Polymeric ion-selective membrane functionalized gate-electrodes

Polymericion-selectivemembranefunctionalized

gate-electrodes:Ion-selectiveresponseofelectrolyte-gatedpoly(3-hexylthiophene)?eld-effect

transistors

KatharinaMelzera,?,AlexandraMaraMünzera,EwaJaworskab,KrzysztofMaksymiukb,AgataMichalskab,GiuseppeScarpaa

ab

TechnischeUniversitätMünchen,InstituteforNanoelectronics,Arcisstraße21,80333München,GermanyUniversityofWarsaw,FacultyofChemistry,Pasteura1,02-093Warsaw,Poland

articleinfoabstract

Wedemonstratetheion-selectiveresponseofanelectrolyte-gatedorganic?eld-effecttransistor(IS-OFET)towardsthetwoprominentsecondmessengersforcell–cellcommuni-cation:K+andCa2+.Theion-selectiveresponseisachievedbymodifyingthegate-electrodewithdifferentpolymericion-selectivemembranes.Thesensingmechanismreliesonthetransductionoftheionicsignalinanelectricaloneduetoaconcentration-dependentchangeinthemembranepotentialatthegate/electrolyteinterfacewhichleadstoachangeintheeffectivegatepotentialandthusalterschargetransportinthesemiconductingchan-nel.ThesesensorscanbesuccessfullyusedtoselectivelydetectconcentrationsofprimaryionsdowntoaconcentrationinthelMrangeeveninsolutionswithanionicbackgroundof150mM.Ourapproachrepresentsavaluablestrategyfortherealizationofportable,multi-purposeandlow-costbiosensingdevices.

Ó2013ElsevierB.V.Allrightsreserved.

Articlehistory:

Received2October2013

Receivedinrevisedform26November2013Accepted12December2013

Availableonline25December2013Keywords:Biosensor

Electrolyte-gatedorganic?eld-effecttransistor

Ion-selectiveresponse

Polymericion-selectivemembraneIonicbackgroundP3HT

1.Introduction

Inthelastfewyearsbiosensingconceptsbasedonelec-trolyte-gatedorganic?eld-effecttransistors(OFETs)havereceivedconsiderableattention(forrecentreviewsthereaderisreferredto[1–3]andreferencestherein).Inthiscontext,?eld-effecttransistorswithorganicsemiconduc-torsasactivelayerespeciallybene?tfromthefact,thattheycanbeusedin?exibleanddisposablesensorsduetothelowfabricationcostsofsolution-processableorganicthin?http://wendang.chazidian.combinedwiththeirhighbiocom-Correspondingauthor.Tel.:+498928925320.

E-mailaddresses:katharina.melzer@nano.ei.tum.de(K.Melzer),alexandra.muenzer@nano.ei.tum.de(A.M.Münzer),ejaworska@chem.uw.edu.pl(E.Jaworska),kmaks@chem.uw.edu.pl(K.Maksymiuk),agatam@chem.uw.edu.pl(A.Michalska),giuseppe.scarpa@nano.ei.tum.de(G.Scarpa).

1566-1199/$-seefrontmatterÓ2013ElsevierB.V.Allrightsreserved.http://wendang.chazidian.com/10.1016/j.orgel.2013.12.016

patibility[4]itmakesthemalsosuitableforimplantsandevenpermitsthedesignofbiodegradabledevices,e.g.forinvivoapplications[5,6].

OFETs,eitherelectrolyte-gated[7–9]orback-gated[10,11],havealreadyproventobeverysensitiveforelec-tricalinteractionsnearthesemiconductor/electrolyteinterface.ButinadditiontothesensitivityoftheOFETto-wardscertainanalytesintheelectrolyte,anothercrucialrequirementforapotentialbiosensorisselectivitytowardsspeci?canalytes.Thereforeitisabsolutelymandatorytointroduceadditionalfunctionallayersorspeci?cbiorecog-nitionsitestothesensor.Theseelementsaremostoftenattachedtothesemiconductorsurface,whichisdirectlyexposedtotheelectrolyte.InthiscontextmucheffortwasputingraftingofeitherantibodiesorDNAstrandsontotheactivelayerinordertodetectthecorrespond-ingantigen[12,13],DNAhybridization[14–16]orthefunctionalizationofthesemiconductorsurfacewithenzymes[17]tocatalyzeaspeci?creaction.

