kinetics of polymerization in microfluidics

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Kinetics of Multicomponent Polymerization Reaction Studied in aMicrouidic FormatDan Voicu, Clement Scholl, Wei Li, Dinesh Jagadeesan, Irina Nasimova, Jesse Greener,*,,#

and Eugenia Kumacheva*,,,,#

Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, CanadaDepartment of Physics, Moscow State University, Moscow 119991, RussiaDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, CanadaBiomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada#FlowJEM, Inc., Toronto, Ontario M5S 3H6, Canada

*S Supporting Information

ABSTRACT: We report a high-throughput study of the

kinetics of a multicomponent polymerization reaction in amicrouidic reactor integrated with in situ attenuated totalreection Fourier transform infrared spectroscopy. Thetechnique was used to study the kinetics of an exemplaryfree-radical polymerization reaction ofN-isopropylacrylamide,

which was initiated by ammonium persulfate in the presence ofthe accelerator N,N,N,N-tetramethylethylenediamine in

water. By monitoring the rate of disappearance of themonomer double bonds, we determined the effects of theconcentration of the monomer, initiator, and accelerator on the rate of polymerization and the effect of the pH of the reactionsystem on the reaction kinetics. This work opens the way for the kinetic studies of complex polymer systems in a microuidicformat.

1. INTRODUCTIONExploring a broad range of experimental variables formulticomponent reactions is time-consuming and cost-inefficient. A systematic optimization of formulations for suchreactions rapidly becomes challenging and time-consuming,especially when the parameter space includes concentrations ofmultiple reagents and the variations in temperature, pH, orpressure. Numerous reiterations are needed to evaluate andquantify the effect of superposition of multiple reactionparameters.

Studies of chemical reactions in a microuidic (MF) formatprovide an efficient experimental platform for the exploration ofa large parameter space and optimization of formulations due tothe ability to vary the concentrations of reagents in a high-throughput manner, especially when this is complemented byrapid on-chip characterization of reaction products. In MFsynthesis, the type and the concentrations of multiple reagentsintroduced in the reaction system are controlled in a high-throughput manner by varying the ratio of their volumetric owrates.1Advantages of MFs as a chemical discovery platform alsoinclude reduced consumption of reagents, excellent controlover heat and mass transfer, improved safety in handlingdangerous species, and the ability to carry out multistepreactions without exposure to ambient conditions. Moreover, incomparison with the challenge in scaling up of conventionalmultireagent reactions, a combination of multiple MF reactors

working in parallel (the numbering up strategy) offers highreproducibility and an increase in productivity.2

Continuous polymerization in ow microreactor systems hasbeen demonstrated for radical polymerization of vinylmonomers,3 coordination polymerization,4 polycondensation,5

anionic,6 and ring-opening polymerization.7 Advantages ofpolymerization reactions in a MF format included excellentcontrol of reaction conditions, the capability to vary the degreeof polymerization by modulating the monomer-to-initiator ratio

by changing their relativeow rates, and the ability to generate,in a high-throughput manner, large libraries of polymers forrapid evaluation.

The potential applications of the MF platform for studies andoptimization of chemical formulations for polymerization

reactions would not be fully realized without rapid, on-chipcharacterization of reagents and products. Implementation ofinsitu chemical characterization opens the possibility for (i) therapid screening of the effect of reaction variables, (ii) feedbackfor reaction control parameters, (iii) detection of transientspecies, which may not exist upon their removal from the MFreactor, and (iv) kinetic studies with sufficient time resolution,specically during the initial stage of the reaction.

