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Microfluidics: Electrokinetics and Fabrication
Dr. Thara SrinivasanLecture 18
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Lecture Outline: Part I
• Reading• From S. Senturia, Microsystem Design, Chapter
13, “Fluids,” p.339-349.
• Today’s lecture, Part I• Electrolytes and Electrokinetic Effects• Electroosmosis• Electrophoresis
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5Electrolytes
• Electrolytes, solutions of ionic species, have unique flow possibilities because electric fields can be used to direct the flow.
• Total charge density of solution and charge density far from bounding surfaces
• Charge density near a wall
( ) 02 =∇∑= φρ andCqzi
ieie
ερφ e−=∇2
∑−=∇−
−
i
TBkoeqiz
iie eCzq )(
02
φφ
εφ )( yφφ =
y
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Ionic Double Layers• Electrolyte in contact with insulating
solid surface• Inner and outer Helmholtz layers are
compact layers of adsorbed ions• Diffuse layer of ions has compensating
net charge
+
- - - - - - - - - -+
++ ++++
++
- --
+ +
++
- -+
Bulk solution (+ = -)
Diffuse layer (+ > -)
Compact layer (+ < -)
potentialzetae
w
DLy
w
,
ˆ
ςφφφ
==
−
3
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5Potential
• For small potential variations, expand exponential • Reference location is in neutral region• Variation in potential of ionic solution has exponential
dependence
=
∑==∇
≈∇
−=∑−=∇
−
−
φ
εφ
φ
φφφε
φφ
ˆ
ˆ
ˆ
ˆ,ˆ
02
212
2
0
ˆ
02
iii
B
ed
i
TBkeqiz
ieie
CzTkqL
eCqzq
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Debye Length
• Debye length (LD) is decay length ~ back to neutral 3 LD from wall• Ionic strength ↑ LD ↓• LD in pure water _____, in 1 mM KCl _____, in 1M KCl
_____.• MEMS channels typically much wider than LD: ______.
∑=i
iiB
e
d
CzTkq
L 02
21ε
4
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5Electroosmosis
• Diffuse double layer has net charge• Electrostatic body force
applied tangentially to diffuse double layer drags fluid along wall
• Glass channels have negative charge (Si-OH-), diffuse layer has net positive charge and shows net flow towards cathode
• Surface-mediated flow
+
- - - - - - - - - -
+++ +
+++++
- --
+ +
++
- -+
Bulk solution
Diffuse layer
Compact layer
Cat
hode
(-)
Ano
de (+
)
Ele
ctric
Fie
ld
glass
Diffuse layer (-)(+)
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xexx EU
dxdP
DtDU ρηρ +∇+−= 2
Electroosmotic Flow• E field (up to 1 kV/cm)
• Ex is applied voltage divided by fluidic path length• Does not disrupt double layer
3LD
U0
DLy
D
xwx
DLy
D
we
eLE
dyUd
eL
−
−
=
−=
ησ
σρ
2
2
5
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5Electroosmotic Flow
• No-slip at channel walls• Plug flow profile for 99.9% of cross section
• Typical experiment, double layer thickness δ = _____.• No shear throughout most of volume
3LD
U0
xEOFDxw
DLy
Dxwx
EUandLEU
eLEU
µη
ση
σ
==
−=−
maxmax
1
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Electrophoresis• Ionic species such as DNA,
protein segments and amino acids migrate under E-field
• For particle with electrophoretic mobility µEP steady-state speed UEP reached when accelerating force is balanced by frictional force from medium
• Generally µEOF > µEP (for SiO21.25 -3×)
• Since different chemical species have different µEP it is possible to separate them while they are being carried by electroosmoticflow
rq
rfandUfqEEU
EP
EPx
xEPEP
πηµ
πηµ
6
6
=
===
q = r =η =
6
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5Chip Electrophoresis Set-Up
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Chip Electrophoresis
• Sample injection
Sample well V1 (+)
Sample Waste V2 = 0
Buffer Well V3 > VJ
Buffer wasteV4 > VJ
Junction
Separation channel
1
11
121
2
AL
R
VRR
RV
e
toJ
J
σ=
+=
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5Chip Electrophoresis
• Sample flow
Sample well V1 < VJ
Sample Waste V2 < VJ
Buffer Well V3 (+)
Buffer wasteV4 = 0
U0
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Chip Electrophoresis
• Sample flow and separation
Sample well V1 < VJ
Sample Waste V2 < VJ
Buffer Well V3 (+)
Buffer wasteV4 = 0
U0
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Fabrication Techniques for Microfluidics
Picture credit: Fluidigm
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Lecture Outline: Part II
• From reader:• Becker, H and Locascio, L., “Polymer Microfluidic Devices,”
Talanta, Vol. 56, 2002, pp. 267-87.• Boone, T. et al., “Plastic Advances in Microfluidic Devices,”
Analytical Chemistry A, February 2002, pp 79-86.
