微流控芯片之一

LabonaChipOr:TheIncredibleShrinkingScienceExperiment!Or:APOIBE!Credits:MathiesLab,UC-BerkeleyQuakeLab,StanfordAgilent,Inc.二十一世纪科学发展趋势•Miniaturization•Automation•Integration•PortableLabonaChip?MicrofluidicsMicrofluidics:TheuseofmicrofabricationtechniquesfromtheICindustrytofabricatechannels,chambers,reactors,andactivecomponentsonthesizescaleofthewidthofahumanhairorsmallerCredit:Dr.KarenCheung,UBCECEWhyusemicrofluidics?1moleculein1mL=1.6x10-18M1moleculein1nL=1.6x10-15M1moleculein1pL=1.6x10-12MCredit:Dr.KarenCheung,UBCECE•Samplesavings–nLofenzyme,notmL•Fasteranalyses–canheat,coolsmallvolumesquickly•Integration–combinelotsofstepsontoasingledevice•Novelphysics–diffusion,surfacetension,andsurfaceeffectsdominate–Thiscanactuallyleadtofasterreactions!Whyusemicrofluidics?1-3min/12samplesMulti-channelmicrochipelectrophoresis1-3minMicrochipelectrophoresisdetectionHighvoltagebuffersamplecapillary10-30minCapillaryelectrophoresisseparationbuffer1-3ｈGelelectrophoresisSomeinterestingLOCapplications•Geneticanalysis–Portabledevicesforpathogendetection–High-throughputbiology•Chemicalsynthesis•Cell•Immunoassayanalysis•Metaboliteanalysis•Drugdeliverysystems•Singlemolecular•EnzymeanalysisCourtesyofDr.BorisStoeberGeneticanalysismicrosystems96-channelradialcapillaryarrayelectrophoresismicroplateAnalChem.1999;71(23):5354-61BacterialPathogensFoodpoisoningWoundinfectionsBiowarfareFoodpoisoning:PathogenicE.coli:1in10,000inCanadaSalmonellaspp.:ashighas1in50eggsWoundinfections:Antibiotic-resistantS.aureus:ashighas50%LungDisease:Pseudomonasspp.MycobacteriumtuberculosisBiowarfare:Anthrax,plague,smallpoxLungDiseaseDr.SharonPeacock,UniversityofOxfordMethodsforGeneticDetectionofPathogensOLDWAY:NEWWAY:Developbacterialpathogendetectorsthatare:Rapid(1hour)Sensitive(detectasinglecell)GeneticallySpecificField-portableGeneral(manydifferenttypesofpathogens)PCR-CEMicrosystemFabricationPortableSystemforInfectiousDiseaseDetectionSystemmeasures8x10x12inches•Completefluorescencedetectionincluding488-nmsolid-statelaser,PMT,optics,anddetectionelectronics•HeaterandRTDelectronics•4high-voltageCEpowersupplies•PDMSmicrovalvehardware•SimplePCinterfaceTime(seconds)Temperature(°C)ThermalCyclingCharacteristicsTime(seconds)5XfasterthanconventionalthermalcyclersApplication:Tuberculosis(TB)detectionDiseasecausedbyMycobacteriumtuberculosis9millionnewcasesofactiveTBeveryyearworldwide2millionTBdeathseveryyear450,000newcasesofmulti-drugresistantTB/yr10%ofTBcasesinSouthAfricaareXDRTBstrains,resistanttofirst-andsecond-lineantibioticsDoctorsWithoutBorders:CurrentTBdetectionmethods1.Fixationandstainingwithacid-faststains(Ziehl-Neelsenorauraminestains)2.Opticalorfluorescencemicroscopeexamination(10,000organisms/mL)3.Cultureinbiosafetylevel3containmentfacilityInselectcases,moleculardetectionisusedtoverifydiagnosisThatTBdestroysmillionsoflivesaroundtheworldeveryyearshowsthatthecurrentapproachisjustnotworking…ThetoolswehavetotreatanddiagnoseTBarewoefullyinadequateandoutdated,andwe'renotseeingthenecessaryurgencytotacklethedisease.Dr.TidovonSchoen-Angerer,Director,DWB’sCampaignfortheAccesstoEssentialMedicinesTheNot-so-DistantFuturePDA20082308??Paramount384根通道扫描检测Emrich,C.A.,etal.,AnalyticalChemistry,2002.74(19):p.5076-5083.10根通道CCD同时检测Dang,F.Q.,etal.,AnalyticalChemistry,2005.77(7):p.2140-2146.目前最高通量微流控芯片平台Aborn,J.H.,etal.,LabonaChip,2005.5(6):p.669-674门控进样多通道检测Xu,X.M.,etal.,AnalyticalChemistry,2002.74(21):p.5517-5522高通量均相免疫分析Bromberg,A.andR.A.Mathies,Electrophoresis,2004.25(12):p.1895-1900.Microbes,cellsandsmallorganismscomeinawidearrayofshapesandsizesYeastBloodCellscryptosporidiumLab-on-a-chipDevicesforCellSeparationandIdentificationMicrofluidicorLab-on-a-chipDevicescanbeusedtoseparatedifferentcelltypesVariousbloodcellseparationshavebeendemonstrated:•J.A.Davis,D.W.Inglis,K.M.Morton,D.A.Lawrence,L.R.Huang,S.Y.Chou,J.C.Sturm,andR.H.Austin,Deterministichydrodynamics:takingbloodapart,Proc.Nat.Acad.Sci.(USA),vol.103,pp.14779-14784,2006.D.W.Inglis,J.A.Davis,T.J.Zieziulewicz,D.A.Lawrence,R.H.Austin,andJ.C.Sturm,Determiningbloodcellsizeusingmicrofluidichydrodynamics,J.Immunol.Meth.,vol.329,pp.151-156,2008.•D.W.Inglis,K.J.Morton,J.A.Davis,T.J.Zieziulewicz,D.A.Lawrence,R.H.Austin,andJ.C.Sturm,Microfluidicdeviceforlabel-freemeasurementofplateletactivation,SubmittedtoLabonaChip,Jan08.Butnoworkyetwithmicroorganisms!Thisprojectwillleadtopublicationswhichdemonstratetheseparationofmicroorganismsonportableinexpensivepolymermicrofluidicdevices.Suchdevicesmayhaveapplicationsin•earlydetectionofhumandiseasessuchassepsisandvariousparasiticdiseases•aswellasmanagementofswimmingpoolanddrinkingwaterquality.WhatisMicro-Fluidics•Microfluidics–microfabricatedstructuresforfluidhandling•EngineersknowhowtomicrofabricateandbuildintegratedsystemsmTAS–MicroTotalAnalysisSystem–Integratemicrofluidiccomponentsintoausefuldevice,a“LabonaChip”•“developmentandapplicationofmicro-andnanofabricateddevicesandsystemsforchemicalandbiochemicalmeasurements.Thetechnologyencompassesextensiveareasofapplicationinclinicaldiagnosti