Received: March 4, 2012Revised: April 21, 2012Published: May 16, 2012

Article

pubs.acs.org/Macromolecules

2012 American Chemical Society 4469 dx.doi.org/10.1021/ma300444k| Macromolecules 2012, 45, 44694475
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Various characterization tools have been utilized for MFpolymerization reactions. Continuous online size exclusionchromatography enabled monitoring of the molecular weightand molecular weight distribution of polymers synthesized in atubular reactor by nitroxide-mediated polymerization.8 Multi-detection gel permeation chromatography of polymer samplescollected at the outlet of a microreactor was used for thecharacterization of linear and branched polymers by combininga concentration- and a mass-sensitive detection technique.9 Insitu Raman spectroscopy was used to characterize withacceptable accuracy the change in composition and degree ofconversion of methacrylate-based droplets in a MF reactor.10

Small-angle light scattering was utilized to monitor andcharacterize the formation and size distribution of multilamellar

vesicles of a diblock copolymer in aqueous solutions.11

Here we present the results of the rstin situMF study of thekinetics of a polymerization reaction using infrared spectros-copy. This approach builds upon other FTIR-based analyticalapproaches to MFs,13 while maintaining the microchanneldimensions within the microprobe region. We conducted athroughput systematic study of the kinetics of a multi-component reaction at different pH values with high temporalresolution by using a MF reactor interfaced with a Fouriertransform infrared (FTIR) spectrometer. Fourier transforminfrared spectroscopy is a well-established technique that isapplicable to full-spectrum characterization of chemical species,

which allows quantitative analysis of multiple reagents andproducts.12 Infrared spectroscopy can also be used tocharacterize solventanalyte interactions, hydrogen bonding,changes to protonation states, and conformation of macro-molecules, and effects of temperature or electromagnetic elds.These factors affect vibrational spectra by changing absorbancepeak intensity and peak position or by causing subtle changesto spectral line shape, which can be revealed through secondderivative spectroscopy.14

We examined an exemplary polymerization reaction: the

polymerization of N-isopropylacrylamide in water, which wasinitiated by ammonium persulfate in the presence of theacceleratorN,N,N,N-tetramethylethylenediamine. This impor-tant reaction is used for the preparation of gels in cellbiology,15

gel electrophoresis,16 and the encapsulation of cells.17We showthe capability of MF synthesis integrated with infraredspectroscopy to rapidly examine the effects of varying theconcentration of the monomer, initiator, and accelerator andthe effect of pH of the solution on the kinetics of thispolymerization reaction.

2. MATERIALS AND METHODS

N-Isopropylacrylamide (NIPAAm) was purchased from Sigma-AldrichCanada and recrystallized prior to use. The initiator ammoniumpersulfate (APS), the accelerator N,N,N,N-tetramethylethylenedi-amine (TEMED), and ethanolamine were purchased from Sigma-Aldrich Canada and used as received. Deionized water was supplied bya Milli-Q Plus system (Millipore Corp.). Aqueous reagent solutionswere prepared prior to experiments and purged with N2 gas for 15min. Phosphoric acid was purchased from Caledon Laboratories, Ltd.Hydrochloric acid was purchased from VWR (Radnor, PA).Dihydrogen phosphate monosodium and sodium hydroxide werepurchased from ACP Chemicals (Quebec, CA).

For pH-dependent polymerization experiments, we used threebuffer solutions with pH values of 2.23, 7.26, and 9.50. The pH 2.23phosphate buffer solution was prepared by mixing H3PO4 with thepredissolved aqueous reagent solution (either NIPAAm, TEMED, orAPS) and titrating it to pH = 2.23 with a 1 M HCl solution. The pH

7.26 phosphate buffer solution was prepared by dissolving NaH2PO4in the predissolved aqueous reagent solution and titrating it with 1 MHCl to pH = 7.26. To prepare pH 9.50 buffer, ethanolamine wasmixed with the aqueous reagent solution and titrated with a 10 MNaOH solution to pH = 9.50.

The ow rate of each reagent solution was independently controlledusing a separate syringe pump (PHD2000, Harvard Apparatus). Allreactions were conducted at 21 1 C. An attenuated total reection