• Today’s lecture, Part II• Replication vs. Direct Techniques• Polymer Replication Techniques• Master Fabrication• Electroplating• Back-End Processes
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Materials for Microfluidics• Important material properties for microfluidic chips
• Micromachinability• Surface charge • Molecular adsorption• Optical properties
• Why polymers?• Polymer granules: _____ cheaper than Si, glass or quartz• Replication processes suitable for automated production
• Injection-molded CD costs: ___________.• Relatively low capital cost compared to silicon IC equipment
• Benefits• Biocompatible, plastics molding is well-developed technology, may not
need coating to suppress EOF, chips may be cheap enough to be disposable (better, recyclable)
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Replication vs. Direct Techniques• Direct fabrication: each part must be made separately
+ Can create certain mechanical structures difficult to create with molding
– Expensive in materials and labor– Routine access to cleanroom for fab and bonding± For economical use, re-use chip
• Replicated microsystems:
+ Cost-effective in materials, continuous processing possible with higher yields and reproducibility
± Back-end processes required for each product; may be able to do wafer level assembly
± Chips may be single-use– Moving parts difficult to create
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5Choosing a Chip Material
• Silicon ~ for special research applications
• Glass ~ for research, or if you can use existing chip, or for organic solvents or high temperatures
• Thermoplastics ~ general industry trend for high-volume, disposable chips
• Elastomers ~ for research applications, quick turnaround with rapid prototyping
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Direct Fabrication• Typical glass microfabrication
process• Etch mask deposition (Cr or Au thin
film) and patterning• Etch mask etching (KI/I2 for Au or
K3Fe(CN)6/NaOH for Cr)• Substrate etching with dilute HF/NH4F• Ultrasonic drilling of access holes into
the cover plate before bonding• Thermal bonding of glass cover plate to
seal microchannels • Attachment of “sipper” capillaries into
the chip reservoirs• Coating of glass channel walls to
suppress EOF Caliper Technologies
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5Direct Fabrication
• Jensen group, MIT • DRIE on silicon substrates
• Mastrangelo group, U. Michigan• Sacrificial etching process to fabricate parylene-C polymer
channels• Rossier et al., École Polytechnique, Lausanne
• Plasma etching of channels into polyimide substrate
• Prof. Luke Lee, UCB• Low energy ion beam etching (Ar+) to make high aspect ratio
Teflon structures• Micronics, Redmond, WA
• Laser cutting of channels on thin film laminate
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Fabrication Techniques for Microfluidics
• Replication vs. Direct Techniques• Polymer Replication Techniques• Master Fabrication• Electroplating• Back-End Processes
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5Polymer Replication
• Molding process• Fabricate a mold insert • Fill the mold with polymer• Harden the polymer • Demold the piece
• Polymer microfluidic chips• Credit card size to 10×20 cm2,
0.5-2 mm thick• Microchannels:
• Reservoirs: 1-3 mm in diameter, drilled through card (0.2-15 µL)
• Types of polymers• Thermoplastics ~ polystyrene,
polycarbonate• Elastomers ~ silicone• Thermosets ~ epoxy, acrylic
Aclara Biosciences
Gyros
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• Casting• Unpolymerized compound is poured into mold
and allowed to polymerize
• Hot embossing• Molding compound is introduced into an open
mold and formed under heat and pressure
• Injection molding• Heat-softened plastic resin is forced into a
mold cavity by high pressure
Polymer Molding Techniques
Åmic
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5Important parameters in polymer molding.
Glass transition temperature
Temperature range at which polymer changes from hard glassy material to soft (not melted) material
Melt temperature
Thermal expansion coefficient
Change in length or volume accompanying change in temperature
Hardness Measured using indentation at a specific applied force
Elasticity Ability of polymer to return to original shape after deformation
Temperature at which polymer melt flows, generally much higher than Tg. Some polymers do not melt but remain soft until they decompose.
