Integration of glass micropipettes with a 3D printed aligner for microfluidic flow cytometer

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ContentslistsavailableatScienceDirect

Sensors

and

Actuators

A:

Physical

jo u r n al h om ep a g e :w w w . e l s e v i e r . c o m / l o c a t e / s n a

Integration

of

glass

micropipettes

with

a

3D

printed

aligner

for

microﬂuidic

ﬂow

cytometer

Abdullah

Bayram

a

_,

_Murat

_Serhatlioglu

b

_,

_Bulend

_Ortac

b

_,

_Serafettin

_Demic

a

_,

Caglar

Elbuken

b

_,

_Mustafa

_Sen

c,∗

_,

_Mehmet

_Ertugrul

_Solmaz

d,∗

a_Department_of_Material_Science_and_Engineering,_Izmir_Katip_Celebi_University,_Izmir,_Turkey

b_UNAM_–_National_{Nanotechnology}_Research_Center,_Institute_of_Materials_Science_and_{Nanotechnology,}_Bilkent_University,₀₆₈₀₀_Ankara,_Turkey

c_Department_of_Biomedical_Engineering,_Izmir_Katip_Celebi_University,_Izmir,_Turkey

d_Department_of_Electrical_and_Electronics_Engineering,_Izmir_Katip_Celebi_University,_Izmir,_Turkey

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received10July2017

Receivedinrevisedform

30November2017

Accepted30November2017

Availableonline2December2017

Keywords: Flowcytometry Hydrodynamicfocusing Micropipette 3Dprinting Optoﬂuidics

a

b

s

t

r

a

c

t

Inthisstudy,afacilestrategyforfabricatingamicrofluidicflowcytometerusingtwoglassmicropipettes withdifferentsizesanda3Dprintedmillifluidicalignerwaspresented.Particleconfinementwasachieved byhydrodynamicfocusingusingasinglesampleandsheathflow.Deviceperformancewasextracted usingtheforwardandside-scatteredopticalsignalsobtainedusingfiber-coupledlaserand photodetec-tors.The3-Dprintingassistedglasscapillarymicrofluidicdeviceisultra-low-cost,notlabor-intensive andtakeslessthan10mintofabricate.Thepresentdeviceoffersagreatalternativetoconventional benchtopflowcytometersintermsofoptofluidicconfiguration.

1. Introduction

Flowcytometryhasproventobeasensitive,quantitativeand non-invasiveapproachtoobtainvaluableinformationfromsingle cells[1–4].Itisroutinelyusedinclinicallaboratoriesforthe identi-ficationandclassificationofcertaincancers,suchasleukemia[5–7] andlymphoma[8,9],andevenforthediagnosisoflife-threatening diseasessuchasAIDS[10,11].Becauseofthedisadvantagesofthe conventionalbenchtopflow cytometerssuchashighcost,large size,maintenance,complexconfigurationandtheneedforlarge volumesofreagents,agreatdealofattentionhasbeenpaidto fab-ricatemicrofluidicdevicesusingmicrofabricationtechnologiesin recentyears.Microfluidicdevicesoffermanyadvantageslike sim-plicity,lowcost,lowconsumptionofreagents,rapidanalysis,small sizeandhighlycontrollableenvironment forparticle manipula-tion.Focusinginflowcytometersisusedtoconfinecellscloseto thecenterofthechannelsothattheycanpassthroughtheoptical interrogationareaoneatatime,aphenomenonthatimproves

sin-∗ Correspondingauthors.