Fourier transform infrared (ATR-FTIR) spectrometer (Vertex 70,Bruker Corp.) was interfaced with the MF reactor using a singlereection diamond ATR crystal (MIRacle, Pike Technologies). Unlessotherwise specied, the spectra were generated from 32 scans at 10kHz scan speed with 4 cm1 spectral resolution. Infrared absorbance ofchemical species of interest was determined by measuring the intensityof an absorption peak and relating it to the molar concentration. Errorbars were generated from the standard deviation from three separatemeasurements. The spectrometer was purged with air supplied from apurge gas generator (model 75-45, Parker Balston) to limit absorptionby ambient CO2(g) and H2O(g). Detection was accomplished using adeuteratedL-alanine-doped triglycene sulfate (DLATGS/D301, BrukerInc.). Opus 6.5 software was used for computer-control of dataacquisition and analysis. Measurements of pH were conducted using aVWR Symphony SB70P pH meter connected to a probe (MI408C,Microelectrode Inc.) with ow-through reference probe (ME16730,

Microelectrode Inc.). Probes and

uidic connections were interfacedwith a customized microuidic reactor (FlowJEM Inc.) using aninterface component (PCIC, FlowJEM Inc.).

3. EXPERIMENTAL DESIGN

A MF reactor was fabricated in polycarbonate, as describedelsewhere.18 Fluid reagents were introduced into the MF reactor viaa threaded interface system,19 which connected 1.6 mm poly(etherether ketone) tubing (IDEX Corp.) to inlets on the reactor. Figure1shows the design of the MF reactor used in the present work. Thereactor had a microchannel width and height of 200 and 50 m,respectively. Unless specied, the cross-sectional area of the micro-channel was 104 m2. Aqueous solutions of APS, TEMED, andNIPAAm with initial concentrations CAPS,i, CTEMED,i, and CNIPAAm,i,respectively, and water were introduced into four syringes andsupplied to the MF reactor through inlets (i)(iv), respectively(Figure1). The mixing between the reagent streams was carried out ina stepwise manner: rst, by mixing the liquids supplied through inlets(i) + (ii) and (iii) + (iv) and then by combining two streams in thereaction chamber (the serpentine channel (v)), where the reagentsmixed and the reaction took place. In the mixing channels the cross-sectional area was reduced from 104 to 7.5 103 m2, due toprotrusions from the channel walls, introduced to enhance mixing ofthe reagents (Figure S1,Supporting Information). The changes in thereaction mixture were characterized after it owed through thereaction chamber and reached the ATR crystal, a temperature probe,and a pH probe (the probes were located at positions P1, P2, and P3,respectively). A detailed description of the experimental setup,including integration of the ATR-FTIR, pH, and temperatureprobeswith the microuidic reactor, is described in detail elsewhere.20 Thesolution containing the polymer product and unreacted reagents exited

the MF reactor through the outlet (vi).

4. DATA ACQUISITION AND ANALYSIS

4.1. Reaction Time and Reagent Concentrations.Thereaction time was calculated as

=t DA Q /T (1)

whereD is the distance between the beginning of the reactionchamber (v) and the ATR-FTIR probe (P1) (D= 160 mm); Ais the average area of the cross section of the microchannel inthe reaction compartment, A = 7.5 103 m2 (7.5 103

mm2); andQTis the total ow rate of the reaction mixture. Thevalue ofQTis

Macromolecules Article

dx.doi.org/10.1021/ma300444k| Macromolecules 2012, 45, 446944754470


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= + + +Q Q Q Q Q T NIPAAm TEMED APS H2O (2)

where QNIPAAm, QTEMED, QAPS, and QH2O are the individualvolumetric ow rates of the solutions of NIPAAm, TEMED,APS, and water, respectively. After on-chip mixing, thesolutions of reagents were diluted to the initial on-chipconcentrations

= C C Q Q /NIPAAm,d NIPAAm,i NIPAAm T (3a)

= C C Q Q /TEMED, d TEMED, i TEMED T (3b)

= C C Q Q /APS,d APS,i APS T (3c)

After a reaction time t, the concentrations of the reagents

changed to CNIPAAm,t, CTEMED,t, and CAPS,t.4.2. Correlating Absorbance to Concentration.The use

of in situ ATR-FTIR characterization enables direct measure-ments of reagent and product concentrations. Figure 2a showsrepresentative IR spectra collected for the individual solutionsof APS, TEMED, NIPAAm, and PNIPAAm. The arrows specifycharacteristic peaks for each species. Prior to the reaction, we

veried that the spectrum of the reaction mixture was aweighted average of the individual reagent spectra. Figure2bshows the variation in the intensity of the IR peaks, labeled inFigure2a, for solutions with solute concentrations varying from1 to 150 mM. Furthermore, we veried that the linear trend ofIR peak intensity vs monomer concentration held until CNIPAAm

