www.rsc.org/loc Volume 9 | Number 18 | 21 September 2009 | Pages 2613–2744

ISSN 1473-0197

Miniaturisation for chemistry, physics, biology, & bioengineering

KumachevaM3 reactors for polymer particle synthesis

FrankeSAW-directed droplet flow

Atencia and LocascioMicrofluidic Palette: diffusive gradient generator

Kaehr and ShearDirected bacterial motility

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hip

Pages 2613–2744 1473-0197(2009)9:18;1-S

www.rsc.orgRegistered Charity Number 207890

As featured in:

See Shear et al., Lab Chip, 2009, 9, 2632–2637.

Smooth-swimming E. coli, captured in a three-dimensional protein chamber, direct the orbital rotation of a microsphere (diameter, 5 μm) along a clockwise trajectory.

Title: High-throughput design of microfluidics based on directed bacterial motility.

Featuring work performed in the Shear Lab (Dept. of Chemistry & Biochemistry, University of Texas, Austin, TX 78712) which focuses on characterizing and controlling dynamic biochemical and cellular systems.

www.rsc.org/loc Volume 9 | Number 18 | 21 September 2009 | Pages 2613–2744

ISSN 1473-0197

Miniaturisation for chemistry, physics, biology, & bioengineering

KumachevaM3 reactors for polymer particle synthesis

FrankeSAW-directed droplet flow

Atencia and LocascioMicrofluidic Palette: diffusive gradient generator

Kaehr and ShearDirected bacterial motility

Volum

e 9 | Num

ber 18 | 2009 Lab on a C

hip

Pages 2613–2744 1473-0197(2009)9:18;1-S

www.rsc.orgRegistered Charity Number 207890

As featured in:

See Shear et al., Lab Chip, 2009, 9, 2632–2637.

Smooth-swimming E. coli, captured in a three-dimensional protein chamber, direct the orbital rotation of a microsphere (diameter, 5μm) along a clockwise trajectory.

Title: High-Throughput Design of Microfluidics Based on Directed Bacterial Motility.

Featuring work performed in the Shear Lab (Dept. of Chemistry & Biochemistry, University of Texas, Austin, TX 78712) which focuses on characterizing and controlling dynamic biochemical and cellular systems.

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Pages 2105–2xxx

www.rsc.org/loc Volume 9 | Number 16 | 21 August 2009 | Pages 2253– 2408

ISSN 1473-0197

Miniaturisation for chemistry, physics, biology, & bioengineering

WhitesidesIce nucleation in supercooled water

IsmagilovSlipChip

den ToonderArtificial cilia micro-mixer

Jo and SchwartzStretching DNA molecules

www.rsc.orgRegistered Charity Number 207890

As featured in:

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A tunable particle-sorter for microfluidic applications using time-modulated dielectrophoresis. By pulsing the dielectrophoretic force in time, the order of separation of particles by size can be changed and mid-size particles can be extracted from a heterogeneous population in one step.

Title: Separation of particles by pulsed dielectrophoresis.

Featuring research from Computational Engineering Programme of Singapore-MIT Alliance.

Volume 8 | Number 12 | 2008

Lab on a Chip Pages 1965–2224

www.rsc.org/loc Volume 8 | Number 12 | December 2008 | Pages 1965–2224

ISSN 1473-0197

Miniaturisation for chemistry, biology & bioengineering

1473-0197(2008)8:12;1-3Point-of-care Microf luidic Diagnostics

THEMED ISSUE

www.rsc.orgRegistered Charity Number 207890

As featured in:

See Weitz et al., Lab Chip,2008, 8(12), 2157–2160.

This is a SEM image of the cross-section of a PDMS channel that has been coated with photoreactive sol-gel onto which polyacrylic acid has been grafted. The polyacrylic acid appears as a rough layer on the channel walls. Grafting the polyacrylic acid changes the wettability of the coated channel from a hydrophobic 105 degrees to a hydrophilic 22 degrees. The grafting can also be controlled spatially. This allows high contrast spatial patterning of microchannel wettability.

Title: Photoreactive coating for high-contrast spatial patterning of microfluidic device wettability

Featuring research from the Weitz group at the Department of Physics, Harvard University, USA.

