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Session2_3and4_Combined.pdf
1. 1
Fabrication of Microfluidic Devices
Geometric features, Materials and Techniques
Supreet Singh Bahga
Department of Mechanical Engineering
Indian Institute of Technology Delhi
Visionary Leadership in Manufacturing Programme
3. Shock Wave Interaction in Microfluidics
Typical geometric features
Fabrication of Microfluidic Devices 3
Fluidic connection
(tubing)
microchannels
reservoirs/wells
sealing layer
sealing layer
reservoir/
well
o Microchannels
• Transverse dimension
of order 10-100 µm
o Reservoir/Well
• Diameter of 1-5 mm
• Volume of order 10 µL
o Fluidic connection
• Tubing made of silcone, tygon
• Connection with
macroscopic world
4. Shock Wave Interaction in Microfluidics
Geometric characteristics: Profile
Fabrication of Microfluidic Devices 4
o Profile: Cross-section of the microchannel
• Depends on the microfabrication method
Geometric characteristics are important for design and fabrication decisions
Rectangular
(micromilling)
D-shaped
(isotropic etching)
Trapezoidal
(anisotropic etching)
Gaussian
(laser ablation)
5. Shock Wave Interaction in Microfluidics
Resolution, Aspect Ratio, Surface Roughness
Fabrication of Microfluidic Devices 5
o Feature resolution
• Ability to distinguish individual feature or adjacent separate features
• Smallest positive or negative feature that can be produced
• High feature density requires fine resolution (not vice versa)
o Aspect Ratio
• Ratio of dimension in one direction to the other
• Usually high aspect ratio means small width and large depth
• Fabricating high aspect ratio channels is challenging
o Surface Roughness
• Affects the wetting behaviour and fluid flow
• Desirable where applications based on surface
chemistry due to larger surface area
• Depends on fabrication method
• Etching produces smooth surfaces
• Laser machining produce rough surfaces
High aspect ratio
microchannels
Laser machined
microchannel
7. Shock Wave Interaction in Microfluidics
o Choice of materials
• Silicon
• Glass: borosilicate, soda-lime
• Thermoplastic polymers: acrylic (PMMA), cyclic olefin copolymer (COC)
• Elastomers: polydimethylsiloxane (PDMS)
o The choice of material affects the functionality and manufacturability
o Functional requirements
• Biocompatibility
• Optical transparency
• Mechanical resilience
• Chemical resistance
• Electrical conductivity, dielectric breakdown, etc
o Manufacturability
• Machinability
• Thermoplastic behaviour
• Isotropic vs anisotropic etching
• Casting
Materials for Microfluidics
Fabrication of Microfluidic Devices 7
8. Shock Wave Interaction in Microfluidics
Microchip Electrophoresis with UV detection
Fabrication of Microfluidic Devices 8
V1
V2
V4
V3
electric field
Injection
electric field
Separation
UV absorbance
detector
Functional requirements
• High surface charge of EOF
• Good UV transmission
• Chemical resistance
• Low surface roughness
Choice of materials
• Silicon: Opaque
• PMMA: Poor UV transmission
• Glass: Satisfies all requirements
Fabrication method
• Laser machining: rough surface
• Wet etching: smooth surface
9. Shock Wave Interaction in Microfluidics
o Silicon dioxide with additives such as sodium carbonate, calcium oxide and
boron oxide
• Different thermal, mechanical, optical properties. Relatively brittle
• Glass for microfluidics: borosilicate, soda-lime, fused silica
• Borosilicate glass and fused silica have better dimensional stability than soda-lime at
high temperatures
o Advantages
• Rigid, dimensionally stable, chemical resistant
• Optically transparent. Good UV transmission
• Substrate available in flat form: rectangular slides, circular wafer
• Better thermal conductivity than plastics and elastomers: useful in electrophoresis
o Disadvantage: Expensive fabrication. Not for low-cost disposable chips
o Method of fabrication
• Most common method is wet etching
• Other methods: plasma etching, laser machining
• Holes for reservoirs: ultrasonic drilling and laser ablation
• Off-the-shelf chips available from: Micronit, PerkinElmer, etc
Glass
Fabrication of Microfluidic Devices 9
10. Shock Wave Interaction in Microfluidics
o Thermoplastics have a wide range of material characteristics that can be
used for chip fabrication
• Relatively low mechanical strength, low melting point and high electrical resistance
• Common thermoplastics: PMMA, polycarbonate, cyclic olefin polymer (COP)
cyclic olefin copolymer (COC), polystyrene
o Advantages
• Properties can be engineered as per functional requirement
• Polycarbonate has exceptional mechanical strength.