= 300 mM, which was the maximum on-chip concentrationused in the present work (section5.4). In the range of analyteconcentrations studied, the intensity of an absorbance peakA

was related to the analyte concentration by the BeerLambertlaw as

=A Cl (4)

where Cis the analyte concentration (mol L1), l is the pathlength (cm) of the evanescent infrared light in the solution, and is the molar extinction coefficient (M1 cm1). Molarextinction coefficients were determined by replacingA/Cin eq4 with the slopes of the calibration graphs in Figure 2b. Weused the variation in absorbance of the double bond ofNIPAAm vstto measure the time-dependent concentration ofthe monomer during the reaction, that is, conversion. Wecalculated the penetration depth, lNIPAAm, to be 1.54 m usingthe incident angle of light at the ATR crystal surface (60 ), theindices of refraction of the liquid media and diamond ATRcrystal (1.5 and 2.4, respectively), and the excitation wavelengthof the band of interest (975 cm1), the spectral position ofNIPAAm characteristic peak.21 Using eq 4, we determinedNIPAAm to be 1.08 10

4 M1 cm1.4.3. Determination of the Rate of Polymerization. We

modulated the total ow rate of the reaction mixture to tunethe reaction time within the interval 0 t 6.75 s, whichlimited the extent of conversion to less that 30% for all reagentconcentrations. A relatively low conversion enabled us to avoid

problems associated with increase in viscosity of the solution,due to the formation of high-molecular weight PNIPAAm, as

well as polymer adsorption on the ATR crystal. We preparedthree stock solutions with CNIPAAm,i= 525 mM, CTEMED,i= 180mM, and CAPS,i = 180 mM and introduced them in the MFreactor. The manipulation of the ow rate of water (the fourthinlet) enabled controlled dilution of the reagent streams. Forexample, we usedQNIPAAm= 0.235 mL h

1,QTEMED= 0.118 mLh1, QAPS = 0.235 mL h

1, and QH2O = 0.118 mL h1 (QT =

0.706 mL h1) to calculate the reaction timet= 6.75 s using eq1. Furthermore, by using eq3, we determined initial on-chipreagent concentrations to be CNIPAAm,d = 175 mM, CTEMED,d=30 mM, and CAPS,d = 60 mM.

Figure 1. Schematic of the MF reactor. Solutions of APS, TEMED,

and NIPAAm and water were supplied via inlets (i)(iv), respectively.Four small wavy channels following the inlets were used to increasehydrodynamic resistance in order to stabilize ow and avoid cross-talkbetween the channels. Mixing of reagents occurred in a stepwisemanner: rst, between liquids supplied through inlets 1 and 2 andbetween liquids introduced via inlets 3 and 4, and then, by mergingresulting streams in a T-junction just before the serpentine channel(reaction chamber (v)), where mixing was enhanced and the reactiontook place. The composition of the reaction mixture was characterizedby ATR-FTIR using a probe placed at point P1. A temperature and apH probe were placed at points P2and P3, respectively. The solutionof the polymer product and unreacted reagents were evacuated fromthe MF reactor via outlet (vi). The average height and width of themicrochannels were 50 and 200 m, respectively. The scale bar is 1cm.

Figure 2. (a) Characteristic IR spectra for independent reagentsacquired for the aqueous solutions of (i) APS, (ii) TEMED, (iii)NIPAAm, and (iv) PNIPAAm, collected at QT = 3 mL h

1. Arrowsmark characteristic ngerprintpeaks chosen for subsequent intensitymeasurements. The groups responsible for the characteristic vibrationswere (i) S2O8

2 (1270 cm1), (ii) CN (1020 cm1), (iii) CCH(975 cm1), and (iv) NH (1560 cm1). All spectra were acquired insituby averaging ve spectra, each composed of 32 scans at 10 kHz.(b) Variation in concentration-dependent absorbance of the IR bandsmarked in (a). The inset shows the absorbance of the corresponding

solutions at concentrations below 20 mM.




