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Synthesis of high-quality nanoparticles using microfluidic platforms
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Synthesis of high-quality nanoparticles using microfluidic platforms
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Content
Synthesis of High-quality
Nanoparticles Using Microfluidic
Platforms
Carson T. Riche
Doctor of Philosophy (Chemical Engineering)
Principle Investigators: Malancha Gupta and Noah
Malmstadt
Mork Family Department of Chemical Engineering and
Materials Science
University of Southern California, Los Angeles, CA
December 2015
Committee Members
Noah Malmstadt
Malancha Gupta
Richard Brutchey
1
Acknowledgement
I would like to thank all those who have supported me throughout my lifetime and
especially during the past five years of my doctoral studies. Thank you to my family
who have stood by me and did not write me off after moving across the country.
Thank you Allison for all your support and always being there for me. Thank
you to the many people who have had an impact on my academic maturation and
provided advice along the way. Thank you to my labmates for your helpful insights
and making the day-to-day life of a grad student more enjoyable. Finally, thank you
to my advisors Noah and Malancha for providing me with many opportunities and
great mentorship during my tenure at USC.
2
1 Executive Summary
While microfluidic research has been a thoroughly investigated field, there are a
couple key holes that we have investigated and attempted to fill with innovative and
practical solutions. The issues can be grouped into two categores: surface chem-
istry tuning and high throughput scale-up. In general, we address these issues using
initiated chemical vapor deposition to modify device materials and we address the
second issue in the context of the synthesis of noble metal nanoparticles. These
research efforts span and integrate fluid dynamics, surface chemistry modification,
and nanoparticle synthesis. In an academic pursuit of fundamental understanding
of these concepts, we have also developed practical solutions that can be employed
by others to advance the field.
This report begins with chapter 1, a general introduction covering topics that are
not addressed in as much detail in the following chapters. In the following four
chapters, the development, optimization, and execution of microreactor systems is
investigated. In chapter 2, the chemical modification of pre-assembled microflu-
idic devices by initiated chemical vapor deposition, is presented as a robust means
of modifying channels after their fabrication. The technique is expandable to any
device materials and the coating efficacy is demonstrated using two different flow
assays. In chapter 3, the synthesis of gold and silver nanoparticles using an ionic
liquid solvent is discussed. These are only possible because of the surface modifi-
cation to lower the surface energy of the channels and facilitate droplet formation
of the ionic liquid. The ionic liquid solvent system allows gold nanoparticles to be
synthesized at room temperature, contrary to typical synthetic protocols requiring
3
elevated temperatures. The silver nanoparticle synthesis requires a carefully timed
reaction that is achieved by changing the residence time of the reaction droplets.
In chapter 4, a new method to merge droplets is presented. Using a spacer droplet
that is selectively extracted, two bookend droplets merge and their the time be-
tween formation and merger can be tuned using several parameters, spacer droplet
size, spacer composition, or flow rate. In chapter 5, a new geometry for produc-
ing droplets is presented. The three dimensional configuration is possible by the
stereolithography (SLA) process, a 3D printing technology. The droplet generating
geometry is convertible to produce a wide range of droplet volumes, spanning three
orders of magnitude. Droplet size is controlled by the size of the chosen outlet
tubing. When operating at lower capillary numbers, the droplet sizes are indepen-
dent of the flow rate ratio. Incorporating these devices into a parallel network, a
general scheme for scaling-up microfluidic throughput is presented. The synthesis
of platinum nanoparticles, a timed and heat triggered reaction, is performed using
the droplet generating devices. Final remarks are included that examine the current
state of the art and an outlook for future directions.
4
Contents
1 Executive Summary 3
2 Background 17
2.1 Importance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.2 Ionic Liquids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.2.1 History . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.2.2 Environmental Impact . . . . . . . . . . . . . . . . . . . . 19
2.2.3 Solvent Properties . . . . . . . . . . . . . . . . . . . . . . 20
2.3 Microfluidic Technologies . . . . . . . . . . . . . . . . . . . . . . 22
2.4 Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.4.1 Gold Nanoparticle Synthesis . . . . . . . . . . . . . . . . . 23
2.4.2 Optical Properties . . . . . . . . . . . . . . . . . . . . . . . 24
2.5 Vapor Phase Polymerization . . . . . . . . . . . . . . . . . . . . . 25
3 Vapor-phase Coating of Microfluidics 29
3.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . 30
3.2.1 Photo- and Softlithography . . . . . . . . . . . . . . . . . . 30
3.2.2 Vapor Phase Polymerization . . . . . . . . . . . . . . . . . 31
3.2.3 Device Testing . . . . . . . . . . . . . . . . . . . . . . . . 31
3.3 Device Modification . . . . . . . . . . . . . . . . . . . . . . . . . 31
3.4 Varying Coating Composition . . . . . . . . . . . . . . . . . . . . 35
3.5 Coating Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . 37
5
3.6 Measuring Barrier Properties . . . . . . . . . . . . . . . . . . . . . 39
3.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
4 Ionic Liquid Droplet Formation 44
4.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
4.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . 46
4.2.1 Chemicals . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4.2.2 Synthesis of 1-butyl-3-methylimidazolium borohydride
(BMIMBH