596K.Melzeretal./OrganicElectronics15(2014)595–601

UnfortunatelyminimalinvestigationwasmadeontheselectivedetectionofpHandphysiologicalelectrolytes(K+,Na+andCa2+)incomplexsamples.Heretheconceptofpolymericion-selectivemembranes,whichhasalreadybeenbroadlyusedinelectrochemicalpotentiometricsen-sors[18–20],canbeadaptedtoobtainaselectiveresponseofion-sensitive?eld-effecttransistors(ISFETs)[21–25].Onecan?ndseveralexamplesinliteratureforinorganicIS-FETs,wherethegateinsulatorwasfunctionalizedwithion-selectivepolymericmembranestoselectivelydetectcer-tainionse.g.thetwoveryprominentsecondmessengersforcell–cellcommunicationK+[24]andCa2+[25].Onebigissueinthesedevicesisthebadadhesionofthepoly-mericmembranetothesurfaceofthegatematerials[22],e.g.Si3N4[26].Byfurtherexploitingthisconceptinorganic?eld-effecttransistorsanotherdif?cultyariseswhentheactivelayeroftheOFETshouldbefunctionalizedbysolution-castingofthepolymericmembrane:mostof-tenthemembrane-solventdegradesthepolymericsemi-conductinglayerorthepolymericgateinsulator.TheseconstraintscanbecircumventedbyapplyingtheapproachSchmoltneretal.[27]pursued.InthisworktheP3HTFETisindirectcontactwithareferenceelectrolytewithagivensodiumconcentrationactingasgatedielectric.OntopofthisreferenceelectrolyteapolymericNa+-selectivemem-brane,embeddedinaPDMS-compartment,separatesthetargetsampleandtheAg/AgClreferenceelectrodefromtheP3HTFET.Thissetupresemblesalotanorganic?eld-effecttransistorgatedwithaconventionalion-selectiveelectrode(ISE),wheretheminiaturizationofthewholesensor,whichisarequirementforafurtherintegrationofthesensorinamicro?uidicsystem,isrestrictedbytherelativehugesizeofthereferenceelectrode.ThereforeaclassofspeciallydesignedISEswasdeveloped,wheretheion-selectivepolymericmembraneisdirectlycoatedontoaconductivesurface,suchasametalwire.Thisallowstheconstructionofverysmallanddurablesolid-stateelec-trodes(0.5–2mmindiameter)[28].Theinternalrefer-encesolutionoftheconventionaldesignismissinginthistypeofelectrode:theion-selectivemembraneiscon-tacteddirectlybythereferencewire.Theconceptofthiscoated-wireelectrodecanbealsoutilizedinISFETsensors.ForexampleLiuetal.[29]coatedaplatinum(Pt)wirewithanion-selectivemembrane,whichwasfurtherconnectedtothegateofaconventional?eld-effecttransistorandmountedinaglasstube.However,inthision-selectivecoated-wire/?eld-effecttransistorelectrodeonlytheion-selectivemembraneisindirectcontactwiththeelectro-lytesolutionandtheresponseofthe?eld-effecttransistoritselftowardsdifferentionconcentrationsinliquidisnotconsidered.

Inpreviouswork,wehavealreadyreportedonpH-sen-sitiveelectrolyte-gatedP3HTFETs[7]andion-sensitiveback-gatedP3HTFETs[11],buttheselectivitytowardscer-tainionsremainedstillanissue.Inthisworkweextendthepreviousworkandreportonanalternativeconcepttotunethesensor’sselectivity:wefunctionalizethegate-electrodeofanelectrolyte-gatedpoly(3-hexylthioph-ene)(P3HT)basedOFETwithdifferentpolymericion-selectivemembranestoobtainaselectiveresponseofthesensortowardsthebiologicallyrelevantionsK+andCa2+.

Asmanypossibilitiesareavailabletofunctionalizethegate-electrodeofelectrolyte-gatedFETsthisopensupnewpathsfortherealizationofselectivebiosensing.In-deed,inrecentexamplestheselectivedetectionofdopa-mine[30]andglucose[31]hasbeensuccessfullydemonstratedviathisapproach.