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After a stabilization time of 5 min, the FTIR spectra wereacquired and the concentration of NIPAAm was determinedfrom the intensity of NIPAAm absorbance peak at 975 cm1byusing eq 4. Following data acquisition, the value of QT waschanged to achieve a new reaction time, without changing theratio betweenCNIPAAm,d,CTEMED,d, and CAPS,d, by modulating allreagent ow rates by the same multiplicative factor. Weexamined the effect of four different reaction times in the rangefrom 2.25 to 6.75 s. The ow rates of all individual reagentstreams are summarized in theSupporting Information, TableS1. The fth data point at t= 0 was acquired by measuring theintensity of the absorption peak of unreacted NIPAAm for themonomer solution at QNIPAAm = 0.235, QTEMED= 0,QAPS= 0,and QH2O = 0.475 (mL h

1), which based on eq 3 yielded

CNIPAAm,d = 175 mM.Table S2 (Supporting Information) summarizes the ow rate

ratios and the corresponding diluted reagent concentrations forevery series of experiments conducted in this work. AsNIPAAm was consumed over the course of polymerization,the variation ofCNIPAAm,tvs tyielded an exponentially decayingcurve (Figure S2, Supporting Information). Such curves were

plotted for various CNIPAAm,d, CTEMED,d, and CAPS,d. Each decaycurve (CNIAAm,t vs t) was t to an exponential decay functionCNIPAAM,t= CNIPAAM,de

bt, whereCNIPAAM,d= 175 mM, and b isthe exponential decay constant (determined from tting). Theinitial rate of decay at t = 0 was acquired by taking thederivative of the decay function with respect to time and settingt= 0 (that is, dM/dt|0= b 175 mM s

1). We converted theinitial rate of decay of the monomer to the initial polymer-ization rate as dM/dt|0= dP/dt|0, where the terms on the leftand right side are the rate of change of the monomerconcentration and the rate of change of the polymerconcentration at t= 0, respectively.

4.4. Determining the Reaction Order of the Reagents.In assuming a steady-state approximation, the rate of freeradical polymerization in the absence of an accelerator speciesis determined as

=

P

tk f

k

kC C

d

d 0p

d

t

1/ 2

APS,d1/ 2

NIPAAm,d(5)

where f is the fraction of initiator radicals reacting with themonomer, and kp, kd, and kt are the rate constants for chainpropagation, initiator decomposition, and chain termination,respectively.22

In the present work, TEMED accelerated the reaction byenhancing decomposition of APS and by forming its ownradical species23 and determined reaction rate as

= P

t

k C C Cd

d

x y z

0APS,d TEMED,d NIPAAm,d

(6)

wherek= kp[f(kd/kt)]1/2.

The equivalent form of eq6 is

= + +

+

P

tx C y C z

C k

ln d

dln( ) ln( )

ln( ) ln

0APS,d TEMED,d

NIPAAm,d (7)

To test the reaction order with respect to a particularreagent, dP/dt|0 was determined for several concentrations ofthe reagent, while the concentrations of the other two reagents

were kept constant. For example, when CAPS,d changed and

CTEMED,dandCNIPAAm,dwere maintained constant, eq7took theform of eq 8a. Similarly, when CTEMED,d or CNIPAAm,d waschanged and the concentrations of two other reagents weremaintained constant, eq 7 took the form of eqs 8b and 8c,respectively.

= +

P

tx C wln

d

dln( ) ln( )a

0APS,d

(8a)

= +

P

ty C wln

d

dln(( ) ln( )b

0TEMED,d

(8b)

= +

P

tz C wln

d

dln( ) ln( )c

0NIPAAm,d

(8c)

wherewa,wb, and wcare constants with the values ln(wa) = lnk+y ln(CTEMED,d) + zln(CNIPAAm,d), ln(wb) = lnk+ xln(CAPS,d)+ z ln(CNIPAAm,d), and ln(wc) = l n k + x ln(CAPS,d) + yln(CTEMED,d). Plotting ln(dP/dt|0) vs ln(C) yields a linear plot

with a slope equal to the reaction order with respect to thereagent with changing concentration.