4
) . . . . . . . . . . . . . . . . . . . . . . . . 47
4.2.3 Microfluidic Device Fabrication . . . . . . . . . . . . . . . 47
4.2.4 Vapor Phase Polymerization onto Microfluidic Devices . . . 48
4.2.5 Microfluidic Synthesis of Gold Nanoparticles . . . . . . . . 48
4.2.6 Microfluidic Synthesis of Silver Nanoparticles . . . . . . . 49
4.2.7 Batch Synthesis of Gold and Silver Nanoparticles . . . . . . 50
4.3 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . 51
4.3.1 Ionic Liquid Droplet Formation . . . . . . . . . . . . . . . 51
4.3.2 Droplet Mixing . . . . . . . . . . . . . . . . . . . . . . . . 55
4.3.3 Synthesis and Characterization of Gold Nanoparticles . . . 57
4.3.4 Synthesis and Characterization of Silver Nanoparticles . . . 61
4.3.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5 Organic Extraction and Droplet Manipulation 65
5.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
5.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . 68
5.2.1 Photo- and Softlithography . . . . . . . . . . . . . . . . . . 68
6
5.2.2 Vapor Phase Polymerization . . . . . . . . . . . . . . . . . 69
5.2.3 Droplet Formation . . . . . . . . . . . . . . . . . . . . . . 70
5.3 Organic Extraction . . . . . . . . . . . . . . . . . . . . . . . . . . 70
5.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
5.4.1 Fluoropolymer coated droplet formation devices . . . . . . 71
5.4.2 Extraction-induced droplet merger . . . . . . . . . . . . . . 79
5.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
6 Three Dimensional Droplet Formation Exhibiting Flow Invariance for
Parallel Processing 87
6.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
6.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . 89
6.2.1 Device Fabrication . . . . . . . . . . . . . . . . . . . . . . 89
6.2.2 Droplet Visualization . . . . . . . . . . . . . . . . . . . . . 90
6.2.3 Platinum Nanoparticle Synthesis in Microfluidic Device . . 90
6.2.4 Recycling the Ionic Liquid . . . . . . . . . . . . . . . . . . 92
6.2.5 Characterization . . . . . . . . . . . . . . . . . . . . . . . 92
6.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
6.3.1 3D-printed microfluidic droplet generators . . . . . . . . . 92
6.3.2 Flow invariant droplet formation . . . . . . . . . . . . . . . 97
6.3.3 Device parallelization . . . . . . . . . . . . . . . . . . . . 99
6.3.4 PtNP synthesis . . . . . . . . . . . . . . . . . . . . . . . . 102
6.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
7 Conclusions and Outlook 107
7
References 126
8
List of Figures
1 Coordination of the imidazolium cation to the gold surface, with
perpendicular orientation of the alkyl tails. Image taken from
reference
141
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2 SEM images of samples synthesized by microwave heating of
a) 150 mg and b) 100 mg HAuCl
4
in BMIMBF
4
at 200
C and (below) gold structures made by microwave heating in
BMIMTf
2
N. Image taken from reference
126
. . . . . . . . . . . . 21
3 Flow within a droplet within a microchannel showing the folding
pattern that occurs due to the no-slip boundary condition at the
channel walls. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
4 UV-vis absorption spectra for spherical gold nanoparticles (top) and
anisotropic gold nanorods (botom). Image taken from reference
59
. 24
5 Schematic of the iCVD reactor with polymerization shown to occur
on the substrate surface. Image taken from reference
46
. . . . . . . 26
6 (a) The cross-section of the iCVD reaction chamber. (b) A silicon
wafer showing a continuous coating down the length of the channel.
Image taken from reference
127
. . . . . . . . . . . . . . . . . . . . 32
7 SEM micrographs of cross-sections of a microchannel (a) before
and (b) after coating. (c) Poly(PFDA-co-EGDA) film on PDMS,
and (d) poly(PFDA-co-EGDA) deposition within the PDMS
channel. Image taken from reference
127
. . . . . . . . . . . . . . . 34
9
8 FITR absorption spectra for (top) a poly(PFDA) film and then
increasing cross-linker ratios (top-bottom) and finally (bottom) a
poly(EGDA) film. . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
9 Silicon wafers with a deposited poly(PFDA-co-EGDA) coating in
(a) a channel with 200 and 1000 mm wide sections and a height of
200mm, and channels with a constant width of 200mm and heights
of (b) 230 mm, (c) 100 mm, and (d) 50 mm. Image taken from
reference
127
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
10 The Rhodamine B fluorescence intensity was measured at one-hour
intervals over 3 hours. Image taken from reference
127
. . . . . . . . 40
11 Lengths of the hexane droplets were measured at (a) the point
of formation and (b) the end of the channel. Image taken from
reference
127
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
12 Schematic representation of the multiple inlet T-junction microflu-
idic device used to synthesize AuNPs and AgNPs. The carrier oil
was injected via inlet 1 while the reagent streams were introduced
via inlets 2 and 4. A pure BMIMTf
2
N stream was injected via
inlet 3 to prevent diffusive mixing between reagent streams before
droplet formation could occur. The arrow in the channel indicates
the direction of droplet flow. Image taken from reference
78
. . . . . 53
10
13 Phase diagram indicating dependence of droplet formation on the
relationship between carrier oil flow rate and flow rate ratio of the
dispersed phase (DF) and continuous phase (CF). Each panel shows
three time points in the formation and break-off of a single droplet
at the indicated conditions. Dripping regime conditions are outlined
in green, jetting regime conditions in blue, and nondroplet-forming
conditions in red. Image taken from reference
78
. . . . . . . . . . . 54
14 Normalized UV-vis spectra of AuNPs produced on device (black)
and in an analogous batch reaction (red). . . . . . . . . . . . . . . . 59
15 TEM micrographs of AuNPs produced in a) a droplet-based
microfluidic device and b) in an analogous batch reaction. Scale
bars are 50 nm. Histograms of AuNP diameters show that the
nanoparticles produced c) on the device were smaller with a
narrower size distribution compared to d) those produced in batch.