Miniaturisation for chemistry, biology & bioengineering

Point-of-care Microfluidic Diagnostics

THEMEDISSUE

1473-0197(2009)9:16;1-U

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PAPER www.rsc.org/loc | Lab on a Chip

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Multiple modular microfluidic (M3) reactors for the synthesis of polymerparticles†

Wei Li, Jesse Greener,‡ Dan Voicu and Eugenia Kumacheva*

Received 2nd April 2009, Accepted 19th June 2009

First published as an Advance Article on the web 9th July 2009

DOI: 10.1039/b906626h

We report a study of the continuous generation of polymer particles in parallel multiple modular

microfluidic (M3) reactors. Each module consisted of sixteen parallel microfluidic reactors comprising

emulsification and polymerization compartments. We identified and minimized the effects of the

following factors that could result in the broadening of the distribution of sizes of the particles

synthesized in the M3 reactors, in comparison with an individual microfluidic reactor: (i) the fidelity in

the fabrication of multiple microfluidic droplet generators; (ii) the crosstalk between parallel droplet

generators sharing liquid supply sources; and (iii) the coalescence of precursor droplets and/or partly

polymerized polymer particles. Our results show that the M3 reactors can produce polymer microgel

particles with polydispersity not exceeding 5% at a productivity of approximately 50 g/h.

Introduction

Microfluidic emulsification provides the ability to generate

droplets with polydispersity below 5% (and in some cases, below

1%) and enables precise control of droplet shapes, compositions,

and morphologies.1–6 Such droplets have already found appli-

cations in the synthesis of polymer particles7–13 and in compart-

mentalized solution synthesis of inorganic nanoparticles.14–19

Continuous multiphase microfluidic synthesis of polymer

particles includes emulsification of the liquid monomers or

polymers and subsequent on-chip solidification or gelation of the

precursor droplets. The productivity of a microfluidic reactor is

determined by the flow rate of the droplet phase, which in the

synthesis of monodisperse polymer particles generally does not

exceed a fraction of a mL/h. This range of flow rates is sufficient

for exploratory purposes, e.g., for the high-throughput screening

of reaction conditions or the optimization of formulations,20

however in order to compete with conventional technologies for

the production of high value polymer particles, the productivity

of microfluidic synthesis has to be significantly increased. Inte-

gration of multiple parallel microfluidic reactors, which ideally

share a common inlet and outlet, paves the way to producing

larger quantities of particles. The mass of particles, M, produced

in an integrated continuous microfluidic reactor is M ¼ nmt (1)

where n is the number of individual parallel reactors, m is the

productivity of a single microfluidic reactor, g/h, and t is the time

of synthesis, h.

This approach referred to as ‘scaling out’ or ‘numbering up’

proved to be a cost-effective and time-efficient single-phase

Department of Chemistry, University of Toronto, 80 St. George Street,Toronto, Ontario, M5S 3H6, Canada

† Electronic supplementary information (ESI) available: Correlationbetween volume of orifice and volume of droplets, opticalcharacterization system, experiment setup, pictures of a module andeight modules of M3 reactor. See DOI: 10.1039/b906626h

‡ Co-first author, Fax/Tel: 416-978-3576; E-mail: ekumache@chem.utoronto.ca

This journal is ª The Royal Society of Chemistry 2009

synthesis, enabling changes in productivity volume by increasing

or decreasing the number of parallel reactors. After a particular

reaction is optimized, synthesis in parallel reactors is conducted

under the same selected conditions.

The challenge in increasing the productivity of microfluidic

particle synthesis in multiple parallel reactors is in preserving the

narrow distribution of sizes of particles synthesized in a single

reactor.21 Recently, the mass production of polymer particles was

implemented in a monolithic device comprising up to 256 cross-

junction droplet generators. The droplets were solidified off-chip

by photopolymerization in the joint outlet tubing. Further

fractionation was required to narrow the distribution of sizes of

the resulting particles.12,22 A systematic assessment of the feasi-

bility of microfluidic emulsification and particle synthesis in the

‘numbering up’ approach has yet to be reported.