5. RESULTS AND DISCUSSION

5.1. Effect of Concentration of the Initiator onPolymerization Kinetics. In the rst series of experiments,

we tested the effect of the concentration of the initiator APS,CAPS,d, on the rate of NIPAAm polymerization. Figure3a showsrepresentative overlaid spectra of the NIPAAm double bondpeak for different tduring the polymerization reaction. Thearrow shows that in the time interval 0 t 6.75 s thecharacteristic NIPAAm absorbance peak decreased withreaction time, indicating consumption of the monomer.

Figure 3. (a) Absorbance spectra acquired in the course ofpolymerization of NIPAAm at different reaction times. The rate ofdecay of the peak at 975 cm1 (CCH) of NIPAAm corresponds tothe rate of consumption of the monomer (the rate of polymerization).The arrow indicates the direction of the peak intensity. CNIPAAm,d= 175mM, CTEMED,d= 30 mM, and CAPS,d= 60 mM. (b) Decay curves formonomer absorbance for CAPS,dof 15 (), 30 (), 45 (), and 60() mM. CTEMED,d = 30 mM; CNIPAAm,d = 175 mM. The slopes,acquired at t= 0 from exponential ts, provide the respective initialrates of polymerization, dP/dt|0. (c) A plot of ln(dP/dt|0) vs ln(CAPS,d)generated based on the data shown in (b). All measurements wereconducted three times. Error bars were generated based on thestandard deviation between all three measurements.




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The experiments were conducted at four values of CAPS,d,while other reagentsconcentrations remained unaltered (TableS2,Supporting Information). Figure3b shows the variation inCNIPAAm,tvst. The initial rate of monomer consumption (dM/dt|0) from each curve was determined by tting the decaycurves and determining the initial slope, as discussed in section4.3. Table S3summarizes the tting results for Figure3b. Byusing dM/dt|

0= dP/dt|

0, we plotted ln(dP/dt|

0) vs ln(C

APS,d)

(Figure3c) and determined the slope to be 0.50. On the basisof eq7a, we determined the order of reaction with respect to

APS to be 0.5, as expected for free radical polymerizationreactions.22

5.2. Effect of Concentration of the Accelerator onPolymerization Kinetics. In the next series of experiments,the values of CAPS,d and CNIPAAm,d were maintained at 30 and175 mM, respectively, and the decay curves for monomerconcentration were collected at four values of CTEMED,d. The

value of dP/dt|0 was determined for each monomerconcentration decay curve, as described in section 5.1. Figure4shows the acquired data and the linear t for ln(dP/dt|0) vs

ln(CTEMED,d). By using eq7b, we determined from the slope ofthe plot the order of the reaction with respect to TEMED to be0.38, which indicated that TEMED produces radicals thatparticipate in polymerization ofNIPAAm. This nding was inagreement with previous work.23

5.3. Effect of the Concentration of (Initiator +Accelerator) Complex on Polymerization Kinetics. Wesimultaneously changed the molar concentrations of both APSand TEMED, while keeping their ratio CAPS,d:CTEMED,dat 1:1.The concentration of the initiator + accelerator complex

immediately after dilution (at the entrance of the reactionchamber (v), Figure 1) was denoted as Cm,d. To examine theeffect of the change in Cm,don the polymerization kinetics, werearranged eq7 as

= + +

P

tx C y C wln

d

dln( ) ln( ) ln( )

0m,d m,d d

(9a)

where ln(wd) = ln k + y ln(CTEMED,d). Rearranging eq 9ayielded

= + +

P

tx y C wln

d

d( ) ln( ) ln( )

0m,d d

(9b)

which is the equation of a line with the slope equal to x+y, thesum of the orders of reactions with respect to APS andTEMED. (In the previous sections, we found thatx = 0.50 and

y = 0.38, respectively.) ForCNIPAAm,d = 175 mM, we collecteddecay curves and determined the initial rate of decay for varyingconcentrations ofCm,d(Figure5). A linear t of the data pointsgave a slope of 0.83, which was within 5% of the expected

value of 0.88 from eq9b.