Image taken from reference
78
. . . . . . . . . . . . . . . . . . . . . 60
16 TEM micrographs of AgNPs produced a) in a droplet-based
microfluidic device and b) in an analogous batch reaction. Scale
bars are 50 nm. UV-vis spectra of AgNPs produced on device
(black) and in a batch reaction (red). Image taken from reference
78
. 61
17 UV-vis spectra for AgNPs produced in a batch reaction with
0 (black), 10 (red), 50 (blue), and 80 (pink) equivalents of 1-
methylimidazole added. The narrow band around 350 nm also
increases in intensity with 1-methylimidazole concentration for
reactions performed on device. . . . . . . . . . . . . . . . . . . . . 63
11
18 UV-vis spectra for AgNPs produced in the microfluidic device for
various residence times, 45 s (blue), 90 s (green), and 165 s (red). . . 64
19 (a) Silicon wafers were masked with a PDMS slab imprinted with
the channel pattern, coated with fluoropolymer using iCVD, and the
PDMS was peeled off revealing the polymer coating on the silicon
wafer. (b) Devices made from the same channel patterns were filled
with a solution of crystal violet to elucidate the morphology of the
channel. Scale bars indicate 1 mm. . . . . . . . . . . . . . . . . . . 73
20 (a) Micrographs contrast the droplet formation process in uncoated
(red/dashed outline) and fluoropolymer coated (cyan/solid outline)
channels. The continuous phase flow rate was 10 mL/h and the
channel widths were 200 or 400 mm. (b) Droplet formation was
imaged at a continuous phase flow rate (Qc) of 200 mL/h in coated
channels with a width of 400 mm. Scale bars indicate 200 mm. . . . 74
21 Plot of droplet length as a function of capillary number for different
flow rate ratios as indicated in the legends in channels with inlet and
main channel widths of (a) 50 and 200 mm and (b) 100 and 400 mm. 76
22 The deviation in the size of droplets in coated (cyan) and uncoated
(red) channels during an hour of operation at two different flow rate
ratios and a continuous flow rate of 10 mL/h and various dispersed
phase flow rates (Qd) as indicated in the legend. The deviations are
calculated based on a constant, total mean. . . . . . . . . . . . . . . 78
12
23 (a) Cartoon of the extraction-induced process to merge two aqueous
droplets (navy and yellow) separated by an organic droplet (gray)
within a fluorous phase (blue). (b) Silicon wafers were masked
with a PDMS slab imprinted with the channel pattern, coated with
fluoropolymer using iCVD, and the PDMS was peeled off revealing
the polymer coating on the silicon wafer. (c) Devices made from the
same channel patterns were filled with a solution of crystal violet to
elucidate the morphology of the channel. (d/e) Micrographs of two
different sets of droplets (two dyed aqueous droplets surrounding a
transparent organic droplet). Each set is shown at different stages
in the merger process (1-4). Scale bars represent 400 mm. . . . . . . 81
24 The relation between the time to merge two aqueous droplets and
the length of the organic droplet (a) for different droplet velocities
and an organic phase of dodecane and (b) for different organics at a
constant droplet velocity of 1.7 mm/s. . . . . . . . . . . . . . . . . 83
25 The relation between the time to merge two aqueous droplets and
the length of one of the aqueous droplets for a droplet velocity of
2.0 mm/s. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
26 60 micrographs of droplets produced using PEEK tubing in the
outlet (I.D. = 178 mm). Scale bar represents 500 mm . . . . . . . . 94
27 60 micrographs of droplets produced using PEEK tubing in the
outlet (I.D. = 254 mm). Scale bar represents 500 mm . . . . . . . . 95
28 60 micrographs of droplets produced using PEEK tubing in the
outlet (I.D. = 508 mm). Scale bar represents 500 mm . . . . . . . . 96
13
29 (a) CAD rendering of a droplet generator with two inlets for the
dispersed and continuous phases and a single outlet that accepts
tubing (O.D. = 1/16”) with various I.D.s to control the droplet
size (b) CAD rendering of a droplet generator fully constructed by
stereolithography (c) Micrographs depicting different views of the
device during the droplet breakup process (d) Micrographs of the
droplet breakup process in fully SLA droplet generators with an
outlet size of 250 or 500 mm . . . . . . . . . . . . . . . . . . . . . 98
30 (a) Micrographs of the droplets formed using the six different
sizes of outlet tubing listed (a) Plot of the droplet diameter vs.
