Introduction to BioMEMS 1st Edition

Visit the link below to download the full version of this book:

https://medipdf.com/product/introduction-to-biomems-1st-edition/

Click Download Now

Introduction to
BioMEMS

Albert Folch
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2013 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business

No claim to original U.S. Government works

Version Date: 20120525

International Standard Book Number-13: 978-1-4665-0938-2 (eBook - PDF)

This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been
made to publish reliable data and information, but the author and publisher cannot assume responsibility for the valid-
ity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright
holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this
form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may
rectify in any future reprint.

Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or uti-
lized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopy-
ing, microfilming, and recording, or in any information storage or retrieval system, without written permission from the
publishers.

For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://
www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923,
978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For
organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged.

Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for
identification and explanation without intent to infringe.
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
This book is dedicated to Lisa Horowitz, wife, collaborator, critic, and, above
all, friend, without whom this book could have never been conceived.
 Contents
List of Figures....................................................................................................xvii
Preface. ........................................................................................................... xxxi
Author. ............................................................................................................ xxxv

CHAPTER 1 How Do We Make Small Things?...................................................... 1

1.1 Why Bother Making Things Small?.......................................... 1

1.1.1 The Small-Scale Benefit............................................... 1
1.1.2 The High-Throughput Benefit...................................... 2
1.1.3 The Quantitative Benefit.............................................. 2

1.2 From Art to Chips. ................................................................. 3

1.3 Photolithography.................................................................... 4
1.3.1 Basics: Photoresist and Photomask............................... 4
1.3.2 Black or White versus Gray Scale. ................................ 5
1.3.3 Resolution.................................................................. 5
1.3.4 The SU-8 Era: High Aspect Ratios................................ 7
1.3.5 Biocompatible Photoresists.......................................... 8
1.3.6 Maskless Photolithography.......................................... 9
1.3.6.1 The Digital Micromirror Device:
Affordable Maskless Photolithography,
at Last...................................................... 10

1.4 Micromachining................................................................... 11
1.4.1 Etching: Wet versus Dry, Isotropic versus Anisotropic...... 11
1.4.2 Deposition and “Lift-Off”.......................................... 12
1.4.3 Nontraditional Substrates.......................................... 14
1.4.4 Laser Cutting. .......................................................... 14
1.4.5 Multiphoton Lithography.......................................... 15

1.5 Micromolding...................................................................... 17
1.5.1 Injection Molding..................................................... 18
1.5.2 Hot Embossing......................................................... 18
1.5.3 Curable Polymers. .................................................... 18

1.6 Soft Lithography................................................................... 19

1.6.1 Basics of Soft Lithography. ........................................ 20

vii
 Contents

1.6.2 The Magic of PDMS.................................................. 22

1.6.3 Microstamping......................................................... 24
1.6.4 Microfluidic Patterning............................................. 26
1.6.5 Stencil Patterning..................................................... 31
1.6.6 Dynamic Substrates.................................................. 33
1.6.6.1 Tunable Molds.......................................... 33
1.6.6.2 Microfluidic Photomasks for Grayscale
Photolithography...................................... 35

1.7 Hydrogel Devices.................................................................. 36

1.8 Nanofabrication Techniques.................................................. 37

1.8.1 Electron Beam Lithography....................................... 37
1.8.2 Scanning Probe Lithography. .................................... 37

1.9 Fabrication Based on Self-Assembly: A “Bottom-Up”

Approach............................................................................ 38

1.10 Summary............................................................................. 40

Further Reading................................................................... 40

CHAPTER 2 Micropatterning of Substrates and Cells. ....................................... 41

2.1 Interaction between Surfaces and Biomolecules....................... 43

2.1.1 Physisorption versus Chemisorption. ......................... 44
2.1.2 Hydrophilic versus Hydrophobic................................ 45
2.1.3 Cell Attachment to Substrates.................................... 45

2.2 Surface Engineering.............................................................. 46

2.2.1 Self-Assembled Monolayers....................................... 46
2.2.2 Deterring Protein Physisorption. ............................... 48
2.2.3 Cross-Linkers........................................................... 51

2.3 Micropatterns of SAMs......................................................... 51

2.3.1 Selective Blocking of SAM Formation......................... 52
2.3.2 Selective Formation of SAM on Prepatterned Surfaces...... 53
2.3.3 Microcontact Printing of SAMs. ................................ 53
2.3.4 Selective Modification/Removal of SAM..................... 53

