1. Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography EECE 491C Unger et al. (Quake group, CALTECH) Science, 2000

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

3. Biochemical Laboratories Expensive Reagents Small amounts of samples available High levels of multiplicity required Portability Equipment Costs Level of training EECE 491C Courtesy www.stanford.edu/group/crg Courtesy www.nature.com/ vol 442- Yager

4. 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 Courtesy http://dei-s1.dei.uminho.pt Courtesy http://www.aero.org

5. Soft Lithography EECE 491C With only one layer it is difficult to create active devices or moving parts

6. 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 EECE 491C

7. Valves Typical channel size X Membrane between layers EECE 491C 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

8. Valves and Pressure Flow Layer: biological assay, fluid manipulation Control Layer: actuate valves Valve opening controlled by fluorescence EECE 491C

9. 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 EECE 491C

10. Elastomeric Peristaltic Pump 50 kPa of applied pressure Channels 100 um wide and 10 um high Durable E coli showed 94% survival rate EECE 491C

11. 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

12. Valves and Pumps EECE 491C Courtesy Carl Hansen

13. Valves and Pumps EECE 491C Courtesy Carl Hansen

14. Microfluidic Large-Scale Integration EECE 491C Thorsen et al. (Quake group, CALTECH) Science, 2002

15. 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 EECE 491C

16. Memory Storage Design 1000 individually addressable 250pL chambers Microfluidic memory storage device Similar to Random Access Memory (RAM) EECE 491C

17. 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 EECE 491C

18. Microfluidic Comparator Chip Allows mixing of 2 separate reagents, unloading 256 rxn chambers EECE 491C

19. The Experiment Ecoli in one compartment Amplex red (AR) in the other column EECE 491C Compartments opened CCP converts AR to resorufin Control using GFP

20. Controls Heterogeneous mixture of E. coli expressing CCP or eGFP Amplified signal dependent only on number of CCP expressing cells in individual chambers EECE 491C

21. 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

22. 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 device EECE 491C Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography

23. 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