fractional droplet number for various outlet tubing sizes. The
solid lines represent the average droplet sizes for a single outlet
size and flow rate ratios of 1:2 and 1:20 (dispersed to continuous
phase - shown as semi-transparent points) (c) Droplet diameter
versus outlet tubing inner diameter for flow rate ratios of 0.05 (left,
diamond) and 0.5 (right, circle) (d) Boxplot of the droplet size
produced droplet generators with the same outlet tubing (I.D. = 254
mm) and different surface chemistries on the channels, as modified
by initiated chemical vapor deposition. . . . . . . . . . . . . . . . . 100
14
31 (a) Schematic of the parallel network assembled by connecting a
distribution manifold to four droplet generators. The continuous
phase was linked using low resistance jumper tubing (I.D. = 762
mm) and the dispersed phase was linked using various lengths of
tubing (I.D. = 127mm) to create a gradient of resistances across the
four branches. (b) Droplet diameters produced by the four branches
of the parallel network (top) by dispersed and continuous phase
flow rates of 10 and 70 mL/h (purple circles) and 30 and 210 mL/h
(black triangles) while operating in and beyond the flow invariant
regime, respectively. . . . . . . . . . . . . . . . . . . . . . . . . . 103
32 Rendering of the device geometry used for the synthesis of platinum
nanoparticles. It contains one inlet for the continuous and two
inlets for the dispersed phases and one outlet. Each port accepts
O.D.=1/16” tubing. . . . . . . . . . . . . . . . . . . . . . . . . . . 103
33 (a) TEM images of PtNPs produced using the microfluidic droplet
generator using new, 1x recycled, and 2x recycled BMIMTf
2
N
ionic liquid. (b) XRD of the PtNPs. (c)
1
H NMR spectra of the
BMIMTf
2
N ionic liquid (*indicates solvent peak), and (d)
19
F
NMR spectra of the BMIMTf
2
N ionic liquid. Scale bars represent
20 nm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
15
34 Top down view of the droplet generating device from Fig. 32. It
is held in place by a custom clamp. The droplet generating device
remains visually unchanged after running the PtNP precursors. The
CAD drawing shows the top-down view of the device. Scale bar is
the same for all images and represents 1 mm. . . . . . . . . . . . . 106
16
2 Background
2.1 Importance
Inorganic nanoparticles on the length scale of 1-100 nm have been used in sens-
ing,
95, 103
energy,
19, 92
imaging,
66, 82, 107
drug delivery,
59, 90
and therapeutic
36, 57, 58
applications. The nanoparticle responses to external stimuli can be carefully tuned
by controlling the size, shape, and composition of the particles. Current fabrica-
tion methods involve volatile solvents whose environmental impact can outweigh
the benefits of the product yield. Ionic liquids (IL) offer an alternative solvent sys-
tem which can aid in controlling size, shape, and stability while eliminating the
need for hazardous solvents or surfactants. The IL solvent can be fully recovered
and reused in subsequent processes. Continuous synthesis methods to produce high
quality nanoparticles, which also reduce harmful by-products and solvent waste,
show promise to transform the nanomanufacturing field with an emphasis on hav-
ing a low environmental impact.
2.2 Ionic Liquids
2.2.1 History
Organic salts with a melting point below 100
C have been formally termed ionic
liquids. Within this class of liquids, those with a melting temperature below 25
C
are referred to as room temperature ionic liquids (RTILs).
153
Hereafter, both chem-
icals will be referred to as ILs, but the ones utilized here generally have melting
points below room temperature. The ‘green chemistry’ classification comes from
the non-volatility of these liquids, in addition to their thermal stability and ease of
17
recycling. The terms ‘liquid salts’ and ‘low melting salts’ have all been used to
refer to ionic liquids. The main advantage of ILs is they require lower working
temperatures compared to traditional molten salts. One example is the popular al-
kali halide eutectic mixture LiCl-KCl (m. p. 355
C), whose uses are limited due to
significant handling and material compatibility issues encountered at high working
temperatures.
In 1914, Paul von Walden investigated the first IL, ethylammonium nitrate ([EtNH
3
][NO
3
],
m. p. 13-14
C).
178
Later, in the 1960s, John Yoke found that mixing two solids,
CuCl and triethylammonium chloride (Et
3
NHCl), resulted in a mixture that was a
liquid at room temperature.
181
This effect is similar to the intermediate in Friedel-
Crafts reactions catalyzed by AlCl
3
. The heptachlorodialuminate salt structure, also
know as the sigma complex, was illuminated later when NMR became a standard
tool for chemists.
In the late 1960’s, the Air Force Academy began to devote resources to the dis-
covery of ILs for use in thermal batteries. A low-melting molten salt would alle-
viate many material incompatibilities previously encountered when working with
traditional high-melting molten salt electrolytes (375 550
C). Thermal batteries
containing the inorganic chloroaluminate NaClAlCl
3
were successfully manufac-
tured. Many more iterations of the chloroaluminate inorganic salts were investi-
gated to achieve lower-melting points and more stable salts. Additionally, theoret-
ical (i.e. Modified Neglect of Differential Overlap) and experimental studies were
conducted to find a cation with a minimal reduction potential, optimal for use in
thermal batteries. This led to the use of dialkylimidazolium cations, specifically
18
1-ethyl-3-methylimidazolium, due to their ease of synthesis and optimal physical,
chemical, and electrochemical properties. While the chloroaluminate anions re-
mained, their use was limited outside of sealed environments due to their water
reactivity that hydrolytically formed HCl. Finally, the discovery of water-stable
anions such as tetrafluoroborate, hexafluorophosphate, as well as nitrate, sulfate,
and acetate salts, resulted in the green solvents we refer to as ionic liquids to-
day. More stable anions have been discovered, including bistrifluoromethylsulfonyl
imide (Tf
2
N
).
