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MultipleandHigh-ThroughputDropletReactionsviaCombinationofMicrosamplingTechniqueandMicrofluidicChipMembers:李娜馮雙霞徐秋燕劉婷婷聶懷軍ContentsBackgroundExperimentABSTRACTDiscussionABSTRACTMicrodropletso?eruniquecompartmentsforaccommodatingalargenumberofchemicalandbiologicalreactionsintinyvolumewithprecisecontrol.Amajorconcernindroplet-basedmicro?uidicsisthedi?cultytoaddressdropletsindividuallyandachievehighthroughputatthesametime.BackgroundAlargenumberofreactionscanbeindependentlyminiaturizedintotinydropletsrangingfromnanolitertopicolitersizeswithouthavingtoincreasethechipsizeandcomplexity.
Microfluidicchipshaveprovidedapowerfulplatformforaccomplishingdropletformationandmanipulationwithinonechipofonlyafewsquarecentimetersinsize.
AdvantagesOverthepastfewyears,droplet-basedmicro?uidicshasattractedincreasingattention.Background
Dropletgenerationformultiplesamplesislimitedbythe“world-to-chip”interfaceproblemandcannotbeaddressedindividuallyDropletgenerationandmanipulationfunctionswithinonechipcaneasilyinterferewitheachotherandaredifficultTobalance,despitebeingseparatedbyalong,windingchannel.DrawbackPassivedropletformationmethods:Thehybriddropletdeviceforgenerationandmanipulationconsistsoffourmajorcomponents.
(a)manipulator(b)multiwellplate(c)capillary(d)PDMSchipLaboratoryreagent
siliconeoil,
FeCl2·4H2O(Sigma?Aldrich),FeCl3·6H2O(AcrosOrganics),ammoniumhydroxidesolution(28%NH3Fluka),andhydrochloricacid(37%HCl,AcrosOrganics)ImprovedSamplingTechnique
CombinedDropletDevicePerformance
High-ThroughputDropletScreening
AggressiveDropletReaction
ImprovedSamplingTechniqueThecapillaryaspiratestheoilwhenthecantileverremainsinthe“up”state.Whenthecantileveristriggeredtostayinthe“down”state,thecapillaryaspiratesthesample.Theresidencetimeintheoil(TO)andsample(TS)couldbeadjustedrespectivelytogeneratedropletswithdesireddistanceandvolume.(c)Relativeintensitywasmeasuredalongthechannelstartingfromtoprightcorner.TheintensityoffluoresceinandDIwaterdropletdoesnotdecreaseorincrease,whichindicatesthatnocross-contaminationbetweenthesetwosampleswasdetected.(b)Dropletarraywasgeneratedbysequentiallyaspirating50uMfluoresceinandDIwater.CombinedDropletDevicePerformanceHere,themergingofdropletswasdemonstratedinaPDMSchip.ThedropletsfusiondoesnotdependondropletdistancebutdropletvelocityandVd/Vc.Aftermixingcompletely,themergeddropletwasoutputtoasinuouschannelfordisplayanddetection.High-ThroughputDropletScreeningThe36pairsofdropletreactionsused~72nLofsolutionandrequired1.8mintocomplete.Therefore,thereagentconsumptionforeachmeasurementcouldbereducedto1nLpersample,andthereactionthroughputis1200h?1,whichcanbemuchfasterbyincreasingthe?owvelocity.ThescreeningdropletscouldbestoredinthePDMSchipafterwestoppedthevacuum.Fromtheseimages,wefoundthatthecoprecipitationissofastthatitimmediatelyformsparticleswhentwodropletscomeintocontactwitheachother.Moreover,ineachvolumeratio,theprecipitationinitiatedbythefusionoftwodropletsdidnotblockthemicrochannelatsuchhighconcentrations.Such?exible,controllableandminiaturizedreactionconditionsareextremelysuitableforaggressive,fast,orevenexplosivereactionsthatgenerateprecipitationorheat.DiscussionThecartridgedropletgenerationmethodprovidesanefficientwayforintroducingdifferentnanoliterdropletsintothemicrofluidicchip.themicrofluidicchipoffersaplatformfordelicatemanipulationsuchasmerging.Thisfeatureisvaluableforreducingthereactionscreeningandoptimizationcostandtimeandisparticularlyusefulfordrugscreening.Comparedwiththeothercartridgedropletgeneration,ourdesignusedadigitalandautomaticmanipulatortomovethecapillaryinsteadofthemultiwellplate.DiscussionSubsequently,thecoveringoilwasingeniouslyusedasacarrier?uid(continuous-phase)toavoidevaporationandcross-contamination.Thisimprovedcartridgetechniqueandmicro?ui
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