2.4 Micropatterns of Proteins...................................................... 54

2.4.1 By Light................................................................... 54
2.4.2 By Microstamping.................................................... 58
2.4.3 By Microfluidic Patterning. ....................................... 61
2.4.4 By Self-Assembly...................................................... 64

2.5 Micropatterns of Cells on Nonbiomolecular Templates. ........... 64

2.5.1 Cells on Micropatterns of Metals or Oxides. ............... 65
2.5.2 Cells on SAM Micropatterns...................................... 67
2.5.3 Cells on Polymer Micropatterns................................. 68

viii
 Contents

2.6 Micropatterns of Cells on Biomolecular Templates................... 71

2.6.1 Micropatterns of Physisorption-Repellent
Background............................................................72
2.6.1.1 HEG-Thiol SAM....................................... 72
2.6.1.2 PEG Interpenetrated Networks. ................. 73
2.6.1.3 Direct Photolithography of PEG-Silane....... 75
2.6.1.4 Pluronic................................................... 75
2.6.1.5 PLL-g-PEG Copolymers. ........................... 76
2.6.1.6 Micropatterns of Cell-Repellent Hydrogels...... 76
2.6.2 Micropatterning Cell–Substrate Adhesiveness............. 78
2.6.2.1 Physical Masking of Background with
Photoresist. ............................................... 78
2.6.2.2 Selective Photochemical Immobilization
of Proteins................................................ 81
2.6.2.3 Removable Microfabricated Stencils............ 81
2.6.2.4 Microstamping of Protein Patterns............. 83
2.6.2.5 Selective Microfluidic Delivery of Proteins...... 84
2.6.2.6 Selective Microfluidic Delivery of Cell
Suspensions.............................................. 85
2.6.2.7 Selective Physisorption on a
Microtextured Surface............................... 86
2.6.3 Cells on Chemisorbed Patterns of Specific Peptide
Sequences. ............................................................... 87
2.6.3.1 Selective Attachment of Peptides on
Heterogeneous Surfaces............................. 87
2.6.3.2 Selective Photochemical Immobilization
of Peptides................................................ 89
2.6.3.3 Selective Microfluidic Delivery of Peptides...... 89
2.6.4 Other Cell Micropatterning Strategies........................ 90
2.6.4.1 Selective Biorecognition by the Substrate.......90
2.6.4.2 In Situ Microfabrication of Protein
Structures. ............................................... 91
2.6.4.3 Microstamping of Cells............................. 92
2.6.4.4 Electroactive Substrates............................. 93

2.7 Summary............................................................................. 95

Further Reading................................................................... 95

CHAPTER 3 Microfluidics................................................................................. 97

3.1 Why Go Small?..................................................................... 98

3.2 Microscale Behavior of Fluids................................................ 99

3.2.1 Viscosity................................................................ 100
3.2.2 Nondimensional Analysis: Reynolds Number and
Peclet Number........................................................ 100
3.2.3 Laminar Flow......................................................... 101
3.2.4 Parabolic Flow Profile............................................. 102

ix
 Contents

3.2.4.1 Circular Cross-Section............................ 103

3.2.4.2 Rectangular Cross-Section....................... 103
3.2.4.3 Triangular (Isosceles) Cross-Section......... 105
3.2.5 Microchannel Resistance......................................... 105
3.2.6 Shear Stress............................................................ 106
3.2.7 Capillary Flow........................................................ 109
3.2.8 Flow through Porous Media. ................................... 109
3.2.9 Diffusion. .............................................................. 109
3.2.10 Surface Tension, Contact Angles, and Wetting.......... 112
3.2.11 The Surface-to-Volume Problem............................... 114

3.3 Fluids in Electrical Fields..................................................... 114

3.3.1 Electrophoresis....................................................... 115
3.3.2 Electro-Osmosis..................................................... 116
3.3.3 Dielectrophoresis.................................................... 118
3.3.4 Electrowetting........................................................ 119

3.4 Fluids in Acoustic Fields...................................................... 120

3.4.1 Acoustophoresis..................................................... 120
3.4.2 Acoustic Streaming................................................. 122

