transistors are both faster and cheaper. There is a natural synergy
between these two key product parameters that is sufficiently strong to drive sales and increase the
revenues needed to support additional investments in the technology R&D and infrastructure. This
model permits the continuing investments needed to develop new and superior products. As
mentioned earlier, this cycle, which results in the number of transistors doubling on a typical chip
approximately every two years, is called Moore's Law. Its origin lies in the natural synergy that
exists for semiconductor products between cost and performance as the size of the transistors is
reduced, driving both the technology and the economics forward.

Identifying Potential Synergies

For the technologist who is considering the strategic impact of nanotechnology on a product, the first
step may be to determine the potential synergies that exist between product parameters as a result
of the introduction of nanotechnology. Which product parameters may be degraded by
nanotechnology must also be understood. In addition to creating new applications and markets, the
key is to identify potential synergies that will drive product improvement so rapidly that existing
customers will want to upgrade to the newer technology.

One must always consider the risk that product acceptance may be driven by highly subjective
factors. In the longer term, sustained market growth is more likely for products that successfully
compete in the market-place based on an unambiguously objective product superiority. The product
should maintain compatibility with existing architectures, infrastructure, and product applications so
that customers can easily incorporate the new products into their existing applications, in addition to
possibly creating new applications.

Implicit in the definition of product characteristics is the ability to manufacture the new products in
sufficient quantity on a schedule that meets the needs of customers, rather than the needs of a
material or technology supplier. The manufacturing issues surrounding products that incorporate
nanotechnology are complex because of the novelty of the technology. It is critical to ensure that a
stable supply line to the customer is established, because a rational customer will frequently choose
a reliable product that just meets the technology, cost, and schedule requirements over a potentially
superior product that is not certain to be delivered on time.

Nanotechnology today presents a number of somewhat intimidating challenges to any technologist

considering its use in a product. Given that nanotechnology is in its infancy, one must also consider
that after nanotechnology is initially incorporated, the product may soon become obsolete as
nanotechnology improves. This presents an opportunity to continuously improve the product in
lockstep with the advances in nanotechnology, which in turn creates options for new markets. It also
presents opportunities for competitors to leapfrog ahead of your product.

A clear understanding of the impact of nanotechnology on the final product characteristics, an

awareness of the rapidly evolving nature of nanotechnology, and consistency with existing
architectures, infrastructure, and metrics are all prerequisites for the successful formulation of a
nanotechnology manufacturing strategy.
Existing Technologies
Stephen Goodnick

The exponential increase in the density of integrated circuits (ICs) predicted by Moore's Law has
been driven primarily by shrinking the dimensions of the individual semiconductor devices
comprising these circuits (Figure 15-1). Smaller device dimensions reduce the size of the circuits
and therefore lead to a reduction of overall die area (the actual area partitioned on a silicon wafer
corresponding to an individual integrated circuit), thus allowing for more transistors on a single die
without negatively impacting the cost of manufacturing. However, getting more functions into each
circuit generally leads to larger die size, and that requires larger wafers.

Figure 15-1. Growth of the density of microprocessors according to

Moore's Law. The vertical axis is numbers of transistors per chip.
(Reprinted by permission of the Intel Corporation; copyright Intel
Corporation.)

[View full size image]

The workhorse of the semiconductor industry over the past three decades has been the metal oxide
semiconductor field effect transistor (MOSFET). Its basic structure is comprised of two conducting
regions (a source and a drain) separated by an insulating (oxide) gate over a channel that can be
turned on or off; this gate is a simple switch and constitutes the basic building block of computer
architectures based on two-state logic.

The critical scale is the gate length, which corresponds to the distance between the source and the
drain. As this length is reduced, all the corresponding dimensions of the device decrease in size or
scale, according to well-defined scaling rules. In addition to reducing the area per transistor on the
die, scaling down the gate length reduces the time it takes to move a charge (electrons) from the
source to the drain, increasing the switching speed of the transistor and hence the clock speed at
which logic circuits operate.

Successive generations of MOS transistor technologies are characterized in terms of this critical
dimension, which, for present state-of-the-art commercial production, has already entered the
nanometer (nm) scale dimension regime. Figure 15-2 shows scanning electron microscope
photographs of Intel's current production transistors at the so-called 65-nm node, and successively
shorter-gate-length devices realized in the research laboratory, down to 15nm. Clearly, present-day
transistor technology is nanotechnology.

Figure 15-2. Scaling of successive generations of MOSFETs into the

nanoscale regime. (Reprinted by permission of the Intel Corporation;
copyright Intel Corporation.)

[View full size image]

As semiconductor feature sizes shrink into the nanometer-scale regime, device behavior becomes
increasingly problematic as new physical phenomena at short dimensions occur and as limitations in
material properties are reached. Clearly, as we scale below 15-nm gate length, we eventually
approach dimensions for which the channel is only a few silicon (Si) atoms long, at which point (or
even much sooner) conventional MOSFET devices cannot scale further, and a saturation of Moore's
Law will occur.

In fact, such a limit is already approaching in terms of the necessary silicon dioxide gate oxide
thickness separating the gate metal from the channel, which, for 25-nm gate length technology,
must be thinner than 1nm, as predicted by the International Technology Roadmap of
Semiconductors (ITRS).[1] Basically, this reduction in thickness is required in order to maintain
acceptable drive current, and to maintain charge control of the channel, by locating the gate as close
to the channel as possible. This is because of the lateral length scale. One nanometer is only a few
atomic layers thick, and for such a thin dielectric, leakage currents through the gate degrade
performance and increase power dissipation. Industry is addressing this challenge by developing
new dielectric materials with high permittivity, so that the effective gate capacitance is increased for
a much thicker dielectric, giving better leakage performance.

Another issue leading to a saturation of Moore's Law is manufacturability as dimensions become

smaller. As a semiconductor device becomes smaller, its output characteristics are increasingly
sensitive to manufacturing and material imperfections. For example, impurity atoms with a valence
higher or lower than Si must be introduced into the Si lattice at dilute concentrations to create free
charges for carrying current; otherwise, the Si would be insulating. This process is referred to as
"doping" the semiconductor, and in ultrasmall devices, the random position of dopant atoms in the
device may cause dramatic changes in the current-voltage characteristics from device to device in
very small structures. In a large device with many dopant atoms, this effect averages out, but in
very small structures, the potential landscape seen by electrons traversing the source to drain varies
widely from device to device because of the particular location of the dopant atoms.

Another source of device-to-device output characteristic variance is random variations in linewidths

associated with lithography. Again, in very small devices, such process fluctuations may dominate
the characteristics of a particular device. This sensitivity of nanoscale devices to process fluctuations
means that not only manufacturing but also circuit and architecture design techniques must be
developed to anticipate large device-to-device variations and even failures (fault-tolerant design).

To meet the challenges of shrinking gate lengths further into the nanometer-scale regimeincreasing
device performance and still maintaining control of charge in the channel with the gateindustry is
moving away from the "classic" planar, bulk Si MOSFET design used during the past two decades. To
increase performance for a given gate length, there is an increased trend toward alternative
materials grown in the active regions of the device, such as strained Si, alloys of Si and Ge, and
even compound semiconductors. Such alternatives to bulk Si increase performance through superior
transport properties and hence faster switching.

To maintain charge as gate lengths shrink, research and production device structures are becoming
increasingly nonclassical and three-dimensional rather than planar. These designs use Si on
insulator technology (where a buried layer of oxide is introduced to isolate the device from the Si
substrate), dual-gate and wraparound gates (in which the gate is above, below, and around the
sides of the channel rather than simply on top), and nanowire shaped channels.

Figure 15-3 illustrates one such technology, the so-called FinFET (due to the fin-shaped gate). The
structure is 3-D, and the channel resembles a 1-D wire with nanometer-scale dimensions
(nanowire). This wirelike nature of the channel becomes important in the consideration of future
technologies based on self-organized 1-D conductors such as carbon nanotubes (CNTs) and self-
assembled semiconductor nanowires.

Figure 15-3. Nonclassical device structures. At left is a schematic of a

FinFET; at right is an SEM photo of a multileg FinFET structure. (Reprinted
by permission of the Intel Corporation; copyright Intel Corporation.)

[View full size image]

Beyond these material and manufacturing issues, there are fundamental limits as device dimensions
shrink. One is that quantum mechanics starts to play a role at small dimensions, in terms of the
wavelike properties of charge carriers such as electrons. Effects such as quantization of motion,
interference effects, and tunneling are all physical effects that modify the performance of devices at
small dimensions.

Another limit is the discrete nature of charge. In small structures, charge can no longer be treated
as a continuous fluid; rather, the number of charges is finite and small, leading to so-called single-
electron charging effects. For very small structures, the change in energy and potential (voltage)
due to one charge tunneling or otherwise moving from one conductor to another gives rise to a
noticeable fluctuation in voltage. This sensitivity is because the capacitance (that is, the
proportionality between charge and voltage, D Q = CDV) is a geometrical quantity that reduces as
the structure size shrinks. If C is sufficiently small (10-17F and less), then the change in voltage, DV,
for a single electron moving from one side to the other (DQ = 1.6 x 10-19C) may be larger than the
thermal voltage, 25mV at room temperature.

All these effects can lead to noticeable degradation of the performance of classical and nonclassical
MOSFETs, eventually leading to the end of the road map for scaling. Beyond that, there has been
extensive work over the past decade related to nanoelectronic or quantum-scale devices, which
actually use quantum mechanical and single-electron effects and operate on very different principles
from conventional MOSFET devices. These alternatives may allow continued scaling beyond the end
of the current scaling road map, as discussed later.

Future Nanoelectronic Device Technologies

As discussed earlier, as semiconductor device dimensions shrink to the nanoscale and beyond, the
physics governing device behavior becomes complicated because of several factors. For large-
dimension devices, the picture of macroscopic current flow in a device is analogous to fluid flow, in
which charges and charge flow (current) appear continuous, and their motion is described by the
same classical hydrodynamic equations used in the field of fluid mechanics. As we shrink to small
dimensions, itís easy to see that at some level, charge is no longer continuous and that the motion
of individual electrons becomes important in the behavior of nanoscale devices.

On the one hand, this sensitivity to individual unwanted charges threatens the reliability and
reproducibility of nanoscale CMOS devices. On the other hand, the ability to control the state of
individual electrons, and correspondingly to represent and store information, represents the ultimate
limit of nanoscale device technology, which is the basis of so-called single-electron transistors and
memory discussed later.

Another way in which the electronic behavior of small structures differs from that of macroscale
systems is that electrons are governed by the laws of quantum mechanics, where matter exhibits
both wavelike and particlelike behavior. One important length scale is the so-called De Broglie
wavelength of an electron, which is the characteristic wavelength of matter waves in the quantum
mechanics picture. The interaction of electrons with structures on this length scale resembles optics
rather than classical dynamics, with effects such as diffraction, interference, quantization of motion,
and tunneling, all of which lead to marked changes from the classical fluid picture of charge
transport. Such wavelike behavior can persist over long dimensions, depending on the so-called
phase coherence length, that is, the length over which an electron "wave" remains coherent.

Quantum computing is a new paradigm that explicitly depends on maintaining phase coherence, and
using the potential information stored in the phase of a quantum mechanical two-state system, to
exponentially extend the processing power compared with a simple binary logic system based on the
same two states. Coherence is destroyed by the interaction of the electron with its energy-
dissipative environment, primarily the vibrational motion of the host material in inorganic and
organic structures. Because this vibrational motion increases with increasing temperature and
thereby reduces the coherence length, quantum mechanical effects tend to wash out at room
temperature. At room temperature, phase coherence lengths in Si, for example, are only a few tens
of nanometers.

Generally, with regard to the behavior of conventional Si MOSFETs, single-charge and quantum
mechanical effects adversely affect performance, creating barriers to further scaling at some future
limit that is rapidly being approached, as discussed earlier. Beyond field effect transistors, however,
there have been numerous proposals and demonstrations of device functionality and circuits based
on single-electron and quantum mechanical effects. These include quantum interference, negative
resistance, and single-electron devices, which are realized in metals, semiconductors, nanowires,
carbon nanotubes, and molecular systems, as discussed in more detail later.

As dimensions become shorter than the phase-coherence length of electrons, the quantum
mechanical wave nature of electrons becomes increasingly apparent, leading to phenomena such as
interference, tunneling, and quantization of energy and momentum as discussed earlier. In fact, as
was elegantly pointed out by IBM physicist Rolf Landauer, for a one-dimensional conductor such as a
nanowire, the system is very analogous to an electromagnetic waveguide with "modes," each
supporting a conductance less than or equal to a fundamental constant 2e2/h.

Such quantization of conductance was first demonstrated at Cambridge University and Delft
University in the late 1980s, in specially fabricated, split-gate field effect transistors at low
temperatures, where the split gate formed a one-dimensional channel in a field effect device.
However, manifestations of quantized conductance, such as universal conductance fluctuations,
noise, and the quantum Hall effect, appear in many transport phenomena. Many schemes were
proposed for quantum interference devices based on analogies to passive microwave structures,
such as directional couplers and even coupled waveguides for quantum computing. Promising results
have been obtained on ballistic Y-branch structures by the research group in Lund, Sweden, where
nonlinear switching behavior and elementary logic functions have been demonstrated, even at room
temperature.

Most attempts at realizing quantum coherent devices suffer from the same problems as scaling of
conventional nanoscale MOSFETs: the difficulty in controlling the desired waveguide behavior in the
presence of unintentional disorder. This disorder can arise from the discrete impurity effects
discussed earlier, as well as the difficulty of process control at true nanometerscale dimensions. A
further fundamental limit to devices based on the quantum mechanical nature of matter at the
nanoscale is the phase coherence length and phase coherence time for maintaining a quantum
coherent state. As mentioned earlier, this time and length scale is typically quite short in Si at room
temperature.

In recent years, scientists have been attempting to exploit another purely quantum mechanical
aspect of charge particles for nanodevice applications: that of electron spin. "Spin" refers to the
intrinsic magnetic moment associated with elementary particles such as electrons, an effect that can
manifest itself only through measurement relative to some particular reference frame in one of two
states: spin-up or spin-down. This twentieth-century discovery has no classical analog, although the
name itself implies an origin of magnetic moment due to a charge particle spinning around its own
axis to generate a magnetic field.

In terms of the practical manifestation of spin, the ferromagnetic behavior of materials used in, for
example, magnetic memory (a multibillion-dollar industry) is intrinsically associated with the
interaction of spin states to form an ordered magnetic system. For nanoscale devices, the fact that
there are two distinct states associated with spin has attracted researchers to the ability to encode
information, either as simply binary information or as a prototypical "qubit" for quantum information
storage. One of the main advantages of controlling the quantum state of spin is that spin is much
more robust at preserving phase coherence compared with the ordinary quantum mechanical phase
of an electron discussed earlier in connection with quantum interference-type devices. Typical spin
coherence times in semiconductors can vary from nanoseconds to milliseconds, something that
provides much more opportunity to realize quantum coherent devices for applications such as
quantum computing.
Previously we mentioned the role of individual random charges as an undesirable element in the
reproducibility of nanoscale FETs due to device-to-device variations. However, the discrete rather
than continuous nature of charge of individual electrons at the nanolevel, and control of the motion
of such electrons, is the basis of a great deal of research in single-electron devices and circuits. The
understanding of single-electron behavior is most easily provided in terms of the capacitance, C, of a
small tunnel junction (that is, two small conductors separated by a very thin insulator).

As mentioned earlier, capacitance is the proportionality constant relating the voltage difference
between a pair of conductors to the net charge (positive on one, negative on the other) on the
conductors; the simplest example is a parallel plate capacitor formed by two plates separated by an
insulator. If a single electron tunnels across the thin junction from one side to the other, the change
in net charge on the conductors results in a corresponding change in electrostatic energy, e2/C.
When physical dimensions are sufficiently small, the capacitance (which is primarily a geometrical)
is correspondingly small, so that the change in energy may be greater than the thermal energy,
3/2kT, resulting in the possibility of a "Coulomb blockade," or suppression of conductance due to the
necessity to overcome this electrostatic voltage barrier. This Coulomb blockade effect allows the
experimental control of electrons to tunnel one by one across a junction in response to a separate
control gate, which can be used to lower this voltage barrier.

Figure 15-4 illustrates the operation of a so-called single-electron transistor, consisting of two tunnel
junctions connecting to a conducting "island" or "quantum dot," to which a second voltage source
Vg, is connected through a separate gate capacitor, Cg. As the gate voltage is increased, the
Coulomb blockade is lifted when integer numbers of electrons tunnel through the structure, hence
allowing control of electron motion one by one. Single-electron transistors, turnstiles, pumps,
elementary logic circuits, and single-electron memories have been demonstrated experimentally,
functioning even up to room temperature. Room-temperature operation is important for practical
applications in that it does not require special cooling or cryogenic technology, which would limit the
applicability for, for example, portable electronics. As in the case of quantum interference devices,
the technological difficulties arise from fluctuations due to random charges and other sources of
manufacturing variation, as well as the difficulty in realizing lithographically defined structures with
sufficiently small dimensions to have single-electron charging energies larger than the thermal
energy, 25meV@300K.

Figure 15-4. Schematic representation of a single-electron transistor

(SET) consisting of two tunnel junctions connecting a conducting island,
biased by drain-source voltage and controlled by gate voltage, Vg . During
off resonance, electrons see a "gap" in energy, which prevents tunneling.
Applying a voltage to the island through the gate allows electrons to
tunnel one at a time, giving rise to a peak in conductivity.

[View full size image]

There has been rapid progress in realizing functional nanoscale electronic devices based on self-
assembled structures such as semiconductor nanowires (NWs) and carbon nanotubes.
Semiconductor nanowires have been studied during the past decade in terms of their transport
properties, and for nanodevice applications such as resonant tunneling diodes, single-electron
transistors, and field effect structures.

Recently, there has been a dramatic increase in interest in NWs because of the demonstration of
directed self-assembly of NWs via epitaxial growth. Figure 15-5 shows a scanning electron
micrograph of such structures grown using vapor-liquid-solid epitaxy, where the dimensions of the
nanowires are less than 10nm. Such semiconductor NWs can be elemental (Si,Ge) or III-V
semiconductors, where it has been demonstrated that such wires may be controllably doped during
growth, and abrupt compositional changes forming high-quality -D heterojunctions can be achieved.
Groups such as those at Harvard and Lund, Sweden, have demonstrated nanowire FETs, bipolar
devices, and complementary inverters synthesized using self-assembly. The ability to controllably
fabricate heterostructure nanowires has led to demonstration of nanoelectronic devices such as
resonant tunneling diodes and single-electron transistors. The scalability of arrays of such nanowires
to circuits and architectures has also begun to be addressed, although the primary difficulty is in the
inability to grow and orient NWs with desired location and direction.

Figure 15-5. Scanning electron micrograph of self-assembled Si

nanowires grown by vapor-liquid-solid epitaxy (after T. Picraux et al.).
Carbon nanotubes are currently the focus of considerable attention because of the many remarkable
properties of this new structural state of carbon. Figure 15-6 shows a schematic of a CNT that is
composed of carbon atoms arranged in a stable tube configuration. It is a highly stable state of
matter, very similar in concept to fullerenes like C60 (buckyballs). The structure can be envisioned
as a graphite sheet (where the carbon atoms form hexagonal rings), which is rolled in a tube a few
nanometers in diameter, as shown in Figure 15-6a. In rolling the tube and joining itself, the carbon
rings forming the graphite structure can align in different offset configurations, characterized by
their chirality. Depending on the chirality, CNTs can be metallic, semiconducting, or insulating, all
the components required in conventional semiconductor IC technology (interconnects, transistors,
and dielectrics). Field effect transistors have been fabricated from CNTs, and basic logic functions
demonstrated by researchers at IBM and other research laboratories, as shown in Figure 15-6b. The
extreme sensitivity of the conductivity of the nanotube to an attached atom or molecule to the wall
or tip of the nanotube, also makes CNTs very attractive as sensors, the subject of considerable
current research. The primary challenge faced in the evolution of this technology is the directed
growth of CNTs with the desired chirality, and positioning on a semiconductor surface, suitable for
large-scale manufacturing.

Figure 15-6. (a) Different states of carbon, including diamond, graphite,

C60, and a carbon nanotube (right) (from Richard Smalley's image
gallery, http://smalley.rice.edu/smalley.cfm); (b) carbon nanotube
inverter formed from p- and n-channel FETs (from IBM, with permission).

[View full size image]

Perhaps the ultimate limit of size scaling are devices comprised of a small number of molecules,
forming the basis of electronic systems realized with molecular devices, or molecular electronics
(moltronics). Figure 15-7 shows a schematic diagram of a nanoscale contact to a molecular device,
through which current is passed. Here the molecular device is an organic chain to which different
side groups or molecules are attached to realize a desired functionality. The molecular chain
structure shown in the lower half of the figure, studied by Mark Reed (Yale) and James Tour (Rice),
showed "negative differential conductance (NDC)" in the current voltage characteristics, that is, a
decreasing current with increasing voltage. From a circuit standpoint, NDC appears as a negative
resistance, which leads to signal amplification and the possibility of bistable behavior because the
circuit does not like to reside in the regime, which is the basis for elementary switching devices.
Elementary molecular electronic architectures have been demonstrated by HP Research Laboratories
using crossbar-type logic.

Figure 15-7. A molecular "junction" (left), and the corresponding

molecular device contacted by external leads.

A very attractive feature of molecular systems is the possibility of bottom-up or self-assembly of

functional systems. Such templated self-assembly is of course the basis of biological systems, which
have exquisite complexity and functionality as well as self-replication and self-repair. Such
"biomimetic" approaches to molecular circuits would represent an inexpensive alternative to the
exponentially increasing cost of top-down nanofabrication, which is currently driving fab costs into
the billions of dollars. However, at present there is no clearcut manufacturing approach to self-
assembly in the near term.

