Nanofabrication
MT6127E
LAB ON CHIP
(LOC)
Name : Abhijith C S
Reg.No : M240269MT
Class : S1 M-Tech 1
OUTLINE
● Introduction To Lab-on-a chip
● History
● Microfluidics and lab-on-a-chip
● Material Used for LOC Devices
● Manufacturing technologies for lab-on-a-chip
● Challenges for LOC fabrication
● Main applications of lab-on-a-chip
● References
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INTRODUCTION TO LOC
Figure 1.Schematic of LOC
https://www.researchgate.net/figure/Lab-on-a-chip-device-left-Principle-of-integration-of-laboratory-process-on-a-chip
[accessed 1 Nov 2024]
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INTRODUCTION TO LOC
● Lab-on-a-chip (LOC) is a miniaturized device that integrates several biological and
biochemical analyses into a single platform. This technology offers a solution for handling
multiple samples simultaneously, making LOC a promising tool for diagnostics, DNA analysis,
and chemical synthesis. By miniaturizing these operations, LOC can significantly reduce
costs, speed up diagnostic processes, and enhance sensitivity and accuracy.
● Miniaturize biochemical operations
● Faster, cheaper, and more efficient
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HISTORY
Figure 2.Evolution of Lab on Chip technology
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MICROFLUIDICS AND LAB ON A CHIP
● Microfluidics: Science and application that manipulates picoliters of
fluids and manufactures micro miniaturized devices.
● Core technology behind lab-on-a-chip, integrating millions of
microchannels.
● Efficient handling of small fluid volumes
● Complete architecture includes:
○ Pumps,electrodes,Valves
○ Electrical fields and electronics
Figure 3. LOC Device
https://www.news-medical.net/life-sciences/Benefits-of-a-Microfluidic-System.aspx
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MATERIAL SELECTION FOR LOC DEVICES
● Glass: Optically transparent, chemical resistant, but expensive and
fragile.
● Polymers: Rigid (PMMA, COC), soft (PDMS), cheaper, easy for
mass production.
● Paper-based materials for low-cost diagnostics.
Figure 4. Glass Substrate Figure 5. Paper Based LOC Device
https://4dtechnology.com/applications/glass-substrates https://pubs.rsc.org/en/content/articlelanding/2008/lc/b814043j
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FABRICATION METHODS: GLASS
● Photolithography
● Chemical Etching
● Micromachining
● Powder Blasting
● Water Jet Cutting
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PHOTOLITHOGRAPHY & ETCHING
Figure 6. Lithography Steps for Fabricating Lab on chip devices
https://www.researchgate.net/figure/Photolithography-to-fabricate-microfluidic-devices-A-A-photoresist-is-spin-
coated-on_fig3_258010193 [accessed 23 Oct 2024]
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PHOTOLITHOGRAPHY & ETCHING
Developer: TMAH(+ resist)
Etchant: Hydrofluoric acid
Figure 7. Process flow of a LOC Device
https://www.researchgate.net/figure/Photolithography-to-fabricate-microfluidic-devices-A-A-photoresist-is-spin-coa
ted-on_fig3_258010193 [accessed 23 Oct 2024]
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Tooling for Glass
MICROMACHINING ● Diamond-Coated Tools: Prevent
chipping/cracking.
● Optimization Needed: Precise spindle speed
& feed rate.
Micromilling Challenges
● Chipping: Tool contact causes enlarged hole
diameters.
● Surface Roughness: Affects LOC device
functionality and fluid flow.
● Cracking: Excess force leads to cracks,
compromising device integrity.
Tool Wear & Overheating
● Diamond Tool Wear: Quick degradation with
overheating.
● Cooling System: Ethanol misting essential to
prevent overheating.
CNC Machining Advantages
Figure 8. Micromachining
● Precision: High repeatability (10 μm),
tolerance up to 100 μm.
https://www.researchgate.net/figure/Fabrication-process-of-glass-microfluidic- ● Geometric Tolerance: Essential for access
devices-by-micromilling-a-schematic-diagram-b_fig1_326541687 [accessed holes; tolerances as tight as 100 μm.
23 Oct 2024]
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1. Abrasive Powder
POWDER BLASTING
● Material: Typically aluminum oxide (Al₂O₃) or silicon
carbide (SiC).
● Particle Size: Ranges from 5–100 micrometers; smaller
particles yield finer features but reduce etch rate.
● Shape: Angular particles for effective etching, improving the
roughness and depth control.
2. Blasting Pressure
● Typical Range: 0.2–1.0 MPa (megapascals).
● Effect: Higher pressure increases etch rate but may lead to
rougher surfaces and more chipping.
● Optimization: Lower pressure for fine features; higher for
faster etching.
3. Nozzle Distance and Angle
Figure 8. Machining Process of Powder blasting ● Distance: Typically 5–15 mm from the glass surface.
● Angle: Often 90° for uniform etching, though angled
blasting can adjust feature profiles.
https://www.researchgate.net/figure/Fabrication-process-of-glass-mic
● Effect: Closer nozzle increases etch rate but risks uneven
rofluidic-devices-by-micromilling-a-schematic-diagram-b_fig1_32654 features; angled blasting may reduce feature precision.
1687 [accessed 23 Oct 2024]
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FABRICATION METHODS: RIGID POLYMERS
● Rigid polymers are a class of polymers that have a high Young's modulus,
meaning they are stiff and maintain their shape under applied stress or
pressure. These materials do not bend or flex easily, providing stability and
dimensional accuracy.
