COMMUNICATION

[ 3 ] 1600005 (1 of 6) A different [ 5 ] uid circuits, eld-effect-type eld-effect-type www.advmattechnol.de and to deliver tem- and to [ 5 ] wileyonlinelibrary.com The device produces fast stable The device produces fast stable [ 6,7 ] are relaxation oscillators (akin to astable oscillators (akin to astable are relaxation [ 3 ] It was also shown that four independent oscillators It was also shown that four independent oscillators uidic oscillators discussed can be used to transport uidic oscillators discussed can be used to transport [ 4 ] The mechanical microfl uidic oscillators developed by oscillators developed by uidic mechanical microfl The on a single chip with periods between 0.4 and 2 h could be 0.4 and 2 h could be on a single chip with periods between gravity. operated in parallel, purely driven by to analyze endothelial cell elongation, with a period of about 10 ms with a limited fre- oscillations with a period of about 10 ms frequencies in this quency tunability of about 30%. Though are much too fast ow mixing, they range are ideal for rapid fl processes. Both compared to many chemical or biological microfl to chemical reagents, but they are not themselves responsive . Mosadegh et al. approach for a mechanical microfl uidic oscillator based on uidic oscillator based on approach for a mechanical microfl elastic diaphragm a simple setup with a single overshooting was shown by Xia et al. porally patterned chemical profi les to living les to living profi porally patterned chemical concentration cells. multivibrators in electronics) based on two fi multivibrators in electronics) acting as compliances. The oscil- valves and two membranes to control subordinate fl lators have been used Dr. J. Páez Chávez Dr. de Ciencias Naturales y Matemáticas Facultad Escuela Superior Politécnica del Litoral Km. 30.5 Vía Perimetral Guayaquil , Ecuador U. Marschner Dr. Microsystems Technology Institute of Semiconductors and Microsystems Engineering of Electrical and Computer Faculty Dresden Universität Technische 01062 Dresden , Germany Prof. S. Siegmund for Dynamics Center Department of Mathematics and Center for Advancing Electronics Dresden Dresden Universität Technische 01062 Dresden , Germany Prof. F. Jülicher Systems Max Planck Institute for the Physics of Complex 01187 Dresden , Germany Prof. F. Jülicher for Advancing Electronics Dresden Center Dresden Universität Technische 01062 Dresden , Germany uidic Coupling uidic Coupling

u- [ 3–7 ] uidic- The development The development 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim & Co. GmbH 2016 WILEY-VCH Verlag © [ 1,2 ]

uidics could stimulate novel con- uidics could stimulate ow rate, and chemical concentration. ow rate, and chemical 1, 1600005 uence of the chemical domain on the fl uence of the chemical domain on 2016,

. −1

ow rate without external control signals and generates ow rate

Technol. Mater.