2.2.2 Environmental Impact
The green chemistry afforded by using ILs as replacement solvents has been a
highly debated issue. Undeniably, they are superior to traditional solvents due to
their non-volatility and ease of recyclability. However, there are many conflict-
ing studies on the effects that ILs have on the environment when they come into
contact with soil or living organisms. Generally, studies have found that longer
alkyl chains on the dialkylimidazolium cation result in higher cytotoxicity.
122, 158
However, the anion effects are less coherent.
?, 102, 105, 117, 118, 157
To draw distinct
conclusions about the cytotoxicity of various ILs, more stringent testing protocols
need to be used for comparison between studies.
The biodegradability of ILs remains an open question. Drawing conclusions from
the available data is difficult due to the variety of uses, disposal methods, contam-
ination levels and ultimate fate or accumulation in the environment. Many degra-
dation pathways (e.g. oxidation, hydrolysis, and photolysis) depend on the local
environment of the waste products. Preliminary results show that ILs with four car-
19
bon alkyl chains are poorly biodegradable.
30, 133, 156
However, anion effects have
also been shown to have an effect on the overall rate of degradation.
116, 154
There-
fore, both ions need to be accounted for.
2.2.3 Solvent Properties
Before discussing the solvation properties of ILs, it is important to note that they are
difficult to purify. Because ILs cannot be distilled in large quantities, they must be
purified after synthesis using a suitable drying agent in an inert atmosphere. Com-
monly, impurities arise from the starting materials or in the processing steps used to
synthesize the ILs. The general steps for synthesizing the dialkylimidazolium ILs
begin by alkylating the starting material (e.g. 1-methylimidazole) in the absence of
air and water. Then, the newly formed halide salt is precipitated and dried under
vacuum. Finally, the IL is prepared by metathesis of the halide salt with the conju-
gate acid of the anion.
47
At this point, a colored product is indicative of impurities
(e.g. unreacted starting materials) in the IL, which can be removed using activated
charcoal, alumina, or silica.
34
Figure 1: Coordination of the imidazolium
cation to the gold surface, with perpendicular
orientation of the alkyl tails. Image taken
from reference
141
The low coordination observed be-
tween cation and anion moieties fa-
cilitates the characteristic low-melting
temperature. However, ILs have the
ability to stabilize colloidal solutions,
such as nanoparticles. Reagent solu-
bility is difficult to predict apriori but
there are some general guiding princi-
20
ples. Looking at the imidazolium cation, the anion can affect whether the overall
solvent properties are hydrophobic or hydrophillic in nature.
110
The chloride anion
will impart hydrophillic properties. A weakly coordinating anion (e.g. PF
6
, BF
4
,
or Tf
2
N), generally results in hydrophobic properties. The latter are easier to purify
due to their ease of drying.
Figure 2: SEM images of samples synthesized by microwave heating of a) 150 mg and b)
100 mg HAuCl
4
in BMIMBF
4
at 200
C and (below) gold structures made by microwave
heating in BMIMTf
2
N. Image taken from reference
126
The solvation of spherical, gold nanoparticles by imidazolium based ILs provides
a good basis to examine the coordinating geometries. Using surface-enhanced Ra-
man spectroscopy (SERS), researchers found that the dialkylimidazolium ring co-
21
ordinates to the gold surface (Figure 1).
126
Both alkyl chains were absent in the
SERS spectra, indicating they are oriented parallel to the surface normal of the par-
ticle and induce steric hinderance to ripening events. Additionally, there was no
evidence of the MeSO
3
anion on the gold surface. However, other anions (e.g.
BF
4
and PF) were found to coordinate with the surface of metal nanoparticles by
XPS and EXAFS.
39, 134, 145
In an extreme case the anion was shown to affect the
shape of the synthesized gold structures from plates to higher ordered polyhedrons
(Figure 2).
126
2.3 Microfluidic Technologies
Miniaturization via microfluidic technologies offers a higher degree of control over
heat and mass transfer compared to batch scale processing and increase through-
put via their continuous operation. Bench top scale reactions via magnetic stir bar
mixing can require more than 60 s to achieve homogenization.
45
Many reactions
begin or even finish within this time period, resulting in uncontrolled mixing, con-
centration distributions, and residence times. Reduction of the reaction volume will
increase control, but decrease overall throughput.
Figure 3: Flow within a droplet within a
microchannel showing the folding pattern that
occurs due to the no-slip boundary condition
at the channel walls.
Microfluidic flows offer the advan-
tage of continuous operation and scale-
up potential using simple paralleliza-
tion.
132
With the advent of multiphase
microfluidic droplet flows, isolated re-
actions could be carried out in indepen-
22
dent and isolated nano- or picoliter vol-
umes.
164
Since this time, similar devices have been used in nanoparticle synthe-
sis,
175
biophysics,
84
and sensing.
