BIOMICROFLUIDICSOVERVIEWMICROFLUIDICSMOTIVATIONBIOMEDICAL APPLICATIONS: LAB-ON-A-CHIPLAB-ON-A-CHIP: GENE CHIPGENE CHIPBIOMEDICAL APPLICATIONS: DRUG DELIVERY AND MICRO-DOSING SYSTEMSDRUG DELIVERY: NEURO-ACTIVE COMPOUNDSMICROFLUIDIC SYSTEMS: PRODUCT OF DEVICE INTEGRATIONPASSIVE VS. ACTIVE VALVESMATERIALS OVERVIEWCOMMON MATERIALSMATERIALS FOR VALVESSlide 16PROCESSESPROCESSES CONT.VALVE PROCESSESVALVE PROCESSES CONT.FUTURE OF BIOMICROFLUIDICSQUESTIONSBIOMICROFLUIDICSBIOMICROFLUIDICSMay 12, 2003 Final ReportSusan Beatty Stacy CabreraSaba Choudhary Dan Janiakwww.mae.ufl.eduOVERVIEWOVERVIEW•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 MicrofluidicsThis illustration show the processing of a glass microfluidic device.http://www.mae.ufl.edu/~zhf/ResearchInterests-ZHFan.htmMICROFLUIDICSMICROFLUIDICS•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, detectorsMOTIVATIONMOTIVATION•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 volumehttp://www.spie.org/web/oer/august/aug00/microfluidics.html•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 timeBIOMEDICAL APPLICATIONS: BIOMEDICAL APPLICATIONS: LAB-ON-A-CHIPLAB-ON-A-CHIP•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 researchLAB-ON-A-CHIP: GENE CHIPLAB-ON-A-CHIP: GENE CHIPGENE CHIPGENE CHIPhttp://www.popcouncil.org/images/gene_chip.gif•Needed in the medical field•System: micropump and flowsensor•High dosage approach used in the pastInsulin – wastage of insulinPainkillers – possibility of addiction •Insulin micropump: mimic action of pancreasMicrofluidics can make possible closed-loop system with glucose sensor•Painkillers: deliver drug locally, not globallyAvoid addictionTested at Maternity Hospital in Dublin, Ireland BIOMEDICAL APPLICATIONS: DRUG BIOMEDICAL APPLICATIONS: DRUG DELIVERY AND MICRO-DOSING DELIVERY AND MICRO-DOSING SYSTEMSSYSTEMShttp://www.yourmedicalsource.com/images/pancreas.jpg•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 technologyDRUG DELIVERY: NEURO-DRUG DELIVERY: NEURO-ACTIVE COMPOUNDSACTIVE COMPOUNDShttp://www.yourmedicalsource.com/images/central_nervous_system_400.jpg•Many micro-devices: valves, pumps, fluidic mixers, and sensors•Device focus: Valves – needed to control flow of fluid•Two types of Valves: Passive and ActiveMICROFLUIDIC SYSTEMS: MICROFLUIDIC SYSTEMS: PRODUCT OF DEVICE PRODUCT OF DEVICE INTEGRATIONINTEGRATIONPassive ValvesNo actuation requiredDesigned to give higher flow in one directionMain application in mechanical micropumpsFlap is controlled by pressure difference across it Active Valves: Slightly more complexNeed a form of actuation (thermal, electrical)Actuation controls the flapPASSIVE VS. ACTIVE VALVESPASSIVE VS. ACTIVE VALVESMATERIALS OVERVIEWMATERIALS OVERVIEWMATERIAL SILICON PLASTICSPOSITIVES Well understoodHighly availableInexpensiveDisposableEasily machinedNEGATIVES ExpensiveNot always bioinertSwellingPairingThe type of material used depends on the structure or device (mircochannel, pump, valve, etc…) being fabricated-cost -compatibilityCOMMON MATERIALSCOMMON MATERIALSPDMS – 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, micromoldingParylene- Can be used as a structural material or coating- Low permeability to moisture- High resistance to corrosionPolyimide- Used for microchannels- Easy to deposit metals (sputter)MATERIALS FOR VALVESMATERIALS FOR VALVESConjugated 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 polymerLarge Immobile Anion: Small Mobile Cation:P+(A-) + C+ + e-  P(AC) P+(A-) + C+ + e-  P + A- + C+MATERIALS FOR VALVESMATERIALS FOR VALVESPEG (Polyethylene Glycol)•Volume change associated with phase transitionParaffin•Volume changeBimetallic Strips•Expansionhttp://www.wam.umd.edu/~smelaPROCESSESPROCESSES•Overview–Soft lithography•Silicon is patterned with a negative photoresist•Polymer is cast onto silicon mold•Polymer is cured and removed from moldhttp://nanotron.ecn.pudue.eduPROCESSES CONT.PROCESSES CONT.–micromachining•Bulk micromachining–Removes from bulk of material-etching•Surface micromaching–Adds to surface of material»Deposistion»Micro contact printingVALVE PROCESSESVALVE PROCESSES•Diaphragm check valve•Begins with etching holes into silicon substrates from bottomhttp://touch.caltech.eduhttp://gmwgroup.harvard.eduVALVE PROCESSES CONT.VALVE PROCESSES CONT.•Metal seals are deposited•Photoresist and polymer are deposited•Resist is removed with acetone and silicon membrane is etchedhttp://touch.caltech.eduFUTURE OF BIOMICROFLUIDICSFUTURE 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