Another difficulty in understanding and using molecular electronic structures is the need to separate
the intrinsic behavior of a molecular device from the contacts themselves. In conventional devices,
contacts are nearly ideal, providing a connection to the other devices and the external world through
interconnects, and not affecting the intrinsic performance of devices except through well-controlled
parasitic contact resistances. As the number of devices per chip scales exponentially, the number of
contacts and interconnects per device increases even faster, and from an architecture standpoint,
system performance is increasingly dominated by the interconnects and not the devices themselves.
In a nanoscale devices, the contacts may in fact dominate the performance of the device, and at a
minimum they are an integral part of the device. This problem is particularly evident in molecular
electronic devices, as the schematic of Figure 15-7 indicates (where the contact is much larger than
the device). This challenge remains one of the many issues to be solved in evolving molecular
electronics in the future.
Reference
1. International Technology Roadmap of Semiconductors, http://public.itrs.net/.
Photonics
Axel Scherer

Photonics has recently become an attractive alternative to electronics for communications and
information processing. Devices that use photons rather than electrons as information carriers can
benefit from higher speeds and reduced cross talk between optical channels. Miniaturization of
compact optical components such as resonators, waveguides, and interferometers has become very
desirable. At the same time, microfabrication has emerged as a powerful technology that enables
the construction of sub-100nm structures in a reproducible and controllable manner. The same
technology that was driven by the continuing desire to miniaturize electronic components on silicon
microchips has now evolved to a precision that allows us to control the flow of photons.

Fully optical chips would deliver the ultimate in speed and would benefit from lower heat and fewer
power problems. A significant bottleneck in current networks is the switching from optical to
electrical media for processing and routing, and then back from electrical to optical. If this
bottleneck can be reworked to smoothly avoid the OEO transformation, tremendous gains can be
attained. The need for data transfer and routing with high band-width is also compelling for many
military applications, where optical solutions to high-frequency signal processing and routing offer
lower power dissipation and higher bandwidth, which produce more robust and compact systems.
Size, weight, and immunity to radio-frequency interference are particularly important for mobile
communications, sensors, and radar systems.

Recent technological advances in silicon optoelectronics have highlighted the need for inexpensive
multiwavelength light sources on silicon photonics. The use of silicon CMOS electronics for the
multiplexing, control, and routing of many parallel optical signal channels on a silicon chip may have
been an inevitable outcome of the lack of adequate electronic interconnection solutions for next-
generation microprocessors. Silicon on insulator (SOI) waveguiding optics may produce much less
expensive alternatives to more conventional telecommunications and data communications
platforms such as GaAs, InP, and Lithium Niobate (LiNbO5).

The most important disadvantage of using silicon optoelectronics has been the lack of sufficient gain
for signal amplification and efficient on-chip light generation. The vision of an on-chip silicon laser
has so far been elusive, although much time and effort have already been invested in various
promising silicon light-amplification strategies, such as porous silicon and erbiumdoped silicon
waveguides.

Silicon nanophotonic components are so small that components for 1,000-wavelength division
multiplexing channels could easily fit in a corner of an electronic chip. Optical nanodevices can now
be constructed from the standard electronic semiconductor materials, such as silicon on insulator
(SOI), Gallium Arsenide (GaAs), and Indium Phosphide (InP). By combining the need for integrated
photonics with the capabilities offered by high-resolution microfabrication, the field of nanophotonics
has emerged. Optical devices that have traditionally been constructed of glass and lithium niobate
can now be scaled down in silicon, GaAs, or InP. Ultrasmall optical systems can also be integrated,
thus realizing for the first time the dream of large-scale, multifunctional, all-optical chips for
information processing. Moreover, because nanophotonics devices are constructed from standard
electronic materials, such devices can be integrated side by side with electronic components,
enabling the construction of hybrid systems of higher complexity.

The emergence of silicon nanophotonic technology in SOI wafers has made a profusion of optical
components available on chip and essentially at zero marginal cost. These components include
resonators, filters, waveguides, modulators, and (with the availability of germanium) detectors. To
these must be added the full functionality of CMOS electronic technology, particularly high-quality
transistors.

Thus there would be a great advantage in a mode-locked source that provides steady output at
many frequencies simultaneously. In passive optical filtering and routing chips, waveguide losses,
insertion losses, and resonator losses all contribute to a deterioration of the input signal. Thus, it is
desirable to include gain in such chips so that the routed signal is amplified before coupling out of
the routing switch. Good-quality mode locking requires high-Q cavities and a good optical
modulator, both functions that are now readily fabricated on an SOI silicon chip. Thus many of the
ingredients for highly dense microoptical circuits and for an internal mode-locked light source in
silicon SOI are already availableexcept for optical gain. A goal, then, is the large-scale integration of
multiwavelength sources within a single integrated chip.

Recently, optical coupling to disk and ring resonators has become an extremely effective way of
fabricating add/drop filters. Much of the work has been demonstrated in glass waveguides, both
monolithically and through micromechanical coupling of microspheres close to thinned-down optical
fibers. An 8x8 crossbar router was recently demonstrated by Little et al. in a planar waveguide
geometry in which high-index glass disks were aligned above the waveguide layers. Very high Qs
and correspondingly narrow spectral filters have been demonstrated.

The minimum feature size required to couple the resonator disk to the waveguide, approximately
150500nm, can already be obtained with high-resolution lithography, UV lithography, and electron
beam lithography. Other lithography techniques, such as embossing, imprinting, and molding, will
undoubtedly follow for the lower-cost development of high-resolution single-level lithography.

The photonic crystal (PC) is one of the platforms that can enable the miniaturization of photonic
devices and their large-scale integration. These microfabricated periodic nanostructures can be
designed to form frequency bands (photonic band gaps) within which the propagation of
electromagnetic waves is forbidden, irrespective of the propagation direction. One of the most
attractive planar photonic crystal devices is a compact and efficient nanocavity. This is due to the
extraordinary feature of Planar Photonic Crystals (PPCs) to localize high electromagnetic fields into
very small volumes for a long period of time. Moreover, PC cavities can be engineered to
concentrate light in the air, and thus they are natural candidates for the investigation of interaction
between light and matter on a nanoscale level. Such nanoscale optical resonators are of interest for
a number of applications, of both practical and scientific importance.

Ultrasmall quantities of biochemical reagents can be placed in the air region where field intensity is
the strongest, and their (strong) influence on the optical signature of the resonator can be
monitored. This can lead to realization of integrated spectroscopy systems (for example, on-chip
Raman spectroscopy). PC nanocavities can have high Q factors (>10,000) and can be highly
integrated (less than 5mm apart), something that makes them promising candidates for realization
of channel drop filters in dense wavelength-division multiplex systems.
Conclusion
The microelectronics industry, and with it a portion of the U.S. economy, faces a critical hurdle as
the physical limits of CMOS technology draw ever closer. Moore's Law has been critical to its rapid
growth as both a metronome and a road map, but an S-curve transition to molecular electronics
may create a plateau more than a decade from now in the steady improvement seen over the past
decades. During the transition, technologies like photonics and new, fault-tolerant architectures will
still increase computing efficiencies, although likely not at a pace commensurate with Moore's Law.
Chapter 16. Drug Delivery
Jianjun Cheng and Suzie Hwang Pun

Therapeutic drugs are usually delivered in bolus doses, either orally or by injection. These
administrations result in initial blood concentrations that are higher than required levels, followed by
a decrease to subtherapeutic levels due to drug degradation and excretion. Therefore, drugs must
be given frequently to maintain therapeutic drug concentrations (Figure 16-1). In the 1970s,
researchers introduced the concept of controlled drug delivery by using carriers to release drugs in a
sustained manner. In the ideal case, drugs are gradually released from a depot so that the drug
concentration is maintained at an effective level over a long period. An example of one such success
is Gliadel, the first FDA-approved biopolymer drug-delivery system for treatment of brain cancer.
Gliadel wafers are implanted into the brain after tumor resection. There, the wafers locally release
carmustine (a chemotherapeutic drug) for several months.

Figure 16-1. Schematic expression of plasma drug level of bolus dose and
controlled release.

Many other promising drugs never make it to clinical trials because of inherent pharmacological
drawbacks. Low-molecular-weight drugs, such as most chemotherapy drugs, are usually insoluble
and highly toxic. Protein and nucleic acid drugs usually have poor stability in physiological
conditions. It is therefore essential for these drugs to be protected en route to their target disease
sites in the body. Drug-delivery systems may rescue potential drug candidates by increasing
solubility and stability.
Drug-delivery technologies are developed to improve the safety and efficacy of drugs, to ensure
better patient compliance, and to improve the shelf life and stability of therapeutic products.
Controlled drug release involves the combination of a biocompatible material or device with a drug
to be delivered in a way that the drug can be delivered to and released at diseased sites in a
designed manner.

The major routes of drug administration are oral, inhalation, injection, and transdermal delivery.
The most well-known route is oral drug delivery, which accounted for about 50 percent of the
market as of 2003. The other routes of administrationinhalation, transdermal, injection and
implantation, and nasal deliveryaccount for the remaining market share at 19 percent, 12 percent,
10 percent, and 7 percent, respectively. In the past 30 years, the field of drug delivery has been
undergoing rapid development and has attracted attention from both academia and pharmaceutical
industries. According to a recent report, the U.S. market alone for drug delivery is estimated at
$43.7 billion in 2003 and is expected to grow more than 11 percent annually in the next five
years.[1]
Nanotechnology in Drug Delivery
Nanotechnology, a multidisciplinary area of science involved in the miniaturization and use of
materials or devices on the nanometer scale, has been undergoing explosive growth and has
become a principal research interest. In the past ten years, nanotechnology has already
demonstrated great impact in almost every frontier area of drug delivery by extending and
improving traditional delivery techniques.

One of the earliest applications of nanotechnology in drug delivery was conceived in the 1970s,
when nanoparticles were designed as carriers of anti-cancer drugs. Since then, many nanoparticle
systems have been developed for use in drug delivery. Biopolymers have been intensively studied
for application in nanoparticulate drug delivery.

Delivery vehicles involved with polymeric systems include polymerdrug conjugates, polymeric
micelles, polymeric nanospheres and nanocapsules, and polyplexes. Inorganic and metallic materials
have also been used in preparation of nanoparticles for drug delivery. Recently nano- and
microfabrication technologies have been applied for drug delivery, resulting in novel devices such as
biochips and microneedles. With the explosive growth in the development of new methods of
nanofabrication, numerous emerging nanosystems will inevitably change the field of drug delivery in
the coming decades.

Nanoparticles for Drug Delivery

Nanoparticle-based delivery vehicles improve drug efficacy by modulating drug pharmocokinetics
and biodistribution. Small-molecule drugs are rapidly eliminated from the circulation by the kidneys.
Injectable nanoparticledelivery vehicles, typically ranging from 5nm to 200nm in size, substantially
increase circulation (particles >5nm avoid kidney clearance) while minimizing removal by cells that
police the blood for foreign particles (macrophages have less propensity for particles <200nm in
size). Oral delivery is currently the most preferred method of drug administration because of its cost
effectiveness and ease of use.

The market for oral drug-delivery systems has been growing at a rate of 8.6 percent per year since
2000. A major area of research in oral delivery is in delivery materials for protein drugs. Because
particle permeability across the intestinal wall is inversely proportional to size, nanoparticles used
for oral delivery offer obvious advantages. The interest in nanoparticle-based drug delivery for other
administration routes is also growing. The following sections focus on polymer, lipid, and inorganic
or metallic nanoparticles that are <500nm in size.

Polymer Conjugates (Polymer-Drug Chemical Linkage)

Polymer-drug conjugates (520nm) represent the smallest nanoparticulate delivery vehicles. The
polymers used for such purposes are usually highly water-soluble and include synthetic polymers
(for example, poly(ethylene glycol) (PEG)) and natural polymers (such as dextran). When
hydrophobic small molecules are attached to these polymers, their solubilities in water can be
substantially improved. For example, a cyclodextrin-based polymer developed at Insert Therapeutics
increases the solubility of camptothecin, an insoluble chemotherapy drug, by three orders of
magnitude.
Small molecules or proteins conjugated to these polymer delivery vehicles can achieve extended
retention in circulation because of reduced kidney clearance. PEG-L-asparaginase (ONCASPAR;
Enzon), an FDA-approved PEGylated protein drug as a treatment for acute lymphoblastic leukemia,
can be administered every two weeks, instead of the two to three times per week required for the
non-PEGylated enzyme. Other PEGylated systems approved by the FDA include PEGadenosine
deaminase (ADAGEN; Enzon) as a treatment for X-linked severe combined immunogenicity
syndrome and PEGinterferon (PEGASYS; Roche and PEGINTRON; Schering-Plough) as treatments for
hepatitis C.[2] Many polymer-small molecule and polymer-protein conjugates are currently in clinical
trials. A promising nanoparticle drug-delivery systema proprietary, albumin-bound paclitaxel
conjugate codeveloped by American Pharmaceutical Partners and American BioSciencehas shown
excellent antitumor efficacy in Phase III clinical trial for the treatment of metastatic breast cancer.

One group of polymers that has attracted enthusiasm recently are dendrimers (Figure 16-2). They
are monodispersed, symmetric, globular-shaped macromolecules comprising a series of branches
around an inner core. Dendrimers are potential nanometer-sized systems for drug delivery, and
their sizes can be controlled simply by adjusting the generation of dendritic branches.

Figure 16-2. Schematic drawing of dendrimer for application in drug

delivery and targeting. (Reprinted with permission from
http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=153,
Thiagarajan Sakthivel, Ph.D., and Alexander T. Florence, Ph.D., D.Sc.,
"Dendrimers & Dendrons: Facets of Pharmaceutical Nanotechnology.")

Polymer Micelles (Polymer Surfactant-Drug Self-Assembly)

Amphiphilic block copolymerspolymers that contain both hydrophilic and hydrophobic regionstend to
self-assemble in aqueous solution into spherical structures called micelles. Polymeric micelles
typically have a hydrophilic corona and a hydrophobic shell. When used as drug-delivery agents,
polymeric micelles are most commonly formulated to include hydrophobic drugs (for example,
doxorubicin, cisplatin, amphotericin B) in the core, leaving the outer hydrophilic layer to form a
stable dispersion in aqueous media.

The stable structure of the polymeric micelles prevents rapid dissociation (release of drug) in vivo.
Polymer micelles typically range from 60 to 100nm, with fairly narrow size distributions. The
micellar corona can be further modified with targeting moieties (for example, antibodies) to deliver
drugs to desired sites. Development of micellar drug-delivery vehicles is in an early stage, with most
formulations still in preclinical studies.[3]

Polymer Nanoparticles (Drug Dispersion or Encapsulation in Polymer Aggregates)

Nanoparticles are solid, small colloidal particles made of polymers having diameters from 50nm to
several hundred nanometers. Depending on the method of preparation, two types of drug-containing
nanoparticles exist: nanospheres (a matrix system in which drugs are uniformly distributed) or
nanocapsules (a reservoir system in which drugs are confined to the core of the particles and are
surrounded by polymer membranes). Many of these systems are made of biodegradable polymers,
such as poly(ortho ester) (Figure 16-3). Poly(ortho ester) nanoparticles release drugs with tunable
release rates, depending on solution pH. Drugs encapsulated in nanoparticles have increased
stability against enzymatic and chemical degradation, an important advantage for unstable drugs
such as proteins and nucleic acids.[4]

Figure 16-3. Scanning electron microscopy image of poly(ortho ester)

nano- and microspheres. Scale bars: 5mm. (Reprinted with permission
from Chun Wang, Qing Ge, David Ting, David Nguyen, Hui-Rong Shen,
Jianzhu Chen, Herman N. Eisen, Jorge Heller, Robert Langer, and David
Putnam, "Molecularly engineered poly(ortho ester) microspheres for
enhanced delivery of DNA vaccines," Nature Materials 3 (2004): 190196.)

Nanoparticles have been tested for the delivery of all types of drugs (small molecules, proteins, and
nucleic acids) in almost all types of administration routes (such as inhalation, oral, and injection).
Although many of these approaches are still in an early stage of their development, some of them
have already shown great potential. An example is Dr. Edith Mathiowitz's (Brown University)
poly(fumaric-co-sebacic) anhydride nanoparticles for the oral delivery of insulin, a promising way to
achieve oral protein delivery.[5]
Polyplexes (Polymer-Nucleic Acids Complex through Charge Interaction)

In nonviral gene therapy, plasmid DNA is introduced into cells to express therapeutic proteins,
whereas in oligonucleotide therapy, oligonucleotides (such as ribozymes and DNAzymes) and small,
interfering RNA (siRNA) are used to suppress disease-associated expression. However, the cell
membrane is a natural barrier for these genetic materials. For therapeutic nucleic acids to be
successfully delivered into the cell, they must be complexed with materials that facilitate cellular
uptake.

Polyplexes, a group of nanoparticulates formed by charge interaction between positively charged

polymers and negatively charged nucleic acids, are developed for such purposes. Polyplexes range in
size from 40nm to 200nm (Figure 16-4). RNA interference (RNAi) is an emerging and promising
approach for oligonucleotide therapy, and there is currently active research in developing materials
for siRNA delivery.

Figure 16-4. Cyclodextrin polycation-based polyplexes developed by Davis

and coworkers (California Institute of Technology).[6] These materials are
being investigated for gene therapy applications at Insert Therapeutics.
Bar is 100nm. (Reprinted with permission from S. J. Hwang, N. C. Bellocq,
and M. E. Davis, "Effects of Structure of beta-cyclodextrin-containing
Polymers on Gene Delivery," Bioconjugate Chemistry 12(2) (2001):
280290.)

Liposomes

Liposomesnano-sized particles (25 to several hundred nanometers) made from phospholipids and
cholesterolsare sometimes referred to as "fat bubbles." Liposomes consist of bilayers of lipids that
can encapsulate drugs. Their properties for use as delivery vehicles are closely associated with lipid
composition, liposomal size, and fabrication methods. For example, saturated phospholipids with
long hydrophobic chains usually form a rigid, impermeable bilayer structure, whereas the
unsaturated phosphatidylcholine-based lipid layers are much more permeable and less stable.

Liposomal drug delivery has achieved great success in the past decade. Several liposome-based
drug-delivery systems have been approved for clinical use. AmBisome (lipid-based delivery of
amphotericin B, Fujisawa Healthcare, Inc., and Gilead Science) was approved for the treatment of
cryptococcal meningitis in HIV-infected patients. The sales of AmBisome were nearly $200 million in
2003 (an increase of 7 percent from 2002). Doxil (Alza) was approved in 1999 for the treatment of
refractory ovarian cancer and is the first and only liposomal cytotoxic agent approved to treat a solid
tumor. The sales of Doxil reached $80 million in 2000.

Inorganic and Metallic Nanoparticles

Delivery of drugs using new inorganic and metallic nano-sized vectors are still in the proof-of-
concept of stage. One unique approach originates from C-60, a soccer ballshaped fullerene.[7]
Another interesting approach is to use magnetic nanoparticles to carry chemotherapeutic drugs to
cancer sites directed by an external magnetic field.

Very recently, other metal nanoparticles have been investigated as therapeutics and drug-delivery
systems. An example from Dr. Naomi Halas's research group (Rice University) is the nanoshell, a
new type of nanoparticle composed of a dielectric silica core coated with an ultrathin gold layer.[8]
Once the nanoshells penetrate tumor tissues, they can be activated for thermal therapy by taking
advantage of their ability to convert absorbed energy from the near-infrared region to heat.

Implantable Drug Delivery

Implantable drug delivery (IDD) devices offer more uniform drug release rates, lower required
doses, and localized delivery. These devices are generally composed of the drug of interest
distributed in a polymer matrix. Examples of marketed implantable drug-delivery formulations
include Norplant for birth control (Wyeth Laboratories), Gliadel for localized delivery of a
chemotherapeutic agent to the brain (Guilford Pharmaceuticals), and Viadur for slow release of
hormones for prostate cancer treatment (Bayer). The sales of Gliadel in 2003 were nearly $20
million (an increase of 32 percent from 2002), and annual Viadur sales are projected to reach $150
million.

Based on these trends, the demand for implantable drug-delivery systems is expected to exceed $2
billion by 2012. There is still room for improvement in IDD technology. Two emerging
nanotechnologies with applications in implantable drug delivery are nanoporous membranes and
biochips.

Nanoporous Membranes

Nanoporous membranes are microfabricated with well-defined pores (diameters in the tens of
nanometers). The membranes can be used to deliver small-molecule, peptide, or protein drugs
(Figure 16-5). One application under investigation involves encapsulation of pancreatic islet cells for
insulin delivery. The reproducible and uniform pore size precisely controls the material exchange
across nanoporous membranes: Nutrients for the cells and secreted insulin can pass through the
pores, but proteins and cells from the immune system that may attack the implanted islet cells are
restricted from entering the biocapsules due to their size.

Figure 16-5. Nanoporous membranes developed by Desai and colleagues

have nanometer-sized pores for controlled material exchange.[9]
(Reprinted with permission from S. L. Tao and T. A. Desai,
"Microfabricated drug delivery systems: From particles to pores,"
 Advanced Drug Delivery Reviews 55 (2003): 315328.)