9
The droplet phase (dispersed phase), is emul-
sified within a carrier (continuous phase). Droplet formation can be passively
achieved in a T-junction
85, 138
or flow-focusing geometry.
5, 83
Typically, droplets
fill the width of the channel but are prevented from contacting the channel wall by
a thin lubricating layer of the continuous phase. Each droplet can be composed
of several different solutes and/or solvents.
166
The separate components are mixed
convectively, i.e. the mixing is forced rather than relying on simple diffusion as in
co-flowing streams. Due to the no-slip condition at the interface between the droplet
edge and the channel wall, a recirculating, folding pattern exists within each droplet
to drive mixing, dependent on the flow velocity (Figure 3)
2.4 Nanoparticles
2.4.1 Gold Nanoparticle Synthesis
The growth of gold nanoparticles is hypothesized to proceed via coalescence of
nuclei and repeated monomer attachment. SAXS and XANES were used to study
the in situ nucleation and growth of gold nanoparticles formed by the reduction of
tetrachloroauric acid by trisodium citrate (Turkevich method). It was found that
the coalescence of small nuclei led to a narrow size distribution. The combination
analysis showed particles are formed by the fast nucleation step, followed by coales-
cence of nuclei, and then slow growth via reduction of the gold precursor.
120
Rates
of nucleation and growth have been studied in aqueous environments, but there is
a lack of data on those kinetics in ILs. Generalities have been made, such as the
23
lower interfacial tension of ILs leads to higher rates of particle nucleation.
7
In con-
ventional aqueous syntheses using either the Turkevich
68
or Brust-Schiffrin
91, 136
methods, the nucleation time can vary from 10 s to a minutes depending on the
specific conditions (e.g. pH and reagent concentrations). These rates appear to be
much faster in an IL solvent and likely need to be studied on a sub-second time
scale.
2.4.2 Optical Properties
Figure 4: UV-vis absorption spectra for
spherical gold nanoparticles (top) and
anisotropic gold nanorods (botom). Image
taken from reference
59
Noble metal nanoparticles have the
ability to confine photons within their
conduction band electrons, leading to
unique absorbance properties. When
irradiated with an oscillating electro-
magnetic field of light, conduction band
electrons can undergo a coherent os-
cillation that is resonant with the fre-
quency of the incident light, known as
the surface plasmon resonance. The
resonance is caused by the attrac-
tion of the positive magnetic core to
the electrons, counteracting the oscil-
lation energy of the excitation wave-
length.
For spherical gold nanoparticles, the
24
coherent oscillation of the conduction
band electrons is symmetric about the core of the particle, regardless of orientation.
This results in a single characteristic surface plasmon resonance largely dependent
on the size of the nanoparticle (Figure 4) The specific wavelength is also dependent
on the particle functionalization and surrounding medium. Changes in the shape of
the curve can be generalized to be dependent on polydispersity or aggregation in
the sample. Larger deviations from uniformity lead to wider absorption bands.
In non-spherical particles, there are two modes of oscillation, one transverse (short
axis) and the other longitudinal (long axis) with respect to the rod orientation. The
longitudinal oscillation results in red shifted absorbance as the length of the particle
increases with the width held constant. The absorbance due to this confinement ef-
fect causes an increase in the light intensity proportional to the square of the wave’s
amplitude.
59
2.5 Vapor Phase Polymerization
To develop a robust, PDMS microfluidic platform for synthesizing nanoparticles,
the surface properties of the material need to be modified without affecting the de-
vice fabrication or operation. A vapor phase process is ideal because it does will
not clog the channels or require a post drying/flushing of the device. In coordina-
tion with developing an environmentally friendly platform for nanoparticle synthe-
sis, the modification of these devices can be achieved using a solventless process.
Avoiding volatile organic solvents is both environmentally conscious and compat-
ible with poly(dimethylsiloxane) (PDMS) devices, which swell in the presence of
25
volatile hydrocarbons. Surface modification via vapor deposition of precursors has
existed for decades in the form of chemical vapor deposition (CVD),
155
atomic
layer deposition (ALD),
43
and molecular beam epitaxy (MBE).
42
In recent years,
variations of CVD have been employed to deposit organic polymer thin films using
plasma enhanced CVD (PECVD), photo initiated CVD (PICVD), oxidative CVD
(oCVD), and initiated CVD (iCVD). Using an initiator molecule in iCVD increases
the deposition rate of organic polymers by more than an order of magnitude.
98, 108
The increased rate of conversion of monomer units to polymer chains is achieved
while having negligible amounts of cross-linking and retaining the pendant func-
tional groups. This low energy process (0.01 W/cm
2
) creates highly functional UV-
responsive,
46
low-surface energy,
44
pH-responsive,
75
click-active,
62, 64
and flexi-
ble
179
conformal polymer films.
The iCVD polymerization is an adsorption limited process. Substrates are main-
Figure 5: Schematic of the iCVD reactor with polymerization shown to occur on the
substrate surface. Image taken from reference
46
26
tained at a moderate temperature on a stage that is back-cooled by a recirculating
chiller (Figure 5). Initiator and monomer molecules are vaporized and flown into
a vacuum chamber containing the substrates. Precursors mix in the gas phase, ini-
tiator molecules are thermally cleaved to form free radicals by a resistively heated
filament wire array, and the radicals react with monomer units to initiate the poly-
merization process. Growth of the polymer chains proceeds on the substrate sur-
face, as trimers and longer chains are too large to be vaporized at these modest
temperatures. Polymerization continues via a typical free radical chain mechanism.