Bidirectional Chemical-Microfl Bidirectional Georgi , Paschew Jörg , Schreiter Andreas , Voigt Merle Cesare Allerdißen , Pini , Uwe Joseph , Marschner Páez Stefan , Chávez and Siegmund , Andreas René , Richter * Schüffny Frank , Jülicher Autonomous Chemical Oscillator Circuit Based on Circuit Based Oscillator Chemical Autonomous Autonomous oscillators are a key component of signal pro- oscillators are a key Autonomous and biology. cessing systems in electronics these oscillators operate on purely mechanical prin- However, ciples with no infl uidic oscillator circuit a microfl we present idic domain. Here phase transition transistor uidic employing a chemofl uidic coupling and a mixing junction for fl for chemical-fl sources of chemical coupling. It operates by constant and fl oscillations of pressure, fl period between The oscillator is shown to have an of alcohol oscillating 200 and 1000 s, chemical concentrations rates in the range of tens ow between 2 wt% and 10 wt%, and fl of µL min Adv. of oscillators that couple chemical or biological systems with the chemical or biological systems with the of oscillators that couple of microfl mechanical domain cepts for the “smart” handling of fl uids and their ingredients. handling of fl cepts for the “smart” the realization of chemical oscillators is chal- In technology, the con- Recently, lenging, in contrast to electronic oscillators. uidic oscillators has been demonstrated. struction of microfl DOI: 10.1002/admt.201600005 www.MaterialsViews.com Dr. J. Páez Chávez Dr. for Dynamics Center Department of Mathematics Dresden Universität Technische 01062 Dresden , Germany G. Paschew, Dr. A. Voigt, M. Allerdißen M. Allerdißen A. Voigt, Dr. G. Paschew, Polymeric Microsystems Institute of Semiconductors and Microsystems Engineering of Electrical and Computer Faculty Dresden for Advancing Electronics and Center Universität Dresden Technische 01062 Dresden , Germany Prof. R. Schüffny J. Schreiter, Highly-Parallel VLSI-Systems and Neuromorphic Circuits Institute of Circuits and Systems Engineering of Electrical and Computer Faculty for Advancing Electronics Dresden and Center Dresden Universität Technische 01062 Dresden , Germany C. Pini, Prof. A. Richter Polymeric Microsystems Institute of Semiconductors and Microsystems Engineering of Electrical and Computer Faculty for Advancing Electronics Dresden & Research Training and Center Group GRK 1865 “Hydrogel-Based Microsystems,” Dresden Universität Technische 01062 Dresden , Germany E-mail: [email protected] COMMUNICATION 1600005 negative feedbackinbiochemicaloscillatingsystems. esting tonotethatnaturealsousestheapproachofadelayand with amixingjunctiontoprovidenegativefeedback.Itisinter- for thechemicalconcentrationsignalandaCVPTcombined an aqueoussolution. transition stimulatedbychangeofthealcoholconcentrationin presence ofbiomolecules. cially concentrationsoforganicsolvents,ions,pHvalue,orthe phase transitioncanbethecontrolsignalofoscillator, espe- Any thermodynamicparameterabletoprovokethevolume the aqueousenvironmentwithdrasticchangesofvolume. ibly tosmallchangesofspecialthermodynamicparameters tion behavior, thesematerialsrespondreversiblyandreproduc- stimuli-responsive hydrogels.Duetotheirvolumephasetransi- volume phasetransitiontransistor(CVPT).CVPTs arebasedon chemical andthefl uidic domainbymeansofachemical frequency tunability. Zhabotinsky reaction,suchastheharshmediaandmissing limited duetothecharacteristicsinheritedfromBelousov– tions. in the1950sandareanongoingtopicofscientifi and Zhabotinskyintheformofchemicaloscillationreactions gels inamicrofl were notusedandkeptsealed. output branchwereadded.Inthereportedexperimentsthey the layoutofoscillatoranadditionalinletand the CVPTwithhydrogel(5)isatambientpressure.Notethatin sink (4)atthebypasschannel.Thefl alcohol solutionatthemixingpoint(3),andaconstantfl water atthebufferchannel,aconstantfl circuit issuppliedbyaconstantpressuresource(1)withpure shows pHoscillations. expansion andcontractiontoachemicalreactionsystemthat with volumephasetransitionbehaviorandthustocoupleits the Belousov–ZhabotinskyreactionintoapH-sensitivehydrogel and frequencysynthesis. ubiquitous intheformofringoscillatorsclockgeneration modern electronicsystems-on-chip,delay-basedoscillatorsare When theundilutedalcoholsolution ( through thedelaylineandpartly backwardintothebufferline. the bypassfl ow, sothatundiluted alcoholsolutionfl the alcoholsolutionisdesigned tobealittlebithigherthan nected tothebypasschannel.Theconstantfl fl hydrogel isswollen,andthustheCVPTclosed,resulting and itcontractsathigheralcoholconcentrations.Whenthe water oraqueoussolutionswithlowalcoholconcentrations, At afi xed temperature,thegelswellsincontactwithpure sodium-acrylate copolymerasthestimuli-responsivehydrogel. as thecontrollingchemicalandan idic passageofthetransistor and thusallowingforincreased hydrogel, thelatterbeginsto shrink, therebyopeningthefl chemical environment. into thepolymerleadstoself-oscillating gelsinanonoscillating www.advmattechnol.de ow ratethroughthedelaylineis determined bythesinkcon- The oscillatoremploysamicrofl The oscillatorwepresentherecouplesbidirectionallythe The principleoftheoscillatorisdepictedin Ceia oscillations Chemical We explain theoscillatorusingexampleof1-propanol [ 9–11] (2 of6) Yoshida etal.showedthatitispossibletointegrate uidic setting. uidic wileyonlinelibrary.com [ 12] [ 13–15] [ 8] [ 19] Incorporatingthecatalystcovalently havebeenfi rst observed byBelousov [ 17]