Biochips

Drug release from IDD devices is not constant, and "burst" effects are still observed. In addition,
drug release cannot be controlled after implantation of IDD devices. Biochips have been developed
to precisely control the amount of drug released. Biochips are usually fabricated using silicon and
contain a number of mini-wells with precisely controlled sizes, each capable of holding a few
hundred nanoliters. These mini-wells are loaded with drugs and are covered with caps of thin metal
foils (usually gold) that are connected to the wires on the face of the chips (Figure 16-6).[10] When
electrical signal is applied, the current dissolves the metal covers and releases the drug. Biochips
can be implanted beneath the skin or into more specific areas such as the spinal cord or brain. The
electronics package outside the chips receives a radiofrequency instruction through a built-in
antenna to order a microprocessor to control the melting of metal foils. MicroCHIPS, Inc., is one of
the key companies developing this technology. Preclinical studies in animals using biochips
developed by MicroCHIPS, Inc., have shown good biocompatibility without significant side effects.
Once successfully developed, the biochip-based drug-delivery technology will allow for precisely
controlled drug administration to patients.

Figure 16-6. A biochip for controlled release developed by Robert Langer

and coworkers. (a) Schematic drawing of biochip; (b) a single reservoir.
(Reprinted with permission from J. T. Santini, M. J. Cima, and R. Langer,
"A controlled-release microchip," Nature 397, no. 6717 (Jan. 28, 1999):
335338.)
Transdermal Drug Delivery
The first transdermal patch technology for drug delivery was approved by the U.S. FDA in 1979. In
the past quarter-century, the U.S. market for transdermal patches has grown to more than $3 billion
per year. [11] Transdermal drug delivery is an attractive, noninvasive approach to drug
administration and is likely to improve the bioavailability of drugs by avoiding first-pass liver
metabolism and by maintaining more uniform drug plasma levels than bolus injections.

Despite these advantages, successful application of transdermal patches has been largely limited to
a handful of drugs, including nicotine (for smoking cessation), scopolamine (for motion sickness),
and hormone replacement. The human skin acts as a protective barrier to prevent entry of most
molecules. A lipid-rich layer in the skin repels water-soluble molecules, and large molecules are also
largely excluded because of their size. Thus, most major families of drugs (hydrophilic small
molecules, peptides, proteins, and nucleic acids) have not been successfully delivered by traditional
transdermal patch technology.

The permeability of the skin to hydrophilic or macromolecule drugs can be increased by physically
creating microscopic holes in the skin using arrays of microneedles. Ideally, the microneedles would
create pores to facilitate drug entry but would remain small enough to be painless. Although
technology was conceived several decades ago, the technology to prepare these systems was not
available. Microfabrication technology, developed by the microelectronics industry, recently has been
used to prepare these structures.
Prausnitz and colleagues first demonstrated this concept in 1998 by preparing silicon-based, solid
microneedles (Figure 16-7). Since then, many variations of these structures have been prepared and
tested with diverse drug families. Materials used to synthesize microneedles include glass, polymers,
metal, and silicon. The microneedles have been successfully applied to deliver small molecules,
oligonucleotides, plasmids, and proteins through the skin, increasing the permeability of these
molecules by several orders of magnitude. Application approaches include using solid microneedles
to pierce holes in the skin, followed by application of a traditional patch; coating solid microneedles
with drugs that are slowly released from the needles after skin penetration; and flowing drug
solutions through hollow microneedles.

Figure 16-7. Solid silicon microneedles with heights ~150nm can be

applied painlessly to enhance transdermal drug delivery. (Reprinted with
permission from M. R. Prausnitz, "Microneedles for transdermal drug
delivery," Advanced Drug Delivery Reviews 56, no. 5 (2004): 581587.)

A pilot human trial revealed that the microneedle arrays are indeed applied painlessly.[12]
Transdermal microneedle delivery was quickly adopted by the pharmaceutical and drug-delivery
industries; several companies are currently developing this technology for transdermal drug
administration. As this technology matures, it has the potential to quickly surpass the market
currently occupied by traditional patch formulations.
Future Trends in Drug Delivery
Nanotechnology has played a large role in advancing the drug-delivery field by enhancing existing
areas of small-molecule and protein delivery and by opening doors for delivery of new families of
nucleic acid-based drugs. The ability to control the properties of nanoscale materials will continue to
impact the pharmaceutical field by providing new technologies for improved drug delivery. We are
optimistic that these developments will lead to delivery vehicles with high target specificity and with
the ability to precisely control drug release.
References
1. O. Gorka, M. R. Hernández, A. Rodríguez-Gascón, A. Domínguez-Gil, and J. L. Pedraz, "Drug
delivery in biotechnology: Present and future," Current Opinion in Biotechnology 14 (2003):
659664.

2. R. Duncan, "The dawning era of polymer therapeutics," Nature Reviews Drug Discovery 2
(2003): 347.

3. T. Nakanishi, S, Fukushima, K. Okamoto, M. Suzuki, Y. Matsumura, M. Yokoyama, T. Okano,

Y. Sakurai, and K. Kataoka, "Development of the polymer micelle carrier system for
doxorubicin," Journal of Controlled Release 74 (2001): 295302.

4. C. Wang, Q. Ge, D. Ting, D. Nguyen, H. Shen, J. Chen, H. N. Eisen, J. Heller, R. Langer, and
D. Putnam, "Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of
DNA vaccines," Nature Materials 3 (2004): 190196.

5. E. Mathiowitz, J. S. Jacob, Y. S. Jong, G. P. Carino, D. E. Chickering, P. Chaturvedi, C. A.

Santos, K. Vijayaraghavan, S. Montgomery, M. Bassett, and C. Morrell, "Biologically erodable
microsphere as potential oral drug delivery system," Nature 386, no. 6623 (1997): 410414.

6. M. E. Davis, S. H. Pun, N. C. Bellocq, T. M. Reineke, S. R. Popielarski, S. Mishra, and J. D.

Heidel, "Self-assemblying nucleic acid delivery vehicles via linear, water-soluble,
cyclodextrin-containing polymers," Current Medicinal Chemistry 11 (2004): 12411253.

7. R. D. Bolskar, A. F. Benedetto, L. O. Husebo, R. E. Price, E. F. Jackson, S. Wallace, L. J.

Wilson, and J. M. Alford, "First soluble M@C-60 derivatives provide enhanced access to
metallofullerenes and permit in vivo evaluation of Gd@C-60[C(COOH)(2)](10) as a MRI
contrast agent," Journal of the American Chemical Society 125 (2003): 54715478.

8. J. L. West and N. J. Halas, "Engineered nanomaterials for biophotonics applications:

Improving sensing, imaging, and therapeutics," Annual Review of Biomedical Engineering 5
(2003): 285297.

9. S. L. Tao and T. A. Desai, "Microfabricated drug delivery systems: From particles to pores,"
Advanced Drug Delivery Reviews 55 (2003): 315328.

10. J. Santini, M. Cima, and R. Langer, "A Controlled-release Microchip," Nature 397 (1999):
335.

11. M. R. Prausnitz, S. Mitragotri, and R. Langer, "Current status and future potential of
transdermal drug delivery," Nature Reviews Drug Discovery 3, no. 2 (2004): 115124.

12. M. R. Prausnitz, "Microneedles for transdermal drug delivery," Advanced Drug Delivery
Reviews 56, no. 5 (2004): 581587.
Chapter 17. Bio-Nano-Information Fusion
Chih-Ming Ho, Dean Ho, and Dan Garcia

The solid-state microelectronics industry started in the late 1940s and has been the main driving
force of the U.S. economy in the past few decades. In the 1980s, microelectromechanical systems
(MEMS) technology demonstrated the capability of fabricating mechanical devices at a scale far
smaller than those made of traditional machining processes. Fan, Tai, and Muller (1988) developed
a micromotor that was on the order of 100mm by using the MEMS fabrication process, which was
derived from the integrated circuit (IC) industry.

Further reduction of the scale into the nanoscale has enabled the fusion between nanotechnology
and biology. By working on the same scale as that of macro functional molecules, such as DNA and
proteins, nanotechnology emerges as an opportunity to further build upon earlier technologies. An
example is the nanomotor developed by Soong et al. (2000), which grew from the amalgamation of
the mitochondrial ATPase and a nanofabricated metal rod. The progression of time has produced
machines of diminishing size, leading the engineering sciences into progressively smaller
dimensions. This movement has facilitated the expansion of the field of nanotechnology to explore
and develop this new scientific frontier.

Technological innovations such as nanotechnology aim to enrich human life. However,

nanotechnology presents a unique technical challenge in that a disparity of nine orders of magnitude
separates the length scales of a human (a meter) and a nanometer. Ultimately, this goal needs to be
achieved through the development of a definitive pathway that fuses existing technology with future
technology to link the nanoscale with human life.

An extremely intelligent, complex, and adaptive system, the human body is managed by natural
processes driven by molecules, such as DNA and proteins, that are on the order of a nanometer. The
challenges in exploring the governing mechanisms across a wide span of length scales is best
depicted by P. W. Anderson in a paper published in Science (1972): "At each level of complexity
entirely new properties appear, and the understanding of the new behaviors requires research which
I think is as fundamental in its nature as any other." For example, a cell might fuse the genetic
information contained in the DNA with nanoscale sensors and actuators to result in perhaps one of
the most efficient and autonomous micron-scale "factories."

The richness of the science that spans a difference of three orders of magnitude in length scale, from
the nanoscale realm to the macroscale realm, significantly exceeds our comprehension. An
imperative task will be to address the question of how we will span the length scales of these
nanoscale capabilities in a way that will eventually enable us to enrich human lives. These basic
processes that occur at the molecular level have opened a world where the integration of individual
components can eventually derive higher-order functionalities, or emergent properties. This leads us
toward a compelling approach that fuses biotechnology, nanotechnology, and information science,
which will enrich the development of revolutionary, application-specific technologies.

To drive the commercialization of nanotechnology, we need to further our understanding of the

nanosciences. During the past decades, our understanding of nanoscale molecules and their
functionalities has been significantly furthered by distinguished scientists in biology, physics, and
chemistry. Nanotechnology, on the other hand, is still in its infancy, but it is the key to realizing a
new industry. The establishment of the National Nanotechnology Initiative (NNI) has further
increased the momentum of progress in these areas.
For this realization to occur, three goals must be achieved. First, core technologies must be
developed to enable us to visualize, pick, place, manipulate, and characterize nanoparticles with a
high degree of precision. Second, we will need to establish manufacturing technologies to enable
systematic integration toward larger length scales with the higher information content embedded
within the composite structures. The final step toward establishment of a nanotechnology industry
will result from the capabilities displayed by emergent behavior at the nanoscale for increasing
functionalities.

Instead of providing a comprehensive review, this chapter uses examples based primarily on our
experience to illustrate the challenges and the potential associated with the impacting field of bio-
nano-information fusion.
Seeing
Perhaps one of the most beneficial tools afforded by the process of realizing the full potential of
nanotechnology will be the ability to visualize nanoscalemolecular activity in real time. Continually
advancing imaging methods have pushed the boundaries of nanoscale resolution.

Fluorescence microscopy greatly enhances the visualization of micro-and nanometer particles in

biological specimens. For example, confocal microscopy augments the fluorescent labeling of
everything from individual proteins to whole cells by offering several benefits over traditional
fluorescent microscopy. Of particular note is that confocal microscopy reduces background
fluorescence by using a filter that blocks out fluorescence located outside the focal point of the lens.
Because it contains multiple excitation sources, confocal microscopy provides the further benefit of
the simultaneous use and visualization of multiple fluorescent dyes. This allows, for example, the
visualization of multiple neuronal cell attributes, as illustrated in Figure 17-1.

Figure 17-1. Ten-day-old mouse cerebellar neuronal culture labeled with

neuronal marker beta III-tubulin and a marker for de novo DNA
methyltransferase (Feng, Chang, Li, and Fan 2005).

Atomic force microscopy (AFM) has evolved as a valuable method for evaluating surface topography
down to the nanoscale, largely because of its incorporation of a flexible cantilever containing a nano-
sized tip. Recently, AFM has been used to study nano-sized pores contained in cell membranes that
facilitate the exchange of solutes and nutrients between their cytoplasm and their environment. For
example, within its outer membrane the bacterium Escherichia coli contains channels called porins
that open and close in response to changes in pH and transmembrane voltage. To study the
conformational changes of the porins under the influence of pH and voltage, Muller and Engel (1999)
employed atomic force microscopy. Upon varying the pH or voltage across the membrane, AFM
confirmed conformational changes in the porin, showing a transition from a columnar structure to
one consisting of a nano-sized hole, as shown in Figure 17-2.

Figure 17-2. High-resolution AFM images of ion gradient and pH-

 dependent conformation changes of porin OmpF: (A) closed OmpF porin
channel; (B) open OmpF porin channel (Müller et al. 1999).

Most recently, using materials that can amplify near field optical waves to visualize subjects far
below the diffraction limit (Fang et al. 2003; Pendry 2001) will open a new territory for advancing
nanotechnologies. The continued enhancement of the nanoscale visualization methods will enable
discoveries of complex processes, including receptor-ligand interactions, DNA translocation across
cellular membranes, and beyond. Such a capability will revolutionize our ability to directly observe
reactions upon which the functionality of future nanotechnological devices will be based.
Manipulation
The exploitation of macro-functional molecules will inherently involve the application of their natural
characteristics. Taking advantage of those interesting properties of nanoscale particles will require
the successful manipulation of their position and properties. For example, a self-assembling
biological system could be employed in a bottom-up fabrication scheme. The fusion of biology with
nanotechnology will not only result in technological innovation but will also encourage future
research into natural biological nanosystems.

Current technology harnesses the ability to deform individual molecules such as proteins or DNA.
DNA is a nanoscale, long-chain macromolecule and behaves like a mass-spring system. Placing a
DNA molecule inside a viscous flow stretches the DNA molecule from its coiled position at
equilibrium by applying stress across the length of the molecule. To stretch DNA molecules, Wong et
al. (2003) designed microfluidic channels with two buffer streams that converge to sandwich a
middle stream containing the DNA solution, effectively extending the DNA molecule, as shown in
Figure 17-3. Such a method proves advantageous in that the DNA extensional rates depend upon
the flow rate of the outer buffer streams, thereby minimizing the effect of the flow from the
centerline on the DNA. Furthermore, the low mixing among the streams enabled independent DNA
control.

Figure 17-3. Relaxation of a DNA molecule after stretching is shown here

in 2.5-second increments (Wong et al. 2003).

DNA/RNA Characterization
A precursor to the use of nanoparticles for practical, beneficial purposes will be the ability to
characterize their properties with respect to composition, structure, and so on. Biomolecular
characterizationwith respect, for example, to proteinshas provided key information about three-
dimensional structure as well as mechanistic behavior. Information gleaned from these studies
serves as the foundation for current development of devices based purely on biomolecular function
(Ho et al. 2004). Toward the realization of improving the human condition through nanotechnology,
a full-scale characterization of DNA will elicit a broader understanding of the body of embedded
information that governs this condition.
The mapping of the human genetic code as part of the Human Genome Project took ten years.
Building on this foundation and developing a technology to quickly sequence an individual's DNA
hold enormous potential for health maintenance and drug development. With specific respect to the
interrogation of composition and structure, one pioneering methodology has been the use of
nanoscale pores to characterize DNA molecules. For example, Meller et al. (2000) have monitored
electrical conductance through an a-hemolysin channel from Staphylococcus aureus to yield
important information regarding nucleotide composition and the effects of temperature on DNA
transport.

Current results can discern transport events involving adenine polymers (poly dA100) as well as
cytosine polymers (poly dC100) (Figure 17-4). These studies enable investigation of several
characteristics of the analyzed molecule, from chain length to its exact composition and structure.

Figure 17-4. Translocation events of both poly(dA)100 and poly(dC)100.

Differentiation between dA and dC translocation was determined using tD
provided in ms10 (Meller et al. 2000).

The use of membrane proteins to examine DNA strands possessed certain limitations, including the
range of conditions in which characterizations could be performed, because the a-hemolysin and
lipid membranes possessed their own ranges of optimal conditions for preserved activity.

To build upon the groundwork that was established by protein- and lipid-based characterization,
Chen et al. (2004) used Si3N4-based nanopores to serve as solid-state characterization systems. Not
confined to the same set of limitations observed with a protein-based setup, the solid-state
nanopores were able to successfully detect translocation, or movement, of DNA through the pore
while possessing the versatility of varied pore diameters to decrease the chances of blockages to
DNA translocation and so on. Furthermore, solid-state nanopores will withstand broader ranges of
pH, temperature, and pressure, as well as voltages that would normally impair the protein/lipid
assembly, thereby allowing the testing of a broader class of molecules in a wider range of
environments.
Characterization
Atomic force microscopy initially evolved as a valuable method for the evaluation of surface
topography. Recently, AFM has been frequently used as a tool for the characterization and
manipulation of nanoscale particles. For example, the field of AFM lithography is used to transfer
nanoscale patterns onto photoresist, a UV or chemically reactive polymer commonly used with
microfabrication. The unparalleled resolution achieved using AFM-based techniques makes it an
ideal tool for nanolithography.

Furthermore, AFM has also been applied in studies involving biomolecules, such as membrane and
motor proteins. Possessing the capabilities for intimate exploration of these biological systems,
atomic force microscopy has been used for protein-folding measurements, as was done by Rief et
al.(1997) with titin immunoglobulin domains. Understanding protein-folding mechanisms is
important because it underlies the use of protein engineering, protein-based device engineering, and
even potential applications in using the characterization of a person's protein-folding properties as a
means of health monitoring.

The use of atomic force microscopy is a prime example that demonstrates how existing technologies
have been applied to the understanding of a requisite component of future nanotechnological
systems.
Integration
The human benefit of advances in nanotechnology will stem from the transition from handling single
nanoparticles to realizing large-scale manufacturing capabilities. Spanning from the nanoscale to the
macroscale is a necessary process in the transition of the nanosciences into industry. Artificial
fabrication technologies are usually considered top-down, meaning that they involve manipulations
at the macroscale, such as cutting or etching bulk materials. Nature, on the other hand, relies on
bottom-up fabrication, involving molecule-by-molecule assembly to create a predesigned subject.
Thus, the goal of artificial bottom-up fabrication involves the directed and orderly integration of
molecules at the nanoscale to form a macroscale device.

An example of bottom-up fabrication is the self-assembling monolayer (SAM) used by chemists

(Ulman 1991, 1995), such as the attachment of nano-sized motor molecules to cantilever beams to
form actuators. Rotaxane, a motor molecule shown in Figure 17-5, has two separate recognition
sites, each associated with a different energy potential. Placing the rotaxane molecule in an oxidant
oxidizes one site, thereby raising the energy level associated with the site (Collier 1999). As a
consequence, the energy profile of the rotaxane molecule is altered so that the ring prefers
association with the other recognition site, thereby causing the ring to move. Applying a reductant
will return the energy profile to its original state, forcing the ring back to its original position. In this
way, a molecular motor is created. This is an example of how to use artificial self-assembly to
integrate atoms into a molecular system.

Figure 17-5. Graphical representation of a rotaxane molecule. Alternating

oxidation and reduction of the molecule results in movement of the ring
structures (Collier et al. 1999).

The rotaxane molecule was further modified to create a molecule containing two rings and four
recognition sites. Anchoring the two rings to a gold surface creates a molecular muscle that, when
placed in an oxidant, causes the two rings to move to the center of the molecule and bend the beam,
a movement that can be detected by a laser beam. An array of molecular muscles attached to
cantilever beams was created, as shown in Figure 17-6. Alternating the application of oxidant and
reductant causes the beam to bend upward and return to its original position. This experiment
illustrates how we combine the top-down and the bottom-up fabrication techniques to form an
integrated micromechanical system from the nanoscale integrated system.

Figure 17-6. A microcantilever beam activated by nanoscale motor

molecules (Huang et al. 2004).
Emergent Systems
A human cell serves as a culmination of what nature has taken millions of years to evolve: an
autonomously responsive system of sensors and actuators that operates based on commands from
an embedded and distributed intelligence. It is a self-regulating, self-governing unit, with its nucleus
serving as its central information processor, and hence it represents a system based on the fusion of
a number of factors. The transfer and transduction of information using various signal pathways
found in cells serve to process and apportion this information to induce a concerted action. For
example, a chemical signal results in a sensory response that elicits mechanical movement or
actuation from the cytoskeletal networkall characteristic behavior in chemotaxis, or chemical-
induced cellular movement.

As a composite system, a cell exemplifies the concept of emergence, where inputs result in
coordinated feedback. The example of a neutrophil hunting down and encircling the Staphylococcus
aureus bacterium (Figure 17-7) demonstrates concerted, self-determining behavior. The bacterium
emits a chemical gradient that is sensed by a cell. The cell, which is able to follow a complex path of
the chemical, moves toward the bacterium and eventually surrounds the bacterium to envelope, or
phagocytoses, it. In this process, the chemical is sensed by the chemical sensors inside the
neutrophil and is processed by the signal pathways. Eventually, the neutrophil acts as a whole to
capture the bacterium.

Figure 17-7. A neutrophil is observed chasing a Staphylococcus aureus

bacterium. The bacterium emits a chemical that is in turn sensed by the
neutrophil, which then coordinates an autonomous actuation directed
toward the phagocytosis of the bacterium (Rogers et al. 1950).

A key element of manufacturing large-scale molecular systems will be the derivation of emergence,
or true mimicry, toward applications in energy production, nanoscale medicine, and so on.
Continued progress in nanotechnological development will result in promising approaches whereby
the input of stimuli (such as light, reactive chemicals, and so on) induces systemic behavior not
previously present to produce emergent behavior.

Showing particular promise are micrometer-sized photonic crystals of porous silicon presented by
Link and Sailor (2003). The optical properties of these crystals change upon the absorption of
chemicals, the fabrication of which is illustrated in Figure 17-8.

Figure 17-8. Surrounding of dichloromethane drop by self-orienting, self-

assembling "smart dust" particles. This is accomplished through
hydrophobic-hydrophobic interaction between the dichloromethane and
the hydrophobic porous silicon (Link et al. 2003).