Here we present a comprehensive study of the generation of

polymer particles in a multiple modular microfluidic (M3) reactor

comprising parallel microfluidic droplet generators and poly-

merization compartments. We identified and examined the effect

of the following factors that could potentially result in the

broadening of the distribution of precursor droplets and the

corresponding polymer particles, in comparison with a single

reactor:

(i) Fidelity in the fabrication of multiple microfluidic droplet

generators. Regardless of the mechanism of droplet formation,

their diameter depends on the dimensions of microchannels.23,24

Fabrication of multiple droplet generators with identical

dimensions is a vital requirement in producing monodisperse

precursor droplets with narrow size distribution. In addition,

geometric coupling - the redistribution of liquids between the

channels with different dimensions, which share a single liquid

supply source - results in the broadening of the total droplet size

distribution.25 Our results showed that the variability in the

volumes of droplets generated in paralell flow-focusing droplet

generators correlated with the variation in volumes of orifices

(see ESI†). Thus in order to produce precursor droplets with

narrow size distribution in multiple parallel microfluidic

Lab Chip, 2009, 9, 2715–2721 | 2715

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reactors, it is important to reduce the variations in the dimen-

sions of microchannels;

(ii) ‘‘Crosstalk’’ between parallel droplet generators sharing

a liquid supply source. Parametric coupling is the effect by which

the generation of droplets in one droplet generator affects the

emulsification in the neighboring droplet generators which are

geometrically connected to the first one.26–28 Strong parametric

coupling results in the broadening of the dimensions of droplets

and the corresponding particles;

(iii) Coalescence of precursor droplets and/or polymer particles.

Since the velocity of droplets reduces when they move along the

polymerization compartment,29,30 the probability of their coa-

lescence increases, thereby leading to the broadening of the

distribution of sizes of the resulting particles.

In the present work, we addressed each of the factors described

above for the synthesis of polymer microgel particles in the

integrated M3 reactor with a modular design.

Fig. 1 Schematics of multiple modular microfluidics (M3) reactors.

(a) An individual microfluidic reactor for the synthesis of polymer

particles comprising an emulsification and a polymerization compart-

ments. (b) A module comprising 16 individual microfluidic reactors

connected by symmetric manifold channels. A wavy channel with the

length of 200 mm follows the emulsification compartment. (c) An M3

reactor comprising eight modules.

Experimental design

Fig. 1 illustrates the constituent components and the entire M3

reactor for the continuous synthesis of polymer microspheres.

Each individual reactor contains the emulsification compartment

(a droplet generator) and the polymerization compartment

(Fig. 1a). In the present work, emulsification of an aqueous phase

(water or a solution of N-isopropylacrylamide (NIPAAm)) was

carried out in the flow-focusing droplet generator (FFDG).3 The

solution of NIPAAm (Liquid A) and an oil continuous phase

(Liquid B) were introduced in the central and side channels of the

FFDG, respectively, and forced in the narrow orifice. In the

orifice the thread of liquid A broke up and released droplets. The

droplets of the solution of NIPAAm moved to the polymeriza-

tion compartment (the serpentine channel) where they were

exposed to UV-irradiation to trigger photo-initiated polymeri-

zation of NIPAAm.

Fig. 1b shows an individual module comprising sixteen parallel

individual microfluidic reactors with the design shown in Fig. 1a.

The module was fabricated as described elsewhere31 by sealing

the planar bottom sheet, the intermediate ‘reactor’ sheet con-

taining the relief features of sixteen parallel microfluidic reactors

and an inlet for Liquid B, and the top ‘adapter’ layer with the

inlet for the injection of Liquid A. In the module, the individual

reactors had distinct emulsification and polymerization

compartments but shared inlets A and B and an outlet C. Liquids

A and B were supplied through the inlets A and B, respectively,

and then split in the manifold fashion between the central and the

side channels, respectively, of sixteen individual reactors.

Fig. 1c shows the M3 reactor comprised of eight modules.

Liquids A and B were supplied via eight-outlet adapters to eight

modules using the tubing of identical length. The outlet tubing

from each module had identical length and was linked to the

particle or droplet collector.

Overall, the M3 reactor contained eight modules comprising

128 individual microfluidic reactors. The modular approach

offered several important advantages, in comparison with the

exploitation of a monolithic reactor. First, troubleshooting

associated with component failure caused by e.g., microchannel

clogging, could be accomplished by simple replacement of

a failed module. (The use of a monolithic reactor could require

2716 | Lab Chip, 2009, 9, 2715–2721

decommissioning for cleaning or even complete device re-

construction). Second, the M3 system could be customized by

introducing or removing modules to meet the requirements for

the specific particle production rate. Finally, the fabrication of

modules was easier and more straightforward than the imple-

mentation of a single monolithic device with a large number of

multiple reactors.