Ithasbeensuggestedtousethese Here weutilizethehydrogelphase [ 16]

However, their applicability is uidicchannelasadelayline c uidic output (6)behind alc N -isopropylacrylamide-

= 10wt%)reachesthe ow source(2)with © ow ratesourceof 2016WILEY-VCHVerlag GmbH &Co. KGaA,Weinheim The 1. Figure c investiga- c ows partly ows [ 18] Alsoin ow u- fi of large-scaleintegratedmicrofl uidic chemicalcircuits.Inthe approach willbeapreconditionfortransistorbasedconcept to microelectronicsweanticipatethatthisdesignautomation Poiseuille lawforrectangularcross-sections. channels aroundthehydrogel and iscalculatedviatheHagen– resistance oftheCVPTdepends onthewidthoftwoside rent hydrogelsizearateof changeisapplied.Thefl hydrogel. Dependingonthealcohol concentrationandthecur- the CVPT, ismodeledbyassigningasinglesizevariabletothe porting InformationSectionS2).Theheartoftheoscillator, detailedinformation,seeSup- components arerealized(for fl the analogyofelectricandfl automation softwareforelectronicintegratedcircuitsusing cycle oftheoscillation. again, eventuallyblockingthevalveseatandstartingnext the dilutedalcoholsolutionreacheshydrogel,gelswells negligible comparedtothelengthofdelaychannel.When channel. Alsolongitudinaldiffusionoccurs,howeverinarange channel, thedilutedsolutionishomogenizedlaterallyto point (Figure 1 b, (3)).Whilethismixturepassesdownthedelay solution, waterisaddedtothealcoholsolutionatmixing buffer channelhasbeenclearedoffthepushed-backalcohol higher thantheconstantsupplyofalcoholsolution.When the increasedflow throughthenowopenCVPTissubstantially source, andthevalveseatgeometryaredimensionedsuchthat tures ofthephysicalchipdesignarelabeledn.c. drain, (5)CVPT, and(6)ambientpressuredrain.Unusedoptionalfea- of aqueousalcoholsolution,(3)mixingjunction,(4)constantfl (b): (1)constantpressurewatersource,(2)fl ow ratesource matic laboratorysetup.c)CVPTlayoutdetail.Circlednumbersin(a)and circuit. b)Photolithographiclayoutofthemicrofl uidic chipandsche- Figure1. )c) b) a) p =const rst phase,numericalmodelsofallneededactiveandpassive ow. Hydrodynamicresistances,thepressureofwater Q Q H2O alc bp The oscillatorcircuitisdesignedwiththehelpofdesign measurement rateflow n.c. Principle oftheoscillator. a)Schematicofthemicrofl 2 4 1 3 buffer ch PDMS onglasschip 10 mm channel delay Q 2 mixing alc 3 = const udc quantities. uidic 5 delay ch R =const Adv. channel buffer 6 Mater. Technol. www.MaterialsViews.com n.c. 1 Q [ 20–22] 4 bp hydrogel 5 const = 2016, Inanalogy H 500 µm 2 O 1, 1600005 p ow rate ow H2O uidic uidic drain 6 COMMUNICATION , −1 1600005 (3 of 6) = 9.8 µL min

alc www.advmattechnol.de , Q Figure 4 a for the oper- −1 wileyonlinelibrary.com = 7.56 µL min

bp ow rate in the buffer line (smoothed to ow rate in the buffer line Q t procedure for the free parameters of the CVPT 88 mbar. By spline interpolation of the maxima spline interpolation By = 88 mbar.

H20 p After a fi and oscillations at the mixing junction, respectively. The time signal The time signal junction, respectively. oscillations at the mixing fl of the oscillator’s eliminate detector noise) is displayed in eliminate detector noise) ational parameters compact model (see Supporting Information Section S2) a close Information compact model (see Supporting by simulation correspondence of the time signals obtained The bypass output is c) with experiment was achieved. 4 (Figure ow rate but cance since it exhibits a constant fl of special signifi and minima the amplitude envelope is determined and used and minima the amplitude envelope is power spectrum of to calculate the long-term signal drift. The b) shows some higher harmonics due to the 4 the signal (Figure measurement is made nonsinusoidal wave form. A comparison the system inherent for a system without hydrogel to determine to instabilities noise, where slow drifts most likely correspond of the pumps and the elasticity of the system. designate the depth, width, and length of a channel in millimeter. the depth, width, and length of a channel designate L - uidic , and D , , and W

