SensorsandActuatorsB160 (2011) 670–676
ContentslistsavailableatSciVerseScienceDirect
Sensors
and
Actuators
B:
Chemical
jou rn a l h o m e pag e :w w w . e l s e v i e r . c o m / l o c a t e / s n b
A
microfluidic
based
differential
plasmon
resonance
sensor
Melih
Okan, Osman
Balci, Coskun
Kocabas
∗BilkentUniversity,DepartmentofPhysics,Ankara,Turkey
a
r
t
i
c
l
e
i
n
f
o
Articlehistory: Received21March2011 Accepted17August2011 Available online 30 August 2011
Keywords:
Surfaceplasmonresonancesensor Phasesensitivedetection Lab-on-a-chipsystems Microfluidicdevices Opticalsensors
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Anewtypeofdifferentialsurfaceplasmon(SPR)sensorintegratedwithamicrofluidicsystemispresented. Theworkingprincipleofthemicrofluidicdeviceisbasedonhydrodynamicmodulationoftwolaminar streamsinsideamicrochanneltoprovideperiodicchangesoftheenvironmentontheSPRsensor.The modulatedreflectanceisthendemodulatedusingalock-inamplifier.Thepresentedsensorprovides sen-sitivitiesofindexofrefractionabout4×10−8RIUtogetherwitha4ordersofmagnitudedynamicrange.
Thismethoddemonstratesasensitivedetectionschemewhichcouldbeusedforlabel-freedetection. © 2011 Elsevier B.V. All rights reserved.
1. Introduction
Phasesensitivedetectionisaremarkablysimpletechniquefor recoveringweaksignalsburiedinanoisybackground.This tech-niqueisbasedonmodulationofasignalofinterestataparticular frequencybyanexternalparameteranddetectingthemodulated signalwithaphase-sensitivedetector(i.e.,alock-inamplifier)[1]. Alock-inamplifier(LIA)amplifiesthesignalatthefrequencyof modulationandrejectstheuncorrelatedsignalfromnoiseatother frequencies.BasicallyLIAdemodulatesthesignalofinterestata particularfrequency.Signalswithasignaltonoiseratioaslowas −100dBcanberecovered.Noncontactatomicforcemicroscopyis agoodexampleofthissensitivedetectionmethod.Themethodof phasesensitivedetectionhasbeencombinedwithmanydifferent modulationtechniquessuchastemperaturemodulation[2], wave-lengthmodulation[3]andspatialmodulation[4].Forexamplelight scatteringfromasinglenanoparticle[4]oracarbonnanotube[5] canbedetectedbymodulationofthepositionoftheparticleand phasesensitivedetection.
Inthisworkweimplementthephasesensitivedetection tech-niquetomicrofluidic systems.Theideaisbasedontheperiodic modulationofliquidmediaflowingwithalowReynoldsnumber insideamicrofluidicchannel.AtlowReynoldsnumberregime,the flowinsidemicrofluidicchannelsislaminar.Takingtheadvantage oflaminarflow,wegeneratearapidperiodichydrodynamic mod-ulationoftwostreamsinsidethechannelwithoutanyturbulent mixing.Hereoneofthelaminarstreamsprovideareferencesignal
∗ Correspondingauthor.Tel.:+903122901965;fax:+903122664579. E-mailaddress:ckocabas@fen.bilkent.edu.tr(C.Kocabas).
andthedifferencebetweenthestreamsisdetectedasadifferential signal.Similarconceptsofhydrodynamicmodulationshavebeen appliedtoelectrochemicalsystemstoreducethebackground elec-trochemicalcurrents[6]andtostudythefrequencyresponseof signalingpathwaysofcells[7].