3.5 Fabrication of Microfluidic Channels.................................... 123

3.5.1 The Building Materials............................................ 123
3.5.1.1 The “Historical” Materials: Silicon
and Glass. .............................................. 123
3.5.1.2 The Advent of Plastics. ............................ 123
3.5.1.3 A New Kid on the Block: PDMS............... 124
3.5.1.4 Other Polymers. ..................................... 125
3.5.1.5 Hydrogel Devices.................................... 126
3.5.1.6 Paper..................................................... 128
3.5.2 3-D Stacking and Bonding....................................... 130
3.5.3 Inlets: the “Macro-to-Micro Interface” Problem. ....... 134
3.5.4 Microchannel Wall Coatings................................... 134

3.6 Operation of Microfluidic Channels: Practical Concerns........ 137

3.6.1 Filling a Microchannel: The “Bubble Curse” and
Methods to Jinx It................................................... 137
3.6.2 Driving the Flow. ................................................... 139
3.6.3 Flow Visualization.................................................. 140

3.7 Droplet Microfluidics.......................................................... 140

3.7.1 Electrowetting Platform: “Digital Microfluidics”. ...... 141
3.7.2 “Oil Carrier” Microdroplet Platform. ....................... 142
3.7.3 “Air Carrier” Microfluidic Platform.......................... 144

3.8 Active Flow Control............................................................ 145

3.8.1 Microvalves............................................................ 146
3.8.1.1 Electrokinetic Valving............................. 146
3.8.1.2 Centrifugal Microvalves (“Lab-CD”)........ 147

x
 Contents

3.8.1.3 Check Microvalves.................................. 147

3.8.1.4 PDMS Microvalve: The Pinch Valve
Design or “Quake Microvalve”................. 148
3.8.1.5 PDMS Microvalve: The “Doormat”
Design................................................ 150
3.8.1.6 PDMS Microvalve: The “Sidewall Design”..... 152
3.8.1.7 PDMS Microvalve: The “Curtain Design”..... 152
3.8.1.8 PDMS Microvalve: The “Plunger Design”...... 153
3.8.1.9 PDMS Valve: Latch-On Design. ............... 154
3.8.1.10 Electrically Actuated PDMS Microvalves.... 155
3.8.1.11 PDMS Microvalves Actuated by
“Braille” Pins.......................................... 156
3.8.1.12 Smart Polymer Microvalves..................... 157
3.8.1.13 Single-Use Microvalves............................ 158
3.8.1.14 “Valve-Less” Approaches......................... 160
3.8.2 Microfluidic Resistors. ............................................ 161
3.8.3 Multiplexers........................................................... 163
3.8.3.1 Multiplexer with Binary Valves................ 163
3.8.3.2 Combinatorial Operation of a Binary
Multiplexer............................................. 164
3.8.3.3 Combinatorial Multiplexer. ..................... 165
3.8.3.4 Multiplexers with Ternary and
Quaternary Valves. ................................. 167
3.8.4 Micropumps. ......................................................... 168
3.8.4.1 Micropumps Driven by Surface Tension....... 168
3.8.4.2 Gas-Permeation Micropumps. ................. 169
3.8.4.3 Three-Valve PDMS Peristaltic
Micropumps........................................... 170
3.8.4.4 “Single-Stroke” PDMS Peristaltic
Micropumps........................................... 171
3.8.4.5 Diaphragm Micropumps......................... 173
3.8.4.6 Piezoelectric Micropumps. ...................... 173
3.8.4.7 Ultrasound-Based Micropumps. .............. 174
3.8.5 Microfabricated Flow Gauges................................... 175

3.9 Micromixers....................................................................... 176

3.9.1 T- or Y-Mixer......................................................... 176
3.9.2 Dilution and Gradient Generators............................ 177
3.9.3 Gradients Delivered through Microjets..................... 182
3.9.4 Microfluidic Pens.................................................... 184
3.9.5 Gradients Delivered through a Semipermeable
Barrier................................................................... 186
3.9.5.1 Gradient Generators that Incorporate
Porous Membranes. ................................ 186
3.9.5.2 Gradient Generators that Incorporate
Hydrogels. .............................................. 187