uidic chan- 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim & Co. GmbH 2016 WILEY-VCH Verlag © ), comprising connectivity Figure 2 1, 1600005 2016, . Videos S1a, S1b, and S1c (Supporting Infor- S1a, S1b, and S1c (Supporting . Videos Figure 3 Photographs of the operating CVPT in four different phases. The liquid with high alcohol content is colored by food color. a) Phase 1: valve a) Photographs of the operating CVPT in four different phases. The liquid with high alcohol content is colored by food color. Design with EDA software Virtuoso by Cadence. Schematic representation of the microfl and laboratory setup for compact model uidic circuit representation of the microfl Schematic Design with EDA software Virtuoso by Cadence. Technol. Mater. The operation of the oscillator by means of the CVPT is In the second phase, a schematic representation of the micro- In the second phase, a schematic representation uidic circuit is generated ( uidic circuit is generated mation) show the chemical-fl uidic oscillations in the whole uidic oscillations in the whole mation) show the chemical-fl and the chemical-fl the oscillation of the CVPT, oscillator, shown in but still neglecting geometry. This facilitates the calculation of This facilitates the calculation but still neglecting geometry. As dimen- including their time dependency. uidic quantities all fl of components and operational parameters sioning of the circuit simulation, a range the pumps can be varied easily for repeated has been determined, of parameters yielding stable oscillation nal optimized dimensioning of the microfl and the fi Once dimensioning nels is chosen to lie well within that range. b). The 1 (Figure is complete, a photomask ready layout is drawn size constraints, effi main objectives in this phase are overall and placement of the cient area utilization, manufacturability, laboratory. inlets and outlets for easy access later in the fl Figure 2. simulation. Connections drawn in blue represent liquid fl ow, solute transport with the liquid fl Building ow is modeled as connections drawn in purple. solute transport with the liquid fl ow, fl drawn in blue represent liquid simulation. Connections represent instances of compact models. blocks in green graphics Adv. Figure 3. has reached the hydrogel (valve just beginning uid with high alcohol concentration closed, mostly low alcohol concentration in delay line. b) Phase 2: fl uid with low alcohol concentration has reached uid with high alcohol concentration in delay line. d) Phase 4: fl to open). c) Phase 3: valve open, mostly fl the hydrogel (valve just beginning to close). www.MaterialsViews.com COMMUNICATION 1600005 sponding tothevaluesofoperationalparameters the microfl uidic oscillator. Figure 5 d showsthesurfacecorre- bifurcation inapiecewise-smoothdynamicalsystemmodeling oscillatory behaviorwaspredictedbythepresenceofaHopf possible toperformdailyexperiments withthesameoscillator that theoperationofoscillator isstableforalongtime.It steady stateoffl parameters aboveleadtodecaying oscillations,resultingina tional parametersbelowthissurface leadtooscillationswhile Information SectionS3). of aCVPTwithaninstantaneousreactiontime(Supporting simplifi can beestimatedwithanaccuracyofafactorabout1.5by a trum (Figure 4 b). Oscillationperiodsforgiveninputparameters location ofthepeakfirst harmonicinthefrequencyspec- method amountsto181.9swhichisclosetheinverseof time signalinFigure 4 a themeanperioddeterminedbythis the calculationofperioddistribution(Figure 5 b). For the lation aredeterminedfromthezero-crossings,whichallowsfor smoothed anddrift-correctedsignalstheperiodsofeachoscil- lead tohigheramplitudesandfasteroscillations.From the shown in cuit areinvestigatedbyvaryingitsoperationalparameters.As for couplingtheoscillatortoother(e.g.,biological)systems. varying alcoholconcentration(Figure 4 d) whichcouldbeuseful Figure4. the FORTRAN-basedcontinuation toolboxTC-HAT. Q lation periodinawiderange(Figure 5 c). Here, theratio and at thebypasschannel. valve (red).c)Simulatedsignalwiththesameoperationconditionsasexperimentalin(a).d)ofthealcoholconcentration (a) (blue).Spectrallinewidthduetowindowing(black).Noisefl interpolation. Theblackdashedlineshowsthelong-termsignaldriftcalculatedfromenvelopes.b)Powerspectrumoftimeshownin parameters: www.advmattechnol.de alc