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Casting
• “Soft lithography”• Dow polydimethylsiloxane (PDMS) is elastomer of choice• PDMS is poured into silicon stamp and allowed to cure at 40-70°C• Once cured, polymer is peeled off stamp• Bonding may be done using simple conformal contact to plastics,
glass, or reaction between two PDMS layers• Multilayer structures possible
Fluidigm
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5Multilayer Soft Lithography
• Rapid turnaround time possible – good for academic research • Demonstration at Fluidigm website
Whitesides group, Harvard
http://www.fluidigm.com/tech.htm#
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Hot Embossing
• Imprinting tool: silicon stamp or metal electroform
• Hard plastic sheet is stamped in a hydraulic press
• P maintained for minutes, T just above Tg to soften plastic
Mild
endo
, Ger
man
y
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5Injection Molding
• Process• Metal electroform mold made
from silicon or glass master• Electroform mounted in mold
insert• Molten thermoplastic polymer
injected into warm mold at high T and P
• Once part cools and solidifies, mold is opened and part is ejected
• Small features and low aspect ratios easy; high aspect ratios harder
Aclara
Steag Lilliput chip
• Injection molding vs. Casting• Injection molding gives
rapid cycle time• Casting gives best
replication fidelity
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• CD fabrication+ Standardized
handling/automation+ Superior flatness, low
thickness variations, high precision in multilevel depths
+ Multiple designs on single tool– Final part usually obtained by
dicing– Limitations due to circular
format–
• CD features• Injection-molding of
PC:
• After molding, disc is metallized and lacquered
• Pits of 9 lengths, smallest is:
• 2 billion pits per disc
Åmic
Gyros
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5Important parameters in polymer chip operation.
Electroosmotic pumping
Controllable surface charge, good insulator for HV operation (dielectric strength, electrical resistance)
Joule heating Thermal conductivity
Chemical properties Chemical resistance, permeability,analyte adsorption and biocompatibility
Optical detection High transmission and low background fluorescence
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Plastics Pro and Con
• Varying surface charge and charge density• Depends on polymer type and fabrication process
• For example, laser-ablation gives higher EOF than hot embossing• Location of charge in PMMA different for casting vs. hot embossed
channels• Can control using surface treatments or may not be necessary
• Background fluorescence• Biggest detection concern working with plastics and short-
wavelength excitation (488 nm)• Confocal epifluoresence rejects background• Can use red or near IR-absorbing fluorophores
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5Replication in the Process Flow
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Fabrication Techniques for Microfluidics
• Replication vs. Direct Techniques• Polymer Replication Techniques• Master Fabrication• Electroplating• Back-End Processes
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5Master Fabrication
• Fabricate master to serve as mold insert or precursor to electroplated mold insert• Batch techniques: photolithography plus etching• Serial techniques such as mechanical micromachining
• Serial techniques• Laser cutting• Laser-assisted chemical etching• Micro electro discharge machining (µEDM)• Stereolithography
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Batch Techniques• Photolithography plus etching
• Wet etching ~ isotropic or anisotropic channel profiles
• Dry etching ~ plasma or DRIE processing
• Patterned photoresist ~ SU-8 epoxy
Åmic
Si masters
SU-8 features
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5Fabrication Techniques for
Microfluidics
• Replication vs. Direct Techniques• Polymer Replication Techniques• Master Fabrication• Electroplating• Back-End Processes
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Electroplating• Set-up and operation
• Anode, cathode, aqueous-metal solution, and power supply.
• When power is on, cations in solution are attracted to cathode. At the cathode, Ni+2
gain e-‘s and are deposited onto the cathode surface.
• Simultaneously, Ni is electrochemically etched from the anode to give ions for the aqueous solution and electrons for the power supply
• H+ also gain e-‘s from the cathode form bubbles of H2 (g)
• Fabrication details• Conductive seed layer
needed
Judy
→ →
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5Electroplating
• Film thickness not limited by mask thickness (PR thickness)
• Plating mask must achieve good step coverage • Adhesion layer is needed (Ni adheres poorly to Si)
CJ Kim group, UCLA
Nickel Plating Solution
Material Quantity
Nickel Sulfate 200g/L
Nickel Chloride 5 g/L
Boric Acid 25 g/L
Saccharin 3 g/L
Judy
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LIGA• LIGA stands for lithography, electroforming and molding (in German)• Deep X-ray lithography used; need synchrotron source • Metal electroform may be used as mold tool for plastics molding
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5Fabrication Techniques for
Microfluidics
• Replication vs. Direct Techniques• Polymer Replication Techniques• Master Fabrication• Electroplating• Back-End Processes
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Back-end Processes
• Tasks• Drilling sample wells• Surface modification• Electrical interconnect• Bonding of a sealing layer• Machining ~ drilling and dicing
• Drilling sample wells • High cost step - done by inserting pins into mold tool• Definition using etching instead is desirable
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5Surface Modification and Interconnect
• Surface modification to tune hydrophobicity/hydrophilicity and control sample adsorption• Wet chemical techniques• Plasma treatments
• Electrical interconnect: metallization• Insert metal pins into reservoirs• Evaporation, sputtering• Plating• Screen printing of conductive ink
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Sealing
• Sealing microchannels• Silicon and glass ~ fusion or anodic bonding• Thermoplastics
• Low temperature thermal annealing using same polymer or one with lower Tg with or without P
• Pressure-sensitive adhesive
• Elastomers • Reversible seal upon contact• Permanent seal using a chemical reaction, Fluidigm, or
by plasma oxidation, Whitesides group
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