Byfunctionalizingthegate-electrodewithpolymericion-selectivemembranes,weshowthattheresponseoftheelectrolyte-gatedP3HTFETtowardsprimaryandinter-feringionsgetsincreased.Furthermore,theionophorepresentintheion-selectivemembraneenablestheselec-tivedetectionofcertainionsinsolutionswithandwithoutionicbackgroundbyformingarelativelystrong,selectiveandreversiblecomplexwithonlythetargetion.Weobtainlowerdetectionlimitsforprimaryionsdowntoaconcen-trationinthelMrangeeveninsolutionswithanionicbackgroundof150mMNaCl.Ourapproachrepresentsavaluablestrategyfortherealizationofportable,multi-pur-poseandlow-costbiosensingdevices.2.Materialsandmethods2.1.Transistorfabrication

Organic?eld-effecttransistors(OFETs)wereprocessedusinghighlyp-dopedsiliconwafers(SiMat)asasubstratewitha200nmthickthermallygrownsilicondioxidelayer(SiO2).Sourceanddrainelectrodes(5nmCrasadhesionlayer,40nmAu)werepatternedontopoftheoxidelayerbyaconventionalnegativeopticalphotolithographypro-cess.Aninterdigitated?ngerstructure(IDES)wasusedaselectrodestructurewithachannellengthof50lmandawidth-to-length-ratioof900.A1wt%solutionofP3HT(RiekeMetals)inanhydrous1,2-dichlorobenzene(DCB,VWR)waspreparedandsonicatedfor30mintoobtainahomogenoussolution.Thesolutionwasthen?lteredthroughapolytetra?uoroethylene(PTFE)syringe?lterwithaporesizeof200nm(VWR)andspin-coated(1000rpm,90s)ontothesurfaceofthewaferinagloveboxsystem(N2).Afterspin-coatingthe?lmwasannealedonahotplateunderanitrogenatmosphereat150°Cfor15min.TheresultingthicknessoftheP3HT?lmwasapproximately50–70nm.

2.2.Functionalizationofthegate-electrode

Theion-selectivegate-electrodeswerefabricatedbycleaningaPt-wirewithacetoneandisopropylalcoholbe-forecoatingthePt-surfacewiththemembrane(seetheSupportingInformationfortheexactcompositionofthemembranecocktails)untilahomogenouslayerwithathicknessofseverallmwasobtained.Afterwardstheelec-trodesweredriedovernightunderambientconditionstoguaranteeacompleteremovalofallsolventresidues.Toobtainanoptimalresponse,thefreshlypreparedmem-branesrequireaconditioningproceduretoachieveanade-quatesaturationwithwaterandanuptakeofprimaryions,whichfurtherimprovesthedetectionlimit[32].Thereforethefunctionalizedelectrodeswereplacedforabout24hinconditioningsolutionscontaining10À3Mofprimaryions

K.Melzeretal./OrganicElectronics15(2014)595–601597

dilutedinDI-waterbeforethe?rstmeasurementwasper-formed.InbetweendifferentmeasurementstheelectrodeswerestoreddryafterrinsingthemwithDI-wateranddry-ingthemwithnitrogen.Priortoeachnewmeasurementtheywereconditionedagainfor2hintheconditioningsolution.

2.3.Electricalcharacterization

Devicecharacteristics(ISDvs.VEGandISDvs.VD)andon-linemeasurements(ISDvs.time)wererecordedusingasemiconductorparameteranalyzersystem(Keithley4200SCS).Tooperatethetransistorinliquid,measurementswereperformedaftermountingthedevicesina?ow-chamber,whichhasaliquidcompartmentvolumeof100ll.TransfercurveswererecordedwithVD=À0.1VandVEGbetween0.6VandÀ0.6Vwithasweeprateof0.008VsÀ1.OnlinemeasurementswereperformedwithaconstantdrainvoltageVD=À0.4Vandanelectrolyte-gatepotentialofVEG=À0.4V.Thesamplingtimewas100ms.3.Resultsanddiscussion