E-mailaddresses:mustafa.sen@ikc.edu.tr(M.Sen),mehmete.solmaz@ikc.edu.tr

(M.E.Solmaz).

glecellanalysisandlimitssampleadsorptiontothechannelwall. Avarietyoffocusingmethodsexploitingdifferentphysical mech-anisms have been developed; hydrodynamic focusing [12–15], dielectrophoresis [16,17], acoustics [18–21] and electroosmosis [22–24].Hydrodynamicfocusingenablesfocusinginawide veloc-ityrangeandhasnospecialrequirementforparticles,cellsand fluidsused.Itisusuallyusedtoguideparticlesorcellsinaconfined spacebymanipulatingthestreamlines.Unlike2Dhydrodynamic focusingthatfocusesinonlyonelateraldimension,confiningthe streamof particlesin 3D ensuresthe uniformflowof particles alongthedetectionarea. 3Dhydrodynamicfocusingimprovesa numberoffeaturesofthemicrofluidicflowcytometersincluding performance,accuracy,stability,sensitivityanddetection resolu-tion[15,25,26].Uptodate,different3Dfocusingstrategieshave beenproposedtofabricatemicrofluidicdevices.Forexample, Sun-dararajanetal.usedsixsheathinletsandafive-layerdesignfor3D focusingofsamplefluidinflow[27].However,theuseof multi-plesyringesandmultiplelayerfabricationmadethedesignrather complicated. Gorthiet al.fabricateda PDMS based single-layer microfluidicdevicethat consistsof threeinlets(oneforsample flowandtwoforsheathflow)andanoutlettorealize hydrody-namic3Dflow focusing[12].AlthoughPDMSdevicefabrication involveda singlelayer,themasterrequiredfor replicamolding

https://doi.org/10.1016/j.sna.2017.11.056

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anddevicefabricationrequiredmultilayerfabricationbymeans ofphotolithography.Testaetal.developedamicro-flowcytometer capableofself-aligned3Dhydrodynamicfocusing[13].Tomakethe device,thedesignwasfirstprintedontwo3mm-thick polymethyl-methacrylates(PMMA)usingahighprecisioncomputernumerical controlmicromillingmachinefollowedbysolventassisted ther-malbonding.Agrawaletal.proposedanewstrategywithintricate microfabricationutilizing two bendsof opposite curvature, sin-glesheathinletsandexploitingsecondaryforcesandcentrifugal effectsfor3Dhydrodynamicfocusingofdye,particlesandcells[15]. Recently,femtosecondlasermicromachiningwaspresentedasa newpotentialfabricationtoolformakingmicrofluidicnetworks thatimplementhydrodynamicfocusingwithtwoinlets;onefor thesampleandoneforthesheathflow[14,28].3Dprinting technol-ogyhasalsobeenemployedtomakecomplexmicrofluidicdevices outofdiscreteelementswithlesseffort[29–31].3Dprintingstill lacksthesufficientpatterningresolutionrequiredforfabricating micronscaledfluidicdeviceswithgoodalignmentaccuracy[32]. Themajorityofreportedmicrofluidicflowcytometersareeither toocomplexorrequiremultiplesheathflowstorealize3D focus-ingandfurtherresearchisneededtomakelesslaborintensiveand cost-effectivemicrofluidicflowcytometerscapableofefficient3D hydrodynamicfocusing.

In this proof of concept study, a facile strategy for making a microfluidicflow cytometerbyusingtwo glassmicropipettes with different size and a 3D printed millifluidic aligner was demonstrated. Micropipettes have already been introduced to microfluidics;forexample,Weitzetal.usedmicropipettesfor cre-atingmonodispersemicrodropletsinsingleormultiple-emulsion forms[33,34].Thefabricationofmicropipettesfromglass capillar-iesusingamicropullerisrelativelyeasywithminimalfabrication time,andthedimensionsofmicropipettetipopeningcanbeeasily manipulatedbyeitherchangingthepullingparametersorgrinding thetipwithamicrogrinder[35–37].Tothebestofourknowledge, thisisthefirststudythatcombines3Dprintingwithmicropipette technologyfor efficienthydrodynamicfocusingofparticles.The proposedfabricationstrategyisfacile,straightforwardand ultra-low-costasittakeslessthanonedollartofabricatetheoptofluidic device.