Experimental

Materials

Light mineral oil, Span 80, N-isopropylacrylamide (NIPAAm),

N,N0-methylene-bis-acrylamide (BIS), and a photo-initiator

This journal is ª The Royal Society of Chemistry 2009

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2-hydroxy-2-methylpropiophenone (HMPP) were purchased

from Aldrich Canada and used as received. Polydimethylsiloxane

(PDMS) was purchased from Dow Corning Inc. Photoresist SU

8–50 was supplied by Microchem Inc.

Fabrication of modules of M3 reactor

The modules of M3 reactors were fabricated in PDMS by using

the soft lithography method.32 The connection of the inlets and

outlets of the modules with tubing was realized using tubing-to-

chip connectors (Upchurch NanoPort N-333), as described

elsewhere (Chips and Tips, Lab Chip, October 8, 2008). The

masks (Pageworks Inc, Cambridge, MA) were printed with

a resolution of 5080 dpi.

The widths of the orifices of the sixteen FFDGs on the mask

and masters were measured using optical microscopy (Olympus

BX41) coupled with a CCD camera (Evolution–VF). The widths

and heights of the orifices in droplet generators fabricated in

PDMS were determined using an optical profilometer (Veeco NT

1100). The dimensions of a FFDG are provided in the ESI.†

Characterization of emulsification in M3 reactor

To study microfluidic emulsification in the M3 reactor, we used

distilled water or an aqueous 5 wt% solution of NIPAAm as the

droplet phase (injected as Liquid A) and light mineral oil with

4 wt% of surfactant Span 80 (injected as Liquid B).

A custom-made optical characterization system (see ESI†) was

developed to monitor the generation of droplets in eight modules

of the M3 reactor. In the present work, module-level statistics

were determined by image analysis of micrographs (Software

Image-Pro Plus 5.0) of the precursor droplets or particles.

Approximately 400 droplets were analyzed per module and over

3000 droplets were analyzed across the entire M3 reactor,

yielding a mean diameter (dm) and polydispersity or coefficient of

variance (CV) of droplets or particles. The value of CV was

calculated as d/dm � 100% (2), where d is the standard deviation

of droplet diameters.

Fig. 2 A typical three-dimensional (3-D) image of the orifice of a single

FFDG, acquired by an optical profilometer. The blue and red plates

show the bottom and the side walls of the orifice, respectively. W and H

represent the width and height of the orifice, respectively.

Photopolymerization of NIPAAm in a M3 reactor

Following the emulsification of an aqueous monomer solution

comprising 5 wt% NIPAAm, 0.5 wt% of BIS and 0.25% of

photoinitiator HMPP, the droplets moving through the poly-

merization compartment of the reactor were exposed to

UV-radiation (Dr. Honle’s UVA Print 40C, F-lamp, 400 W,

l ¼ 330–380 nm). In order to protect the monomer from

UV-radiation prior to formation of droplets, the inlets and the

emulsification compartments were covered with aluminium foil.

The time of polymerization (determined by the time of residence

of the precursor droplets in the polymerization compartment)

was approximately 15 s. The polymer particles were collected at

the outlet of the reactor and analyzed.

In the control experiment, we performed off-chip batch post-

polymerization. The droplets of the monomer solution were

collected from the outlet C, transferred into a reservoir con-

taining mineral oil mixed with 4 wt% of surfactant Span 80, and

exposed to UV irradiation for 15 s.

This journal is ª The Royal Society of Chemistry 2009

Results and discussion

Fidelity in the fabrication of multiple microfluidic droplet

generators

Since the volume of the orifice in the flow-focusing droplet

generator is a critical parameter determining the dimensions of

droplets (see ESI† and ref. 25 and 33), we assessed the fidelity of

the fabrication of multiple parallel droplet generators by

measuring the variation in the width and the height of the orifices

in successive steps of microfabrication. First, we examined the

change in the average width of the orifice, Wa, in the multiple

16-channel droplet generators in the following steps: printing of

mask / SU-8 master / unsealed PDMS mold / module.

Second, for every microfabrication step, we determined the

maximum difference, DW, between the widths of two orifices in

a 16-channel droplet generator.