Theorganic?eld-effecttransistorswerefabricatedbyspin-coatingathinlayerofP3HTdissolvedinDCBontoSisubstrateswithalreadyprede?nedinterdigitatedgoldelectrodes(seealsotheschematicinFig.1,furtherdetailsonthefabricationprocessarereportedinSection2).APt-wire,coatedwithdifferentpolymericion-selectivemem-branes,immersedinthesampleelectrolyte,servesaselec-

Pt-wiresasgate-electrodes.Fig.2ashowstheIDSvs.VEGandIDSvs.VDcharacteristicsofaP3HTOFETgatedwitheitherapristinePt-electrode(OFET)orexemplarilywithaPt-wirecoatedwithaK+-selectivePVC-membrane(IS-OFET).Aselectrolytea10À2MsolutionofprimaryionsinDI-waterwasused.ThethresholdvoltageofthePt-gatedOFETisVth=À0.24V,whichshiftstowardsmorepositivegatevoltages(Vth=À0.07V)bycoatingtheelectrodewithanion-selectivemembrane,resultinginaslightlyhigherdraincurrentoftheIS-OFET.WeobtaintransconductancevaluesofÀ49lSandÀ40lSfortheOFETandIS-OFET,respectively.

Theseresultsclearlydemonstratethatthefunctionali-zationofthegate-electrodedoesnotimpairthedeviceper-formanceoftheelectrolyte-gatedOFET:thefunctionalizedandtheunfunctionalizedOFETbothshowaclear?eld-effectcharacteristicwithaslighthysteresis,ON-currentvaluesofabout20lAandanon/off-ratioofabout100.TheoperatingperformanceoftheIS-OFETwasevalu-atedbyapplyinga?xedsource-drainvoltageVD=À0.4Vanda?xedgatevoltageVEG=À0.4Vandmeasuringthedraincurrentonlinewhiledecreasingtheion-concentra-tionstepwisefromhightolowmolarities.AsanexampleatypicaltimeresponsecurveofaK+-selectiveOFETandanormalPt-gatedOFETtowardsdecreasingKClconcentra-tionsisshowninFig.2b.Theresponsecurvesforthediffer-entmembranetypesandtowardsdifferentionslooksimilar.ItisevidentfromtheonlinemeasurementsthatonlytheIS-OFETshowsaclearresponsetoachangeintheionconcentration,withasensitivitylimittowardsits+À10

curvesaredepictedinFig.S2(seeSupportingInformation).Takingintoconsideration,thatalongwithchangesintheionconcentrationthepHvalueofthetestsamplesmayalsovary,wetestedthein?uenceofpHalterationsontheresponseoftheIS-OFETaswellastheunfunctionalizedPt-gatedOFET(seeSupportingInformation,Fig.S1).TheobtainedpHsensitivityofabout15%perpHdoesnotex-ceedtheonealreadypublishedforanunfunctionalizedelectrolyte-gatedP3HTOFET[7].Consideringthatoverallchangesofthetestsolutionsarewithintherangeof0.5pHunits,thisgivesanegligibleerror.3.1.Potassiumsensing

Fig.3ashowsexemplarilytheresponseofaPVC-basedK-selectiveOFETtowardsdifferentionswitheitherthesamechargeastheprimaryion(K+vs.Na+)ortoaninter-feringionwithadifferentcharge(Ca2+).ThevaluesofISDwereextractedfromthecorrespondingonlinemeasure-mentsaftera5minequilibrationtimeandnormalizedwithrespecttothedraincurrentataconcentrationof10À4M.AsareferencetheresponseofanormalOFETgatedwithapristinePt-wiretowardsdifferentKClconcentra-tionsisshown(blackdots).