● High Stiffness,Durability,Chemical Resistance,Thermal stability
● PMMA,Polycarbonate,PETG
● Fabrication Methods:
● Injection Moulding
● Hot Embossing
● 3D Printing
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INJECTION MOULDING
Moulding
Figure 9. Injection Moulding parameters: polymer
or mould tem
perature, injection
pressure or speed,
shot size, cooling time.
https://www.hsv-tmp.com/the-injection-moulding Figure 10. Mould and Device
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A polymer workpiece is stamped with the desired features by applying
heat and pressure.
HOT EMBOSSING
Setup:
● Workpiece Positioning: Polymer piece placed in a hot
embossing machine
● Embossing Tool: Heated tool with chip design is pressed onto
the polymer with a set pressure
Heating and Pressure:
● Heating: Softens the polymer, allowing for easier imprinting.
● Pressure Application: Imprints the tool’s features onto the
softened polymer surface
Embossing Moulds:
● Materials: Typically made from metals for high thermal stability,
but can also be silicon or polymers.
Enhanced Production with Rollers:
● Roller Embossing: Uses a continuous rolling die instead of
Figure 11. Hot Embossing Process individual stamping.
A Considered Approach to Lab-on-a-Chip Fabrication ● Efficiency: Speeds up production, but has higher start-up costs
G.D. Kipling, S.J. Haswell, and N.J. Brown due to specialized equipment.
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FABRICATION METHODS: SOFT POLYMERS
● Soft polymers, also known as elastomers or elastic polymers, are a
class of materials characterized by their low stiffness and flexibility.
These polymers have a low Young's modulus, allowing them to stretch,
bend, and deform under stress without breaking.
● Flexibility and Elasticity,Low Young's’ Modulus,Low Thermal
Resistance,Surface Modifiability,Biocompatibility
● PDMS,PU
● Fabrication Methods:
● Soft Lithography
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SOFT LITHOGRAPHY
● Replica Moulding
● Micro Transfer Moulding
A Considered Approach to Lab-on-a-Chip Fabrication Figure 11. Moulding methodology
G.D. Kipling, S.J. Haswell, and N.J. Brown
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FABRICATION METHODS: PAPER
● Paper-based microfluidic devices are fabricated by patterning paper with hydrophobic barriers to
define hydrophilic channels and zones.
● Paper-based microfluidic devices are portable
● Process small volumes of fluids
● Perform multiplexed assays
● Are simple to fabricate without cleanroom facilities
● Made from inexpensive and readily available materials
● Do not require computer-controlled pumps to operate.
Fabrication of paper-based microfluidic devices involves two main steps:
i) Patterning paper
ii) Customizing the devices for their intended applications, including applying reagents to the devices for assays.
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FABRICATION METHODS: PAPER
Paper Cutting Technique
● Simple, ancient method for fabricating channels
● Uses programmable knife cutter, laser cutter, or manual scissors/knife
Encasing & Durability
● Channels encased with tape or glass slides for support
● Requires solid backing to maintain stability
Advantages
● No chemicals required
● Basic form needs only scissors or razor
Parafilm-Based Cutting (Recent Method)
● Paper fused with parafilm using hot press, creating: Figure 12. Paper Based LOC Fabrication
○ l-paper: Laminated paper
○ i-paper: Infused paper
● l-paper: Laser etching to create channels
A Considered Approach to Lab-on-a-Chip Fabrication
● i-paper: Channels cut and bonded with unmodified paper G.D. Kipling, S.J. Haswell, and N.J. Brown
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FABRICATION METHODS: PAPER
Inkjet Printing Technique
● Uses commercial inkjet printer with solvent in place of ink
● Paper made hydrophobic, then patterned by printing solvent
in specific areas
Examples of Technique
● Polystyrene-Coated Paper: Inkjet-printed toluene removes
hydrophobic coating in desired patterns
● Nitrocellulose Membrane: Organic solvent dissolves
specific areas
Figure 13. Printing Based LOC Fabrication
Advantages
● Inexpensive and widely available printers
● Can potentially print hydrophobic ink directly to form barriers
(requires suitable ink viscosity)
● Reagents can be printed for one-step device fabrication
Limitations
A Considered Approach to Lab-on-a-Chip Fabrication
● Multiple passes required to apply sufficient material
G.D. Kipling, S.J. Haswell, and N.J. Brown
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CHALLENGES IN LOC FABRICATION
● Dimensional tolerances: Accuracy in feature sizes critical for
functionality.
● Scaling up for mass production: Cost, time, and material challenges.
● Miniaturization and Precision
● Material Selection and compatibility
● Integration of multiple functions
● Cost and Scalability
● Sensitivity and Detection
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APPLICATIONS OF LOC TECHNOLOGY
● Clinical diagnostics: LOCs can perform a variety of clinical tests, such as
measuring blood glucose, and cholesterol, or counting HIV cells.
● DNA analysis: LOCs can perform DNA extraction and analysis, such as
polymerase chain reaction (PCR) to amplify DNA sequences.
● Drug discovery and delivery: LOCs can be used to research drug discovery
and delivery.
● Environmental investigation: LOCs can be used to analyze pollutants in real
time.
● Food: LOCs can be used in food applications.
● Regenerative medicine: LOCs can be used to develop tissue-engineered
constructs, such as organoids, scaffolds, and artificial organs.
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REFERENCES
1. Nguyen, N. T., and Wu, Z. 2005. "Micromixers—A Review." Journal of Micromechanics and
Microengineering, 15(2), pp. R1–R16.
2. Whitesides, G. M. 2006. "The Origins and the Future of Microfluidics." Nature, 442(7101), pp. 368–373
3. A Considered Approach to Lab-on-a-Chip Fabrication G.D. Kipling, S.J. Haswell, and N.J. Brown
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THANK YOU
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