The "smart dust" particles are composed of two sides: a green, "water-fearing" (hydrophobic) side,
and a red, "water-loving" (hydrophilic) side. Furthermore, because of their amphiphilic nature, the
smart dust particles will orient themselves spontaneously at a water surface to form a monolayer so
that the hydrophilic side faces the water and the hydrophobic side faces the air.

If porous silicon particles are incubated in water with a drop of dicholoromethane solvent, the smart
dust particles will self-assemble and orient themselves around the drop of dichloromethane so that
the hydrophilic side (red) faces the water and the hydrophobic side faces the solvent drop, as shown
in Figure 17-8. The individual particles aggregate together to form a large, macroscopic collection
that emerges as a result of the particle self-assembly. As demonstrated by Link and Sailor, the
smart dust particles prove useful in the detection of a chemical such as dichloromethane. The
modification of the particles with recognition elements may add further use to the particles by
facilitating the detection and isolation of pathogenic organisms in food or water.

Beyond the practical application of this work to detection and similar uses, a compelling approach to
deriving an intrinsic, higher-order behavior from the system has been established. This was
accomplished through the addition of a new condition to the solution, represented by the drop of
dichloromethane.

We are currently at a burgeoning stage with respect to the development of emergent behavior in
artificial systems, and continued efforts will seek to embed increased quantities of information in
artificial systems to derive even more complex higher-order functionality, such as usable energy or
other coordinated activity. The push toward true fusion will inevitably arrive at the achievement of
true mimicry. This will be an essential precursor to realizing the human benefit of nanotechnology.
Conclusions
This work has outlined the requisite strategies for realizing the ultimate goal of nanotechnology: to
benefit the human condition. Fundamental studies in the nanosciences have provided the building
blocks on which nanotechnology will drive the creation of novel devices with applications in
energetics, electronics, materials, medicine, and beyond. These systems will address the differences
between being integration- or fusion-based by possessing embedded intelligence through a series of
nanoscale sensors and actuators. The example of coordinated smart dust activity provides a
promising demonstration of basic emergent behavior. Future work will seek to dramatically increase
the amounts of information contained within fabricated systems to provide progressively advanced
outputs in response to various impulses. For example, by inputting a specific stimulus (such as
sunlight) into these devices, an autonomous reactivity (peptide-driven energy transduction) will
ultimately produce a usable output (electricity).

Bridging the elements of nanotechnology with beneficial larger-scale systems will parallel current
and continued advancements in methodologies with which nanotechnology will develop. These will
include the handling abilities to enable us to see and manipulate nanoparticles with the goal of
characterizing them. Manufacturing strategies will transition single-molecule studies toward large-
scale fabrication of systems that possess increasing information content. Finally, the realization of
systems based on the fusion of biology, nanotechnology, and informatics will result in truly
emergent, or biomimetic, systems that combine sensors and actuators that respond to specific
stimuli.

Although the nanotechnology industry is in a nascent stage, rapid advancements and a streamlined
road map of progress ensure that the future is quite promising. The realization of this industry's
potential will have revolutionary and compelling impacts upon humankind. For example, the fruition
of rapid DNA screening and diagnosis modalities will open the gateway to designing custom
therapeutics tailored to individuals based on their genetic makeup. An achievement of this
magnitude would serve dual roles. First, nanotechnology would be cemented as the visionary
industry for the next millennium. Second, the true benefits for humankind enabled by the
maturation of this technology will have been realized.

However, to reach this point in the road map, we must address in depth several key areas previously
outlined. Through the use of emerging technologies and methodologies for discoverysuch as the use
of superlens material for direct imagery of nanoscale processes or the enhancements of single-
molecule manipulation abilitieswe will achieve an unprecedented, more complex level of control of
biological processes. This, in turn, will give us a deeper understanding of how these biomolecules
and their respective activities contribute to a global functionality (such as the systemic performance
of the human body) to create an emergent behavior in nature. In this way, nanotechnology will then
be poised to reproduce this behavior to combat disease, to produce advanced energy sources, and to
support other advancements that will redefine the way we live.
Acknowledgments
The authors would like to gratefully acknowledge The Institute for Cell Mimetic Space Exploration
(CMISE, a NASA URETI), the National Institutes of Health (NIH), the National Science Foundation
(NSF), and the Defense Advanced Research Projects Agency (DARPA) for the support of this work.
References

Chen, P. , Gu, J. , Brandin, E. , Kim, Y. , Wang, Q. , and Branton, D. , "Probing single DNA
molecules transport using fabricated nanopores," Nano. Lett. 4 (2004): 2293.

Collier, C. P. , Wong, E. W. , Belohradsky, M. , Raymo, F. M. , Stoddart, J. F. , Kuekes, P. J. ,

Williams, R. S. , and Heath, J. R. , "Electronically Configurable Molecular-Based Logic Gates,"
Science 285 (1999): 391.

Fan, L. S. , Tai, Y. C. , and Muller, R. S. , "IC-processed Electrostatic Micromotors," Technical Digest,

IEDM (1988b): 666.

Fang, N. , and Zhang, X. , "Imaging properties of a metamaterial superlens," Applied Physics Letters
82, no. 2 (2003): 161.

Feng, J. , Chang, H. , Li, E. , and Fan, G. , "Dynamic Expression of De Novo DNA Methyltransferases
Dnmta3a and Dnmt3b in the Central Nervous System," Journal of Neuroscience Research 79, no. 6
(2005): 734.

Ho, D. , Chu, B. , Lee, H. , and Montemagno, C. D. , "Protein-driven energy transduction across

polymeric biomembranes," Nanotechnology 15 (2004): 1084.

Huang, T. J. , Brough, B. , Ho, C. -M. , Liu, Y. , Flood, A. H. , Bonvallet, P. A. , Tseng, H. -R. ,

Stoddart, J. F. , Baller, M. , and Magonov, S. , "A Nanomechanical Device Based on Linear Molecular
Motors," Applied Physics Letters (November 29, 2004).

Huang, T. J. , Tseng, H. -R. , Sha, L. , Lu, W. , Brough, B. , Flood, A. H. , Yu, B. -D. , Celestre, P. C.
, Chang, J. P. , Stoddart, J. F. , and Ho, C. -M. , "Mechanical Shuttling of Linear Motor-Molecules in
Condensed Phases on Solid Substrates," Nano Letters, in press.

Link, J. R. , and Sailor, M. J. , "Smart dust: Self-assembling, self-orienting photonic crystals of

porous Si," Proceedings of the National Academy of Sciences 100, no. 19 (2003): 10607.

Meller, A. , Nivon, L. , Brandin, E. , Golovchenko, J. , and Branton, D. , "Rapid nanopore

discrimination between single polynucleotide molecules," Proc. Nat. Acad. Chi.-USA 97 (2000):
1079.

Müller, D. J. , and Engel, A. , "Voltage and pH-induced Channel Closure of Porin OmpF Visualized by
Atomic Microscopy," Journal of Molecular Biology 285 (1999): 1347.
Pendry, J. , "New electromagnetic materials emphasise the negative," Physics World (2001).

Rief, M. , Gautel, M. , Oesterhelt, F. , Fernandez, J. , and Gaub, H. , "Reversible unfolding of

individual titin immunoglobulin domains by AFM," Science 276 (1997): 1109.

Rogers, D. , "Neutrophil crawling," video, 1950,

http://expmed.bwh.harvard.edu/projects/motility/neutrophil.html.

Soong, R. K. , Bachand, G. D. , Neves, H. P. , Olkhovets, A. G. , Craighead, H. G. , and

Montemagno, C. D. , "Powering an Inorganic Nanodevice with a Biomolecular Motor," Science 290
(2000): 1555.

Ulman, A. , An Introduction to Ultrathin Organic Films: From Langmuirblodgett to Self-Assembly

(Boston: Academic Press, 1991).

Ulman, A. , Characterization of Organic Thin Films (Boston: Butterworth-Heinemann, 1995).

Wong, P. K. , Lee, Y. K. , and Ho, C. M. , "Deformation of DNA molecules by hydrodynamic

focusing," J. Fluid. Mech. 497 (2003): 55.
Section Four: Convergence and Integration
Chapter 18. Convergence and Integration

Chapter 19. Ethical Considerations in the Advance of Nanotechnology

Chapter 18. Convergence and Integration
Mihail C. Roco

Unifying science based on the material unity of nature at the nanoscale provides a new foundation
for knowledge, innovation, and integration of technology. Revolutionary and synergistic advances at
the interfaces between previously separated fields of science, engineering, and other areas of
relevance are ready to create nano-bio-info-cogno (NBIC) transforming tools, products, and
services. Developments in systems approaches, mathematics, and computation in conjunction with
NBIC allow us to understand the natural world and scientific research as closely coupled, complex,
hierarchical entities.

At this unique moment of scientific and technical achievement, it becomes possible to improve
human performance at individual and group levels, as well as to develop suitable revolutionary
products. These are primary goals for converging new technologies. Most nanotechnology
applications are realized at the confluence of nanotechnology with other technologies. NBIC
addresses long-term advances in key areas of human activity, including working, learning, aging,
group interaction, organizations, and overall human development (Roco and Bainbridge 2003).
Fundamentally new tools, technologies, and products will be integrated into individual and social
human architectures. This chapter outlines research and education trends and discusses the
potential for the development of revolutionary products and services.
Framework for Science and Technology Development
In the next ten or twenty years, concentrated efforts from a number of disciplines are likely to bring
greater unity to sciencea reflection of the unity of the natural world. This foundation will lead to the
synergistic combination of four major provinces of science and technology, each of which is currently
progressing at a rapid rate in connection with the others: (1) nanoscience and nanotechnology; (2)
biotechnology and biomedicine, including genetic engineering; (3) information technology, including
advanced computing and communications; (4) cognitive sciences, including cognitive neuroscience
and systems approach concepts. Their synergistic integration from the nanoscale is expected to
bring significant advances. Collectively, the convergence of these scientific and technological
domains is here referred to as NBIC, shorthand for the various fields and subfields encompassed by
the nano-, bio-, info-, and cogno- prefixes. NBIC convergence is using and interacting with the broad
base of more established technologies.

With proper attention to ethical issues and societal needs, these converging technologies could lead
to a tremendous improvement in human abilities, societal outcomes, U.S. productivity, and the
quality of life. Six areas of relevance for human performance have been identified (Roco and
Bainbridge 2003; Radnor and Strauss 2004) as most important: human cognition and
communication, health and physical capabilities, group and societal outcomes (including new
products and services), national security, science and education, and business and organizations.

The integration of NBIC tools is expected to lead to fundamentally new products and services, such
as entirely new categories of materials, devices, and systems for use in manufacturing, construction,
transportation, medicine, emerging technologies, and scientific research. Fundamental research will
occur at the confluence of physics, chemistry, biology, mathematics, and engineering.
Nanotechnology, biotechnology, and information technology will play an essential role in the
research, design, and production of these new products and services.

Industries increasingly will use biological processes in manufacturing. Examples are pharmaceutical
genomics; neuromorphic technology; regenerative medicine; biochips having complex functions;
molecular systems having multi-scale architectures; electronic devices having three-dimensional,
hierarchical architectures; software for realistic multiphenomena and multi-scale simulations;
processes and systems phenomena from the basic principles at the nanoscale; new flight vehicles;
and quantitative studies using large databases in social sciences. Cognitive sciences will provide
better ways to design and use the new manufacturing processes, products, and services, as well as
lead to new kinds of organizations.

Within the U.S. Government, the National Science Foundation (NSF), the National Aeronautics and
Space Administration (NASA), the Environmental Protection Agency (EPA), the Department of
Defense (DoD), and the Department of Energy (DOE) already have several seed R&D projects in the
area of converging technologies. These projects are based on unifying science and education,
creating infrastructure for research at the confluence of two or more NBIC domains, developing
neuromorphic engineering, improving human performance, advancing "learning how to learn," and
preparing for the societal implications of converging technologies. Ethical and other societal
implications must be addressed from the beginning of any major program. Industry involvement is
evident in seed projects and in strategic R&D plans of several companies. User and civic group
involvement is essential if we are to take advantage of the technology sooner and develop a
complete picture of societal implications.

We need a systematic, deliberative, and responsible approach. This chapter briefly outlines the key
areas of relevance to converging NBIC technologies, several trends, and current NBIC outcomes.
The Opportunity
Advancing a coherent approach for converging technologies with a focus on human potential,
increased productivity, and revolutionary products and services is timely for five main reasons:

1. Accelerated human progress has become possible at the individual and collective levels. We
have arrived at the moment when we can measure signals from, and interact with, human cells
and the nervous system. We have also begun to replace or regenerate body parts as well as
build machines and other products that are suitable for direct interaction with human tissue
and the nervous system.

2. Unifying science based on the material unity at the nanoscale, and knowledge integration from
that scale, will provide a new foundation for technological innovation and the development of
humanities (philosophy, the arts, and so on). This implies the need to understand biosystems
and changes in matter at their roots. Nanoscale concepts have been rejuvenated by new tools
for measurement, control, and manipulation. The systems approach has been powered by
advances in hierarchical architecture, mathematics, and information technology. The natural
laws of interdependence were recognized by many ancient civilizations. However, because they
lacked a coherent understanding of connections, the concepts were reflected only
philosophically. More than five centuries ago, the leaders of the Renaissance saw "unity in
nature," but this concept was followed by disciplinary specialization because of limited
integrative knowledge. Only now can we begin to connect and integrate various disciplines and
provide cause-and-effect explanations from the nanoscale to the macroscale, moving beyond
the Renaissance ideal.

3. The accelerated rate and scale of changes in key technologies suggest the need for a fresh
approach. The context for the development of new products and processes evolves rapidly.
Several paradigm changes are expected in each of the four NBIC domains:

Nanotechnology is expected to move from its current focus on scientific discovery toward
a focus on systematic design methods and technological innovation, leading to the
development of manufacturing methods for mass production.

Biotechnology will move toward molecular medicine, nanosystems approaches, and

pharmaceutical genomics, and biomaterials will be integrated at an increased rate in
industrial products.

Information technology, in the quest for smallness and speed, will be enhanced by a focus
on new architectures, three-dimensional design, functionality, and integration with
application-driven developments in areas such as biosystems and knowledge-based
technologies. A special opportunity will be created by the ability to analyze large,
complex, hierarchical systems.

Cognitive sciences will focus on explaining the brain, the mind, and human behavior
based on an understanding of physical, chemical, and biological processes at the level of
the neuron, and from a systems approach. Increased attention will be given to
humantechnology coevolution. Technologies based on large, hierarchical, dynamic,
complex systems will address new opportunities such as quantitative social sciences.

4. Because of the significant impact of NBIC convergence, there is a need for anticipation
("learning before doing"), deliberate choices (for logical and democratic decisions), and
precautionary measures (for unexpected consequences).

5.
 4.

5. Science and technology are increasingly recognized as the main sources of overall human
development (UNPD 2001; Greenspan 2001).

A new infrastructure based on the four NBIC research and development platforms will be necessary
to create the products listed here. Ideally, this infrastructure must be available anywhere, on short
notice, to any industry and all those interested. A broader range of R&D issues will be investigated.
For example, R&D challenges in nanoscale engineering are as follows: three-dimensional
architectures that incorporate materials, devices, systems, space, and time; directed assembling,
patterning, and templating of heterogeneous nanosystems, multiphenomena, and multi-scale
design; integration of nanoscale elements into larger scales; the creation and use of intermediary
standard components; thermal and chemical stability of nanostructures; operational and
environmental safety; and reliability and reproductivity at the nanoscale.

Criteria for Progress

To measure and better evaluate performance, it will be necessary to adopt new socioeconomic
indices; one example is a modified GNP to incorporate changes in the human condition, to reflect the
impact on the environment, to prepare the infrastructure (including education and training), and to
measure other annual accumulations having societal implications. New holistic criteria may be
considered for evaluating progress, such as reducing the entropy of a systemthat is, less energy
dissipation per computation and transmission of information; less material, energy, water, and
pollution in nanotechnology; and less change or degradation in biotechnology. New indices are
necessary for recognizing accumulations in infrastructure, a better-educated workforce, more-
productive tools, and knowledge creation during a time interval.
Outlook for Industry
Ongoing R&D programs in nanotechnology promise to increase the efficiency of traditional industries
and to bring radically new applications, for the following reasons:

Numerous newly designed, advanced materials and manufacturing processes will be built by
2015 using control at the nanoscale level in at least one key component. Silicon transistors will
reach dimensions of 10nm or smaller and will be integrated with molecular or other kinds of
nanoscale systems.

Suffering from chronic illnesses has already been reduced through advances in technology. It is
conceivable that by 2015, techniques for detecting and treating tumors in their first year of
occurrence could be developed that might greatly mitigate suffering and death from cancer.

The convergence of science and engineering at the nanoscale level will establish a mainstream
pattern for applying and integrating nanotechnology with biology, electronics, medicine,
learning, and other fields. The science and engineering of nanobiosystems will become
essential to human health care and biotechnology. Life-cycle sustainability and biocompatibility
will be pursued in the development of new products.

Knowledge development and education will originate from the nanoscale instead of the
microscale level. A new education paradigm based, not on disciplines, but on unity of nature
and integration of education and research, will be tested for educational grades K16.

Nanotechnology businesses and organizations will be restructured with an eye toward

integration with other technologies, distributed production, continuing education, and the
formation of consortia of complementary activities. Traditional and emerging technologies will
be equally affected.

Nanotechnology's capabilities for systematic control and manufacture at the nanoscale level will
evolve in four overlapping generations of new products. Each generation is marked here by the
creation of the first commercial prototypes using systematic control of the respective phenomena
and manufacturing processing:

The first generation of products emerged in 2001 in the form of passive nanostructures used to
tailor macroscale properties and functions: nanostructured coatings, the dispersion of
nanoparticles, and bulk materials such as nanostructured metals, polymers, and ceramics.

Second-generation productsactive nanostructures for mechanical, electronic, magnetic,

photonic, biological, and other effects, integrated into microscale devices and systemswill begin
to emerge several years after the first generation. Examples might include new transistors,
components beyond CMOS amplifiers, targeted drugs and chemicals, actuators, artificial
muscles, and adaptive structures.

Within five to ten years of the second generation, a third can be expected. These products will
include nanosystems with 3-D features, using various syntheses and assembling techniques
(such as hierarchical, self-organizing bioassembling robotics with emerging behavior), as well
as evolutionary approaches. Key challenges include networking at the nanoscale and
developing hierarchical architectures. Research focus will shift toward engineering
heterogeneous nanostructures and supramolecular systems, some with emerging or
 evolutionary behaviors. This includes directed multi-scale, self-assembling, artificial tissues and
sensorial systems; quantum interactions within nanoscale systems; processing of information
using photons or electron spin; assemblies of nanoscale electromechanical systems (NEMS);
and the convergence of nano-, bio-, info-, and cognitive platforms integrated from the
nanoscale level and up.

Within five to ten years of the third generation, the fourth generation can be expected to bring
heterogeneous molecular nanosystems, where each molecule in the nanosystem has a specific
structure and plays a unique role. Molecules will be used as devices. From their engineered
structures and architectures will emerge fundamentally new functions. The design of new
atomic and molecular assemblies is expected to increase in importance. This includes
macromolecules "by design"; nanoscale machines; directed and multi-scale self-assembly that
exploits quantum control; and nanosystem biology for health care, the human-machine
interface at the tissue and nervous-system level, and the convergence of nano-bio-info-
cognitive domains.

Although expectations for nanotechnology may be overestimated in the short term, the long-term
implications for health care, productivity, and the environment appear to be underestimated.
Concluding Remarks
The natural laws of interdependence were recognized by many ancient civilizations, and the
idealized concept of unity in nature was promulgated during the Renaissance more than five
centuries ago. However, only now have we begun to connect and integrate various disciplines based
on recent advancements in knowledge and to provide cause-and-effect explanations from the
nanoscale to the macroscale, thereby moving beyond the Renaissance ideal. With the proper
consideration of ethical aspects and societal needs, paradigm changes and the synergism of the four
components of nano-bio-info-cogno are expected to bring revolutionary changes in technology, the
economy, and society, as well as to increase human potential.
Acknowledgments
Opinions expressed here are those of the author and do not necessarily represent the position of the
National Science and Technology Council or the National Science Foundation.
References

Greenspan, A. 1999. Public statement of the Joint Economic Committee of the U.S. Federal Reserve,
on June 14, 1999, Washington, DC.

Radnor, M. & J. Strauss, Eds. 2004. Commercialization and Managing the Converging New
Technologies. Report sponsored by the National Science Foundation, Arlington, VA.

Roco M.C. & W.S. Bainbridge, Eds. 2003. Converging Technologies for Improving Human
Performance. NSF-DOC Report. Boston: Kluwer.

Roco, M.C. & W.S. Bainbridge, Eds. 2004. Annals of the New York Academy of Sciences 1013: 1259.

United Nations Development Programme. 2001. Human Development Report: New York: Oxford
University Press.
Chapter 19. Ethical Considerations in the
Advance of Nanotechnology
William Sims Bainbridge

Ethics is important in industry for a variety of reasons. A well-established professional ethics is a

necessary basis for cooperation between companies, government agencies, and other organizations.
The public needs to have confidence in the ethical conduct of a corporation's business, or it may be
suspicious of the corporation's products and services in the marketplace. Without widespread
confidence from academia and nonprofit organizations, a corporation may find itself the target of
negative activism and political agitation.

Ethical principles are among the most significant means by which a company builds morale and
support from its own employees, including the technical and scientific staff who are relied upon for
profitable innovation. Stockholders and potential investors know that the reputation of a company is
among its most valuable assets. Finally, without a well-articulated and seriously implemented set of
ethical principles, the management of a corporation cannot take full pride in its own
accomplishments nor be confident it is making the right decisions for the well-being of the company
and of society at large.