Fig. 2 shows a typical image of the orifice of FFDG acquired

by using an optical profilometer. Table 1 shows the variation of

the average width of the orifice, Wa, following consecutive

microfabrication steps, with the target width of the orifice of

85 mm. The value of Wa gradually increased from 85.2 mm (mask)

to ca. 87.5 mm (device) (Table 1). More importantly, the

maximum difference, DW, between the widths of two orifices on

a module, increased in every step of microfabrication, until it

reached 3.3 mm, which was 4.1% of the target width of the orifice.

Furthermore, we examined the variation in the mean orifice

height, Ha, and the maximum difference, DH, between the

heights of two orifices in a 16-FFDG module (Table 1). The

average height, Ha of the orifices changed from 150 mm (master)

to 149 mm (module). The variation in DH in multiple parallel

channels of up to 10–12 mm could be caused by the lack of

alignment of the wafer during the spin-coating process and the

flow of the photoresist from the edge of silicon wafer to the center

of wafer during the curing process. By optimizing the process of

spin-coating of SU-8, we reduced the maximum difference in the

heights, DH, of two orifices in the 16-FFDG module to

Lab Chip, 2009, 9, 2715–2721 | 2717

Table 1 Reproduction of the dimension of orifices in a 16-FFDGmodulea

Fabrication steps Wa (mm) DW (mm) Ha (mm) DH (mm) x (mm)

Mask 85.1 1.3 — — �1SU-8 master 88.2 2.4 150 4.8 �1PDMS mold 87.9 2.6 149 4.5 �1Module 87.5 3.5 149 4.4 �1

a Wa is the average width of sixteen orifices on a module. DW is themaximum difference between the widths of two orifices on a module.Ha is the average height of sixteen orifices on a module. DH is themaximum difference between the heights of two orifices on a module. xis the error of measurements.

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approximately 4.5 mm, that is, to 3.0% of the target height of

150 mm.

‘Crosstalk’ between parallel droplet generators sharing a liquid

supply source

‘Crosstalk’ (or coupling) between parallel microfluidic droplet

generators sharing a common inlet is caused by the hydrody-

namic coupling between the parallel connected streams. Adjacent

droplet generators are affected by variations in pressure in

neighboring microchannels when droplets are formed,26 thereby

broadening the distribution of sizes of the droplets. We decou-

pled the streams of liquids in the neighboring droplet generators

by elongating the hydrodynamic path of the droplet phase prior

to its entrance to the orifice and in this manner, we increased the

hydraulic resistance between the FFDGs.34 In Module 1, an

additional 40 mm-long wavy channel for the droplet phase was

introduced upstream from the orifice in each FFDG. In the

control experiments conducted in Module 2, the droplet phase

was supplied to the orifices via 6 mm-long straight channels.

The geometries of individual FFDG in Module 1 and Module

2 are shown in Fig. 3. To distinguish the effect of coupling from

the broadening of droplet size distribution due to their coales-

cence, we characterized the size of droplets immediately after

their generation in the orifices of FFDGs.

In our experiments, the capillary numbers Ca for water (Caw)

and oil (Cao) were calculated as Ca ¼ mU/g where m is the

Fig. 3 Schematics (not to scale) of an individual FFDG in Module 1

(a) and Module 2 (b). In (a) the droplet phase is supplied to the orifice via

a 40 mm-long serpentine channel. In (b) the droplet phase is supplied to

the orifice via a 6 mm-long straight channel. All other dimensions of the

microchannels in Modules 1 and 2 are identical. The average width and

height of the orifices is 87 and 145 mm, respectively.

2718 | Lab Chip, 2009, 9, 2715–2721

viscosity of the liquid, g is the interfacial tension between the

droplet and continuous phases, and U is the average velocity of

the liquid. For the oil and water phases supplied to the droplet

generator the value of Caw varied from 4.93 � 10�4 to 2.96 �10�3, and the value of Cao varied from 1.48� 10�2 to 8.89� 10�2.

Table 2 shows the results of emulsification of water in two

modules, for the varying flow rates of the droplet and continuous

phases and at constant ratio of flow rates of droplet-to-contin-

uous phases. Unless specified, emulsification occurred in the

dripping mode.24 Several trends are evident in Table 2. First, the

size of droplets generated in both modules decreased with

increasing absolute flow rates of the liquids.9,33 Second, at low

flow rates of the liquids, emulsification conducted in Module 1

yielded droplets with a notably lower value of CV than in

Module 2. This observation was consistent with earlier reports

on stronger parametric coupling occurring at low flow rates.35 At

higher flow rates of the liquids the advantages of the increased

hydrodynamic path in Module 1 diminished and the distribution

of sizes of droplets generated in the two modules became

comparable. Third, for QA > 1 mL/h, a transition to the jetting

regime occurred in Module 2, leading to the broadening in the

distribution of sizes of droplets. Under identical flow conditions

no transition to jetting was observed in Module 1. The difference

in the mechanism of the formation of droplet was caused by the

higher pressure at which the aqueous threads were introduced in

droplet generators in Module 2. Based on the results presented in

Table 2, we conclude that the formation of monodisperse drop-

lets was favored in Module 1, especially when their targeted size

was larger than 100 mm.