Hereweimplementthishydrodynamicmodulationtechnique withsurfaceplasmonresonance(SPR)sensors.Overthelastdecade, surfaceplasmon sensorshaveattractedmuch interestowingto theirhighlevelofsensitivityandabilityofsurfacespecific detec-tion.Withasuitablesurfacechemistry,SPRsensorsprovideunique meansof studyinginteractionof biomoleculesonsurfaces.The Kretschmannconfigurationismostcommonlyusedtechniqueto excitesurfaceplasmononaflatmetalsurface.Thephase match-ing conditioncan beachievedat the resonanceangle which is writtenas
ksp=k0nglasssin(r) (1)
wherekspandk0arethewavevectorofsurfaceplasmonsand
exci-tationphotonandristheresonanceangle.Theresonanceangle
depends onthewavevector ofthesurfaceplasmon.The dielec-tric constantof themediumonthemetallayerdetermines the wavevectoroftheSP.ThegeneralsensingmechanismofSPR sen-sorsisbasedondetectingchangesintheintensityofthereflected lightasthedielectricconstantofthemediumchanges.The sensi-tivityofSPRsensorsispredictedashighas10−7RIU[8],however, randomfluctuationsbecauseoflasernoise,thermaldriftand vibra-tionssignificantlyreducetheminimumdetectablesignalof the sensor.Furthermore,duringthemeasurements,thegradualchange ofthebackgroundlevel,likelybecauseofthermaleffects,reduces therepeatabilityofthemeasurements.Theseproblemsfosterthe development of new techniques to eliminate the random and
0925-4005/$–seefrontmatter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.snb.2011.08.046
Fig.1. Schematicrepresentationofthemicrofluidicdeviceandexperimentalsetupusedforhydrodynamicmodulation.Athinlayerofgoldfilmwithathicknessof50nm isfabricatedinsidethemicrofluidicchannels,formingaY-junction.Theflowinsidethechannelisdrivenbyagravityinducedpressuredifferencethatgeneratesrateofflow about∼10L/s.ThepressureoftheonearmoftheY-junctionismodulatedbyasolenoidvalveatafrequencyof2.5Hz.Surfaceplasmon-polaritonongold-liquidinterface isexcitedusingahighrefractiveindexprism,theKretschmannconfiguration.Thereflectedlightfromgoldfilmisdetectedbyaphotodiodeandalock-inamplifier.The referencesignalisusedtodrivethesolenoidvalve.Theinsetgraphshowsthepressureasafunctionoftime.
systematicerrorsassociatedwiththeexperimentalsetuporthe environment.Wesummariescoupleofdevelopedmethodsto over-cometheseproblems.Wuetal.[9]andLietal.[10]formedan interferometerwhichdetects thephase changeof thereflected lightfromthemetalsurface.Thismethodispartiallyimmuneof theenvironmentaleffects,thereforeprovidesahighlevelof sensi-tivity.Zhangetal.[11]introducedasecondarySPRsensoradjacent tothemainsensorasareference.Simultaneouslydetectingthe sig-nalfromthereferencesensorandthemainsensorprovidesmore reliablemeasurements.Morerecently,Williamsetal.[12] intro-ducedsignal-lockingSPRsensorwhichusesaperiodicexcitation ofanalyteandareferenceSPRsensorwithfrequencydomain sig-nalprocessingtoreducetheuncorrelatedsignal.Thesemethods andothersimilarones[9,13–21]requireverytediousalignment for interferometers or a complicated data processing. SPR sen-sorsbasedonspectroscopyofsurface-plasmonsintegratedwith multichannel detectors provide higher sensitivities [22]. Slavík andHomolademonstratedasensitiveSPRsensorbasedon long-rangesurfaceplasmon-polaritonswhichprovidessensitivitiesof 2.5×10−8RIU[23].Here,weintroduceasimple,yetvery sensi-tiveSPRsensorbasedonaphasesensitivedetectionschemeusing ahydrodynamicmodulationinsideamicrochannelwithratesof flowatlowReynoldsnumbers.Thepresentedmethodeliminates mostoftherandomfluctuationsandbackgroundshiftduringthe measurementsduetorandomvibrations,thermaldriftandlaser noise.The highsensitivity of SPRsensor togetherwiththe sig-nalrecoverybythephasesensitivedetectionprovideextremely
high sensitivities even at very large uncorrelated background noise.
2. Materialsandmethods
Fig.1 shows the schematicrepresentation of the fabricated microfluidicdevice.Athree-waysolenoidvalve(LFAA1201418H, TheLeeCorporation),derivedwithafunctiongenerator,controls thepressureontheonearmoftheY-junctionmicrofluidic chan-nel.Theotherarmiskeptataconstantpressure.Agravitydriven pressurecontrollerisusedtocontroltheinputpressures.ATM polarizedHe–Nelaserisusedtoexcitesurfaceplasmonsonthegold layeratbottomofthemicrofluidicchannel.Thereflectedbeamis detectedwithanunbiasedphotodiode(Newport818)connectedto thelock-inamplifier.Thelock-inamplifier(LIA,StanfordResearch, SR830)isoperatedatcurrentamplificationmodewithagainof 106.Thecontrolsignalofthevalveisusedasthereferencesignalof
theLIA.Theamplitudeandthephaseofthedifferentialsignalare recordedusingacomputerandadata-acquisitionsoftware.