Ethical questions of many kinds may arise in the general area of research, manufacturing, and
application of nanotechnologies. For example:

Who is responsible for preventing and dealing with possible harm to health or the
environment?

How can intellectual property rights be defined and defended when the boundary between
nanoscience and nanotechnology is so ambiguous?

How can the public's right to know about technologies that may affect their lives be balanced
against an innovator's right to protect trade secrets and against the cost of collecting and
disseminating correct information?

What priority should be placed on developing new products and techniques that will be highly
beneficial for some people, versus defending the interests of individuals and groups that may
not benefit from them?

Although this chapter draws upon a number of sources, it especially reflects the deliberations that
led to two major reports on the societal implications of nanoscience and nanotechnology (Roco and
Bainbridge 2001, 2005).
The Nature of Ethics
It would be convenient if there were a complete consensus both about the rules for ethical behavior
and about the best scholarly and scientific approach for analyzing ethical problems. Unfortunately,
beyond a few very simple principles that are more a reflection of Western democratic institutions
than of deep philosophical thought, there is no consensus. One reason is that several distinct
societal institutions and academic disciplines make it their business to address ethical issues, and
they do not agree entirely about fundamental principles. Another reason is that competing interests
and ideologies take opposing positions on key issues.

The traditional source of ethical principles is religious doctrine (Stark and Bainbridge 1987, 1996).
Western religions are often seen to be supportive of technological progress, in part because they
often conceptualize the world as an environment prepared by God for human benefit, and they may
go so far as to suggest that God has given humanity dominion over nature. However, specific
technologies may run afoul of one or another traditional doctrine, as is the case with human
reproductive cloning in the judgment of many theologians and other believers (Bainbridge 2003). A
good continuing source of theologically based analysis of the ethics of science and technology is the
journal Zygon.

In modern societies, with traditions of the separation of church and state, there has been hope that
firm ethical principles could be established on a secular basis, perhaps by academic philosophers.
Philosophy is the academic discipline most dedicated to asking penetrating questions and doubting
widespread assumptions. As such, it is an excellent part of a well-rounded liberal education, but it
may be poorly prepared to give definitive answers to the questions it raises. Nonetheless, academic
training in the philosophy of ethics is a valuable part of preparation for decision makers or their
advisers, because it helps them see important factors that may not be obviousnot only potential
ethical problems but also solutions to them.

Participants at the conference Societal Implications of Nanoscience and Nanotechnology II:

Maximizing Human Benefit (Roco and Bainbridge 2005) were divided on the issue of the contribution
professional ethicists can make. Philosophers of ethics analyzed issues relating to equity and the
quality of life, contributing insights that seemed valuable. However, other participants doubted
whether academic ethicists possess the knowledge about nanotechnology or reliable techniques of
philosophical analysis that could give their views greater weight than those of interested amateurs
among the general public, or could arrive at judgments that were not simply political in nature.

A fundamental debate in philosophy concerns the extent to which good and evil can be objectively
defined or instead are a matter of a judgment made by human beings from their particular
standpoints and interests (Kant 1787; Moore 1951; Rawls 1971). The extreme view, expressed most
famously by German philosopher Friedrich Nietzsche (18861887), is that morality is a scam
practiced by dominant people to gain power over submissive people, and unfortunately many people
today behave as if they believed this theory. A more manageable position is that morality is
negotiated between people in order to enhance cooperation and to serve their mutual interests and
their enlightened self-interest (Homans 1974; Gauthier 1986).

By means of traditional political procedures, government agencies establish rules in such areas as
environmental protection and workplace safety; legislatures write laws regulating industry and
prohibiting actions that are deemed to be dangerous; courts apply and interpret the law in particular
cases brought to them by plaintiffs who have their own interests and often intense feelings. At times,
the actions of social movements trump those of these other political actors, especially when a
movement is able to set the terms of debate about a particular issue. Some individual promoters of
nanotechnology have spread unreasonable views about its power for good or evil, and there is a
danger that their views are defining the issues. In the modern world, it is impossible to escape the
fact that ethical issues are always political issues.

Both sociology and anthropology study the factors and processes that establish, sustain, and
challenge morality. Thus, these disciplines have much wisdom to offer concerning the dynamics of
ethical debates. Sociologists and anthropologists tend personally to sympathize with powerless
groups in society, and to be somewhat suspicious of the corporations and government agencies that
generate new technologies. Perhaps ironically, this bias illustrates one of the most valuable insights
they have to offer: Ethical principles are not objective or uniform across humanity but instead are
rooted in specific social groups. The sociologist notes that ethical principles reflect the material
interests of the people who promote them, whereas the anthropologist celebrates the cultural
relativism of varying moralities across radically different societies.

In practical terms, this perspective can be very useful in dealing with a concrete ethical dispute. On
the one hand, it suggests that it may not always be possible to achieve an ethical consensus and
that it can be especially difficult to bring opponents around to one's own way of thinking. Although
these observations seem pessimistic, they can save wasted effort in trying to achieve an agreement
that is actually out of reach.

On the other hand, awareness that other people have their own distinct needs and values can help
one learn to accommodate those interests. In addition, awareness that others may have really
different cultural beliefs and values can facilitate honest bargaining with them. Understanding need
not mean surrender, but it can help frame issues in ways that have the best chance of finding
mutually satisfactory compromises.
Ethics of Individual Behavior
Sociology, social psychology, and criminology suggest insights that can help an organization
encourage individuals to adhere to a code of ethical behavior (Bainbridge 1997, 2004). For example,
an industrial corporation may have established very enlightened standards of behavior with respect
to environmental pollution, workplace hazards, and intellectual property rights. But this may not do
much good if social disorganization, pressures to overachieve, and internal conflict impel many
members of the organization to violate these rules. Here are three suggestions that can be applied
to work with nanotechnology but that also apply very generally:

1. Do not consistently leave any members of the group out of the communication channels or the
network of social relationships. An extensive body of scientific research has found that
individuals whose bond to society is weak or broken are no longer under social control and thus
are especially free to violate rules.

2. Do not allow any individual to be under such extreme pressures to perform that he or she will
feel forced to take unethical shortcuts. Job performance pressures can motivate some
individuals to innovate in valuable ways, but when people's self-esteem and economic well-
being depend on accomplishing things that are beyond their abilities, they are apt to take
shortcuts or to engage in deception.

3. Do not allow any subgroups or divisions of the organization to become so autonomous that
they develop a deviant subculture. Group cohesion and solidarity are valuable assets, as long
as they reinforce dedication to the legitimate goals of the organization. Too much solidarity
within a division, however, can cause the group to secede socially and psychologically from the
larger organization, and excessive cohesion encourages groupthink, which is a harmful
tendency to make decisions without considering valid criticism or the wider ethical context.
Nano-Specific Issues
Nanotechnology is primarily a multiplier for other technologies, providing enhanced performance,
reliability, or economy. However, with respect to health and environmental issues, nanotechnology
may pose some unique hazards (Royal Academy of Engineering 2003; Meridian Institute 2004). In
many cases, the chemical, electrical, and mechanical properties of nanoscale particles are
measurably different from those of bulk samples of the same substances.

Thus, it is essential to develop good methods for characterizing nanomaterials (for example, to
determine the size distribution of particles) and good theories that would allow one to estimate the
probable risk, if any, of a particular nanomaterial on the basis of a growing body of knowledge about
the category to which it belongs.

It will be impossible to subject all distinguishable kinds of nanomaterials to extensive testing. Thus,
direct empirical research is required on the impacts of a range of representative nanomaterials,
research that then can be the basis for comparison of similar materials that are not tested so
intensively. Risk assessment for nanomaterials covers four related stepshazard identification, hazard
characterization, exposure assessment, and risk calculationwhich then prepare the way for risk
management (Luther 2004: 43).

Hazards must be assessed realistically in terms of the life cycle of the technology: Research and
development hazards may differ from those in manufacturing, in the use of the product, and in
disposal when the product is no longer serviceable. Suppose research does find that carbon
nanotubes cause health problems when injected into animals in substantial doses. Suppose also that
carbon nanotubes become the key component in future manufacture of nanoelectronics, comparable
to computer chips. During the period of their actual use, and presumably after disposal as well, a
very small physical mass of nanotubes would be sealed safely inside the electronic components of a
device, posing no realistic threat to anyone. But there might possibly be a period of measurable
hazard at the point of manufacture, when the nanotubes were being generated and assembled into
components. This, then, would be an issue for workplace ethicsto be negotiated by management and
labor in the context of government regulationsbut would not raise ethical questions concerning the
general public.

Hazards may be higher in cases of accidents or misuse. For example, nanoscale-engineered

substances designed to hold hydrogen in the fuel tanks of future hydrogen-powered automobiles
might be entirely contained and therefore safe in normal use, but they might pose a risk in severe
accidents when the fuel tank ruptures. On the other hand, severe accidents and misuse will typically
entail unusual risks even without nanotechnology, and it would be unreasonable to demand that
every technology be entirely safe even when used unsafely.

Quite apart from possible risks, some critics argue that the benefits of nanotechnology themselves
raise ethical issues, because they may not be available to everyone. Clearly, there are substantial
political disagreements in society about whether socioeconomic inequality is unethical and, if so,
under what circumstances and for what reasons. We can hope, as did the economists who
participated in the societal implications conference mentioned earlier, that the free market will
rapidly distribute the benefits more widely. However, this cannot be taken for granted, and in areas
of public interest such as health care, governments may need to consider special efforts to maximize
the distribution of benefits.
Converging Technologies
Nanotechnology-related ethical issues are likely to become much more complex in the coming years,
as progress in nanoscience makes possible more and more linkages to other technologies. This is
has been described as convergence at the nanoscale:

The phrase "convergent technologies" refers to the synergistic combination of four major
"NBIC" (nano-bio-info-cogno) provinces of science and technology, each of which is currently
progressing at a rapid rate: (a) nanoscience and nanotechnology; (b) biotechnology and
biomedicine, including genetic engineering; (c) information technology, including advanced
computing and communications; (d) cognitive science, including cognitive neuroscience.
(Bainbridge 2002: ix; cf. Roco and Montemagno 2004)

Ultimately, this convergence will not consist merely of a collection of separate interdisciplinary fields
that splice together different sciences and technologies in a piecemeal fashion. Rather, it will consist
of a completely integrated set of theories and tools that provides comprehensive understanding and
control of nature.

On one level, convergence is seen as the only way of continuing the rate of technological progress
that humanity saw throughout the twentieth century. Demographers have noticed diminishing
returns from medical science, as the rate of increase in the extension of the human life span
markedly declined, but there is hope that nano-bio convergence can finally cure cancer and other
diseases that have resisted a century's efforts and can begin to undo the degenerative effects of
natural aging. It is believed that nano-info convergence can continue Moore's Lawthe doubling of
computer power at constant cost every 18 monthsfor another two decades, and this would mean
computers having 8,000 times the power of today's machines.

But on another level, there is also realistic hope that entirely new things may be accomplished, even
within the next very few years. Stimulated by defense needs, nano-bio-info convergence could result
in sensors that can instantly identify even small quantities of any chemical substance or biological
pathogen. While the patient is still in the doctor's office, this could mean definitive identification of
an infectionviral or bacterialallowing the doctor to begin proper treatment immediately.

For the first time, we have the real potential to create a host of cognitive technologies based on
cognitive science supported by bio-nano-info innovations. These revolutionary changes raise
profound ethical issues concerning privacy, equity, and possibly even the transformation of human
nature.
Practical Responses
Depending on the nature of the organization, any or all of the following four suggestions may help in
dealing with ethical issues related to nanotechnology.

Strengthen professional ethics. No one company can go it alone, especially not small and medium-
sized companies, but they can work together through professional organizations to set appropriate
ethical standards, with periodic review to keep abreast of rapidly changing technical and social
realities.

Delegate specific ethics-related duties. Ethics should be the explicit responsibility of high-level
managers and of committees with wide representation, including labor as well as management and
people representing a variety of functions in the company. This can be especially important in large
corporations, where there is considerable division of labor and where communication problems can
sometimes be severe.

Employ outside consultants. They would not make decisions, which are properly the task of
corporate management, but would frame alternatives and inform the company about the wider
debate currently in progress concerning particular issues of interest. Regularly, management and
other representative employees could participate in seminars or similar activities facilitated by a
consultant, sometimes primarily to communicate and reinforce standing company policies
concerning ethical behavior and sometimes to inform participants about new issues that are on the
horizon concerning nanotechnology ethics.

Encourage leaders to be well informed. Key personnelincluding top management but also including
other informal opinion leaders within the company and those who must maintain particular technical
expertiseshould individually inform themselves about the new possibilities for nanotechnology and
for technological convergence at the nanoscale. Expect change, and look for signs of it. For a
professional, incompetence is unethical.

The views expressed in this essay do not necessarily represent the views of the National
Science Foundation or the United States.
References

Bainbridge, William Sims. 1997. Sociology. New York: Barron's.

Bainbridge, William Sims. 2002. "Public Attitudes toward Nanotechnology," Journal of Nanoparticle
Research 4: 561570.

Bainbridge, William Sims. 2003. "Religious Opposition to Cloning," Journal of Evolution and
Technology 13, retrieved September 1, 2004, from www.jetpress.org/volume13/bainbridge.html.

Bainbridge, William Sims. 2004. "Social and Ethical Implications of Nanotechnology." In Handbook
of Nanotechnology, ed. B. Bhushan. Berlin: Springer, 11351151.

Gauthier, David. 1986. Morals by Agreement. Oxford, England: Oxford University Press.

Homans, George C. 1974. Social Behavior: Its Elementary Forms. New York: Harcourt, Brace
Jovanovich.

Kant, Immanuel. 1787. A Critique of Pure Reason. New York: Wiley [1900].

Luther, Wolfgang (ed.). 2004. Industrial Applications of NanomaterialsChances and Risks.

Düsseldorf, Germany: Future Technologies Division, VDI Technologiezentrum.

Meridian Institute. 2004. International Dialogue on Responsible Research and Development of

Nanotechnology. Alexandria, Virginia: Meridian Institute.

Moore, George Edward. 1951. Principia Ethica. Cambridge: Cambridge University Press.

Nietzsche, Friedrich Wilhelm. 18861887. Beyond Good and Evil and The Genealogy of Morals. New
York: Barnes and Noble [1996].

Rawls, John. 1971. A Theory of Justice. Cambridge, Massachusetts: Harvard University Press.

Roco, Mihail C., and William Sims Bainbridge (eds.). 2001. Societal Implications of Nanoscience and
Nanotechnology. Dordrecht, Netherlands: Kluwer.

Roco, Mihail C., and William Sims Bainbridge (eds.). 2003. Converging Technologies for Improving
Human Performance. Dordrecht, Netherlands: Kluwer.
Roco, Mihail C., and William Sims Bainbridge (eds.). 2005. Societal Implications of Nanoscience and
Nanotechnology II: Maximizing Human Benefit. Dordrecht, Netherlands: Kluwer.

Roco, Mihail C., and Carlo Montemagno (eds.). 2004. The Coevolution of Human Potential and
Converging Technologies. New York: New York Academy of Sciences (Annals of the New York
Academy of Sciences, volume 1013).

Royal Academy of Engineering. 2003. Nanoscience and Nanotechnologies: Opportunities and

Uncertainties. London: The Royal Society.

Stark, Rodney, and William Sims Bainbridge. 1987. A Theory of Religion. New York: Toronto/Lang.

Stark, Rodney, and William Sims Bainbridge. 1996. Religion, Deviance and Social Control. New York:
Routledge.
Epilogue
In late 1959 and again in 1983 Nobel Laureate and Caltech physics professor Richard Feynman
delivered talks entitled, respectively, There's Plenty of Room at the Botto and Infinitesimal
Machines.[1],[2] Both offered questions and suggestions for research on what we now call
"nanotechnology." By any name the subject matter was provocative and ahead of its time, so
for many years these gems were not seen in the context of "real science" so much as novelties
reflecting the rich, revered, idiosyncratic imagination for which Feynman was renownedand still
is, almost two decades after his death. Even in 1983 Feynman himself said "There is no use for
these machines, so I still don't understand why I'm fascinated by the question of making small
machines...." Would that he had lived long enough to see the remarkable developments
recounted in this book.
[1] Delivered before the American Physical Society, December 29, 1959, and transcript reprinted in Caltech's alumni magazine,

Engineering & Science, February, 1960.

[2] R. Feynman,Infinitesimal Machinery, IEEE Journal of Microelectromechanical Systems, 2, no. 1 (March 1993), 414.
Copyright 1993, IEEE. The article is an edited transcript of the 1983 talk and is reproduced with the kind permission of Carl and
Michelle Feynman, and the IEEE.

Although it is located here as an epilogue to the other chapters, the 1983 talka seminar at Jet
Propulsion Laboratorycould as easily have stood at the other end as the book's foreword. A few
comments on its presence and position are therefore in order.

Foremost, reprinting Infinitesimal Machines makes available the edited text of a fascinating
speech whose distribution and appreciation are only a small fraction of that accorded
Feynman's celebrated 1959 Plenty of Room speech. That earlier visionand its exhortation to
initiate research at microscale and belowis widely cited as the first public emergence of
nanotechnology. The later talk, given and videotaped at JPL on February 23, 1983, was almost
unknown beyond the fortunate attendees from the Caltech/JPL community until it was
rediscovered, edited and published in 1993.[1],[2]
[1] Of the many people we have to thank for the lecture-to-article journey, a special debt is owed to
Journal editor William
Trimmer for discovering and pursuing the possibility and to Professor Steve Senturia, now retired from MIT, for yeoman editing
that at once preserved both science and Feynman's charm. NB: the JPL lecture is not that sold under the title "Tiny Machines,"
a commercially distributed video of Feynman's 1984 talk at Esalen in Big Sur, California to an audience of artists and other non-
scientists.

[2] An illuminating analysis of the role of the two speeches and associated articles can be found in
Apostolic Succession by
Chris Toumey, "Engineering and Science" LXVIII, 1/2, 2005, available at http://pr.caltech.edu/periodicals/EandS/Esarchive-
frame.html.

Of course, any successor to Plenty of Room will unavoidably capture the attention of both the
nano-community and Feynman fans. But, more specifically, the JPL talk sheds light on the
ways of Feynman's thinking about things small, both mechanical and electronic, and the
breadth of technology that his enthusiasms embraced. At the same time, because of skillful
editing and "clean up" it preserves much of the Feynman personality and style that captivated
students and researchers alike.

Feynman's interest in computing can be traced tothe World War II Manhattan Project at Los
Alamos, where his application of innovative parallel computating methods tripled the
throughput of arduous atomic bomb calculations perfomed by legions of calculation-punching
staff who were the computers of the day. Fifteen years later at the time of Plenty of Room,
computers were just transitioning to semiconductor technology, although vacuum tubes and
even drum memory still remained much in use. By the time of his 1983 talk, the PC had
arrived, Moore's law was being aggressively exercised, and Feynman's focus on computing had
grown. Indeed Infinitesimal Machinery came in the middle of Feynman's year-long Caltech
course "The Physics of Computation" which he taught with Carver Mead and John Hopfield.
They had to hold it without him in 19811982, but with poor results, while Feynman battled
cancer. His enthusiasm upon returning overcame their intention to abandon the course after
the disastrous Feynmanless year. It was in this context that the JPL talk was given.[3]
[3] A deeper perspective of Feynman's involvement with computing can be found inFeynman and ComputationExploring the
Limits of Computer, ed. Anthony J.G. Hey (Philadelphia: Perseus Books, 1999). This is a collection articles by Mead, Hopfield
and other notables who worked with Feynman. It also includes several of Feynman's own articles.

Placing Infinitesimal Machines as the final chapter reflects a belief that readers will appreciate it
far more having first delved into contemporary nanotechnology. Moreover, the imagination and
scope of Feynman's discussion are fitting symbols of the rich treasure of articles in this volume.

In that light and in closing, it bears mention that by motivating, organizing and editing these
papers, Lynn Foster has made a major contribution to the field. This is no surprise, of course,
to those who have watched him regularly encourage a thoughtful awareness of
nanotechnology, in contrast to the hype that has persisted since the late 1990s. Initially
working regionally to create the first Trade Study on Nanotechnology, he went on to contribute
to and organize conferences with a national reach. Between the covers of this collection Lynn
has brought together diverse authoritative perspectives that reveal the dimensions of
nanotechnology, all the while written to be widely accessible. For the reporter who needs to get
up to speed quickly, the scientist suddenly confronted with a research-driven business issue, or
simply an inquisitive citizen wondering about all this "nano-hoopla," this volume offers a ready
reference that is at once untainted by hyperbole and yet readable. For this we all owe Lynn
Foster no small thanks.

Michael Krieger, Caltech '63

Willenken Wilson Loh & Stris
Chapter 20. Infinitesimal Machinery
Richard Feynman[1]
[1] This manuscript is based on a talk given by Richard Feynman on February 23, 1983, at the Jet Propulsion Laboratory, Pasadena,

California. It is reprinted with the permission of his estate, Carl Feynman executor.

The author, deceased, was with the California Institute of Technology, Pasadena.

Introduction of Richard Feynman by Al HibbsWelcome to the Feynman lecture on "Infinitesimal

Machinery." I have the pleasure of introducing Richard, an old friend and past associate. He was
educated at MIT and at Princeton, where he received a Ph.D. in 1942. In the War he was at Los
Alamos, where he learned how to pick combination locksan activity at which he is still quite skillful.
He next went to Cornell, where he experimented with swinging hoops. Then, both before and during
his time at Caltech, he became an expert in drumming, specializing in complex rhythms, particularly
those of South America and recently those of the South Pacific. At Caltech, he learned to decode
Mayan hieroglyphs and took up art, becoming quite an accomplished draftsmanspecializing in nude
women. And he also does jogging.