Due to the non-solvated polymer chains and lack of mobility, termination by dis-
poroportionation and chain coupling is generally lower than levels seen in solution
phase polymerization. However, due to the high concentration of free radicals typi-
cally present, termination by primary radical termination cannot be neglected.
76, 77
The solventless reaction is ideal to avoid solubility issues of cross-linked polymers
and fluorinated species. PDMS swells in the presence of non-polar organic sol-
vents and it is preferable to modify microchannels post bonding so as to not disturb
the oxidation/condensation chemistry associated with plasma bonding. However,
liquid-phase processing can clog channels or alter the geometry of the channels.
For this reason, a surface polymerization process is ideal to limit modification
to the surfaces of the channels. Modification of pre-assembled microfluidic de-
vices requires the diffusion of precursors into and down the length of the channels.
This is the reason there could be limitations in coating long, serpentine channels.
21
Cross-linked fluoropolymers are one of the most difficult polymers to synthesize in
solution phase due to solubility issues. However, their low-surface energy and neg-
ligible chain mobility are favorable properties for creating non-stick surfaces and
27
barrier coatings.
28
3 Vapor-phase Coating of Microfluidics
This work has been published
127
3.1 Motivation
Microfluidic devices have been successfully applied in cell separations,
35
synthe-
sis,
80
and bioanalysis.
54
Glass, silicon, and thiolene devices are highly inflexible
and require costly and lengthy fabrication.
61, 73, 109
In contrast, inexpensive elas-
tomeric PDMS allows for facile multi-layer fabrication
31
and direct integration of
pumps, valves, and mixers,
?, 163
but its permeability causes swelling in the pres-
ence of organic solvents
8196
and absorption of low-molecular-weight molecules
from flow streams.
167
Eliminating these weaknesses will allow for PDMS devices
to be used in organic synthesis reactions and analytical techniques that require a
fixed concentration of analyte.
101
Previous methods that attempted to modify pre-
assembled channels alter the geometries, require harmful chemicals, and only coat
one device at a time. Paraffin wax
125
and sol-gel coatings
1, 114, 131
are applied by
liquid-phase processing where a solution is flown through the channel and bulk
modification can occur. UV-polymerization requires specific mixtures of neutral
and charged monomers and can lead to gel formation that clogs the channels.
55
Fluorocarbons have optimal material properties for use as a barrier coating. For ex-
ample, fluorinated self-assembled monolayers (SAM) have been used to modify the
surfaces of PDMS slabs.
69, 176
Photocurable perfluoroether,
129
THV ,
11
PTFE,
111
and fluorinated PDMS
15
have been investigated as alternative bulk materials to re-
place PDMS. However, these materials do not have the advantages of PDMS, which
29
is easily fabricated into complex networks and does not require synthesis.
The use of solventless vapor-phase polymerization to apply polymer coatings elim-
inates monomer solubility and solvent compatibility issues typically associated with
liquid-phase polymerization.
98
Vapor-phase deposition of parylene-based and acrylate-
based polymeric coatings has thus far been primarily used to modify planar slabs
of PDMS prior to bonding.
20, 22, 63, 74, 180
3.2 Materials and Methods
3.2.1 Photo- and Softlithography
Standard photolithography techniques were used to create an SU-8 50 photoresist
(MicroChem) mold on a silicon wafer using an emulsion transparency (CAD/Art
Service, Inc.). PDMS channels were fabricated by casting a 2 mm thick layer of
Sylgard 184 (10:1 base/crosslinker ratio) onto the mold and curing in an oven at 65
C for 4 hours. The channel used for the absorption and swelling experiments had
a depth of 450 mm, the channel width at the three-branched inlet was 200 mm, and
the main channel width was 1000 mm. 2 mm diameter holes were punched at the
inlets to the channels. The channels were assembled by treating the slab with the
channel imprint and another 2 mm thick slab of cured PDMS with a corona genera-
tor (Electro-Technic Products, Inc.), bringing them into intimate contact, and curing
in the oven at 65
C for 4 hours.
51
30
3.2.2 Vapor Phase Polymerization
The pre-assembled microfluidic devices were modified in a custom-designed iCVD
chamber (GVD Corporation). The reactor pressure was 125 mTorr, the stage tem-
perature was 35
C, and the filament temperature was 200
C. The initiator di-tert-
butyl peroxide (DTBP) (98%, Sigma), monomer 1H,1H,2H,2H-perfluorodecyl acry-
late (97%, Sigma), and cross-linker ethylene glycol diacrylate (90%, Sigma), were
used as received. Table 1 shows the flow rates of DTBP, PFDA, and EGDA.
