1. BIOMICROFLUIDICS May 12, 2003 Final Report Susan Beatty Stacy Cabrera Saba Choudhary Dan Janiak www.mae.ufl.edu

2. OVERVIEW Microfluidics Introduction Biomicrofluidics –Lab-on-a-chip –Drug delivery and Micro-dosage systems Materials –For Microfluidics –For valves Processes –For Microfluidics –For valves Future of Microfluidics This illustration show the processing of a glass microfluidic device. http://www.mae.ufl.edu/~zhf/Resear chInterests-ZHFan.htm

3. MICROFLUIDICS The control of tiny amounts of gases or liquids in a miniaturized system of channels, pumps, valves, and sensors. The motivation stems from trying to be more efficient on a smaller scale (several tests on a single micro chip). Example in Nature: human body’s oxygen (blood) transport system mTAS: systems of channels, valves, pumps, detectors

4. MOTIVATION Macro scale = laminar, random, and turbulent flow Micro scale = laminar flow Laminar flow allows controlled mixing Low thermal mass Efficient mass transport Good (large) ratio of channel surface area: channel volume http://www.spie.org/web/oer/august/aug00/microfluidics.html

5. Used for analyzing thousands of samples at once Can perform clinical diagnoses, scan DNA, run electrophoretic separations System: substrate with integrated microchannels and devices Experiment: uses fluid sample in picoliter range Advantage: conserve sample and time BIOMEDICAL APPLICATIONS: LAB-ON-A-CHIP

6. Also known as DNA chips or DNA microarrays Used for analyzing thousands of Genes at once DNA probes and DNA sample Can analyze cancerous cells Can determine which genes or turned on or off by a drug Advantage: accelerate the pace of genetic research LAB-ON-A-CHIP: GENE CHIP

7. GENE CHIP http://www.popcouncil.org/images/gene_chip.gif

8. Needed in the medical field System: micropump and flowsensor High dosage approach used in the past Insulin – wastage of insulin Painkillers – possibility of addiction Insulin micropump: mimic action of pancreas Microfluidics can make possible closed-loop system with glucose sensor Painkillers: deliver drug locally, not globally Avoid addiction Tested at Maternity Hospital in Dublin, Ireland BIOMEDICAL APPLICATIONS: DRUG DELIVERY AND MICRO-DOSING SYSTEMS http://www.yourmedicalsour ce.com/images/pancreas.jpg

9. DRUG DELIVERY CONT. http://www.adam.com/b2b/products/healthillus/images/18035.jpg

10. Current research at Michigan University on Neural Microfluidic Devices for the intracerebral delivery of neuro-active compounds Challenge: Must get the drug to CNS, across blood-brain barrier and before drugs are degraded and metabolized High dosage approach can have detrimental effects on other parts of body Challenge can be faced with microfluidic technology DRUG DELIVERY: NEURO- ACTIVE COMPOUNDS http://www.yourmedicalsource.com /images/central_nervous_system_4 00.jpg

11. Many micro-devices: valves, pumps, fluidic mixers, and sensors Device focus: Valves – needed to control flow of fluid Two types of Valves: Passive and Active MICROFLUIDIC SYSTEMS: PRODUCT OF DEVICE INTEGRATION

12. Passive Valves No actuation required Designed to give higher flow in one direction Main application in mechanical micropumps Flap is controlled by pressure difference across it Active Valves: Slightly more complex Need a form of actuation (thermal, electrical) Actuation controls the flap PASSIVE VS. ACTIVE VALVES

13. MATERIALS OVERVIEW MATERIALSILICONPLASTICS POSITIVESWell understood Highly available Inexpensive Disposable Easily machined NEGATIVESExpensive Not always bioinert Swelling Pairing The type of material used depends on the structure or device (mircochannel, pump, valve, etc…) being fabricated -cost-compatibility

14. COMMON MATERIALS PDMS – Polydimethylsiloxane - Used as a structural material for microchannels - Low interfacial free energy - Stable against humidity, temperature - Can be used as a stamp for processes such as microcontact printing, micromolding Parylene - Can be used as a structural material or coating - Low permeability to moisture - High resistance to corrosion Polyimide - Used for microchannels - Easy to deposit metals (sputter)

15. MATERIALS FOR VALVES Conjugated polymers “Organic semiconductors” Doping level depends on the oxidation state of the polymer Volume change associated with oxidation state Volume change occurs as a result of ions moving into and out of the polymer Large Immobile Anion: Small Mobile Cation: P + (A - ) + C + + e -  P  (AC) P + (A - ) + C + + e -  P  + A - + C +

16. MATERIALS FOR VALVES PEG (Polyethylene Glycol) Volume change associated with phase transition Paraffin Volume change Bimetallic Strips Expansion http://www.wam.umd.edu/~smela

17. PROCESSES Overview –Soft lithography Silicon is patterned with a negative photoresist Polymer is cast onto silicon mold Polymer is cured and removed from mold http://nanotron.ecn.pudue.edu

18. PROCESSES CONT. –micromachining Bulk micromachining –Removes from bulk of material-etching Surface micromaching –Adds to surface of material »Deposistion »Micro contact printing

19. VALVE PROCESSES Diaphragm check valve Begins with etching holes into silicon substrates from bottom http://touch.caltech.edu http://gmwgroup.harvard.edu

20. VALVE PROCESSES CONT. Metal seals are deposited Photoresist and polymer are deposited Resist is removed with acetone and silicon membrane is etched http://touch.caltech.edu

21. FUTURE OF BIOMICROFLUIDICS Automation of complex experimental procedures Transformation of macroscale lab tests to a device the size of a postage stamp, available to the individual, with the skill of the technician More rapid DNA sequencing and general biological procedures Key Factor: future fabrication techniques are compatible with current batch processing techniques Small ridges along the channel walls can force mixing by a kneading motion, http://depts.washington.edu/bioe/shrunklab.pdf.

22. QUESTIONS