Richard received the Nobel prize, but I believe it was for physics and not for any of these other
accomplishments. He thinks that happened in 1965, although he doesn't remember the exact year. I
have never known him to suffer from false modesty, so I believe he really has forgotten which year
he got the Nobel prize.

When Dick Davies asked me to talk, he didn't tell me the occasion was going to be so elaborate, with
TV cameras and everythinghe told me I'd be among friends. I didn't realize I had so many friends. I
would feel much less uncomfortable if I had more to say. I don't have very much to saybut of
course, I'll take a long time to say it.
Revisiting "There's Plenty of Room at the Bottom"
In 1960, about 23 years ago, I gave a talk called "There's Plenty of Room at the Bottom," in which I
described the coming technology for making small things. I pointed out what everybody knew: that
numbers, information, and computing didn't require any particular size. You could write numbers
very small, down to atomic size. (Of course, you can't write something much smaller than the size of
a single atom.) Therefore, we could store a lot of information in small spaces, and in a little while
we'd be able to do so easily. And of course, that's what happened.

I've been asked a number of times to reconsider all the things that I talked about 23 years ago, and
to see how the situation has changed. So my talk today could be called "There's Plenty of Room at
the Bottom, Revisited."

As I mentioned in the 1960 talk, you could represent a digit by saying it is made of a few atoms.
Actually, you'd only have to use one atom for each digit, but let's say you make a bit from a bunch
of gold atoms, and another bit from a bunch of silver atoms. The gold atoms represent a one, and
the silver atoms a zero. Suppose you make the bits into little cubes with a hundred atoms on a side.
When you stack the cubes all together, you can write a lot of stuff in a small space. It turns out that
all the books in all the world's libraries could have all their informationincluding pictures using dots
down to the resolution of the human eyestored in a cube 1/120 inch on a side. That cube would be
just about the size you can make out with your eyeabout the size of a speck of dirt.

If, however, you used only surfaces rather than the volume of the cubes to store information, and if
you simply reduce normal scale by twenty-five thousand times, which was just about possible in
those days, then the Encyclopedia Britannica could be written on the head of a pin, the Caltech
library on one library card, and all the books in the world on thirty-five pages of the Saturday
Evening Post. I suggested a reduction of twenty-five thousand times just to make the task harder,
because due to the limitations of light wavelength, that reduction was about ten times smaller than
you could read by means of light. You could, of course, read the information with electron
microscopes and electron beams.

Because I had mentioned the possibility of using electron beams and making things still smaller, six
or eight years ago someone sent me a picture of a book that he reduced by thirty thousand times. In
the picture, there are letters measuring about a tenth of a micron across [passes the picture around
the audience].

I also talked in the 1960 lecture about small machinery, and was able to suggest no particular use
for the small machines. You will see there has been no progress in that respect. And I left as a
challenge the goal of making a motor that would measure 1/64 of an inch on a side. At that time,
the idea that I proposed was to make a set of handslike those used in radioactive systemsthat
followed another set of hands. Only we make these "slave" hands smallera quarter of the original
hands' sizeand then let the slave hands make smaller hands and those make still smaller hands.
You're right to laughI doubt that that's a sensible technique. At any rate, I wanted to get a motor
that couldn't be made directly by hand, so I proposed 1/64 of an inch.

At the end of my talk, Don Glaser, who won the Nobel prize in physicsthat's something that's
supposed to be good, right?said, "You should have asked for a motor 1/200 inch on a side, because
1/64 inch on a side is just about possible by hand." And I said, "Yeah, but if I offered a thousand-
dollar prize for a motor 1/200 inch on a side, everybody would say 'Boy, that guy's a cheapskate!
Nobody's ever going to do that.'" I didn't believe Glaser, but somebody actually did make the motor
by hand!
As a matter of fact, the motor's very interesting, and just for fun, here it is. First look at it directly
with your eye, to see how big it is. It's right in the middle of that little circleit's only the size of a
decimal point or a period at the end of a sentence. Mr. McLellan, who made this device for me,
arranged it very beautifully, so that it has a magnifier you can attachbut don't look at it through the
magnifier until you look at it directly. You'll find you can't see it without the magnifier. Then you can
look through the magnifier and turn this knob, which is a little hand generator which makes the juice
to turn the motor so you can watch the motor go around [gives the McLellan motor to the audience
to be passed around].
What We Can Do Today
Now I'd like to talk about what we can do today, as compared to what we were doing in those days.
Back then, I was speaking about machinery as well as writing, computers, and information, and
although this talk is billed as being about machinery, I'll also discuss computers and information at
the end.

My first slide illustrates what can be done today in making small things commercially. This is of
course one of the chips that we use in computers, and it represents an area of about three
millimeters by four millimeters. Human beings can actually make something on that small a scale,
with wires about six microns across (a micron is a millionth of a meter, or a thousandth of a
millimeter). The tolerances, dimensions, and separations of some of the wires are controlled to
about three microns. This computer chip was manufactured five years ago, and now things have
improved so that we can get down to about one-half micron resolution.

These chips are made, as you know, by evaporating successive layers of materials through masks.
[Feynman uses "evaporating" as a generic term for all semiconductor process steps.] You can create
the pattern in a material in several ways. One is to shine light through a mask that has the design
that you want, then focus the light very accurately onto a light-sensitive material and use the light
to change the material, so that it gets easier to etch or gets less easy to etch. Then you etch the
various materials away in stages. You can also deposit one material after anotherthere's oxide, and
silicon, and silicon with materials diffused into itall arranged in a pattern at that scale. This
technology was incredible twenty-three years ago, but that's where we are today.

The real question is, how far can we go? I'll explain to you later why, when it comes to computers,
it's always better to get smaller, and everybody's still trying to get smaller. But if light has a finite
wavelength, then we're not going to be able to make masks with patterns measuring less than a
wavelength. That fact limits us to about a half a micron, which is about possible nowadays, with
light, in laboratories. The commercial scale is about twice that big.

So what could we do today, if we were to work as hard as we could in a laboratorynot commercially,

but with the greatest effort in the lab? Michael Isaacson from the Laboratory of Submicroscopic
Studies (appropriate for us) has made something under the direction of an artist friend of mine
named Tom Van Sant. Van Sant is, I believe, the only truly modern artist I know. By truly modern, I
mean a man who understands our culture and appreciates our technology and science as well as the
character of nature, and incorporates them into the things that he makes.

I would like to show you, in the next slide, a picture by Van Sant. That's art, right? It represents an
eye. That's the eyelid and the eyebrow, perhaps, and of course you can recognize the pupil. The
interesting thing about this eye is that it's the smallest drawing a human being has ever made. It's a
quarter of a micron across250 millimicronsand the central spot of the pupil is something like fifteen
or twenty millimicrons, which corresponds to about one hundred atoms in diameter. That's the
bottom. You're not going to be able to see things being drawn more than one hundred times
smaller, because by that time you're at the size of atoms. This picture is as far down as we can
make it.

Because I admire Tom Van Sant, I would like to show you some other artwork that he has created.
He likes to draw eyes, and the next slide shows another eye by him. This is real art, right? Look at
all the colors, the beauty, the light, and so forthqualities that of course are much more appreciated
as art. (Maybe some of you clever lit guys know what you're looking at, but just keep it to
yourselves, eh?)
To get some idea of what you're looking at, we're going to look at that eye from a little bit further
back, so you can see some more of the picture's background. The next slide shows it at a different
scale. The eye is now smaller, and perhaps you see how the artist has drawn the furrows of the
brow, or whatever it is around the eye. The artist now wants to show the eye to us on a still smaller
scale, so we can see a little more of the background. So in this next slide, you see the city of Los
Angeles covering most of the picture, and the eye is this little speck up in the corner!

Actually, all these pictures of the second eye are LANDSAT pictures of an eye that was made in the
desert. You might wonder how someone can make an eye that bigit's two and one-half kilometers
across. The way Van Sant made it was to set out twenty-four mirrors, each two feet square, in
special locations in the desert. He knew that when the LANDSAT passes back and forth overhead, its
eye looks at the land and records information for the picture's pixels. Van Sant used calculations so
that the moment the LANDSAT looked at a particular mirror, the sun would be reflecting from the
mirror right into the eye of the LANDSAT. The reflection overexposed the pixel, and what would have
been a two-foot square mirror instead made a white spot corresponding to an area of several acres.
So what you saw in the first picture was a sequence of overexposed pixels on the LANDSAT picture.
Now that's the way to make art! As far as I know, this is the largest drawing ever made by man.

If you look again at the original picture, you can see one pixel that didn't come out. When they went
back to the desert, they found that the mirror had been knocked off its pedestal, and that there were
footprints from a jack rabbit over the surface. So Van Sant lost one pixel.

The point about the two different eyes is this: that Van Sant wanted to make an eye much bigger
than a normal eye, and the eye in the desert was 100,000 times bigger than a normal eye. The first
eye, the tiny one, was 100,000 times smaller than a normal eye. So you get an idea of what the
scale is. We're talking about going down to that small level, which is like the difference in scale
between the two-and-one-half-kilometer desert object and our own eye. Also amusing to think
about, even though it has nothing to do with going small, but rather with going bigwhat happens if
you go to the next eye, 100,000 times bigger? Then the eye's scale is very close to the rings of
Saturn, with the pupil in the middle.

I wanted to use these pictures to tell us about scale and also to show us what, at the present time, is
the ultimate limit of our actual ability to construct small things. And that summarizes how we stand
today, as compared to how the situation looked when I finished my talk in 1960. We see that
computers are well on their way to small scale, even though there are limitations. But I would like to
discuss something elsesmall machines.
Small MachinesHow to Make Them
By a machine, I mean things that have movable parts you can control, that have wheels and stuff
inside. You can turn the movable parts; they are actual objects. As far as I can tell, this interest of
mine in small machines is a misguided one, or more correctly, the suggestion in the lecture "Plenty
of Room at the Bottom" that soon we would have small machines was certainly a misguided
prediction. The only small machine we have is the one that I've passed around to you, the one that
Mr. McLellan made by hand.

There is no use for these machines, so I still don't understand why I'm fascinated by the question of
making small machines with movable and controllable parts. Therefore I just want to tell you some
ideas and considerations about the machines. Any attempt to make out that this is anything but a
gamewell, let's leave it the way it is: I'm fascinated and I don't know why.

Every once in a while I try to find a use. I know there's already been a lot of laughter in the
audiencejust save it for the uses that I'm going to suggest for some of these devices, okay?

But the first question is, how can we make small machines? Let's say I'm talking about very small
machines, with something like ten microns (that's a hundredth of a millimeter) for the size of a
motor. That's forty times smaller than the motor I passed aroundit's invisible, it's so small.

I would like to shock you by stating that I believe that with today's technology we can easilyI say
easilyconstruct motors one-fortieth of this size on each dimension. That's sixty-four thousand times
smaller than the size of McLellan's motor, and in fact, with our present technology, we can make
thousands of these motors at a time, all separately controllable. Why do you want to make them? I
told you there's going to be lots of laughter, but just for fun, I'll suggest how to do itit's very easy.

It's just like the way we put those evaporated layers down, and made all kinds of structures. We
keep making the structures a little thicker by adding a few more layers. We arrange the layers so
that you can dissolve away a layer supporting some mechanical piece, and loosen the piece. The
stuff that you evaporate would be such that it could be dissolved, or boiled away, or evaporated out.
And it could be that you build this stuff up in a matrix, and build other things on it, and then other
stuff over it. Let's call the material "soft wax," although it's not going to be wax. You put the wax
down, and with a mask you put some silicon lumps that are not connected to anything, some more
wax, some more wax, and then silicon dioxide or something. You melt out or evaporate the wax,
and then you're left with loose pieces of silicon. The way I described it, that piece would fall
somewhere, but you have other structures that hold it down. It does seem to me perfectly obvious
that with today's technology, if you wanted to, you could make something one-fortieth the size of
McLellan's motor.

When I gave the talk called "Plenty of Room at the Bottom," I offered a thousand-dollar prize for the
motorI was single at the time. In fact, there was some consternation at home, because I got married
after that, and had forgotten all about the prize. When I was getting married, I explained my
financial position to my future wife, and she thought that it was bad, but not so bad. About three or
four days after we came back from the honeymoon, with a lot of clearing of my throat I explained to
her that I had to pay a thousand dollars that I had forgotten aboutthat I had promised if somebody
made a small motor. So she didn't trust me too much for a while.

Because I am now married, and have a daughter who likes horses, and a son in college, I cannot
offer a thousand dollars to motivate you to make movable engines even forty times smaller. But Mr.
McLellan himself said that the thousand dollars didn't make any differencehe got interested in the
challenge.
Of course, if we had these movable parts, we could move them and turn them with electrostatic
forces. The wires would run in from the edges. We've seen how to make controllable wireswe can
make computers, a perfect example of accurate control. So there would be no reason why, at the
present time, we couldn't make little rotors and other little things turn.
Small MachinesHow to Use Them
What use would such things be? Now it gets embarrassing. I tried very hard to think of a use that
sounded sensibleor semisensibleyou'll have to judge. If you had a closed area and a half wheel that
you turned underneath, you could open and shut a hole to let light through or shut it out. And so
you have light valves. But because these tiny valves could be placed all over an area, you could
make a gate that would let through patterns of light. You could quickly change these patterns by
means of electrical voltages, so that you could make a series of pictures. Or, you could use the
valves to control an intense source of light and project pictures that vary rapidlytelevision pictures. I
don't think projecting television pictures has any use, though, except to sell more television pictures
or something like that. I don't consider that a useadvertising toilet paper.

At first I couldn't think of much more than that, but there are a number of possibilities. For example,
if you had little rollers on a surface, you could clean off dirt whenever it fell, and could keep the
surface clean all the time.

Then you might think of using these devicesif they had needles sticking outas a drill, for grinding a
surface. That's a very bad idea, as far as I can tell, for several reasons. First, it turns out that
materials are too hard when they are dimensioned at this small scale. You find that everything is
very stiff, and the grinder has a heck of a job trying to grind anything. There's an awful lot of force,
and the grinder would probably grind down its own face before it ground anything else. Also, this
particular idea doesn't use the individualization that is possible with small machinesyou can
individually localize which one is turning which way. If I make all the small machines do grinding,
I've done nothing I can't do with a big grinding wheel. What's nice about these machinesif they're
worth anythingis that you can wire them to move different parts differently at different times.

One application, although I don't know how to use it, would be to test the circuits in a computer that
is being manufactured. It would be nice if we could go in and make contacts at different places
inside the circuit. The right way to do that is to design ahead of time places where you could make
contacts and bring them out. But if you forgot to design ahead, it would be convenient to have a
face with prongs that you could bring up. The small machines would move their little prongs out to
touch and make contact in different places.

What about using these things for tools? After all, you could drill holes. But drilling holes has the
same problemthe materials are hard, so you'll have to drill holes in soft material.

Well, maybe we can use these tools for constructing those silicon devices. We have a nifty way of
doing it now, by evaporating layers, and you might say, "Don't bother me." You're probably right,
but I'd like to suggest something that may or may not be a good idea.

Suppose we use the small machines as adjustable masks for controlling the evaporation process. If I
could open and close these masks mechanically, and if I had a source of some sort of atoms behind,
then I could evaporate those atoms through the holes. Then I could change the hole by changing the
voltagesin order to change the mask and put a new one on for the next layer.

At the present time, it is a painstaking job to draw all the masks for all the different layersvery, very
carefullyand then to line the masks up to be projected. When you're finished with one layer you take
that layer off and put it in a bath with etch in it; then you put the next layer on, adjust it, go crazy,
evaporate, and so on. And that way, we can make four to five layers. If we try to make four hundred
layers, too many errors accumulate; it's very, very difficult, and it takes entirely too long.

Is it possible that we could make the surfaces quickly? The key is to put the mask next to the device,
not to project it by light. Then we don't have the limitations of light. So you put this machine right
up against the silicon, open and close holes, and let stuff come through. Right away you see the
problem. The back end of this machine is going to accumulate goop that's evaporating against it,
and everything is going to get stuck.

Well then, you haven't thought it through. You should have a thicker machine with tubes and pipes
that brings in chemicals. Tubes with controllable valvesall very tiny. What I want is to build in three
dimensions by squirting the various substances from different holes that are electrically controlled,
and by rapidly working my way back and doing layer after layer, I make a three-dimensional
pattern.

Notice that the silicon devices are all two-dimensional. We've gone very far in the development of
computing devices, in building these two-dimensional things. They're essentially flat; they have at
most three or four layers. Everyone who works with computing machinery has learned to appreciate
Rent's law, which says how many wires you need to make how many connections to how many
devices. The number of wires goes up as the 2.5 power of the number of devices. If you think a
while, you'll find that's a little bit too big for a surfaceyou can put so many devices on a surface, but
you can't get the wires out. In other words, after a while this two-dimensional circuit becomes all
wires and no devices, practically.

If you've ever tried to trace lines in two dimensions to make a circuit, you can see that if you're only
allowed one or two levels of crossover, the circuit's going to be a mess to design. But if you have
three-dimensional space available, so that you can have connections up and down to the transistors,
in depth as well as horizontally, then the entire design problem of the wires and everything else
becomes very easy. In fact, there's more than enough space. There's no doubt in my mind that the
ultimate development of computing machines will end up with the development of a technologyI
don't mean my technology, with my crazy machinesbut some technology for building up three-
dimensional circuits, instead of just two-dimensional circuits. That is to say, thick layers, with many,
many layershundreds and hundreds of them.

So we have to go to three dimensions somehow, maybe with tubes and valves controlled at small
scale by machines. Of course, if this did turn out to be useful, then we'd have to make the machines,
and they would have to be three-dimensional, too. So we'd have to use the machines to make more
machines.

The particular machines I have described so far were just loose pieces that were moving in
placedrills, valves, and so forth that only operate in place. Another interesting idea might be to
move something over a surface or from one place to another. For example, you could build the same
idea that we talked about before, but the thingsthe little bars or somethingare in slots, and they can
slide or move all over the surface. Maybe there's some kind of T-shaped slot they come to, and then
they can go up and down. Instead of trying to leave the parts in one place, maybe we can move
them around on rollers, or simply have them slide.
Electrostatic Actuation
Now how do you pull them along? That's not very hardI'll give you a design for pulling. [At the
blackboard. Feynman draws a rectangular block with a set of alternating electrodes creating a path
for the block.] If you had, for example, any object like a dielectric that could only move in a slot, and
you wanted to move the object, then if you had electrodes arranged along the slot, and if you made
one of them plus, and another one minus, the field that's generated pulls the dielectric along. When
this piece gets to a new location, you change the voltages so that you're always pulling, and these
dielectrics go like those wonderful things that they have in the department store. You stick
something in the tube, and it goes whshhhht! to where it has to go.

There is another way, perhaps, of building the silicon circuits using these sliding devices. I have
decided this new way is no good, but I'll describe it anyway. You have a supply of parts, and a
sliding device goes over, picks up a part, carries it to the right place, and puts it inthe sliding devices
assemble everything. These devices are all moving, of course, under the electrical control of
computer stuff below them, under their surfaces. But this method is not very good compared to the
present evaporation technique, because there's one very serious problem. That is, after you put a
piece in, you want to make electrical contacts with the other pieces, but it's very difficult to make
good contacts. You can't just put them next to each otherthere's no contact. You've got to
electrodeposit something or use some such method, but once you start talking about
electrochemically depositing something to seal the contact, you might as well make the whole thing
the other way by evaporation.

Another question is whether you should use AC or DC to do the pulling: you could work it either
way. You could also do the same thing to generate rotations of parts by arranging electrostatic
systems for pulling things around a central point. The forces that will move these parts are not big
enough to bend anything very much; things are very stiff at this dimensional scale.

If you talk about rotating something, the problem of viscosity becomes fairly important; you'll be
somewhat disappointed to discover that if you left the air at normal air pressure in a small hole ten
microns big, and then tried to turn something, you'd be able to do it in milliseconds, but not faster.
That would be okay for a kit of applications, but it's only milliseconds. The time would be in
microseconds, if it weren't for viscous losses.

I enjoy thinking about these things, and you can't stop, no matter how ridiculous things get, so you
keep on going. At first, the devices weren't movingthey were in place. Now they can slide back and
forth on the surface. Next come the tiny, free-swimming machines.
Mobile Microrobots
What about the free-swimming machine? The purpose is no doubt for entertainment. It's
entertaining because you have controlit's like a new game. Nobody figured when they first designed
computers that there would be video games. So I have the imagination to realize what the game
here is: You get this little machine you can control from the outside, and it has a sword. The
machine gets in the water with a paramecium, and you try to stab it.

How are we going to make this game? The first problem is energy supply. Another one is controlling
the device. And if you wanted to find out how the paramecium looks to the device, you might want
to get some information out.

The energy supply is, I think, fairly easy. At first it looks very difficult because the device is free-
swimming, but there are many ways to put energy into the device through electrical induction. You
could use either electrical or magnetic fields that vary slowly, generating EMFs inside.

Another way, of course, is to use chemicals from the environment. This method would use a kind of
battery, but not as small as the device. The whole environment would be usedthe liquid surrounding
the device would be the source of a chemical reaction by which you could generate power. Or you
could use electromagnetic radiation. With this method you would shine the light on the device to
send the signal, or use lower frequencies that go through waterwell, not much goes through water
but light.

The same methods can be used for control. Once you have a way to get energy inby electrical
induction, for exampleit's very easy to put digits or bits on the energy signal to control what the
machine is going to do. And the same idea could be used to send signals out. I shouldn't be telling
people at JPL how to communicate with things that are difficult to get at or are far awaythis is far
away because it's so small. You'll figure out a way to send the signals out and get them back
againand enhance the pictures at the end.