Fig.2showsthefabricationstepsofthesensor.The fabrica-tionstartswithastandardUVphotolithographytopatternthethin layerofgoldfilm(thicknessof50nm)andfollowedby metalliza-tionandlift-offprocess.Themicrofluidicchannelsarefabricated by standard rapid prototyping using the soft lithography tech-nique. A photoresist master (SU-8-50 Micro Chem.) fabricated by UV photolithography is used to mold Polydimethylsiloxane (PDMS)elastomer.PDMSmicrofluidicchannelwithaY-junction
672 M.Okanetal./SensorsandActuatorsB160 (2011) 670–676
Fig.2.Preparationofthedifferentialplasmonicsensor.Athinlayerofgoldwithathicknessof50nmispatternedonaglassslidebystandardUVphotolithography.The Y-junctionmicrofluidicchannel,moldedfromaphotoresistmaster,issealedontheglassslidebymicrowaveplasmatreatment.Arefractiveindexmatchingfluidisusedto attachtheglassslidetothehighrefractiveindexprismwithrefractiveindexof1.78.
geometry is sealed on a glass slide using a 900W homemade microwaveplasmasystem.Duringthesealingprocess,thegold stripisregisteredunderneaththemicrofluidicchannel.The fab-ricatedmicrofluidicsystemisattachedonahighrefractiveindex prism(Thorlabs,N-SF11,refractiveindexof1.78)usinganindex matchingfluid.Thesurfaceplasmon-polaritonsonthegoldstrip isexitedbya5mWHe–NelaserwiththeKretschmann configura-tion.Asiliconphotodiode(Newport818)connectedtothelock-in amplifierisusedtodetecttheintensityofthereflectedbeam.
3. Resultsanddiscussion
Athree-waysolenoidvalveisusedtocontrolrateofflowof oneofthearms.Maximumoperationfrequencyofthesolenoid valveisaround200Hz.Fig.3ashowsthefabricatedmicrofluidic chipwhichhasfourSPRsensors.Totestthedeviceseveralissues, suchasexcitation angleand frequencyof modulation, mustbe considered.First,wegeneratealaminar flowusingtwoliquids, whicharenamedasliquidAandliquidB,withrefractiveindex dif-ferencearound0.01RIU.HereliquidAisDIwater(nA=1.33)and
liquidBis 10%ethylglycol(EtG,nB=1.34)inwater. Fig.3band
cshowstheopticalmicrographsofthechannelfilledwithliquid AandliquidBfortwodifferentpressurelevels.Thelaminarflow boundarybetweenthetwostreamsisseenduetolargerefractive indexdifference(0.01RIU).ByswitchingthepressureofliquidA betweentwodifferentpressurelevels(∼15kPaand13kPa)while keepingthepressureofliquidBconstant(∼13kPa),we periodi-callymoduletheindexof refractionofthemediumontheSPR sensor.Astheindexofrefractionchanges,thesurfaceplasmon res-onanceangleandreflectedpowerchangesaccordingly.Tofindthe
optimumoperationpointwemeasurethereflectionofthelaser beamfromthegoldsurfaceasafunctionofincidenceangle.Fig.3d showstheintensityofthelaserbeamreflectedfromthegoldstrip underneaththemicrofluidicchannelfilledwithliquidA(RA())and
liquidB(RB()).Thereflectivitydependsontheincidenceangleand
thewavelengthofthelaser.TheSPRangleforDIwateris56.76◦and for10%EtGis57.49◦.Theresonanceangleshiftstolargeranglesas weincreasetheindexofrefractionoftheliquidbyaddingethyl glycol.Fig.3eshowsthechangeoftheintensityofthereflected beamasfunctionoftimeforthreedifferentconcentrationsofethyl glycol(10%(redcurve),2%(greencurve),and0.4%(bluecurve)). (Forinterpretationofthereferencestocolorintext,thereaderis referredtothewebversionofthisarticle.)Forconcentrationsless than0.4%,thechangeinthereflectivityduetothemodulationis buriedundernoise.Themodulationofthereflectanceprovidesthe differentialsignal.Astheliquidsoscillateontopofthegoldlayer, theSPRanglemodulatesatthesamefrequencyaswell.The dif-ferenceofthereflectivityforthetwocasesgeneratesaperiodic signalonthedetector.Theoutputofthelock-inamplifierprovides theamplitudeandthephaseoftheperiodicsignalbetweenthe liquids.