• COP and COC have good UV transmission
• Can be used in rapid, low-cost fabrication methods, e.g., hot embossing, thermoforming
o Disadvantage
• Cannot be used for very high temperature applications and with organic solvents
• Autofluorescence at short wavelengths (488 nm)
• Hydrophobic: polystyrene is less hydrophobic among others
o Method of fabrication
• Hot embossing, injection moulding, thermoforming
• Micromilling, laser machining: for low volumes production
• Off-the-shelf chips available from: Microfluidic ChipShop
Thermoplastics
Fabrication of Microfluidic Devices 10
11. Shock Wave Interaction in Microfluidics
o PDMS (polydimethylsiloxane) is the most commonly used elastomer for microfluidic
fabrication
• Belongs to broader class of polymers called silicones
o Advantages of PDMS
• Cheap, non-toxic, chemical stability
• Optically transparent
• Ease of fabrication using various replication methods (casting): good for prototyping
• Functional components such can electrodes, electromagnetic coils can be integrated
• Deformable: can be used to make valves
o Disadvantages
• PDMS swells in presence of organic solvents
• Permeable to oxygen (advantage for biological studies)
• Surface wettability not consistent
o Method of fabrication
• Replication methods such as soft lithography
• Commercial products: Sylgard 184 (Dow Corning),
RTV 615 (Momentive Performance Materials)
Elastomers: PDMS
Fabrication of Microfluidic Devices 11
12. Shock Wave Interaction in Microfluidics
Comparison of different materials
Fabrication of Microfluidic Devices 12
Property Glass/Silicon Thermoplastics Elastomers
Young’s modulus (GPa) 50-90/130-180 1.4-4.1 ~0.0005
Thermostability very high medium to high medium
Solvent compatibility very high medium low
Hydrophobicity hydrophilic hydrophobic hydrophobic
Surface charge very stable stable not stable
Optical transparency high/no medium to high high
Permeability to oxygen Very low low to medium high
13. Shock Wave Interaction in Microfluidics
Materials for specific applications
Fabrication of Microfluidic Devices 13
Applications Glass/Silicon Thermoplastics Elastomers
Capillary
electrophoresis
excellent good moderate
Organic synthesis excellent moderate to good poor
Droplet formation excellent good moderate
Polymerase Chain
Reaction
excellent good good
Cell culture moderate moderate good
Protein crystallization poor moderate good
Cost of production high low medium
14. Shock Wave Interaction in Microfluidics
o Glass
• For research purposes, not for low-cost applications
• Using organic solvents
• High temperatures
o Thermoplastics
• High volume production
• Practical applications
• Low-cost, disposable
o Elastomers
• For rapid prototyping
• For research applications, not for commercial use
o Silicon
• Not used for majority of microfluidic applications
• To be used only for special research purposes
Summary: Choosing a chip material
Fabrication of Microfluidic Devices 14
Glass
Thermoplastic
PDMS
16. Shock Wave Interaction in Microfluidics
Typical geometric features
Fabrication of Microfluidic Devices 16
Fluidic connection
(tubing)
microchannels
reservoirs/wells
sealing layer
sealing layer
reservoir/
well
o Microchannels
• Transverse dimension
of order 10-100 µm
o Reservoir/Well
• Diameter of 1-5 mm
• Volume of order 10 µL
o Fluidic connection
• Tubing made of silcone, tygon
• Connection with
macroscopic world
17. Shock Wave Interaction in Microfluidics
Fabrication methods: Direct vs Replication
Fabrication of Microfluidic Devices 17
microchannels
reservoirs/wells
sealing layer
Features to be fabricated
• Microchannels
• Reservoirs