It's very curious that what looks obvious is impossible. That is, how are you going to propel yourself
through the liquid? Well, you all know how to do thatyou have a tail that swishes. But it turns out
that if this is a tiny machine a few microns long, the size of a paramecium, then the liquid, in
proportion, is enormously viscous. It's like living in a thick honey. And you can try swimming in thick
honey, but you have to learn a new technique. It turns out that the only way you can swim in thick
honey is to have a kind of an "S" shaped fin. Twisting the shape pushes it forward. It has to be like a
piece of a screw, so that as you turn it, it unscrews out of the thick liquid, so to speak. Now, how do
we drive the screw?

You always think that there aren't any wheels in biology, and you say, "Why not?" Then you realize
that a wheel is a separate part that moves. It's hard to lubricate, it's hard to get new blood in there,
and so forth. So we have our parts all connected togetherno loose pieces. Bacteria, however, have
flagella with corkscrew twists and have cilia that also go around in a type of corkscrew turn. As a
matter of fact, the flagellum is the one place in biology where we really do have a movable,
separable part. At the end of the flagellum on the back is a kind of a disc, a surface with proteins
and enzymes. What happens is a complicated enzyme reaction in which ATP, the energy source,
comes up and combines, producing a rotational distortion [here, Feynman is using his hands to
simulate a molecule changing shape and experiencing a net rotation]; when the ATP releases, the
rotation stays, and then another ATP comes, and so forth. It just goes around like a ratchet. And it's
connected through a tube to the spiral flagellum that's on the outside.

Twenty years ago when I gave my talk, my friend Al Hibbs, who introduced me today, suggested a
use of small devices in medicine. Suppose we could make free-swimming little gadgets like this. You
might say, "Oh, that's the size of cellsgreat. If you've got trouble with your liver, you just put new
liver cells in." But twenty years ago, I was talking about somewhat bigger machines. And he said,
"Well, swallow the surgeon." The machine is a surgeonit has tools and controls in it. It goes over to
the place where you've got plaque in your blood vessel and it hacks away the plaque.

So we have the idea of making small devices that would go into the biological system in order to
control what to cut and to get into places that we can't ordinarily reach. Actually, this idea isn't so
bad, and if we back off from the craziness of making such tiny things, and ask about a device that is
more practical today, I think it is worth considering having autonomous machinesthat is, machines
that are sort of robots. I would tether the machines with thin wiresswallowing wires isn't much. It's
a little bit discouraging to think of swallowing those long tubes with the optics fibers and everything
else that would have to go down so the guy can watch the inside of your duodenum. But with just
the little wires, you could make the device go everywhere, and you could still control it.

Even the wires are really unnecessary, because you could control the machine from the outside by
changing magnetic fields or electric induction. And then we don't have to make the motors, engines,
or devices so very tiny as I'm talking about, but a reasonable size. Now it's not as crazily small as I
would likea centimeter or one half of a centimeterdepending on what you want to do the first few
times, the scale will get smaller as we go along, but it'll start that way. It doesn't seem impossible to
me that you could watch the machine with X-rays or NMR and steer it until it gets where you want.
Then you send a signal to start cutting. You watch it and control it from the outside, but you don't
have to have all these pipes, and you aren't so limited as to where you can get this machine to go. It
goes around corners and backs up.

I think that Hibbs's "swallowable surgeon" is not such a bad idea, but it isn't quite appropriate to the
tiny machines, the "infinitesimal machines." It's something that should be appropriate for small
machines on the way to the infinitesimal machines.
Making Precise Things from Imprecise Tools
These machines have a general problem, and that's the refinement of precision. If you built a
machine of a certain size, and you said, "Well, next year I want to build one of a smaller size," then
you would have a problem: you've only got a certain accuracy in dimensions. The next question is,
"How do you make the smaller one when you've only got that much accuracy?" It gets worse. You
might say, "I'll use this machine to make the smaller one," but if this machine has wobbly bearings
and sloppy pins, how does it make an accurate, beautiful, smaller machine?

As soon as you ask that question, you realize it's a very interesting question. Human beings came
onto the earth, and at the beginning of our history, we found sticks and stonesbent sticks and
roundish funny stones, nothing very accurate. And here we are today, with beautifully accurate
machinesyou can cut and measure some very accurate distances.

How do you get started? How do you get something accurate from nothing? Well, all machinists
know what you do. In the case of large machinery, you take the stones, or whatever, and rub them
against each other in every which way, until one grinds against the other. If you did that with one
pair of stones, they'd get to a position at which, no matter where you put them, they would fit. They
would have perfectly matched concave and convex spherical surfaces.

But I don't want spherical surfacesI want flat surfaces. So then you take three stones and grind
them in pairs, so that everybody fits with everybody else. It's painstaking and it takes time, but
after a while, sure enough, you've got nice flat surfaces. Someday, when you're on a camping trip,
and everything gets boring, pick up some stones. Not too hardsomething that can grind away a little
bit, such as consolidated or weak sandstones. I used to do this all the time when I was a kid in
Boston.

I'd go to work at MIT and on the way pick up two lumps of snow, hard snow that was pushed up by
the snowplow and refrozen. I'd grind the snow all the way till I got to MIT, then I could see my
beautiful spherical surfaces.

Or, for example, let's say you were making screws to make a lathe. If the screw has irregularities,
you could use a nut that's breakable; you would take the nut apart and turn it backwards. If you ran
the screw back and forth through the nut, both reversed and straight, soon you would have a perfect
screw and a perfect nut, more accurate than the pieces you started with. So it's possible.

I don't think any of these things would work very well with the small machines. Turning things over
and reversing and grinding them is so much work, and is so difficult with the hard materials, that
I'm not really quite sure how to get increased precision at the very small level.

One way, which isn't very satisfactory, would be to use the electrostatic dielectric push-pull
mechanism. If this device were fairly crude in shape, and contained some kind of a point or tooth
that was used for a grinder or a marker, you could control the position of the tooth by changing the
voltage rather smoothly. You could move it a small fraction of its own irregularity, although you
wouldn't really know exactly what that fraction was. I don't know that we're getting much precision
this way, but I do think it's possible to make things finer out of things that are cruder.

If you go down far enough in scale, the problem is gone. If I can make something one-half of a
percent correct, and the size of the thing is only one hundred atoms wide, then I've got one hundred
and not one hundred and one atoms in it, and every part becomes identical. With the finite number
of atoms in a small object, at a certain stage, objects can only differ by one atom. That's a finite
percentage, and so if you can get reasonably close to the right dimensions, the small objects will be
exactly the same.

I thought about casting, which is a good process. You ought to be able to manufacture things at this
scale by casting. We don't know of any limitationexcept atomic limitationsto casting accurate figures
by making molds for figures that match the originals. We know that already, because we can make
replicas of all kinds of biological things by using silicone or acetate castings. The electron microscope
pictures that you see are often not of the actual object, but of the casting that you've made. The
casting can be done down to any reasonable dimension.

One always looks at biology as a kind of a guide, even though it never invents the wheel, and even
though we don't make flapping wings for airplanes because we thought of a better way. That is,
biology is a guide, but not a perfect guide. If you are having trouble making smooth-looking
movable things out of rather hard materials, you might make sacs of liquid that have electric fields
in them and can change their shapes. Of course, you would then be imitating cells we already know
about. There are probably some materials that can change their shape under electric fields. Let's say
that the viscosity depends on the electric field, and so by applying pressure, and then weakening the
material in different places with electric fields, the material would move and bend in various ways. I
think it's possible to get motion that way.
Friction and Sticking
Now we ask, "What does happen differently with small things?" First of all, we can make them in
very great numbers. The amount of material you need for the machines is very tiny, so that you can
make billions of them for any normal weight of any material. No cost for materialsall the cost is in
manufacturing and arranging the materials. But special problems occur when things get smallor
what look like problems, and might turn out to be advantages if you knew how to design for them.

One problem is that things stick together by molecular attraction. Now friction becomes a difficulty.
If you were to have two tungsten parts, perfectly clean, next to each other, they would bind and
jam. The atoms simply pull together as if the two parts were one piece. The friction is enormous,
and you will never be able to move the parts. Therefore you've got to have oxide layers or other
layers in between the materials as a type of lubricantyou have to be very careful about that or
everything will stick.

On the other hand, if you get still smaller, nothing is going to stick unless it's built out of one piece.
Because of the Brownian motion, the parts are always shaking; if you put them together and a part
were to get stuck, it would shake until it found a way to move around. So now you have an
advantage.

At the end of it all, I keep getting frustrated in thinking about these small machines. I want
somebody to think of a good use, so that the future will really have these machines in it. Of course,
if the machines turn out to be any good, we'll also have to make the machines, and that will be very
interesting to try to do.
Computing with Atoms
Now we're going to talk about small, small computing. I'm taking the point of view of 1983 rather
than of 1960, and will talk about what is going to happen, or which way we should go.

Let's ask, what do we need to do to have a computer? We need numbers, and we need to
manipulate the numbers and calculate an answer. So we have to be able to write the numbers.

How small can a number be? If you have N digits, you know the special way of writing them with
base two numbers, that is, with ones and zeros. Now we're going to go way down to the
bottomatoms! Remember that we have to obey quantum-mechanical laws, if we are talking about
atoms. And each of these atoms is going to be in one of two statesactually, atoms can be in a lot of
states, but let's take a simple counting scheme that has either ones or zeros. Let's say that an atom
can be in a state of spin up or of spin down, or say that an ammonia molecule is either in the lowest
or the next lowest state, or suppose various other kinds of two-state systems. When an atom is in
the excited statea spin uplet's call it a "one"; a "zero" will correspond to spin down. Hereafter when I
say a one, I mean an atom in an excited state. So to write a number takes no more atoms than
there are digits, and that's really nothing!
Reversible Gates
Now what about operationscomputing something with the numbers? It is known that if you can only
do a few operations of the right kind, then by compounding the operations again and again in
various combinations, you can do anything you want with numbers.

The usual way of discussing this fact is to have these numbers as voltages on a wire instead of
states in an atom, so we'll start with the usual way. [Feynman draws a two-input AND gate at the
blackboard.] We would have a device with two input wires A and B, and one output wire. If a wire
has a voltage on it, I call it a "one"; if it has zero voltage, it's a "zero." For this particular device, if
both wires are ones, then the output turns to one. If either wire is one, but not both, or if neither is
one, the output stays at zerothat's called an AND gate. It's easy to make an electric transistor circuit
that will do the AND gate function.

There are devices that do other things, such as a little device that does NOTif the input wire is a one,
the output is a zero; if the input wire is a zero, the output is one. Some people have fun trying to
pick one combination with which they can do everything, for example, a NAND gate that is a
combination of NOT and ANDit is zero when both input wires are ones, and one when either or both
inputs are not ones. By arranging and wiring NAND gates together in the correct manner, you can
do any operation. There are a lot of questions about branchings and so forth, but that's all been
worked out. I want to discuss what happens if we try to do this process with atoms.

First, we can't use classical mechanics or classical ideas about wires and circuits. We have atoms,
and we have to use quantum mechanics. Well, I love quantum mechanics. So, the question is, can
you design a machine that computes and that works by quantum-mechanical laws of physicsdirectly
on the atomsinstead of by classical laws.

We find that we can't make an AND gate, we can't make a NAND gate, and we can't make any of the
gates that people used to say you could make everything out of. You see immediately why I can't
make an AND gate. I've only got one wire out and two in, so I can't go backwards. If I know that the
answer is zero, I can't tell what the two inputs were. It's an irreversible process. I have to
emphasize this fact because atomic physics is reversible, as you all know, microscopically reversible.
When I write the laws of how things behave at the atomic scale, I have to use reversible laws.
Therefore, I have to have reversible gates.

Bennett from IBM, Fredkin, and later Toffoli investigated whether, with gates that are reversible, you
can do everything. And it turns out, wonderfully true, that the irreversibility is not essential for
computation. It just happens to be the way we designed the circuits.

It's possible to make a gate reversible in the following cheesy way, which works perfectly. [Feynman
now draws a block with two inputs, A and B, and three outputs.] Let's suppose that two wires came
in here, but we also keep the problem at the output. So we have three outputs: the A that we put in,
the B that we put in, and the answer. Well, of course, if you know the A and the B along with the
answer, it isn't hard to figure out where the answer came from.

The trouble is that the process still isn't quite reversible, because you have two pieces of information
at the input, that is, two atoms, and three pieces of information at the output. It's like a new atom
came from somewhere. So I'll have to have a third atom at the input [he adds a third input line,
labeled C]. We can characterize what happens as follows:

Unless A and B are both one, do nothing. Just pass A, B, and C through to the output. If A and B are
both one, they still pass through as A and B, but C, whatever it is, changes to NOT C. I call this a
"controlled, controlled, NOT" gate.

Now this gate is completely reversible, because if A and B are not both ones, everything passes
through either way, while if A and B are both ones on the input side, they are both ones on the
output side too. So if you go through the gate forward with A and B as ones, you get NOT C from C,
and when you go backward with NOT C as the output, you get C back again at the input. That is,
you do a NOT twice, and the circuit, or atom, is back to itself, so it's reversible. And it turns out, as
Toffoli has pointed out, that this circuit would enable me to do any logical operation.

So how do we represent a calculation? Let's say that we have invented a method whereby choosing
any three atoms from a set of N would enable us to make an interaction converting them from a
state of ones and zeros to a new state of ones and zeros. It turns out, from the mathematical
standpoint, that we would have a sort of matrix, called M. Matrix M concerts one of the eight
possible combination states of three atoms to another combination state of the three atoms to
another combination state of the three atoms, and it's a matrix whose square is equal to one, a so-
called unitary matrix. The thing you want to calculate can be written as a product of a whole string
of matrices like Mmillions of them, maybe, but each one involves only three atoms at a time.

I must emphasize that, in my previous example with AND gates and wires, the wires that carried the
answer after the operation were new ones. But the situation is simpler here. After my matrix
operates, it's the same registerthe same atomsthat contain the answer. I have the input represented
by N atoms, and then I'm going to change them, change them, change them, three atoms at a time,
until I finally get the output.
The Electron as Calculating Engine
It's not hard to write down the matrix in terms of interactions between the atoms. In other words, in
principle, you can invent a kind of coupling among the atoms that you turn on to make the
calculation. But the question is, how do you make the succession of three-atom transformations go
bup-bup-bup-bup-bup in a row? It turns out to be rather easythe idea is very simple. [Feynman
draws a row of small circles, and points often to various circles in the row through the following
discussion.]

You can have a whole lot of spots, such as atoms on which an electron can sit, in a long chain. If you
put an electron on one spot, then in a classical world it would have a certain chance of jumping to
another spot. In quantum mechanics, you would say it has a certain amplitude to get there. Of
course, it's all complex numbers and fancy business, but what happens is that the Schrödinger
function diffuses: the amplitude defined in different places wanders around. Maybe the electron
comes down to the end, and maybe it comes back and just wanders around. In other words, there's
some amplitude that the electron jumped to here and jumped to there. When you square the
answer, it represents a probability that the electron has jumped all the way along.

As you all know, this row of sites is a wire. That's the way electrons go through a wirethey jump
from site to site. Assume it's a long wire. I want to arrange the Hamiltonian of the worldthe
connections between sitesso that an electron will have zero amplitude to get from one site to the
next because of a barrier, and it can only cross the barrier if it interacts with the atoms [of the
registers] that are keeping track of the answer. [In response to a question following the lecture,
Feynman did write out a typical term in such a Hamiltonian using an atom-transforming matrix M
positioned between electron creation and annihilation operators on adjacent sites.]

That is, the idea is to make the coupling so that the electron has no amplitude to go from site to
site, unless it disturbs the N atoms by multiplying by the matrix M2, in this case, or by M1 or M3 in
these other cases. If the electron started at one end, and went right along and came out at the other
end, we would know that it had made the succession of operations M1, M2, M3, M4, M5the whole
set, just what you wanted.

But wait a minuteelectrons don't go like that! They have certain amplitude to go forward, then they
come back, and then they go forward. If the electron goes forward, say, from here to there, and
does the operation M2 along the way, then if the electron goes backwards, it has to do the operation
M2 again.

Bad luck? No! M2 is designed to be a reversible operation. If you do it twice, you don't do anything;
it undoes what it did before. It's like a zipper that somebody's trying to pull up, but the person
doesn't zip very well, and zips it up and down. Nevertheless, wherever the zipper is at, it's zipped up
correctly to that particular point. Even though the person unzips it partly and zips it up again, it's
always right, so that when it's finished at the end, and the Talon fastener is at the top, the zipper
has completed the correct operations.

So if we find the electron at the far end, the calculation is finished and correct. You just wait, and
when you see it, quickly take it away and put it in your pocket so it doesn't back up. With an electric
field, that's easy.

It turns out that this idea is quite sound. The idea is very interesting to analyze, to see what a
computer's limitations are. Although this computer is not one we can build easily, it has got
everything defined in it. Everything is written: the Hamiltonian, the details. You can study the
limitations of this machine, with regard to speed, with regard to heat, with regard to how many
elements you need to do a calculation, and so on. And the results are rather interesting.
Heat in a Quantum Computer
With regard to heat: everybody knows that computers generate a lot of heat. When you make
computers smaller, all the heat that's generated is packed into a small space, and you have all kinds
of cooling problems. That is due to bad design. Bennett first demonstrated that you can do
reversible computingthat is, if you use reversible gates, the amount of energy needed to operate the
gates is essentially indefinitely small if you wait long enough, and allow the electrons to go slowly
through the computer. If you weren't in such a hurry, and if you used ideal reversible gateslike
Carnot's reversible cycle (I know everything has a little friction, but this is idealized)then the amount
of heat is zero! That is, essentially zero, in the limitit only depends on the losses due to
imperfections.

Furthermore, if you have ordinary reversible gates, and you try to drag the thing through as quickly
as you can, then the amount of energy lost at each fundamental operation is one kT of energy per
gate, or per decision, at most! If you went slower, and gave yourself more time, the loss would be
proportionately lower.

And how much kT do we use per decision now? 10 10 kT! So we can gain a factor of 1010 without a
tremendous loss of speed, I think. The problem is, of course, that it depends on the size that you're
going to make the computer.

If computers were made smaller, we could make them very much more efficient. It hadn't been
realized previous to Bennett's work that there was, essentially, no heat requirement to operate a
computer if you weren't in such a hurry. I have also analyzed this model, and get the same results
as Bennett with a slight modification, or improvement.

If this device is made perfectly, then the computer could work ballistically. That is, you could have
this chain of electron sites and start the electrons off with a momentum, and they simply coast
through and come out the other end. The thing is donewhshshshsht! You're finished, just like
shooting an electron through a perfect wire.

If you have a certain energy available to the electron, it has a certain speedthere's a relation
between the energy and the speed. If I call this energy that the electron has kT, although it isn't
necessarily a thermal energy, then there's a velocity that goes with v, which is the maximum speed
at which the electron goes through the machine. And when you do it that way, there are no losses.
This is the ideal case; the electron just coasts through. At the other end, you take the electron that
had a lot of energy, you take that energy out, you store it, and get it ready for shooting in the next
electron. No losses! There are no kT losses in an idealized computernone at all.

In practice, of course, you would not have a perfect machine, just as a Carnot cycle doesn't work
exactly. You have to have some friction. So let's put in some friction.

Suppose that I have irregularities in the coupling here and therethat the machine isn't perfect. We
know what happens, because we study that in the theory of metals. Due to the irregularities in the
positions or couplings, the electrons do what we call "scattering." They head to the right, if I started
them to the right, but they bounce and come back. And they may hit another irregularity and
bounce the other way. They don't go straight through. They rattle around due to scattering, and you
might guess that they'll never get through. But if you put a little electric field pulling the electrons,
then although they bounce, they try again, try again, and make their way through. And all you have
is, effectively, a resistance. It's as if my wire had a resistance, instead of being a perfect conductor.

One way to characterize this situation is to say that there's a certain chance of scatteringa certain
chance to be sent back at each irregularity. Maybe one chance in a hundred, say. That means if I did
a computation at each site, I'd have to pass a hundred sites before I got one average scattering. So
you're sending electrons through with a velocity v that corresponds to this energy kT. You can write
the loss per scattering in terms of free energy if you want, but the entropy loss per scattering is
really the irreversible loss, and note that it's the loss per scattering, not per calculation step
[heavily emphasized, by writing the words on the blackboard]. The better you make the computer,
the more steps you're going to get per scattering, and, in effect, the less loss per calculation step.

The entropy loss per scattering is one of those famous log2, numberslet me guess it is Boltzmann's
constant, k, or some such unit, for each scattering if you drive the electron as quickly as you can for
the energy that you've got.

If you take your time, though, and drive the electron through with an average speed, which I call
the drift speed, vD (compared to the thermal speed at which it would ordinarily be jostling back and
forth), then you get a decrease in the amount of entropy you need. If you go slow enough, when
there's scattering, the electron has a certain energy and it goes forward-backward-forward-bounce-
bounce and comes to some energy based on the temperature. The electron then has a certain
velocitythermal velocityfor going back and forth. It's not the velocity at which the electron is getting
through the machine, because it's wasting its time going back and forth. But it turns out that the
amount of entropy you lose every time you have 100% scattering is simply a fraction of kthe ratio of
the velocity that you actually make the electron drift compared to how fast you could make it drift.
[Feynman writes on the board the formula: k(vD/v t).]

If you drag the electron, the moment you start dragging it you get losses from the resistanceyou
make a current. In energy terms, you lose only a kT of energy for each scattering, not for each
calculation, and you can make the loss smaller proportionally as you're willing to wait longer than
the ideal maximum speed. Therefore, with good design in future components, heat is not going to be
a real problem. The key is that those computers ultimately have to be designedor should be
designedwith reversible gates.

We have a long way to go in that directiona factor of 1010. And so, I'm just suggesting to you that
you start chipping away at the exponent.

Thank you very much.

