第1-4章-微流控芯片

第1-4章微流控芯片目录一．发展背景二．制备技术三．流体控制四．典型实例五．商品简介目录一．发展背景二．制备技术三．流体控制四．典型实例五．商品简介Doyouknow?•Biochip生物芯片•Lab-on-a-Chip芯片实验室Labchip•MicrofluidicChip微流控芯片•MicroTotalAnalysisSystem(MicroTAS,TAS)微全分析系统Researchintominiaturizationisprimarilydrivenbytheneedtoreducecostsbyreducingtheconsumptionofexpensivereagentsandbyincreasingthroughputandautomation.Forexample,mostareawareoftheincreasingcostofhealthcare,driveninpartbythecostofimplementingthelatestdiagnosticassays.Theseassays,whichareusuallyperformedinmicrotiterplatesthatconsumehundredsofmicrolitersofreagents,wouldbenefitfromtheuseofmicrofabricatedarraysofnanolitervolumevials.Byreducingreagentconsumptionbyafactorof103–104,thesedevicescouldprovidedramaticsavingsfortherepetitiveassaysoftenperformedindiagnosticlaboratories.Whyminiaturization？Anal.Chem.2000,72,330A-335AInthesamewaythatintegratedcircuitsallowedfortheminiaturizationofcomputersfromthesizeofaroomtothesizeofanotebook,miniaturizationhasthepotentialtoshrinkaroomfullofinstrumentsintoacompactlab-on-a-chip.Anal.Chem.2000,72,330A-335A尺寸效应（cm→100m）•尺寸1/100•分子扩散时间1/10,000(1h→0.36s)•体积1/1,000,000试剂用量1t→1g,ml→nl•传热速度1500oC/s由此将带来：–方法上的变革–理论上的突破–还有巨大的经济和社会效益微流控分析芯片•微流控分析芯片目的是通过化学分析设备的微型化与集成化，最大限度地把分析实验室的功能转移到便携的芯片中。•微流控分析芯片通过微机电加工技术把整个实验室的功能，包括采样、稀释、加试剂、反应、分离、检测等集成在几平方厘米的微流控芯片上，且可多次使用，因而极大地减少了样品和分析试剂的用量，降低了分析的成本，加快了分析的速度，具有广泛的适用性。TheEarlyDays:1975-1989•ThefirstanalyticalminiaturizeddeviceAgaschromatographicairanalyzerfabricatedonasiliconwaferTerry,S.C.Ph.D.Thesis,Stanford,Stanford,CA,1975Terry,StephenC.;etal.IEEETransactionsonElectronDevices,1979,ED-26(12),1880•Aminiaturegasanal.systembasedontheprinciplesofgaschromatog.•ThemajorcomponentsarefabricatedinSiusingphotolithog.andchem.etchingtechniques,whichallowssizeredns.ofnearly3ordersofmagnitudecomparedtoconventionallaboratoryinstruments.•consistsofasampleinjectionvalve,a1.5-m-longcapillarycolumn.Athermalconductivitydetectorfabricatedonaseparatesiliconwafer.•sepns.ofgaseoushydrocarbonmixts.areperformedin10s.发展历史PhotographofagaschromatographintegratedonaplanarsiliconwaferfabricatedbyTerryandco-workersatStanfordUniversity.•However,theresponseofthescientificcommunitytothisfirstsiliconchipdevicewasvirtuallynone,presumablybecauseofthelackoftechnologicalexperience(oftheseparationscientists)todealwiththiskindofdevice.•theresearchworkrelatedtominiaturizationonsiliconfocusedonthefabricationofcomponentssuchasmicropumps,microvalves,andchemicalsensors.TheRenaissance:1990-1993•thereemergenceofsilicon-basedanalyzersDesignofanopen-tubularcolumnliquidchromatographusingsiliconchiptechnologyManz,A.;etal.SensorsandActuators,B:Chemical(1990),B1(1-6),249•Anovelconceptofhighpressureliquidchromatog.