2. Materialsandmethods

2.1. Materials

Glass capillary with filament (O.D./I.D.: 1/0.6mm; length: 90mm)(Narishige, Japan), blood gas capillary tubes (O.D./I.D.: 2.3/1.85mm;length:125mm)(Marianfeld,Germany),polystyrene microbeads with a diameter of 5.95±0.12␮m (Polysciences, Inc.,USA),phosphate-bufferedsaline(PBS)(SigmaAldrich,USA), sealant(Pattex,Henkel,Germany),ahightemperaturemold mate-rial(HTM140M,EnvisionTEC,USA),asinglemode(SM)bluelaser illumination fiber (LP405-SF10,Thorlabs, USA), forward scatter (FSC)andsidescatter(SSC)fibers(M43L01,Thorlabs,USA). 2.2. Devicefabrication

First,asmallglasscapillarytube(O.D./I.D.:1/0.6mm;length: 90mm) was pulled using a micropuller (PC-10 Micropulling Machine, Narishige, Japan) to produce two microneedles with thefollowingparameters;option2,ﬁrst-pullpositionadjustment plate: 6mm, second-pull positionadjustmentplate: 2mm, one typelightandonetypeheavyweights,no.1heaterlevel:65and no.2heaterlevel:37[35].Thetipofthesmallmicropipettewas grinded tohavea tipopeninginner diameterofapproximately 150␮musingamicrogrinder(EG-401,Narishige,Japan)(Fig.1AI).

Thedesiredtipopeningdiameterwasadjustedusingtheocular micrometerofthemicrogrinder.Then,alargeglasscapillarytube (O.D./I.D.:2.3/1.85mm;length:125mm)waspulledthesameway asthesmallcapillarytubeusingthefollowingparameters;option 1,twotypelightandtwotypeheavyweights,no.1heaterlevel:75. Thelargemicropipettewaspulledinawaytohavea microchan-nelwithanapproximately90␮minnerdiameterandalengthof nolessthan10cm.Thetipofthelargemicropipettewasgrinded only to measure thetip opening diameter properly (Fig. 1AII). Both micropipettes were cleaned thoroughly in distilled water usingultrasonicbeforeuse.Thesmallmicropipettewas center-positioned inside the large micropipette using a micropipette aligner(Fig.1AIII,BI)aprocessthattookonlyafewminutes.The micropipette alignerwas firstdesigned using a 3D CADdesign software (SolidWorks2016,USA) (Fig.S1A)and then produced fromahightemperaturemoldmaterial(HTM140M)usinga3D rapid prototype manufacturingsystem (Perfactory 4 Mini with ERM,EnvisionTEC,USA)withhighprecision.Asfortheassembly ofthedevice,thelargemicropipettewasfirstinsertedinthe corre-spondingholeofthealignerandasealantwasusedtobothfixthe micropipetteandpreventanyleakagefromthesmallgapbetween thecapillaryandthealignerhole.Then,thesmallmicropipettewas insertedintothecorrespondingholeofthealignertopositionthe smallmicropipetteinsidethelargeoneunderastereomicroscope andthesamesealantasbeforewasusedformicropipettefixation andleakage prevention(Fig. S1B).Priortouse,alldevices were checkedforleakagebypumpingwaterfromthetwoinletsat pres-suresupto2bars,whichistheupperlimitthepressurepumpcan provide.

2.3. Devicecharacterization

The3Dhydrodynamicfocusingabilityofthedevicewas inves-tigatedusingdeionizedwater(DI)coloredwitha bluefooddye and colorless PBSas sample and sheathsolutions, respectively. Apressurepump(Elveflow,OB1)wasusedtopassthesolutions throughthemicropipettes.Inthissetting,thePBSsolutionfrom thelargemicropipette hydrodynamicallyfocusedthebluecolor solutionintroducedfromthesmallmicropipettebycompletely sur-roundingit(Fig.1BII).Theimpactoftheratiobetweensheathand sampleflowpressuresonthe3Dhydrodynamicfocusingwas inves-tigatedinarangefrom0.96to1.064(sheath/sampleflowpressures) (Fig.2A).The3Dhydrodynamicfocusingwasrecordedusinga cam-era(BaslerAceacA2040-90uc,BaslerAG,Germany)attachedtoa microscope(KrüssMSL4000,Germany).