3.10 Combinatorial Mixers......................................................... 191

3.10.1 Homogenizers........................................................ 192

xi
 Contents

3.10.1.1 Homogenization Directed by Pulsatile

Flow: The “Dahleh Micromixer”............... 192
3.10.1.2 Homogenization by 3-D Serpentines. ....... 194
3.10.1.3 Homogenization by Tesla Mixer............... 197
3.10.1.4 Homogenization Directed by Surface
Topology. ............................................... 197
3.10.1.5 Homogenization Induced by Surface
Charge Patterns...................................... 198
3.10.1.6 Homogenization Induced by Bubble-
Based Acoustic Streaming........................ 198
3.10.2 Micromixers Incorporating Dynamic Elastomeric
Microelements........................................................ 200
3.10.2.1 Microvalve-Based Mixers. ....................... 200
3.10.2.2 Tunable Microtopography. ...................... 203
3.10.2.3 Vortex-Type Mixer.................................. 203

3.11 Summary........................................................................... 205

Further Reading................................................................. 205

CHAPTER 4 Molecular Biology on a Chip........................................................ 207

4.1 The Importance of Miniaturizing Molecular Biology. ............ 208

4.2 The Importance of Point-of-Care Diagnostics: Where Is Cost

Really, Really, Really Important?.......................................... 208

4.3 Sample Preparation: A Bloody Example................................ 209

4.3.1 Fluid Conditioning for Cell-Free Analysis................. 209
4.3.2 Fluid Conditioning for Cell Analysis........................ 211

4.4 The Problem with Microfluidic Sample Separation................. 211

4.4.1 Capillary Electrophoresis on a Chip. ........................ 212
4.4.2 Continuous-Flow and “Free-Flow” Electrophoresis. ....... 215
4.4.3 Isoelectric Focusing................................................ 216
4.4.4 Continuous-Flow Magnetic Separations. .................. 216
4.4.5 Molecular Sieving................................................... 217

4.5 Microfluidic Immunoassays................................................. 218

4.5.1 The Pregnancy Test................................................. 219
4.5.2 Homogeneous Phase Immunoassays. ....................... 221
4.5.3 Heterogeneous Phase (Surface-Bound)
Immunoassays. ...................................................... 222
4.5.4 Capture and Enrichment of Biomolecules................. 223

4.6 Chips for Genomics and Proteomics..................................... 224

4.6.1 Microarrays of DNA-Based Molecules...................... 225
4.6.1.1 Oligonucleotide Chips............................. 225
4.6.1.2 DNA Microarrays................................... 226

xii
 Contents

4.6.1.3 DNA Chips versus DNA Microarrays. ...... 227

4.6.1.4 Self-Assembled Microarrays of Beads........ 228
4.6.1.5 Electroaddressable Deposition of DNA
and Protein. ........................................... 229
4.6.2 Automated DNA Purification. ................................. 230
4.6.3 A Microfluidic cDNA Synthesizer............................ 231
4.6.4 Microfluidic Elongation of DNA to Produce
“Optical Maps”....................................................... 232
4.6.5 PCR Chips............................................................. 232
4.6.5.1 Chip Substrates and Surface Treatments....... 232
4.6.5.2 PCR Chip Architectures.......................... 233
4.6.5.3 PCR Reaction Volume, Temperature
Control, and Speed.................................. 236
4.6.6 High-Throughput Protein Immunoblotting
on a Chip.............................................................. 237
4.6.7 Protein Crystallization Chips................................... 238
4.6.8 Measuring DNA–Protein Interactions Using PDMS
Mechanical Traps................................................... 240

4.7 Electrospray Mass Spectrometry. ......................................... 241

4.8 Biochemical Analysis Using Force Sensors............................ 242

4.9 Summary........................................................................... 245

Further Reading................................................................. 246

CHAPTER 5 Cell-Based Chips for Biotechnology. ............................................ 247

5.1 Microfluidic Flow Cytometers.............................................. 247
5.2 Cell Sorting........................................................................ 253
5.2.1 Red Blood Cell Assays............................................. 253
5.2.2 Electrokinetic Routing of Cells. ............................... 254
5.2.3 Dean Flow in Spiral Microchannels.......................... 255
5.2.4 Pinched-Flow Fractionation..................................... 255
5.2.5 Tunable Hydrophoretic Focusing. ............................ 257
5.2.6 Cell Sorting Using Surface Acoustic Waves............... 257