5.4. Effect of Monomer Concentration on Polymer-ization Kinetics. To investigate the effect of monomerconcentration on the polymerization kinetics, we used CAPS,d= CTEMED,d= 30 mM and modulated CNIPAAm,d in the range of90305 mM (Supporting Information, Table S2). The initialrate of decay of the monomer concentration was measured foreach CNIPAAm,d, and a plot of ln(dP/dt) vs ln(CNIPAAm,d) wasgenerated (Figure 6). Using eq8c, we used the slope of the

graph in Figure6 to determine the reaction order with respectto NIPAAm. This method gave us the order of 1.09, withrespect to the monomer, close to 1.00, the order of freeradicalpolymerization reaction with respect to the monomer.24

5.5. Effect of pH on Polymerization Kinetics. Weconducted the polymerization reaction at three different pH

values, in order to monitor changes to polymerization kineticsas a function of pH. To maintain a particular value of pH, weused three buffer solutions at pH 2.23, 7.26, and 9.50. First, weensured that the pH value was maintained at the original value

Figure 4. Variation of ln(dP/dt|0) vs ln(CTEMED,d). CAPS,d = 30 mM;CNIPAAm,d= 175 mM.

Figure 5. Variation of ln(dP/dt|0) vs Cm,d. In all cases the reactionmixture included CNIPAAm,d= 175 mM.

Figure 6. Variation in ln(dP/dt|0) vs ln(CNIPAAm,d). The reactionmixture included CAPS,d= CTEMED,d= 30 mM.




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during the polymerization reaction, by monitoring the pH inreal-time off-chip (bulk) experiments at CNIPAAm,d = 175 mM,CAPS,d = 30 mM, and CTEMED,d = 30 mM. Next, the bufferedreagent solutions were injected into the MF reactor, and theirow rates were adjusted to achieve different reaction times untilthe reaction mixture reached the IR probe. The absorbancepeak of NIPAAm was measured for each reaction time, asdiscussed in section 5.1, and the corresponding C

NIPAAm was

calculated using eq4. Figure7 shows the change inCNIPAAmin

each buffer solution. The initial reaction rates, dP/dt|0, in pH2.23, 7.26, and 9.50 buffer solutions were determined to be2.27, 2.97, and 3.50 M L1 s1, respectively. This trend was inagreement with previously reported increase in dP/dt|0 withincreasing pH of the reaction system.25,26

6. CONCLUSIONS

We demonstrated a systematic, high-throughput study of a

multicomponent polymerization reaction in a MF reactorintegrated with in situ FTIR. The technique was used to studythe kinetics of a free-radical polymerization reaction of N-isopropylacrylamide, which was initiated in water byammonium persulfate in the presence of the accelerator

N,N,N,N-tetramethylethylenediamine. The MF format ofthese studies allowed rapid exploration of the reactionparameter space and thus enabled the determination of thereaction kinetics. The MF study was also used to examine theeffect of pH of the reaction mixture on polymerization kinetics.This work opens the way for the kinetic measurements ofcomplex polymer systems. With the use of feedback control ofprogrammable syringe pumps this work opens the way for fullyautomated on-chip characterization of polymerization reactionsfor optimization of chemical formulations.

ASSOCIATED CONTENT

*S Supporting Information

Design of the MF reactor, residence times in the reactioncompartment achieved at different ow rates, and an IRspectrum of the reaction mixture. This material is available freeof charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION

Notes

The authors declare no competing nancial interest.

ACKNOWLEDGMENTS

The authors thank NSERC Canada (I2I program) and MaRSInnovation (Proof of Principle Program) for nancial supportof this work.

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Figure 7. Variation in CNIPAAm vs time at different pH values of thereaction mixture: 2.23 () , 7 .26 (), 9 .50 (). The initialconcentrations of monomer, initiator, and accelerator were 175, 30,and 30 mM, respectively, for all pH values.


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