Next,thedevicewastestedwithmicroparticlesofuniformsize usinganopticaltestsystem.Thetestsystemconsistedofthe fol-lowingcomponents; asinglemode(SM)bluelaser illumination fiber,forwardscatter(FSC)andsidescatter(SSC)fibers,twophoto diodes(FSCandSSC)(DET02AFC,Thorlabs,USA),a405nmlaser source(LP405-SF10,Thorlabs,USA),apressurepumpandan oscil-loscope(Tektronix,MDO3104)(Fig.3AandFig.S2A).Inaddition, aflatPMMAplatewithfiberguidancegrooveswasusedto posi-tionallthefibers(Fig.S2BandC).Anadhesivetapewasusedtofix thefibersinthegroovescarvedontheplatebyCO2laser(Epilog Zing30W,EpilogLaser,USA).Basically,thelaserilluminationfiber withadiameterof125␮mwaspositionedperpendicular(90◦)to themicrochannelwherethemicrochanneldiameterandthewidth ofthefocusedsamplesolutionwere∼130and∼18␮m, respec-tively.Theopticalfiberwiththefollowingspecifications(numerical aperture(NA):0.12,modefielddiameter(MFD):3.6±0.5␮mand centerwavelength:405nm)wasusedtotranslateasinglemode (SM)lasertotheinterrogationzonewherethebeamdiameter cal-culatedwithGaussianbeamapproximationis11.48_␮m.Tocollect thescatteredlightthroughthephotodetector,FSCandSSCfibers werepositionedwithanglesof167◦and210◦tothelaser

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illumina-Fig.1.Theopticalimagesofsmall(AI)andlarge(AII)micropipettesusedformountingtheglassmicropipettebasedﬂowcytometrydevicetogetherwithmagniﬁedimages

showingthesizeoftherespectivetipopenings.Animageoftheintegrateddevicewiththetop(i)andside-view(ii)microscopeimagesofasmallmicropipettepositioned

inalargemicropipetteusingthealigner(AIII).Schematicofthedevice(Bl)andtheprincipleforhydrodynamicfocusing(Bll).Thesheathﬂowintroducedthroughtheinlet

ofthe3D-printedalignerfocusesthesampleﬂuidintroducedfromthesmallmicropipette.

Fig.2. Theimpactofthevaryingsheathﬂuidpressureonthehydrodynamicfocusingwhenthesampleﬂuidpressureiskeptconstant(pressureofsheath/pressureofsample:

0.960,etc.)(A).Aplotshowingthecorrelationbetweenthefocusedsampleﬂuidwidthandthepressureratioofsheathandsampleﬂows(B).Thetop(CI)andside(CII)view

microscopeimagesof3Dfocusingachievedataratioof1.004betweensheathandsampleﬂowpressures.

tionfiber,respectively.PBSandpolystyrenemicrobeadscontaining PBSsolutionswereusedassheathandsamplesolutions, respec-tively.Priortouse,themicroparticle(diameter:5.95±0.12␮m) stocksolutionwasdilutedinamixture(PBSsolution+bluefood dye)filteredusing0.2␮mporesyringefiltertorealizeafinal con-centrationof∼1000particles/␮l.Thebluecolormixturewasused

simplyforbettervisualization.Themicroparticlecontaining sus-pension wasalso sonicatedfor15mintominimizeaggregation duringexperiments.PressurepumpwasusedtopassPBS(sheath) andpolystyrenemicrospherecontainingsuspensionthroughthe largeandsmallmicropipettesatasheath/samplesolutionpressure