• Sealing layer
Direct Fabrication
• Features are directly fabricated on
the desired substrate
• Etching of glass and silicon
• Micromilling and laser machining
• Xurography
Replication
• Chip is replicated from a master mold
• Soft-lithography: of PDMS casting
• Injection molding, hot embossing
• Scalable and low-cost
18. Shock Wave Interaction in Microfluidics
Photolithography
Fabrication of Microfluidic Devices 18
o Defining geometric features on a photosensitive material by selective
exposure to radiation
o One of the step in many in direct fabrication and replication techniques
o Photoresist: Polymer resin, UV-sensistive initiator, and solvent
o Photomask: Fused silica patterned with chromium using electron beam
lithography, high resolution transperancy (~5000 dpi)
UV radiation (300-400 nm)
Photomask
Photoresist
Wafer
Positive Photoresist Negative Photoresist
19. Shock Wave Interaction in Microfluidics
Photolithography: Process
Fabrication of Microfluidic Devices 19
Clean and prepare
surface
Coat with photoresist
Pre-expose “soft” bake
Align and expose
Post-expose bake
Develop
Pre-develop “hard”
bake
Remove solvent from photoresist so that it can be put in
contact with photomask. Around 100°C on hotplate or oven.
To cure before developing
To increase resistance to subsequent processes, e.g., etching
To avoid particle contamination and poor adhesion.
Piranha clean (sulphuric acid and hydrogen peroxide)
Spin coating. Calibration of film thickness vs spin speed.
Performed on an aligner with mercury lamp radiation.
Devices with single layer of photoresist don’t need alignment.
Removal of uncured regions of photoresist.
For positive resists: tetramethyl ammonium hydroxide (TMAH)
For negative resists: based on organic solvents
20. Shock Wave Interaction in Microfluidics
Wet etching
Fabrication of Microfluidic Devices 20
o Material removal by a liquid chemical etchant
1. Deposit etch mask
Substrate
Etch mask
2. Pattern photoresist
Photoresist
3. Etch the etch mask
4. Strip photoresist
5. Etch substrate
6. Remove etch mask (optional)
Isotropic etching of glass
Silicon can be etched
anisotropically
(111) plane
• Etch mask: Cr/Au thin film. Avoid residual stresses
to prevent cracks.
• Photoresist can be used for shallow channels.
• Etching of etch mask: KI/I2 for Au or
K3Fe(CN)6/NaOH for Cr
• Glass etching with HF/NH4F. Typical etch rates 1-10
µm/min. Etch rate depends on glass composition.
21. Shock Wave Interaction in Microfluidics
Micromilling
Fabrication of Microfluidic Devices 21
o Subtractive process that uses rotating cutting tool for material removal
• Machining of microchannels and wells
• Plastics: PMMA, COC, PS, etc.
• Machining of moulds for hot embossing
and injection moulding
• Useful for quick prototyping (30 mins)
• Surface roughness 0.4-2 µm.
• Width: order 100 µm
• Surface roughness depends on feed rate
and spindle speed. Need optimization.
• Burrs: common in ductile plastics (COC).
Less in brittle plastics (PMMA, PS)
• Avoid heating and melting: avoid low feed
rates and high spindle speed
22. Shock Wave Interaction in Microfluidics
o Most common lasers: carbon dioxide (infrared), excimer (UV, 193-351 nm)
• Excimer lasers are better because CO2 laser may cause thermal damage
• Excimer lasers can be focused and give better resolution
• Common material: PMMA
o Inverted bell shaped/Gaussian channel profile
• Width and depth increases with power (order 1-10 W)
• Multiple pass: same width but depth changes (not linearly)
o Surface roughness: 5-10 µm. Reduced by annealing
o Alternatively cut thin sheet
(PDMS, double sided tape) and bind.