Fig. 4a shows a typical snapshot of the emulsification of water

in an individual FFDG of Module 1. Polydispersity of the

droplets generated did not exceed 1.5%. Fig. 4b–d shows the

micrographs of the droplets collected from two, four, and eight

FFDGs connected in a manifold manner. Between the orifice and

the recombination points, the droplets moved in a ‘high-way’

manner: each droplet followed the path of the preceding one.

This trajectory maintained itself beyond the first and second

recombination points (Fig 4b and 4c, respectively), and was

disrupted in the downstream channel collecting droplets from

eighth droplet generators. Polydispersity of the entire population

of droplets collected at the exit of the Module 1 (Fig. 4d) was

below 3%.

Table 2 Mean droplet size (dm) and CV of water droplets generated inModule 1 and Module 2

Flow ratea

(mL/h) Module 1 Module 2

QA QB dm (mm) CV (%) dm (mm) CV (%)

0.2 0.4 122.0 1.6 118.8 5.30.3 0.6 109.3 2.2 107.2 5.00.4 0.8 100.8 2.6 99.7 4.40.5 1 95.1 3.7 94.9 3.80.6 1.2 91.1 4.2 91.2 3.81.2 2.4 85.9 4.7 82.0 5.1b

a The flow rates of QA and QB are given per an individual FFDG.b Formation of droplets in the jetting regime.

This journal is ª The Royal Society of Chemistry 2009

Fig. 4 Emulsification of water in mineral oil mixed with 4% Span 80 in

Module 1. (a) Typical optical microscopy images of droplets generated in

a FFDG of the module. The flow rates of water (QA) and mineral oil (QB)

supplied to the module are 6.4 and 9.6 mL/h, respectively (corresponding

to 0.4 and 0.6 mL/h per individual FFDG, respectively). (b) Typical

optical microscopy images of droplets emerging from two (b), four (c),

and eight (d) FFDGs. The scale bar is 500 mm.

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In the rest of our work, we used M3 reactors comprising eight

modules with the design shown in Fig. 3a.

Fig. 5 (a) Variation in mean diameter, dm (top) and CV (bottom) of

droplets generated in eight modules. The dotted lines represents dm and

CV for the droplets generated in the M3 reactor. Error bars are smaller

than the symbols and are not included. (b) Gaussian distributions

generated by fitting histograms of droplet diameters (plotted with 2 mm

bin) for an individual FFDG (/); an individual module (----), and the M3

reactor (—). QA ¼ 0.45 mL/h; QB ¼ 0.73 mL/h.

Emulsification in an eight-module M3 device

The results of emulsification of water in the M3 reactor con-

taining eight modules are shown in Fig. 5. The performance of

each module within the M3 reactor is summarized in Fig. 5a. The

mean diameter dm of droplets produced in individual modules

varied from 135 to 144 mm, with the coefficient of variance

varying from 1.5 to 4.1%. The average value of dm for the

droplets generated in the M3 reactor was 141 mm and the coef-

ficient of variance was 3.7%. Since 91% of the droplet diameters

fell within 5% of their median size, the precursor droplets were

considered to be monodispersed.21

In Fig. 5b we depicted the Gaussian distributions for the

dimensions of droplets produced in an individual FFDG, in an

individual module, and in the M3 reactor. The full widths at half

maximum of the distribution curve were 4.9, 5.5 and 7.0 mm,

respectively. The broadening in size distribution occurred for

collections of droplets produced from disparate sources.