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Fig.3. Schematicillustrationofthesetupusedtotesttheglassmicropipettebasedﬂowcytometrydevice(A).Componentsofthesetupareasfollows;anassembledﬂow

cytometrydevice,a405nmlasersource,apressurepump,anoscilloscope,Siphotodetectors,ﬁberforexcitationlaserandtwocollectorﬁbers.Thearrangementofthe

ﬁbersusedforexcitationlaser,forwardscatteredlight(FSL)andsidescatteredlight(SSL)isshownintheﬁgure.Forwardscatter(FSC)andsidescatter(SSC)channelsignals

recordedwhilepassingmicroparticlesofuniformsizethroughthemicroﬂuidicchannelfor2s(Bl)withaninsetshowing100mssnapshot(Bll).Representativehistograms

ofFSC(CI)andSSC(CII)signals.Thenumberofdatausedforthehistogramsis339andthecalculatedcoefﬁcientvariations(CV)ofFSCandSSCsignalsare26.98%and25.54%,

respectively.FSC-SSCscatterplotobtainedwithmicroparticlesofuniformsize(D).

ratioof1.004.Theoscilloscopewasusedtoquantifythevoltage signalsfromthephotodetectorsata0.5MHzsamplingrate.

3. Resultsanddiscussions

Thedesign ofthepresentmicrofluidicflowcytometerdevice isquitesimpleandeasilycomprehensible(Fig.1BI-II).Acomplete deviceiscomposedofthreecomponents;amicropipettealigner, asmallandalargemicropipettes(Fig.1AIII).Precisefabricationof alignerholesisimportantforsuccessfulmicropipettealignment. ManufacturerreportsthatHTM140isverydurableandhigh pre-cisionmaterialdesignedtowithstandboththeheatandpressure ofvulcanizingamodelwithgreatdetailandnolossofdimensional stability.GiventhedesigndimensionsofthemodelinFig.S1A,the averagediametersofsmallandlargeholesofthreedifferent align-ers weremeasured tobe1049.9±8.1␮m and 2303.5±8.9␮m, respectively(Fig.S3A,B).Itissafetosaythatthe3Drapid proto-typemanufacturingsystemalongwithHTM140materialprovides dimensionaccuracyforprecisealignment ofmicropipettes.The assemblyofthedevicetooklessthan10minincludingthetime neededtogrindthetipofthesmallmicropipette.Themicropipette alignerscanberetrievedeasilyandusedrepeatedlyforfabrication ofa newmicrofluidic flowcytometerdevice.Theonly

consum-ablesusedtofabricateanewdevicearethesealantandtheglass capillaries,whichmakesthedeviceultra-low-costasbothofthe consumablescostlessthanonedollar.

The3Dhydrodynamicfocusingabilityofthedevicewas demon-stratedusingdeionizedwater(DI)coloredwitha bluefooddye andphosphatebuffersaline(PBS)assampleandsheathsolutions, respectively.Thedifferentcolorsofthetwosolutionsmadeit pos-sibletoeasilyobservetheconfinementofthesamplesolutionin themicrochannelofthelargemicropipette(Fig.2A).Hydrophilic surface is important and desirable for microfluidic systems to achieve variousfunctionssuchasfacilitatingfluidflow intothe microchannels[38].Thewatercontactangletest resultshowed thatHTM140ishydrophilicwithanaveragecontactanglevalue of37.1◦ (Fig.S4).Usingthe3Dprintedmicropipettealignerwith easy-to-operatetwo-inletconfiguration;thesheathsolution com-pletely surrounds and confinesthesample solution ina highly efficientmanner(Figs.1AIIand2A).Theresultsshowedthatthe microchannelwasfilledwiththebluecolorsolutionattheratioof 0.96.Whentheratiowasraisedto1.064,theflowthroughthesmall micropipettewasblockedbythesheathsolution.Thesmall differ-encebetweenthetworatiosdemonstratesthatthepressureofthe twofluidsmustbecontrolledpreciselyforanefficient3D focus-ing.Therelationshipbetweenthewidthofthehydrodynamically