Tounderstandmoreinsideabouttheworkingprincipleofthe device,wedriveanexpressionforthedifferentialsignal.The reflec-tivityfromthegoldsurfaceisa linearcombinationofRA()and
RB().Thetotalreflectivitycanbewrittenas
R()= x wRA()+
w−x
w RB() (2)
wherexisthepositionofthelaminarflowboundarywhichisa peri-odicfunctionandwisthewidthofthechannel.Astheboundary oscillates,thedifferentialsignal (S)can befoundbytaking the
Fig.3.(a)Theimageofthefabricatedchipwhichhas4SPRsensor.ThedevicehasaY-junctiongeometrywithtwoinputandavent.Thegoldstripisregisteredunderneath themicrochannel.(bandc)Zoomedopticalmicrographsofthemicrofluidicchannelshowingtheboundaryofthelaminarflowforthetwopressurelevels.Thelabels‘A’and ‘B’showtheliquids(waterand10%ethyleneglycolinwater,respectively)withdifferentindexofrefraction.(d)Experimentalreflectancecurvesforthegoldstripcovered by‘A’and‘B’,respectively.TheSPRanglesforwaterand10%ethyleneglycolinwater56.7and57.49degrees,respectively.(e)Timetraceofthereflectedbeamwhilethe mediuminthechannelismodulatedbetween‘A’and‘B’.Theresponsetimeoftheboundaryisaround100ms.(f)Differentialsignalobtainedbythelock-inamplifierasa functionoftheexcitationangle.ThereferencesignalofLIAisat2.5Hzandthetimeconstantis3s.
differenceofthereflection.Thedifferentialsignalcanbewritten as
S=R= |x|
w(RA()−RB()) (3)
where|x|istheoscillationamplitudeoftheboundary.Forsmall changesintheindexofrefractionwherethedifferencebetween RA()andRB()isverysmall,wecanfurthersimplifytheequation
as S=C|x|
wn dR()
d (4)
wherenisthedifferenceintheindexofrefractionbetweenthe liquids,andC istheproportionality constantwhich definesthe changeoftheresonanceanglewithrespecttothechangeinindex ofrefractionofthemedium.Thedifferentialsignalisdirectly pro-portionalwiththeoscillationamplitude,thedifferenceofindexof refractionandtheslopeofthereflectivitycurve.Thedifferential
signalobtainedforwaterand10%ethylglycolasafunctionofthe incidenceangleisgiveninFig.3f.Thesignalgoestominimawhere thereflectivitycurvescrossanditgoestomaximaatananglewhich providesthesteepestslopeinthereflectivitycurve.
To understand the mechanism of the hydrodynamic modu-lation, the frequency dependent measurements are performed. Fig. 4a shows the power spectrum of the signal obtained by changingtheinternalfrequencyofthelock-inamplifier.Forthis measurementthemodulationfrequencyiskeptconstantat3Hz. Thetimedependentsignalshowsanonsinusoidalformwhichhas higherorderharmoniccomponents.Theintensityofthethird har-monicislargerthanthesecondharmoniccomponentbecauseof thesquarelikewaveformoftheboundaryofthetwoliquids.The frequencydependenceofthedifferentialsignalisgiveninFig.4a. Weobtaintheoptimumfrequencyofoperationaround2–3Hz.The optimumfrequencyofoperationdependsonthegeometryofthe channelandtherateofflows.
674 M.Okanetal./SensorsandActuatorsB160 (2011) 670–676
Fig.4. (a)Powerspectrumofthedifferentialsignalobtainedforthehydrodynamicmodulationfrequencyof3Hz.(b)Thefrequencydependenceofamplitudeofthesignal.