The stabilityandtheoperationrangeofoscillatorcir- The operationalparameterscanbeusedtotunetheoscil- /Q p (4 of6) H20

pb ed analyticalmodelwhichisbasedonthe assumption Time signalsoftheoscillator. a)Timesignalofthefl iskeptataconstantvalueof1.25.Theexistence forwhich aHopfbifurcationoccurs,computedvia 5 Figure a, highervaluesofflow andpressuresources Q alc

= 9.8µLmin ow rates andalcoholconcentrations.We found wileyonlinelibrary.com

−1 , c , alc

= 10wt%, Q bp ©

= 7.56µLmin 2016WILEY-VCHVerlag GmbH &Co. KGaA,Weinheim [ 23] owrateatthebufferline(smoothedforeliminationofdetectornoise).Operational Q Opera- oorobtainedfromacomparisonmeasurementofthesystemwithouthydrogelin

alc −1 , Q , , p , pb

H2O ,

= 88mbar. Redgraphsshowtheamplitudeenvelopesobtainedbyaspline driven withasalt(e.g.,NaCl chemical. Thiswidenstheapplicability inbiologywherealkali molecules likeglucose,ororganicsolvents. pH valueortheconcentrationsofotherions(e.g.,salts),bio- responsive hydrogelswithinaqueoussolutions,forexample, parameter abletoprovokeavolumephasetransitionofstimuli- based ontheprinciplesshownherecanbeanythermodynamic a widevarietyofchemicals.Thecontrolsignalanoscillator tunable overawiderange,andthesystemcanbecoupledto the ingredientsarenontoxic,behaviorofoscillatoris domain. IncontrasttoBelousov–Zhabotinsky-typeoscillators cuit withbidirectionalcouplingofthechemicalfl three months. chip containingthesamehydrogelforaperiodofmorethan e.g., yeastcells. erate enzymeswhichareresponsibleforethanolproduction, the currentsystemcouldbeoperatedtocontrolcellsthatgen- hydrogel materialandsize. reaction timeoftheCVPTwhichcanbescaledbychoice of line andthefl period canbescaledupordownbythevolumeofdelay mechanism ofalcoholism. anol areGolgicellswhichcould beusedinasetuptostudythe and ethanolproduction.Another cellspeciessensitivetoeth- duction orgenerateanoscillatory fl system wouldeitherstabilizethecellcultureandethanolpro- instead ofalcohol.Dependingontheoperationalparameters 2 (seeFigure 1 a) containsthecellgrowthstimulant glucose be putintothedelaylineofoscillator, whereinputchannel In summary, wehavepresentedaCVPTbasedoscillatorcir- As thePNIPAAmhydrogelisalsosensitivetowardethanol, ow ratesofthesources,takingintoaccount [ 29] For example,acellculturechambercould [ 30] [ 25] Thecurrentoscillatorcanalso be ) insteadofalcoholasthe active Adv. uctuation ofcellpopulation Mater. Technol. www.MaterialsViews.com [ 24–27] Theoscillation 2016, 1, 1600005 uidic [ 28]