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focusedsampleandthepressureratiobetweensheathand sam-pleflowsisgiveninFig.2B.Thewidthofthesamplesolutionwas measuredapproximately1.53mmawayfromthetipofthesmall micropipette(Fig.S5).Therelationshipappearstobealmostlinear, whichsuggeststhatthewidthofthe3Dfocusedsamplesolution canbepreciselycontrolledbytheratiobetweensheathand sam-pleflowpressures.Inaddition,sideviewmicroscopeimagesofthe microchannelweretakenbothhorizontallyandverticallyataratio of1.004(sheath/sampleflowpressure)toseethefocusedflowand thusverifythe3Dhydrodynamicfocusingwiththepresentdevice (Fig.2CI-II).Bothimagesshowedthatthesampleflowwasfocused closetothecenterofthemicrochannel.

Next,theperformanceofthemicrofluidicflowcytometerdevice in3Dhydrodynamicfocusingofmicroparticleswasevaluatedusing anopticaltestsystem.Withoutanyparticleflow,theFSCandSSC signalsshowDCoffsetvaluesduetocollectingsomeamountof light.Fig.3BIshows2-sFSCandSSCchannelsignalsrecordedwhile microparticlesofuniformsizewerepassingthroughthe microflu-idicchannel. Eachpeak observedin Fig.3BI-II correspondsto a microparticlepassingbytheinterrogationpoint.Fromtothedata with∼170events/sthroughput,anFSCpeakwasrecordedforeach SSCsignal,whichindirectlyprovesthatallofthemicroparticles werefocused properly and passedthrough thelaser interroga-tionregionat thesame pointalong the microchannel.Fig.3BII showsaclose-upviewofpeakeventsfor100ms.Sincetheevents werewellseparated,thereisagreatpossibilitytofurtherincrease thethroughput.Thesignalswerepost-processedwithMATLABto obtainthenumber,peakvaluesandpositionsoftheevents.Gating wasappliedtoimprovethepopulationdistributionwithcommon propertiesasseen incommercialflowcytometers and toavoid multi-particleeventssuchasaggregatedparticles.Fig.3CI-IIshows thehistogramsofthepeaksobservedinFSCandSSCsignalsgiven inFig.3BI,respectively.Thecalculatedcoefficientofvariation(CV) valuesobtainedforFSCandSSCsignalswere26.98%and25.54%, respectively.LowerCVvaluescouldbeachievedbyadjustingthe sheathandsmallsolutionpressuresmoreprecisely[39].Accurate alignmentoftheilluminationfiberandFSC/SSCfibersiscritical.In thissetup,thesefiberswerealignedusingguidelinegroovescarved onaPMMAsubstratebyCO2laser(Fig.S6AI-II).Inotherwords,the illuminationandFSC/SSCfiberswerealignedautomaticallyonce theywerefixedontheplateusingatape.However,thealignment betweenthesefibersandglassmicropipettewasdonemanually usinganXYZstage(Fig.S6BandC).Thismightbealimitationforthe currentsystemasitmightbetime-consumingforresearcherswho arenotfamiliarwithsuchinstruments.Toovercomethislimitation, anewstrategywillbedevelopedtobypassthemanualalignment stage.Anotherlimitationofthecurrentsetupissamplerecovery. Thisissuewillalsobeaddressedin thefuture bycollectingthe outgoingsampleinachannelwithminimaldilution.Acellsorting mechanismmayalsobeintegratedintothesystemtodivertcells ofinterest.ScatterplotinFig.3Ddepictsthecorrelationbetween FSCandSSCsignalsfor2stimeduration.Itisobviousthatmostof theeventsweregatheredinasmallregion,aresultthatconfirms theproperfunctioningofthedevice.Ascomparedtocommercial state-of-the-artopticalflowcytometers,bulkoptics(laserdiodes, opticallenses,mirrors,filtersetc.)andmechanicalholders/aligners areexcludedfromthepresentsetup.Thepresentsetupusesfiber optics,whichprovidesgreatdealofflexibilitywhenconsidering theintegrationandstabilityofopticalelements.