TheK+-selectiveOFETshowsalinearresponsetothelogarithmoftheK+ionactivityintherangeof10À5M–10À1M.ThesensitivitytowardsNa+orCa2+ionsisnotonlylesspronouncedoverthewholeconcentrationrange,com-+paredwithanormalPt-gatedOFETtheion-selectiveOFETshowsahighersensitivitytowardsallthreeions.Thisisprobablycausedbyasuperpositionoftheion-sensitivere-sponseofthetransistor[11]withtheresponseatthefunc-tionalizedgate-electrodeduetochangesofthepotentialattheion-selectivemembrane.Thesensingmechanismreliesonpartitionequilibriumbetweenthemembraneandthesolution,withastronginteractionbetweentheanalyteionsandtheionophore,resultinginamembranepotentialdependentontheanalyteconcentration.Thispotentialeitherlowersorincreasestheeffectivegatepotential,whichispresentatthesemiconductingchannel.Theincor-porationofpositivelychargedprimaryionsresultsinamembranepotential,whichgetsmorepositivebyanincreasingprimaryionconcentrationpresentinthesam-ple[35].TherightpanelofFig.3acomparesthemeanva-lueandthestandarddeviationoftheresponseofthreedifferentK+-selectiveOFETs.Themaximumsensorre-sponseisgivenbythedifferencebetweenthedraincurrentvalueforaKClconcentrationof10À10Mand10À1M.Theseresultsdemonstratethattheoverallresponsestowardsthesametypeofionofdifferentdevicesarecomparable;moreoverthesensorresponseofeachsinglemembrane-modi?edOFETisreversibleandrepeatable(seeSupportingInformation,Fig.S3).

Ofteninbiologicalbuffersystemsorincell-culturemonitoringarelativelyhighconcentrationofvariousback-groundionsispresent,forexamplethecommonly

used

10mMphosphatebufferedsaline(PBS,pH7.4)hasanionicbackgroundof138mMNaCland2.7mMKCl.SincetheionsK+andCa2+areprominentsecondmessengersforcell–cell-communicationevents,sensitivityandselec-tivityoftheion-selectiveOFETshouldalsobeguaranteedundertheseconditions,e.g.inPBS-bufferedelectrolytes.Thereforesamplesolutionsconsistingofdifferentprimaryionconcentrations(concentrationrange10À1–10À10M)witha?xedionicbackgroundof150mMNaClwerepre-pared.Toanalyzeifthesensor0sresponsegetsin?uencedbytheionicbackground,theresponseoftheK+-selectiveOFETtowardsdifferentconcentrationsofprimaryionsinsolutionswithandwithoutanionicbackgroundarecomparedinFig.3b.

ForhighKClmolaritiesaslightlylowerresponseto-wardsdifferentionconcentrationswasobtainedandatmolaritiesCKCl<10À4MthesensitivitytowardsdifferentK+activitiessaturatesifthesolutioncontainsaconstantio-nicbackgroundof150mMNaCl.TherightpanelofFig.3bdepictsthemeanvalueandthestandarddeviationoftheresponseofthreedifferentK+-selectiveOFETseitherwithorwithoutionicbackground.Theoverallresponseob-tainedforthemeasurementinanionicbackgroundof150mMNaClisonlybyabout10%lowerthantheresponsetowardsdifferentconcentrationsofprimaryionsdilutedinpureDI-water.

3.2.Calciumsensing

TheresponseofaCa2+-selectiveIS-OFETtowardsdiffer-entprimaryionactivitiesordifferentconcentrationsofinterferingions(K+andNa+)isplottedinFig.4a,heretheresponseofanormalPt-gatedOFETtowardsdifferentCaCl2concentrationsisshownasareferencecurve.Athighconcentrationsagoodselectivitybetweeninterferingandprimaryionswasobtainedbutationactivitiesbelow10À6MtheIS-OFET’sresponsetowardsitsprimaryionisquitesimilartotheoneobtainedfortheinterferingions.TheresponseofaCa2+-selectiveIS-OFETtowardsitspri-maryionshouldbegenerallyweakerthantheoneofaK+-selectiveIS-OFETtowardsitsprimaryion.ThemaximumpossibleshiftinthemembranepotentialforamonovalentionisgivenbytheNernstlimit,whichpredictsashiftofÀ59.5mV/decat300K,fordivalentionstheNernstequationsuggestsatheoreticalresponselimitofÀ29.8mV/dec[36].

TherightpanelofFig.4acomparesthemeanvalueandthestandarddeviationoftheresponseofthreedifferentCa2+-selectiveOFETs.AgainthemaximumsensorresponseisgivenbythedifferencebetweenthedraincurrentvalueforaCaCl2concentrationof10À10Mand10À1M.

Toanalyzeifthesensor’sresponseisin?uencedbytheionicbackground,theresponseoftheCa2+-selective

OFET