COMMUNICATION - ′ -(2- ask. ask. 1600005 N,N (5 of 6) = 1.25. d) Bifurcation www.advmattechnol.de bp ask for 30 min. Under ask for 30 min. Under / Q exible programmability programmability exible alc . Q . Under constant stirring, the the . Under constant stirring, σ 1 − wileyonlinelibrary.com ask equipped with a magnetic stirrer and a septum ask equipped with a magnetic stirrer and a septum uidics. uidics. ushed with argon in the sealed fl uidic chip a standardized soft-lithographic procedure was used. For the fabrication of the active components, a PDMS mould with the fabrication of the active components, a PDMS mould with For : For the fabrication of the : For Level Chip Fabrication—Channel : In a Synthesis and Structuring of the Hydrogel-Based Component -isopropylacrylamide (NiPAAm) and sodium acrylate with a total -isopropylacrylamide (NiPAAm) and sodium acrylate with a total also is the fi rst step toward the goal of fl also is the fi within microfl methylene-bisacrylamide was weighted out and fi lled into the fl methylene-bisacrylamide was weighted out and fi distilled water was added in order to obtain a polymer solution Finally, with a concentration of 1.25 mol L mixture was fl inert argon atmosphere 2 mol% of the photoinitiator 2-hydroxy-4′ hydroxyethoxy)-2-methylpropiophenone was added to the solution. The solution was then stirred under argon atmosphere for 30 min. pits of width 300 µm × 300 µm and depth 140 µm was prepared. Such lled with the polymeric solution under inert atmosphere a mould is fi Experimental Section microfl First, the molding master was realized by structuring a three-layer dry- substrate. lm-resist, ORDYL SY355 from ELGA EUROPE, on a glass fi The polydimethylsiloxane (PDMS) mixture, SYLGARD 184 10A:1B, was degassed at 3 mbar for 60 min, then poured over the molding master, nally cured in an oven at 60 °C for 40 min. and fi round bottom fl N amount of 1.25 mol was weighted out. The ratio of NiPAAm to sodium acrylate corresponded to 97.5 mol% NiPAAm to 2.5 mol% sodium acrylate. Additionally a portion of the crosslinker 2 mol% eld ned uidic circuits 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim & Co. GmbH 2016 WILEY-VCH Verlag © uidic oscillators with only one uidic oscillators with ops (for data storage), and oscil- uidic oscillators in general. ip-fl 1, 1600005 On the other hand the bidirectional coupling uidics is the introduction of basic concepts 2016, [ 31 ] uidic oscillators can address a similar range of appli- Analysis of the oscillatory behavior. a) Time signals of the fl ow rate at the buffer line for different operational parameters. b) Period distribu- Time signals of the fl a) Analysis of the oscillatory behavior. uidic and the chemical domain allows us to introduce Technol. Mater. Analogous to microelectronics, we expect that a future Analogous to microelectronics, xed protocols. xed a control layer which enables event controlled programs and of the fl Figure 5. tions for the time signals shown in (a). c) Mean period as a function of operational parameters. Error bars indicate 3 tions for the time signals shown in (a). c) Mean active component enables simple integration in larger circuits, e.g., coupled oscillators where effects like phase synchroniza- tion and shifts of the oscillation frequency can be utilized. Cir- can be used to realize hardware defi cuits based on CVPTs lators (to provide timing). We envision microfl lators (to provide timing). We with the equivalent of these building blocks, based on CVPTs. Chemofl cations as their microelectronic counterparts: e.g., providing a clock signal for sequential operations, reproducible timing, and synchronization of concurrent processes. Furthermore, the demonstrated tunability is a key factor for synchronization to external references and for calibration in mass production. The simple concept of chemofl programs as needed for automated analysis or synthesis with fi trend of microfl processing. In digital cir- information from transistor-based cuits, three fundamental basic building blocks are logic gates (for fl data processing), metal and alkaline earth ions are ubiquitous in cell signaling. metal and alkaline earth ions are ubiquitous role in cell biology, As chemical oscillations play a fundamental will be a future fi e.g., in tissue formation, we hope that this of application for chemofl surface obtained from a mathematical model of the chemical oscillator. The points represent the parameter values for which the system undergoes a which the The points represent the parameter values for the chemical oscillator. surface