•asiliconchipwithanopen-tubularcolumnandaconductometricdetector.•A5×5mmchipcontaininganopen-tubularcolumnof6m×2m×15cmwasfabricated,whichhastheor.separationefficienciesof8000and25,000platesin1and5min,resp.•Thetotalcolumnvolumeis1.5nLandthedetectioncellvolume1.2pL.MicrographofLiquidChromatographchipmanufacturedbyManzandco-workersatHitachiLtd.•TheconceptofminiaturizedtotalchemicalanalysissystemorTASwasproposedbyManzetal.•themainreasonforminiaturizationwasthereforetoenhancetheanalyticalperformanceofthedeviceratherthantoreduceitssize.•itwasalsorecognizedthatasmallsizepresentedtheadvantageofasmallerconsumptionofcarrier,reagent,andmobilephase.GrowingtoCriticalMass:1994-1997•In1994,thenumberofpublishedpapersrelatedtoTASincreasedabruptlysincemoreresearchgroupsjoinedtheeffortstodevelopthearea.•Microfabrication•Design•Separations•BiochemicalReactors•Detection分类与特点•分类：材料：硅、玻璃、石英、聚合物、复合材料功能：分离、采样与前处理、检测、化学合成等•特点：高效、低耗、集成、一致性好、昂贵目录一．发展背景二．制备技术三．流体控制四．典型实例五．商品简介微结构的形成1．经典的光刻技术Photolithographproceduresformakingglasstemplate.(a)Spinecoatingofphotoresist,(b)coveredwithphotomask,(c)exposure,(d)developing,(e)etching,and(f)removalofphotoresist.•适合硅、玻璃、石英等材料，与传统的半导体工业的方法一致。•分为湿法和干法两种，干法的分辨率较湿法高，相应的制造成本也高。Analyst,2004,129,305–308制备技术之微结构的形成2．模版浇注法（模塑法）Processoverviewformassmanufacturingofplasticmicrofluidicsystems•适合聚合物材料。•大批量生产时成本低。Anal.Chem.,2002,74,78A-86A微结构的形成3．模版热压法Schematicrepresentationofthefabricationmethodinvolvinghotembossingofthermoplasticpolymerpelletsandthermalbonding.•适合热塑性聚合物。AppliedPhysicsLetters,2002,80,3614-3616微结构的形成4．激光刻蚀法用激光直接在聚合物或玻璃上加热形成微结构.Anal.Chem.,1997,69,2035-2042MicrofilterSensorsandActuatorsB672000203–208芯片的封装1．热键合对玻璃和石英材质刻蚀的微结构一般使用热键合方法，将加工好的基片和相同材质的盖片洗净烘干对齐紧贴后平放在高温炉中，在基片和盖片上下方各放一块抛光过的石墨板，在上面的石墨板上再压一块重0.5kg的不锈钢块，在高温炉中加热键合。玻璃芯片键合时，高温炉升温速度为10oC/分，在620oC时保温3.5小时，再以10oC/分的速率降温。石英芯片键合温度高达1000oC以上。此方法对操作技术要求较高。现代科学仪器，2001，4，8-12制备技术之芯片的封装2．阳极键合•在玻璃、石英与硅片的封接中已广泛采用阳极键合的方法。即在键合过程中，施加电场，使键合温度低于软化点温度。•在500-760伏电场下，升温到500oC时，可使两块玻璃片键合。在两块玻璃板尚未键合时，板间空气间隙承担了大部分电压降，玻璃板可视为平行板电容器，板间吸引力与电场强度的平方成正比，因此，键合从两块玻璃中那些最接近的点开始，下板中可移动的正电荷（主要是Na+）与上板中的负电荷中和，生成一层氧化物（正是这层过渡层，使两块玻璃板封接），该点完成键合后，周围的空气间隙相应变薄，电场力增大，从而键合扩散开来，直至整块密合。现代科学仪器，2001，4，8-12芯片的封装3．室温键合Anal.Chem.2004,76,5597-5602芯片的封装4．贴合将聚合物薄片直接覆盖在玻璃或石英板上。5．压合Schematicillustrationofsealingandconnectionmethod.Thetopandbottomplatesarepressedbyascrewandholders.Anal.Chem.2