5.3 Cell Trapping. .................................................................... 258

5.3.1 Neuro-Cages.......................................................... 258
5.3.2 PDMS Microwells................................................... 258
5.3.3 PEG Microwells...................................................... 260
5.3.4 Dielectrophoretic Traps........................................... 261
5.3.5 Micromagnetic Traps.............................................. 262
5.3.6 Hydrodynamic Traps.............................................. 263
5.3.7 Trapping Cells Using Antibodies.............................. 266
5.3.8 Trapping and Culturing Microfabricated Cell
Assemblies............................................................. 267
5.3.9 Microdroplet Cultures and Assays............................ 268

xiii
 Contents

5.4 Microfluidic Cell Culture Laboratories. ................................ 270

5.4.1 Limitations of Traditional Cell Culture Technology........ 271
5.4.2 The Cell-on-a-Chip Revolution................................ 272
5.4.3 Seeding Cells in Microchannels............................... 273
5.4.4 From Serial Pipetting to Highly Parallel
Micromixers, Pumps, and Valves............................. 274
5.4.5 From Incubators to “Chip-Cubators”........................ 276
5.4.6 From High Cell Numbers in Large Volumes
(and Large Areas) to Low Cell Numbers in Small
Volumes (and Small Areas)...................................... 276

5.5 Gene Expression Cellular Microarrays (“Cellomics”)............. 277

5.6 Micro-Bioreactors............................................................... 278

5.7 Cells on Microelectrodes..................................................... 282

5.8 Patch Clamp Chips. ............................................................ 286

5.9 Cryopreservation................................................................ 294

5.10 Assisted Reproductive Technologies..................................... 295

5.11 Whole Animal Testing........................................................ 297

5.12 Summary........................................................................... 298

Further Reading................................................................. 298

CHAPTER 6 BioMEMS for Cell Biology............................................................ 301

6.1 An Enabling Technology: The Hurdles.................................. 301

6.1.1 From Random Cultures to Microengineered
Substrates.............................................................302
6.1.2 From “Classical” to “Novel” Substrates: The Cell
Biologist’s Dilemma................................................ 302
6.1.3 From Cells in Large Static Volumes to Cells in Small
Flowing Volumes.................................................... 303
6.1.4 From a Homogeneous Bath to Microfluidic Delivery...... 303

6.2 Cell-Substrate Signaling...................................................... 304

6.2.1 Cell Behavior Controlled by Cell Shape..................... 304
6.2.2 Microtopographical Signaling.................................. 310
6.2.3 Muscle Cell Differentiation...................................... 312

6.3 Cell–Cell Communication................................................... 314

6.3.1 Control of Cell–Cell Contacts at Single-Cell Scale. .... 314
6.3.2 Control of Cell–Cell Spacing Using
Micromechanical Actuators..................................... 315

xiv
 Contents

6.3.3 Quorum Sensing in Bacteria.................................... 317

6.3.4 Signal Transduction Studies Using Biomimetic
Devices.................................................................. 318

6.4 Cell Migration.................................................................... 320

6.4.1 Cellular Traction.................................................... 321
6.4.2 Chemotaxis............................................................ 323
6.4.2.1 Neutrophil Chemotaxis........................... 323
6.4.2.2 Cancer Cell Migration............................. 328
6.4.2.3 Bacterial Cell Migration. ......................... 329

6.5 BioMEMS for Cellular Neurobiology.................................... 336

6.5.1 Axon Guidance...................................................... 336
6.5.1.1 Axon Guidance by Biochemical Surface
Micropatterns......................................... 338
6.5.1.2 Axon Guidance by Microtopography........ 342
6.5.1.3 Axon Guidance by Insoluble (Surface)
Gradients................................................ 344
6.5.1.4 Axon Guidance by Soluble Gradients........ 348
6.5.1.5 Axon Guidance by Glial Cells.................. 350
6.5.2 Neuronal Polarization............................................. 351
6.5.3 Synaptogenesis....................................................... 353
6.5.4 Emergent Properties of Neuronal Networks.............. 356
6.5.4.1 Bottom-Up Approach: Neuronal
Cultures.............................................. 356
6.5.4.2 Brain Slices on a Chip.............................. 359
6.5.4.3 Caenorhabditis elegans in a Chip.............. 361
6.5.5 Olfaction. .............................................................. 363
6.5.6 Glial Biology.......................................................... 365