obtained from a mathematical model of Below the surface, surface the system responds with damped oscillations settling down to a stable equilibrium. values above the Hopf bifurcation. For behavior appears in the system. this equilibrium becomes unstable and stable periodic Adv. www.MaterialsViews.com COMMUNICATION 1600005 lamp, wavelengthofmaximumemission365nm,power16mWcm by exposingthefi lled andsealedmouldtoUV-light(mercuryshort-arc and sealedwithathinglassslide.Photopolymerizationwasachieved numerically traced. provided bytheGermanResearch Foundation (RI1294/7,GRK1865 for AdvancingElectronicsDresden” (cfaed).Additionalfundingwas Research Foundation (DFG)withintheClusterofExcellence“Center supervised byA.R.Thisworkwas supportedinpartbytheGerman characterization, dataevaluation,and modeling.Thewholeprojectwas J.S., C.P.,A.R.,andF.J.provided crucialinputregardingoscillator took thevideos.ThemaintextwaswrittenbyA.V. withsupportfrom dynamic behavioroftheoscillatorwithsupportfromG.P.andC.P. M.A. C.P.manufacturedthemicrofl uidic circuitandcharacterizedthe S.S. TheworkingdesignoftheCVPTwasexperimentallydeveloped by oscillator andcarriedoutitsbifurcationanalysisundersupervision of developed byA.V. J.P.C.developedadynamical systemmodelofthe device modeling.Thesimplifi ed analyticmodelofthe oscillatorwas layout undersupervisionofR.S.withadditionalhelpfromA.V. for developed theconcept.J.S.performedsimulation,design,and the coreideaforoscillator. G.P.,J.S.,A.V., andU.M.further G.P., J.S.,andA.V. contributedequallytothiswork.G.P.andA.R.had Acknowledgements from theauthor. Supporting InformationisavailablefromtheWileyOnlineLibraryor Information Supporting the parameterspace( to generatethebifurcationsurface,locusofHopfbifurcationsin the numericalcontinuationintwofreeparameters.Therefore,order problems implementedinAUTO97.TC-HAT, however, does notallow pseudoarclength numericalcontinuationappliedtoboundary-value orbits ofnonsmoothdynamicalsystems.Thispackageexploitsthe for thenumericalcontinuationandbifurcationdetectionofperiodic continuation packageTC-HAT. pump actedinbackwardmode. mixture (10wt%)ofpropan-1-olinMilliporewater. Thesecondsyringe by de-ionizedMilliporewater. Onesyringepumpwasoperatedwith a syringe pumpsandapressurepump.Thepumpwasoperated present setup. introduced forfurtherexperiments.Ithadnegligibleinfl and bufferchannellength400mm.Inthebypasspathawas and bufferchannelwidth0.4mm,delaylength500 parameters wereobtained:depthofallchannels0.165mm,delay 500 µm.From thecompactmodelsimulationfollowingfabrication the deswollenstateamountedto300µm;chamberwidthwas Information SectionS2. models, simulation,andthedesignprocesscanbefoundinSupporting were generatedbyuseofthetoolVirtuoso.Adetaileddescription Design Systems,Inc.Schematicrepresentationsofthefl use oftheDesignFramework II(DFI)softwarepackageofCadence simulation, anddesignofthemicrofl uidic circuit wascarriedoutby 40 SSCinthechamber. an exposuretimeof2minatapower50Wandoxygenfl Then thePDMSchipwasplasmabondedontoaglasssubstratewith manually placedbetweentheholdersinrealizedPDMSchip. for 20sataconstanttemperatureof5°C. www.advmattechnol.de BifurcationAnalysis : Thebifurcationanalysiswasperformedwiththe OperationoftheMicrofl uidic Circuit : Thechipwasoperatedbytwo DimensioningoftheComponents : Thewidthofthehydrogelin Modeling, DesignandLayoutUsingElectronicAutomationTools : PackagingoftheChip : Theso-producedactivecomponentwas (6 of6) wileyonlinelibrary.com Q bp , Q , alc [ 23] ) forvariousfi xed valuesof ThisisaFORTRAN-basedtoolbox © 2016WILEY-VCHVerlag GmbH &Co. KGaA,Weinheim uidic systems uidic uence inthe p H20 ow of ow was −2 ) 3] .J un , .T e , .L si C F aezea C Huang, C. Valenzuela , F. C. Tsai , M.-L. Yen , C.-T. Huang, J.-J. Bai, [30] F.-W. Xue, C. Zhao, X.-Q. Wang , L. [29] Sens.ActuatorsBChem. Kretschmer , K. Wenzel , J. Richter , A. [28] 2] . . O , . Le B h , . . Frai Lab Chip Furlani , P. E. Ahn, B. Lee, K. Oh, W. K. [20] Lima, C. F. L. J. Santos, M. L. J. Segundo, A. M. Iranifam, M. [10] Alexander vonHumboldtFoundation, Germany. was supportedbyaGeorgForster ResearchFellowship grantedbythe “Hydrogel-based Microsystems”)andtheEuropeanSocialFund. J.P.C. 2] . Bli Y u P E otes R A igl B ii , J.Microelectro- Ziaie, B. Siegel, A. R. Loftness, E. P. Gu, Polym.Adv. Technol. Y. Baldi, Richter , A. A. [27] Kuckling, D. Arndt, Devadoss , Adv. C. Mater. K.-F. Pich, Liu, A. H. [26] Türke , R. A. Yu Richter , , Q. A. Bauer , M. [25] J. Moore, IEEEInd.Electron. S. J. Quero, Beebe, J. M. D. SIAMJ.Appl.Dyn.Syst. Dankowicz, [24] J. H. 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