We test thesensitivity ofthe fabricatedsensorby changing theconcentrationoftheethyleneglycolfrom5.0×10−2Mdownto 4.0× 10−5M.Foreachconcentrationwetakethepowerspectrum
ofthephotocurrentandrecordthedifferentialsignalfromthe spec-trum.Fig.5ashowsthepowerspectrumforvariousconcentrations ofEtG.Fig.5bshowstheamplitudeofthedifferentialsignalasa functionofrefractiveindexdifference.Thesignalshowsalinear dependenceforaverybroadrangeofrefractiveindexchange.The fabricatedsensorprovidesverywidedynamicrangecoveringmore than4ordersofmagnituderefractiveindexchange.Usually sen-sitivityanddynamicrangeofasensorprovideatradeoffdueto thelimitedbandwidth.ThedifferentialSPRsensorsimultaneously provideshighsensitivityandwidedynamicrange.Fig.5cshows
therealtimeresponseofthesensorforverylowrefractiveindex changes.WeaddsmallamountofEtGinwaterandrecordthe differ-entialsignal.Asteplikeresponseisobserved.Thecalculatedchange ofrefractiveindexforeachstepisgivenonthecurve.Thestabilityof thebackgroundlevelisalsoimportantforreliablemeasurements. Anotheradvantageofthepresentedsensoristhatbackgroundlevel isconstantoveralongperiodoftime.TheinsetatFig.5cshowsthe timetraceofthesignallevelfor1.5-htimescale.Thestandard devi-ationofthesignalisaround10pAwhichprovidesarefractiveindex changeof7×10−8RIU.Theoriginofthisextremestabilityisthat, thetwolaminarstreamsprovideaselfreferencedetectionscheme forthermaldrifts.Thereforethebackgroundlevelshowsextreme stabilityoverlongtimescales.Theresponseofthedeviceforlow
Fig.5. (a)Powerspectrumofthephotocurrentforvariousethyleneglycolconcentrations.(b)Thevariationoftheintensityofthedifferentialsignalversusrefractiveindex differenceofthetwolaminarstreams.(c)Realtimeresponsecurveofthedifferentialsignal.Theinsetshowsthetimetraceofthesignalforalongtimescale.Thenumbers onthecurveshowsthecalculatedrefractiveindexchanges.(d)Thechangeofthedifferentialsignalforlowrefractiveindexchanges.Thestandardvariationofeachpointis lessthanthesizeofthescatteredplot.Theminimumdetectablerefractiveindexdifferenceisaround7×10−8RIU.
Fig.6.(a)Variationofthedifferentialsignalasafunctionoftime.(b)Histogramofthedifferentialsignal.
refractiveindexchangesisgiveninFig.5d.Theerrorinthedata pointsislessthanthesizeofthescatteredplot.
Tounderstandtheultimatesensitivitylimitofthedevicewe analyzesourcesofnoise.Fig.6ashowsthenoiseofthe differen-tialsignal.ThehistograminFig.6bhasastandardvariationaround 0.3pAwhichcorresponds4×10−8RIU.Theinternalnoiseofthe LIA,shot noise of thedetector, and mechanical deformation of thePDMSchannelarethemainsourceofnoiseinthesetup.The noiselevelofthesensorisaround20pA.Theinternalelectronic noiseoftheLIAisaround0.12pAfor3stimeconstantat2.5Hz. Totalnoiseofthedetectorandlaserisaround2.5pA.Thelimiting noisesourceseemsduetomechanicaldeformationorcorrelated scatteringduetoimpuritiesintheliquid.Sincethelaserbeamis reflectedfromtheglasssideofthedevice,themechanical defor-mationofPDMSduringthehydrodynamicmodulationdoesnot affecttherecordedsignaltoomuch.Wespeculatethatthe mini-mumdetectablesignalislimitedbyimpuritiesorinhomogeneities intheliquidswhichgenerateacorrelatednoiseatthemodulation frequency.
4. Conclusion
Asaconclusion,wepresentanewtypeofmicrofluidicdevice thatuseshydrodynamicmodulationschemeforaphasesensitive detection.Weimplementthismethodtoasurfaceplasmon sen-sorintegratedinamicrofluidicdevice.Thefabricatedsensorcan detecttherefractiveindexdifferenceassmallas4×10−8RIUwith anextremelystablesignallevelandmorethan4ordersof magni-tudedynamicrange.Theprimaryconclusionofthisstudyisthatby usingahydrodynamicmodulationandphasesensitivedetection technique,a simpleplasmonsensorwithintensityinterrogation canproviderefractiveindexsensitivitiesashighasplasmonsensors withspectralinterrogation.
Acknowledgements
ThisworkwassupportedbytheScientific andTechnological Research Council of Turkey (TUBITAK)Grant No. 110T304 and Marie Curie International Reintegration Grant (IRG) Grant No. 256458.
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Biographies
MelihOkaniscurrentlyaseniorundergraduatestudentatBilkentUniversity, DepartmentofPhysics.
OsmanBalcireceivedhisBSdegreefromBilkentUniversity,DepartmentofPhysics in2009. Heis currentlya Ph.D.studentatBilkent University,Departmentof Physics.
CoskunKocabasreceivedhisBSdegreein2001fromMiddleEastTechnical Univer-sity,DepartmentofPhysics.HereceivedhisPhDdegreefromUniversityofIllinois atUrbanaChampaign,DepartmentofPhysicsin2007.Between2007and2009he workedasapostdoctoralresearcheratHarvardUniversitydepartmentofChemistry andChemicalBiology,Prof.GeorgeWhitesides’group.Heiscurrentlyanassistant professoratBilkentUniversity,DepartmentofPhysics.Hiscoreresearchinterests includedynamicmicrofluidicsystemsandsensors.