4. Conclusion

Inconclusion,thefabricationofalow-costandsimplemicroﬂow cytometrydevicecapableofhydrodynamicfocusingwas demon-strated usingdifferent size glasscapillaries and a micropipette

alignerprintedwitha3Drapidprototypingmanufacturing sys-tem.Theassemblyofthedevicetooklessthan10minincluding micropipettetipgrindingandtheﬁnaldeviceisultra-lowcost.The deviceshowedanexcellentperformanceinhydrodynamic focus-ingofDIwatercoloredwithabluefooddye.Thedevicewasalso usedfor3Dhydrodynamicfocusingofmicroparticlesofuniform sizewheredistinctFSCandSSCsignalsofmicroparticlespassing throughtheopticalinterrogationpointweresuccessfullyrecorded. Giventheseparationbetweeneachevent,thedevicehasthe poten-tialforfurtherincreaseinthroughput.Thedeviceofferssimplicity, low-costandgoodperformanceinhydrodynamicfocusingandhas a greatpotentialtobeusedin a widerange ofﬂow cytometry applications.

AppendixA. Supplementarydata

Supplementarymaterial relatedto this articlecanbe found, intheonlineversion,atdoi:https://doi.org/10.1016/j.sna.2017.11. 056

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Biographies

AbdullahBayramreceivedhisB.Sc.inPhysicsfromIzmirInstituteofTechnologyin

2012andhisM.Sc.fromtheDepartmentofMaterialScienceandEngineeringatIzmir

KatipCelebiUniversityin2014.HeispursuinghisPh.D.atthesamedepartment.

MuratSerhatlioglureceivedaB.Sc.inElectricalandElectronicsEngineeringfrom

FiratUniversityin2012.HeispursuinghisPh.D.atBilkentUniversity,National

NanotechnologyResearchCenter,Ankara,Turkey.

Dr.BulendOrtacisanassistantprofessoratBilkentUniversity,National

Nanotech-nologyResearchCenter,Ankara,Turkey.

Dr.SerafettinDemicisanassociateprofessorattheDepartmentofMaterialScience

andEngineering,IzmirKatipCelebiUniversity,Izmir,Turkey.

Dr.CaglarElbukenisanassistantprofessoratBilkentUniversity,National

Nano-technologyResearchCenter,Ankara,Turkey.

Dr.MustafaSenreceivedhisM.Sc.degreeinMolecularBiologyandGeneticsfrom

IstanbulTechnicalUniversityin2010andPh.D.degreeinBio-enginneringfrom

TohokuUniversityin2013.Hecurrrentlyworksasanassistantprofessoratthe

DepartmentofBiomedicalEngineering,IzmirKatipCelebiUniversity.Hismain

researchfocusisintheﬁeldofmicro-andnanobiosensordevelopmentandtheir

applicationsinsinglecellandmicro-tissueanalysis.

Dr.MehmetE.SolmazreceivedhisB.Sc.degreeinMicroelectronicsfromSabanci

Universityin2004andPh.D.degreefromTexasA&MUniversityin2010.Hewas

apartofNanophotonicsResearchGroupatUniversityofSouthernCalifornia

dur-inghispostdoctoralresearch.CurrentlyheisanassociateprofessorinElectrical

andElectronicsEngineeringDepartmentofIzmirKatipCelebiUniversity,Izmir,

Turkey.Hisresearchfocusesonopticalsensingapplicationsusingsmartphonesand