Acronyms and Abbreviations
AFM atomic force microscopy

AI artificial intelligence
ANSI American National Standards Institute
CMOS complementary metal oxide semiconductor
CMP chemical mechanical planarization or chemical mechanical
polishing
CNTs carbon nanotubes
CPSC Consumer Products Safety Commission
CRADA Cooperative Research and Development Agreement
CVD chemical vapor deposition
DoD Department of Defense
DOE Department of Energy

DPN dip-pen nanolithography

DRAM dynamic random access memory
IBEA Institute for Biological Energy Alternatives
IDD implantable drug delivery
LEDs light-emitting diodes
MEMS microelectromechanical systems

MMS molecular microswitch

MOSFET metal oxide semiconductor field effect transistor
MRI magnetic resonance imaging
MURI Multi-University Research Initiative
NASA National Aeronautics and Space Administration
NBIC nano-bio-info-cogno
NBs nanobelts
NCN Network for Computational Nanotechnology
NDA nondisclosure agreement
NDC negative differential conductance
NEMS nanoelectromechanical systems
NER Nanoscale Exploratory Research
NIEHS National Institute of Environmental Health Studies
NIH National Institutes of Health

NIL nanoimprint lithography

NIOSH National Institute for Occupational Safety and Health

NIRTs Nanoscale Interdisciplinary Research Teams
NIST National Institute of Standards and Technology
NNCO National Nanotechnology Coordination Office
NNI National Nanotechnology Initiative

NNIN National Nanotechnology Infrastructure Network

NNUN National Nanofabrication Users Network
NSE Nanoscale Science and Engineering
NSECs Nanoscale Science and Engineering Centers
NSEE Nanoscale Science and Engineering Education
NSET Nanoscale Science, Engineering and Technology
NSF National Science Foundation

NSP Nanotechnology Standards Panel

NSRCs Nanoscale Science Research Centers
NUE Nanotechnology Undergraduate Education
NWs nanowires
OSHA Occupational Safety and Health Administration
OTT office of technology transfer
PECVD plasma-enhanced chemical vapor deposition

ROADMs reconfigurable optical add/drop multiplexers

SAA Space Act Agreement
SAM self-assembling monolayer
SBIR Small Business Innovation Research
SEM scanning electron microscopy
SET single-electron transfer
SOI silicon on insulator
SPIONs superparamagnetic iron oxide nanoparticles
SPM scanning probe microscopy
STM scanning tunneling microscope
STTR Small Business Technology Transfer
SWNTs single-walled nanotubes
TEM transmission electron microscopy
URETI University Research, Engineering and Technology

USPTO U.S. Patent and Trademark Office

Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

21st Century Nanotechnology Research and Development Act 2nd 3rd

Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Academic freedom
Academic research [See Research; academic]
Accuracy
Aerosol pyrolysis
AFM (atomic force microscopy) 2nd
Agglomeration of nanoparticles
AI (artificial intelligence) 2nd
Aircraft development 2nd
Airflow, modeling
Albumin-bound paclitaxel conjugate
Alivisatos, Paul
AmBisome
Amphiphilic block copolymers
Anderson, P. W.
Armchair Quantum Wire
Army Research Laboratories
Arryx
Artificial intelligence (AI) 2nd
Atomic force microscopy (AFM) 2nd
Atoms, computing with
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Bawendi, Moungi
Bayh-Dole Act 2nd 3rd 4th
Beckman, Arnold
Berg, Paul
Biochips
Biogen
Bioinformatics
Biological development approaches 2nd [See also Self-assembly]
Biomolecular characterization
Biosensors 2nd
Biotechnology 2nd 3rd 4th 5th
Bock, Larry
Bottom-up development 2nd [See also Self-assembly]
Boyer, Herbert 2nd
Brain, computational power of human 2nd
Bubble-memory
Buckytubes [See Nanotubes, carbon]
Business applications [See Commercialization]
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Caltech OTT
Cancer, nanotechnology and 2nd 3rd
Carbon black
Carbon nanotubes (CNT) [See Nanotubes, carbon]
Catalytic activity
Centers for Learning and Teaching (NCLT)
Chemical mechanical planarization (CMP) 2nd
Chemical sensors 2nd 3rd
Cheminformatics
Chemistry 2nd 3rd 4th 5th
City of Hope National Medical Center 2nd
CMOS (complementary metal oxide semiconductors) transistors
CMP (chemical mechanical planarization) 2nd
CNT (carbon nanotubes) [See Nanotubes, carbon]
Coblentz, William
Cognitive sciences, future development
Cohen, Stanley
Cold fusion
Combinatorial materials discovery
Commercialization
challenges 2nd 3rd
characteristics 2nd 3rd
development and 2nd
future 2nd 3rd
incorporating nanotechnology
incorporating new technology
marketing/sales
testing
time line 2nd
Companies, types of nanotechnology
Complementary metal oxide semiconductors (CMOS) transistors
Composite materials
Computing, changes in 2nd
Confidentiality 2nd
Confidentiality agreements
Confocal microscopy
Consistency, physical
Consultants
ethics
faculty as 2nd
Consumer Products Safety Act
Convergent technologies 2nd
Cooperative Research and Development Agreement (CRADA)
Copyrights
Crick, Francis
Current flow
Cynicism
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Data storage density

Dendrimers
Department of Defense (DoD) 2nd 3rd 4th
Department of Energy (DOE) 2nd 3rd
Deployable sensors
Deutsch, David
Digitization
Disclosure forms, invention
Discontinuities, S-curve 2nd
Disillusionment
Distribution of benefits, societal
DNA
characterization
detection
discovery
ethics
genetic engineering 2nd
Human Genome Project
manipulating
mapping human 2nd
Minimal Genome Project
reproducing
DoD (Department of Defense) 2nd 3rd 4th
DOE (Department of Energy) 2nd 3rd
Donations to academic institutions
Doxil
Drug delivery
current technology
growth in nanotechnology
implantable
nanoparticles
transdermal
Drug development applications 2nd
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Education support, U.S. government 2nd

Education, integrated
Electrical energy
Electronic behavior
Eli Lilly
Emergent behavior, development
Energy, nanotechnology and 2nd 3rd 4th
Entrepreneurs
actions 2nd
challenges 2nd
characteristics 2nd 3rd
technology requirements
Environment
concerns 2nd 3rd
nanotechnology applications 2nd
regulation
research
Environmental Protection Agency (EPA)
Escherichia coli bacterium
Ethics
basis
free genetic expression
nanotechnology-specific
organizational approaches
promoting ethical behavior
research on
Evolution
artificial
industry
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Fabrication [See Manufacturing]

Federal Food, Drug and Cosmetic Act
Federal funding [See Funding; U.S. federal]
FEI Co.
Feynman, Richard 2nd 3rd
Financing [See Funding]
FinFET semiconductors
Firearms technology
Flip chips
Fluorescence microscopy
Food availability
Foster, Richard
Frauds
Freedom, academic
Friction
Fuel cells
Fuels [See also Energy, nanotechnology and]
Funding
academic research 2nd 3rd 4th 5th 6th
business 2nd 3rd
increase in
international
U.S. federal
about 2nd
Department of Defense 2nd 3rd
Department of Energy
Environmental Protection Agency
history 2nd
intellectual property 2nd
legislation 2nd 3rd
NASA 2nd
NIH 2nd
NSF
U.S. Army
venture capital 2nd 3rd 4th
Fusion, cold
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Gates, logic 2nd 3rd 4th 5th

Genentech 2nd
Genes [See DNA]
Genetic engineering 2nd
Gliadel 2nd
Gold 2nd
Grand challenges (NNI)
Groupthink
Guns
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Hazard assessment [See also Safety]

Health regulation
Heat generation
Hewlett-Packard
Heyneker, Herb
High-throughput experimentation
Human Genome Project [See also DNA]
Humans, computational power of 2nd
Hybrid development
Hype curve
Hype cycle
Hype, technology
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

IBEA (Institute for Biological Energy Alternatives)

ICs (Integrated circuits) [See Semiconductors]
IDD (implantable drug delivery) devices
Ideas, characteristics of
Iijima, Sumio
Image resolution
Imaging technology
Imago
Implantable drug delivery (IDD) devices
Infinitesimal Machinery (Feynman) 2nd
Informal Science Education (NISE)
Information technology (IT), future development
Infrastructure support, U.S. government 2nd
Initial public offerings (IPOs)
Innovation 2nd 3rd [See also Progress, Research]
Inorganic nanoparticles
Institute for Biological Energy Alternatives (IBEA)
Institute for Soldier Nanotechnologies
Instructional Materials Development (NIMD)
Insulin, creating human 2nd 3rd
Integrated circuits (ICs) [See Semiconductors]
Integration of sciences 2nd
Integration, industry
Intellectual property (IP)
academic research 2nd 3rd 4th
advantages
as company assets
ethics
government role
growth of nanotechnology-related
importance
licensing [See Licensing]
patents [See Patents]
protecting
risks of acquiring
royalties
technology transfer [See Technology transfer]
types
Intematix
Internet, development of
Invention disclosure forms
Investment [See Funding]
IP (intellectual property) [See Intellectual property]
IPOs (initial public offerings)
IT (Information Technology), future development
Itakura, Keiichi
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Japanese government funding

Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Landauer, Rolf
LEDs (light-emitting diodes)
Legal issues 2nd
Legislation
21st Century Nanotechnology Research and Development Act 2nd 3rd
Bayh-Dole Act 2nd 3rd 4th
Consumer Products Safety Act
Federal Food, Drug and Cosmetic Act
Occupational Safety and Health Act
Toxic Substances Control Act
Lessig, Larry
Licensing
about 2nd
advantages 2nd 3rd 4th
risks 2nd 3rd 4th
Ligands
Light emission technology
Light-emitting diodes (LEDs)
Liposomes
Litigation, intellectual property 2nd
Logic devices 2nd 3rd 4th 5th
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Magnetic resonance imaging (MRI)

Management
Manufacturing
bottom-up [See also Self-assembly]
business model
firearms
future trends 2nd
research on
semiconductors [See Semiconductors; manufacture]
top-down 2nd
Materials
characteristics 2nd
composite
future development
history 2nd
nanomaterials businesses
nomenclature
Medicine [See also National Institute of Environmental Health Sciences, NIH, NIOSH]
applications
cancer detection/treatment 2nd 3rd
carbon nanotubes
drug delivery [See Drug delivery]
drug development 2nd
future development 2nd 3rd 4th 5th
insulin 2nd 3rd
MRIs
soft nanoscale structures
regulation
safety [See Safety]
Memory, computer 2nd 3rd 4th
MEMS (microelectromechanical systems) 2nd 3rd 4th
Metal oxide semiconductor field effect transistors (MOSFETs) 2nd 3rd
Metallic nanoparticles
Metrology
Micelles, polymer
MicroCHIPS, Inc.
Microelectromechanical systems (MEMS) 2nd 3rd 4th
Microelectronics 2nd
Microneedles
Microscopy 2nd
Military applications 2nd 3rd
Miniaturization development, approaches to 2nd
Minimal Genome Project
MIT, research at
MMSs (molecular microswitches)
Modeling 2nd 3rd
Molecular electronics (moltronics) 2nd 3rd
Molecular Imprints
Molecular microswitches (MMSs)
Moltronics (Molecular electronics) 2nd 3rd
Moore's Law 2nd 3rd 4th 5th
Moore's Second Law
Moore, Gordon 2nd 3rd 4th
MOSFETs (metal oxide semiconductor field effect transistors) 2nd 3rd
MRI (magnetic resonance imaging)
Multi-University Research Initiative (MURI)
Multi-walled nanotubes (MWNTs) 2nd
Multiporphyrin nanostructures
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Nano-bio-info-cogno (NBIC) convergence 2nd

Nanobarcodes
Nanobelts (NBs) 2nd
Nanobiotechnology 2nd
Nanocantilevers
Nanocapsule drug-containing nanoparticles
Nanoelectromechanical systems (NEMS)
Nanoelectronics 2nd
Nanoelements assembly
Nanoinstrumentation 2nd
Nanolithography 2nd
Nanomaterials [See Materials]
Nanomotors
Nanoparticles 2nd
Nanophotonics 2nd 3rd 4th
Nanoporous membranes
Nanoribbons
Nanorings
Nanoscale Exploratory Research (NER)
Nanoscale Interdisciplinary Research Teams (NIRTs)
Nanoscale particles, manipulating
Nanoscale pores
Nanoscale Science and Engineering (NSE) program
Nanoscale Science and Engineering Centers (NSECs)
Nanoscale Science and Engineering Education (NSEE)
Nanoscale Science Research Centers (NSRCs) 2nd 3rd
Nanoshells
Nanosoftware 2nd
Nanosphere drug-containing nanoparticles
Nanosprings
Nanostructures, multiporphyrin
Nanotechnology
characteristics 2nd 3rd
defined 2nd
fad vs. trend 2nd 3rd
future development 2nd 3rd 4th 5th
history
interfaces with
limitations
relation to other sciences
social implications 2nd
terminology 2nd 3rd
Nanotechnology Standards Panel (NSP)
Nanotechnology Undergraduate Education (NUE)
Nanotubes, carbon
characteristics 2nd 3rd 4th 5th
 commercial applications
computer memory cells
development
electrical transmission
history
in semiconductors 2nd 3rd
multi-walled 2nd
patents
production 2nd
single-walled 2nd 3rd 4th 5th
Nanowhiskers
Nanowires (NWs) 2nd 3rd 4th 5th
Nantero, Inc. 2nd
NASA (National Aeronautics and Space Administration)
Ames Research Center 2nd 3rd 4th 5th
funding 2nd
technology transfer program
National Academy of Sciences
National Aeronautics and Space Administration (NASA) [See NASA]
National Institute of Environmental Health Sciences
National Institute of Occupational Safety and Health (NIOSH) 2nd
National Institute of Standards and Technology (NIST) 2nd 3rd
National Institutes of Health (NIH) 2nd 3rd 4th 5th
National Nanofabrication Users Network (NNUN)
National Nanotechnology Advisory Panel
National Nanotechnology Coordination Office (NNCO) 2nd
National Nanotechnology Infrastructure Network (NNIN)
National Nanotechnology Initiative (NNI) 2nd 3rd 4th 5th 6th
National Science Foundation (NSF) 2nd 3rd
Naval Research Laboratory, U.S.
NBIC (nano-bio-info-cogno) convergence 2nd
NBs (nanobelts) 2nd
NCLT (Centers for Learning and Teaching)
NCN (Network for Computational Nanotechnology) 2nd
NDAs (nondisclosure agreements) 2nd
NEHI Working Group
NEMS (nanoelectromechanical systems)
NER (Nanoscale Exploratory Research)
Network for Computational Nanotechnology (NCN) 2nd
Neural networks
Neurons, functions enabled by
NIH (National Institutes of Health) 2nd 3rd 4th 5th
NIMD (Instructional Materials Development)
NIOSH (National Institute of Occupational Safety and Health) 2nd
NIRTs (Nanoscale Interdisciplinary Research Teams)
NISE (Informal Science Education)
NIST (National Institute of Standards and Technology) 2nd 3rd
NNCO (National Nanotechnology Coordination Office) 2nd
NNI (National Nanotechnology Initiative) 2nd 3rd 4th 5th 6th
NNIN (National Nanotechnology Infrastructure Network)
NNUN (National Nanofabrication Users Network)
Nomenclature, nanomaterials 2nd 3rd
Nondisclosure agreements (NDAs) 2nd
Norplant
NSE (Nanoscale Science and Engineering) program
NSECs (Nanoscale Science and Engineering Centers)
NSEE (Nanoscale Science and Engineering Education)
NSET (Subcommittee on Nanoscale Science, Engineering, and Technology) 2nd
NSF (National Science Foundation) 2nd 3rd
NSP (Nanotechnology Standards Panel)
NSRCs (Nanoscale Science Research Centers) 2nd
NUE (Nanotechnology Undergraduate Education)
NWs (nanowires) 2nd 3rd 4th 5th
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Occupational Safety and Health Act

Office of Science and Technology Policy
Offices of Technology Transfer (OTTs) 2nd 3rd
Optical technology 2nd 3rd 4th
Optical traps
OTTs (Offices of Technology Transfer) 2nd 3rd
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Paclitaxel conjugate, albumin-bound

Panasonic
Partnering, business/academic
Patents
about
academic research 2nd 3rd 4th 5th
acquiring 2nd
as company assets
commercial
enforcing
licensing [See Licensing]
limitations on development
litigation based on
nanotechnology-related 2nd
selling
U.S. vs. foreign
United States Patent and Trademark Office 2nd 3rd
Patterson, John
PECVD (plasma-enhanced chemical vapor deposition)
PEG-adenosine deaminase
PEG-interferon
PEG-L-asparaginase
Photonic crystals
Photonics 2nd 3rd 4th
Physical sensors
Plasma-enhanced chemical vapor deposition (PECVD)
Polymer micelles
Polymer nanoparticles
Polymer-drug conjugates
Polyplexes 2nd
Power 2nd 3rd 4th
Precision, improving
President's National Science and Technology Council
Products [See Commercialization]
Progress [See also Innovation]
disruptive 2nd
exponential nature 2nd
Protein binding, detection
Public equity markets
Publications on nanotechnology
Pure Food and Drug Act
Pyrolysis, aerosol
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Quantum computing 2nd 3rd 4th

Quantum dots 2nd
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Radios, transistor
Rent's Law
Research
academic
focus areas 2nd
funding 2nd 3rd 4th 5th 6th
intellectual property and 2nd 3rd 4th
transfer to commercial arena [See Technology transfer]
academic/commercial partnering
commercial
focus areas
high-throughput experimentation
product integration
resources
DNA [See DNA]
environmental
ethics
manufacturing
modeling 2nd 3rd
safety 2nd 3rd
U.S. government-supported [See Funding; U.S. federal]
Resolution, image
Reversible gates 2nd 3rd
Riggs, Arthur
Rights
government 2nd 3rd
transferring [See Technology transfer]
Rip-offs
Risk assessment [See also Safety]
Robotics
Rotaxane
Royalties
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

S-curves 2nd
SAA (Space Act Agreement)
Safety
assessment
government support/regulation 2nd 3rd
nanomaterials 2nd 3rd
research on 2nd 3rd
SAM (self-assembling monolayer)
Samsung
Samueli, Henry
SBIR (Small Business Innovation Research) 2nd
Scaling
Scams
Scanning tunneling microscopes (STMs) 2nd
Screens, display
Self-assembling monolayer (SAM)
Self-assembly 2nd 3rd 4th 5th [See also Biological development approaches]
Semiconductor Research Corporation (SRC)
Semiconductors
current technology 2nd 3rd 4th 5th
future technology 2nd
industry performance
manufacture 2nd 3rd 4th
Moore's Law 2nd 3rd 4th 5th
Sensors
applications 2nd 3rd
carbon nanotubes as
commercialization 2nd
design challenges 2nd
future development 2nd 3rd
integration 2nd
materials
modeling physiological
production
tools for
types 2nd
Simulation 2nd 3rd 4th 5th
Single-walled nanotubes (SWNTs) 2nd 3rd 4th 5th
Skepticism
Small Business Innovation Research (SBIR) 2nd
Small Business Technology Transfer (STTR) 2nd
Small machines
applications
friction
moving
precision
 production
Smalley, Richard
"Smart dust" particles
Smith, Hamilton
SnifferSTAR 2nd
Soft nanoscale structures
Software
as design tool
biological development model
human intelligence as model
nano- 2nd
simulation 2nd 3rd 4th 5th
Solar cells
Solar energy
Somatostatin synthesis 2nd
Sony
Space Act Agreement (SAA)
Spin, electron
SPIONs (superparamagnetic iron oxide nanoparticles)
SRC (Semiconductor Research Corporation)
Start-up companies
Stevens, Mark
STMs (scanning tunneling microscopes) 2nd
Stock markets
Storage, computer 2nd 3rd 4th
Strategic partnering
STTR (Small Business Technology Transfer) 2nd
Subcommittee on Nanoscale Science, Engineering, and Technology (NSET) 2nd
Subsumption architecture
Sunscreens
Superparamagnetic iron oxide nanoparticles (SPIONs)
Surfactants
"Swallowable surgeons"
Swanson, Robert 2nd 3rd
SWNTs (single-walled nanotubes) 2nd 3rd 4th 5th
Synthetic fuels
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Technology transfer
academic culture and
barriers to
business relationships
defined
from government/academic research 2nd 3rd [See also OTTs]
process 2nd
reasons
risks
Technology triggers
Television screens
Terminology, nanotechnology 2nd 3rd
There's Plenty of Room at the Bottom (Feynman) 2nd 3rd
Top-down development 2nd
Toxic Substances Control Act
Trade secrets 2nd
Trademarks
Transdermal drug delivery
Transistor capability and Moore's Law
Transistor radios
Triggers, technology
Turbulence, modeling
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

U.S. Naval Research Laboratory

United States government
federal labs
legislation/regulation
funding/oversight of academic research 2nd 3rd [See also Funding; U.S. federal]
IP from academic research 2nd 3rd 4th
safety 2nd
role in nanotechnology 2nd 3rd 4th [See also Funding; U.S. federal]
transfer to business [See Technology transfer]
United States Patent and Trademark Office (USPTO) 2nd 3rd
University Research, Engineering and Technology (URETI) centers
User-friendliness
USPTO (United States Patent and Trademark Office) 2nd 3rd
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Van Sant, Tom

Venter, Craig
Venture capital investment 2nd 3rd 4th
Vertical integration
Viadur
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

Water availability
Watson, Jim
Web as biological growth model
Wind energy
Workforce support, U.S. government 2nd 3rd
Index
[SYMBOL] [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [Z]

ZettaCore, Inc. 2nd 3rd

Zinc oxide (ZnO) 2nd
Zygon (journal)