Polymerization of microgel particles

Next, we conducted continuous on-chip polymerization of

microgel particles by photopolymerizing NIPAAm monomer

compartmentalized in droplets. An aqueous solution of

NIPAAm, a photoinitiator HMPP, and a crosslinking agent BIS

was emulsified in mineral oil containing 4 wt% of Span 80. The

viscosity of the aqueous solution of NIPAAm and interfacial

tension between the monomer solution and oil were 1.25 cP and

2.8 mN/m, respectively. The change in the macroscopic proper-

ties of the droplet phase, in comparison with water, led to the

transition of the emulsification from the dripping mode to the

This journal is ª The Royal Society of Chemistry 2009

jetting regime24 at QA > 0.2 mL/h, thereby increasing the poly-

dispersity of the droplets. To maintain the narrow distribution of

sizes of the precursor droplets and to achieve a high productivity

in particle synthesis, we decreased the average width of the

orifices in the FFDGs from 85 to 45 mm and ensured that the

maximum difference between the volumes of the orifices was

within 5%. All other dimensions of the device remained

unchanged.

Fig. 6a illustrates emulsification of the aqueous solution of

NIPAAm. The average size of the droplets was 94.5 mm at the CV

¼ 1.2%. After emulsification, the droplets moved to the poly-

merization compartment where they were exposed to UV-irra-

diation for 15 s. No clogging was observed in the course of the

2–3 hour-long microfluidic polymerization process. Fig. 6b

shows polyNIPAAm particles. The size of the particle was

80.1 mm, that is, it was smaller than the precursor droplets, due to

the polymerization of NIPAAm. The value of CV of the particles

synthesized in the module increased to 2.9%; hence the narrow

size distribution of the droplets was preserved in the course of

Lab Chip, 2009, 9, 2715–2721 | 2719

Fig. 6 Microfluidic photopolymerization of microgel particles in the M3

reactor. (a) Typical optical microscopy image of aqueous NIPAAm

droplets generated in an individual FFDG of a module of M3 reactor.

(b) Microgel particles following their on-chip polymerization. In a,b the

flow rates of the monomer solution and mineral oil were 0.4 and 0.6 mL/h

per FFDG, respectively. (c) Size distribution of the droplets (dotted

curve) and microgel particles (solid curve). (d) Microgel particles

produced by microfluidic emulsification of an aqueous monomer

solution, followed by their off-chip photopolymerization. The scale bar is

500 mm.

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photopolymerization. The increase in CV resulted from the

reduction in dm (see eqn (2)) and presumably, very limited coa-

lescence of droplets.

The ‘high-way’ motion of the droplets was maintained at

QA < 0.1 mL/h. At higher flow rates (leading to higher produc-

tivity of the reactor), as shown in Fig. 6a, the ‘high-way’ motion

was disrupted, however each droplet was separated from others

with a thin layer of the continuous phase. The productivity of the

reactor was 51.2 mL/h for the eight-module M3 reactor, with

polydispersity of the microgel particle not exceeding 5% (Fig. 6c).

The narrow size distribution of microgel particles was

preserved due to the very limited coalescence of droplets flowing

through the polymerization compartment. The droplets imposed

a minimum pressure upon each other and received approxi-

mately the same amount of UV irradiation. For comparison, we

collected droplets of the monomer solution from the outlet of

a module and photopolymerized them off-chip in the batch

process under 15 s UV-irradiation. We observed substantial

coalescence of the droplets (Fig. 6d).

Summary and outlook

We report continuous synthesis of poly(N-isopropylacrylamide)

microgel particles in the integrated multiple modular micro-

fluidic (M3) reactor. The effects of the variation in the dimensions

of microchannels, the coupling (feed-back) between individual

droplet generators, and coalescence of precursor droplets were

addressed and minimized, in order to produce polymer particles

with narrow size distribution without post-fractionation.

The modular approach described in the present work provides

the ability to clean and replace individual modules, as well as to

alter the productivity of the microfluidic reactor without

2720 | Lab Chip, 2009, 9, 2715–2721

affecting the size of particles. A higher productivity of the reactor

can be achieved by combining a larger number of modules.

In the present study, we used an aqueous monomer solution to

generate microgel particles. In principle, non-polar monomers or

reactive non-polar polymers can be emulsified and polymerized

in the M3 reactor fabricated in the material with suitable

properties, e.g. in cycloolefines or polycarbonates. In such reac-

tors, further increase in productivity can be achieved by using

higher flow rates of the liquids.

Acknowledgements

The authors acknowledge financial support of ONTARIO

RESEARCH COMMERCIALIZATION PROGRAM (ORCP)

and NSERC Canada (I2I program).

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