Monolithic Microfabricated Valves and Pumps by

Multilayer Soft Lithography

EECE 491C

Unger et al. (Quake group, CALTECH)

Science, 2000

How complex and how big?

• ENIAC, first large scale electronic and digital computer

• 30 tons, 19,000 vacuum tubes, 200 kW

• Towards integrated circuits

• Large Scale Integrated Circuits (LSI)

EECE 491C

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Courtesy www-ivs.cs.uni-magdeburg.de

Biochemical Laboratories

• Expensive Reagents• Small amounts of

samples available• High levels of

multiplicity required• Portability• Equipment Costs• Level of training

EECE 491C

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Courtesy www.stanford.edu/group/crg

Courtesy www.nature.com/ vol 442- Yager

Microelectromecanichal structures (MEMS)

• Bulk micromachining:• Single-Crystal silicon

lithographically patterned then etched

• Stress between layers

• Surface Micromachining:• Additive method• Patterning. Max thickness 20 um

• Limited materials• Stiff materials = hard to make

smaller features

EECE 491C

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Soft Lithography

EECE 491C

•With only one layer it is difficult to create active devices or moving parts

Multilayer Soft Lithography • Can bond different layers of

elastomer• Elastomer: silicon rubber, 2

component, polymer and cross-linker

• Each layer has excess of one of the 2

• Upon contact layers form hermetic seal

• Can easily create multilayer devices

• Can create electro-magnetic devices by doping

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Valves

• Typical channel size X

• Membrane between layers

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100m

10m

30m

• Response time ~1ms• 1mN of force (100kPa)• Pneumatic activation:

dense packing possible

• Fluid is introduced with pins

• Can accept up to 300 kPa without leakage

Valves and Pressure

• Flow Layer: biological assay, fluid manipulation

• Control Layer: actuate valves• • Valve opening controlled by

fluorescence

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close open

From Valves to Pumps

• A - on/off valve 200x100• B - on/off valve 30x50• C - peristaltic pump• D - grid of valves• E - switching valve• F - section of 7 layer

device• Scale bars: 200 um

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Elastomeric Peristaltic Pump

• 50 kPa of applied pressure

• Channels 100 um wide and 10 um high

• Durable• E coli showed 94%

survival rate

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Valves and Pumps• Durable• Low dead volumes• Complete sealing even in presence of

particulates• Easy to produce• Cheap• Rapid prototyping• Multiple layers possible• Transparent• Biocompatible• Countless applications

EECE 491C

Courtesy nature.com vol 442 Whitesides, Quake

Valves and Pumps

EECE 491C

Courtesy Carl Hansen

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Valves and Pumps

EECE 491C

Courtesy Carl Hansen

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are needed to see this picture.

Microfluidic Large-Scale Integration

EECE 491C

Thorsen et al. (Quake group, CALTECH)

Science, 2002

The Multiplexor

• Microvalves are scalable and leakproof

• Can now have multiplexed addressing and control

• Binary tree• fluid channels• control channels• Only 20 control for

1024 flow channels

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2log2 n

n

Memory Storage Design

• 1000 individually addressable 250pL chambers

• Microfluidic memory storage device

• Similar to Random Access Memory (RAM)

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Memory Storage

• Row Multiplexor: fluid trafficking (RAM word line) refreshes compartments within a row

• Column Multiplexor: controls vertical input-output valves for specific central compartments

• Display Monitor

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Microfluidic Comparator Chip

• Allows mixing of 2 separate reagents, unloading

• 256 rxn chambers

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The Experiment

• Ecoli in one compartment• Amplex red (AR) in the other

columnEECE 491C

• Compartments opened• CCP converts AR to resorufin• Control using GFP

Controls

• Heterogeneous mixture of E. coli expressing CCP or eGFP

• Amplified signal dependent only on number of CCP expressing cells in individual chambers

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Conclusions

• Ability to integrate and control many fluidic elements• Selective manipulation and recovery• Scalable devices• Can envision chemical and biochemical analysis• High throughput screening applications, liquid

display technology• Creation of microfluidic LSI• Rapid, simple fabrication• Disadvantages of PDMS

EECE 491C

Critique

• Well presented, ground-breaking• Limited discussion of other techniques available• Weak Biological experiments or applications• Limited discussion of flaws of the materials used

• Certain figures are not very detailed• Would have been interesting to see a picture of the

entire deviceEECE 491C

Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography

Critique

• Well presented, ground-breaking, great intro• Explanatory analogies• Weak Biological experiments-weaker ending• More thorough discussion of flaws of the materials

used

• One figure mislabeled• Great device pictures

EECE 491C

Microfluidic Large Scale Integration