6.6 Developmental Biology on a Chip......................................... 366

6.7 Yeast Biology...................................................................... 367

6.8 Plant Cell Biology............................................................... 369

6.9 Microfluidics for Studying Cellular Dynamics....................... 371

6.10 Summary........................................................................... 372

Further Reading................................................................. 373

CHAPTER 7 Tissue Microengineering............................................................. 375

7.1 Microscaffolding................................................................. 375

7.1.1 Cellular Micropatterns in 3-D Microscaffolds. .......... 376
7.1.2 Skin Microengineering............................................ 380
7.1.3 Vasculature on a Chip............................................. 381
7.1.4 Muscle Cells........................................................... 382

xv
 Contents

7.2 Micropatterned Cocultures.................................................. 384

7.2.1 Liver Cells.............................................................. 384
7.2.2 Lung Cells.............................................................. 386

7.3 Stem Cell Engineering......................................................... 387

7.4 Morphogenesis................................................................... 392

7.5 Summary........................................................................... 394

Further Reading................................................................. 394

CHAPTER 8 Implantable Microdevices. .......................................................... 395

8.1 Dental Implants.................................................................. 395

8.2 Implantable Microelectrodes................................................ 396

8.2.1 The Michigan Probes. ............................................. 398
8.2.2 The Utah Electrode Array........................................ 401
8.2.3 Microfabricated Cochlear Implants.......................... 402
8.2.4 Microfabricated Electrocorticography Arrays............ 403
8.2.5 Microelectrodes for Visual Prostheses...................... 405
8.2.6 A Microelectronic Contact Lens............................... 406
8.2.7 Flexible, Thin-Film Microelectronic Circuits for
Monitoring Clinical Parameters............................... 406

8.3 Delivery of Soluble Signals into the Body. ............................. 408

8.3.1 Microneedles.......................................................... 408
8.3.2 Microfluidic Drug Delivery to the Eye. ..................... 411

8.4 Microtools for Surgery. ....................................................... 412

8.4.1 Micromachined Surgical Tools................................. 412
8.4.2 Catheters and Surgical Gloves Equipped with
Microsensors.......................................................... 412
8.4.3 “Gecko” Surgical Tape............................................. 414

8.5 Insect Research................................................................... 415

8.6 Summary........................................................................... 417

Further Reading................................................................. 417

Appendix. ......................................................................................................... 419

xvi
 List of Figures
Figure 1.1 Benefits of microfabrication..................................................................... 2
Figure 1.2 Photolithography................................................................................... 4
Figure 1.3 3-D photoresist structures....................................................................... 6
Figure 1.4 SU-8 photoresist.................................................................................... 7
Figure 1.5 Tilted microstructures............................................................................ 8
Figure 1.6 Water-soluble thermoresponsive photoresist for protein patterning.................. 9
Figure 1.7 Laser lithography of 30-μm-thick SU-8 structures........................................ 9
Figure 1.8 Digital micromirror device.................................................................... 10
Figure 1.9 Etching using a photoresist mask............................................................. 11
Figure 1.10 Metal deposition and lift-off................................................................. 12
Figure 1.11 Micromachining of a cantilevered tip..................................................... 13
Figure 1.12 State-of-the-art of 3-D micromachining.................................................. 13
Figure 1.13 Metal patterns on a flexible plastic substrate............................................. 14
Figure 1.14 Laser-cut laminated devices for diagnostics..................................................... 15
Figure 1.15 Direct laser writing............................................................................. 15
Figure 1.16 Laser deposition of “corrals” for containing cell growth and motility............ 16
Figure 1.17 Multiphoton lithography with the DMD.................................................. 17
Figure 1.18 Photolithographic versus soft lithographic patterning methods.................... 20
Figure 1.19 PDMS micromolding.......................................................................... 21
Figure 1.20 Structural integrity of PDMS walls. The ridges on the PDMS walls were
present on the walls of the trenches from which these structures were replicated................ 21
Figure 1.21 PDMS chemical formula...................................................................... 22
Figure 1.22 Selective inking of a flat stamp.............................................................. 25
Figure 1.23 Micromolding in capillaries. SEMs of polyurethane microstructures on Si/
SiO2 formed using a commercially available, UV-curable polyurethane prepolymer used
for optical parts.................................................................................................... 27
Figure 1.24 Microfluidically patterned polyurethane 3-D structures............................. 27

xvii