Laser maching/ablation
Fabrication of Microfluidic Devices 22
Laser-cut double sided tape
23. Shock Wave Interaction in Microfluidics
o Casting
• Unpolymerized compound is poured
• Removed after polymerization
• Elastomers (PDMS)
o Hot embossing
• Thermoplastic is softened by heating above
glass transition temperature
• A pattern is stamped on the plastic substrate
o Injection moulding
• Thermoplastic is softened by heating and
pushed into a mould using high pressure
Replication methods for polymers
Fabrication of Microfluidic Devices 23
Heat
Heat
Heat
Pressure
24. Shock Wave Interaction in Microfluidics
Soft-lithography: Casting
Fabrication of Microfluidic Devices 24
1. Fabricate master
2. Pour the elastomer
3. Peel off after curing
SU-8 (negative photoresist) on Si/Glass
PDMS: two part mixture.
Prepolymer and crosslinker in ratio of 10:1
Curing at 65°C for 4 hours.
Longer time at room temperature.
Drawback:
High aspect ratio channels collapse due to softness
25. Shock Wave Interaction in Microfluidics
o Most common lasers: carbon dioxide (infrared), excimer (UV, 193-351 nm)
• Excimer lasers are better because CO2 laser may cause thermal damage
• Excimer lasers can be focused and give better resolution
• Common material: PMMA
o Inverted bell shaped/Gaussian channel profile
• Width and depth increases with power (order 1-10 W)
• Multiple pass: same width but depth changes (not linearly)
o Surface roughness: 5-10 µm. Reduced by annealing
o Alternatively cut thin sheet
(PDMS, double sided tape) and bind.
Laser maching/ablation
Fabrication of Microfluidic Devices 25
Laser-cut double sided tape
26. Shock Wave Interaction in Microfluidics
Hot embossing
Fabrication of Microfluidic Devices 26
1. Fabricate master
2. Support thermoplastic material
3. Contact with heat and pressure
4. Release shaped thermoplastic
Master can be etched silicon, plated metal, photoresist.
Cylindrical rollers can be used for higher throughput.
Almost any thermoplastic material can be embossed.
E.g., PMMA, PC and COC.
Temperature is maintained just above the glass transition temp.
PMMA (120-130°C) and PC (160-175°C)
Stamped in a hydraulic press (20-30 kN, few mins.)
27. Shock Wave Interaction in Microfluidics
o Variotherm process:
• Two-part mould cavity with micro-mould insert is heated above glass transition
temperature of the polymer
• Polymer is also heated and forced by a hydraulic ram
• Both polymer and mould are cooled below glass transition temperature
• Mould is opened and part is ejected
o Mould inserts can be fabricated using electroforming from silicon or
glass master
o Advantage:
o Shortest cycle time for polymeric chips
o Disadvantage:
• Complex micro-mould insert
o Polymers for injection moulding:
• PMMA, PC, PS, COC, COP
Injection moulding
Fabrication of Microfluidic Devices 27
28. Shock Wave Interaction in Microfluidics
Technical comparison
Fabrication of Microfluidic Devices 28
29. Shock Wave Interaction in Microfluidics
Cost comparison
Fabrication of Microfluidic Devices 29
30. Shock Wave Interaction in Microfluidics
o Glass
• Reservoirs: Ultrasonic drilling in the cover plate
• Thermal bonding of glass chip to glass cover plate
• Temperatures 500-600°C for several hours
• Pressed with high strength
• Silicon to glass bonding using anodic bonding
o Thermoplastics
• Reservoirs: Drilling, inserting pins in mould (injection moulding)
• Thermal bonding, pressure-sensitive adhesive
o Elastomers
• Reservoirs: punching holes using biopsy punch
• Irreversible sealing between glass/PDMS and
PDMS chip by air/oxygen plasma cleaning
and physical contact
• Heating at 70°C can improve a weak seal
Bonding and reservoirs
Fabrication of Microfluidic Devices 30
Glass
Thermoplastic
PDMS