3.2.3 Device Testing
A 1 mM solution of Rhodamine B (Alfa Aesar) in water was continuously flown
through the channels at 700 mL h
1
. Fluorescence images were captured each hour
with an 800 ms exposure and the epiflluorescent illumination was turned off be-
tween imaging. The fluorescence intensity at a given distance was plotted as an
average over the length of a 550 mm segment. Hexane droplets were formed in a
continuous aqueous phase (dyed orange), driven by a syringe pump at 9 mL h
1
,
and observed as they flowed down the length of the channel. The length of each
droplet was measured at the T-junction (i.e. the point of droplet formation) and at
the end of the channel. Contact angle goniometry (Rame-hart Model 290-F1) was
used to study the surface energy of the coatings on a reference silicon wafer.
3.3 Device Modification
The pre-assembled PDMS microfluidic devices were fabricated using conventional
photo- and softlithography methods and then modified in a vacuum chamber us-
ing vapor-phase polymerization, specifically iCVD. The iCVD method was used to
31
Figure 6: (a) The cross-section of the iCVD reaction chamber. (b) A silicon wafer showing
a continuous coating down the length of the channel. Image taken from reference
127
simultaneously deposit a continuous fluoropolymer film onto the interior surfaces
of multiple pre-assembled PDMS channels. The processing chamber is depicted in
Figure 6a.
Devices with a multiple-inlet droplet formation geometry were chosen to demon-
strate the utility of the polymer as a barrier coating. The devices contained channels
with widths of either 200 or 1000 mm and a uniform height of 450 mm (Figure 6b).
In the iCVD process, monomer and initiator vapors are introduced into a vacuum
chamber where a heated filament array decomposes the initiator into free radicals.
The free radicals and monomer molecules adsorb onto the surface of a cooled sub-
strate where polymerization occurs via a free radical chain mechanism. Polymer-
ization within a confined geometry requires optimization of the process parameters
32
to achieve a continuous coating throughout the entire device. Monomer and initiator
molecules must diffuse through the channel inlets, down the length of the channel,
and then react on the channel surface. A low operating pressure (125 mTorr) was
required to maximize the mean free path (300-800 mm) of the precursor molecules
to facilitate transport within the channels. Since PDMS is permeable to gases, the
precursor molecules can diffuse into the PDMS before polymerizing. Fluorocar-
bons have a low solubility in PDMS; therefore, the PFDA molecules likely remain
on the PDMS surface and do not diffuse into the bulk.
81
Due to their low molecular
weight, initiator radicals (MW73) can readily diffuse into the PDMS. However,
EGDA (MW170) should diffuse more slowly due to its larger size.
104
An excess
of initiator was used to compensate for the decrease in surface concentration due to
diffusion into the PDMS.
To demonstrate that the polymer film coated the entire luminal surface, a PDMS
slab with the channel imprint was reversibly bonded to a silicon wafer and exposed
to the iCVD process. After the deposition, the slab was peeled off and the re-
sultant coating was a continuous film of poly(PFDA-co-EGDA) in the unmasked
region (Figure 6b). Unlike previous modification techniques that visibly roughen
the channel surface
124
or alter the geometry of the channel,
1, 114, 131
the iCVD tech-
nique creates a transparent film that does not impede optical or fluorescent imaging
inside the channel and does not alter the geometry as seen in the scanning electron
microscopy (SEM) micrographs of the channel cross-section in Figure 7.
SEM micrographs were used to examine the cross section of a channel (200 mm
width, 230 mm height) before and after coating as seen in Figure 7a,b. The coating
33
Figure 7: SEM micrographs of cross-sections of a microchannel (a) before and (b)
after coating. (c) Poly(PFDA-co-EGDA) film on PDMS, and (d) poly(PFDA-co-EGDA)
deposition within the PDMS channel. Image taken from reference
127
clearly does not impede the channel or alter its geometry. Figure 7c shows that the
film is relatively smooth and has a roughness of less than 1 mm. Figure 7d shows
that the coating is continuous in the channel, including at the edges. The micro-
graphs are representative of the entire channel.
34
Table 1: Process conditions and functionality for various coatings (Rhodamine B intensity
measured 20 mm from the channel wall).
Sample
Flow Rate (sccm)
Contact Angle (
) Rhod. B Intensity Hexanes droplet decrease (%)
DTBP PFDA EGDA
A - - - - 1.18 0.06 66 3
B 2.6 0.2 0 120.1 0.5 0.26 0.02 29 3
C1 2.6 0.2 0.7 120.7 0.8 0.00 0.01 1 1
C2 2.6 0.2 1 107.6 0.7 0.11 0.02 5 2
C3 2.6 0.2 1.4 82.7 1.4 0.33 0.06 33 4
C4 2.6 0 0.7 62.3 2.1 - -
3.4 Varying Coating Composition
The iCVD process has the unique advantage of producing films with various cross-
linking densities by modulating the cross-linker flow rate. The cross-linking density
had a significant effect on the performance of the barrier coating. In addition, the
variations in cross-linking density led to differences in the composition of the film
and thus the surface energy that could be observed in contact angle measurements.
The various conditions tested are summarized in Table 1. A homopolymer
poly(EGDA) film had a contact angle of 62:3 2:1
while a homopolymer
poly(PFDA) film had a contact angle of 120:1 0:5
, consistent with previously
reported values.
44
As expected, cross-linked films with various EGDA
concentrations had contact angles within this range, and the contact angle was
inversely proportional to the EGDA concentration. Based on absorption and
swelling studies, an ideal cross-linking density was identified at an EGDA flow rate
of 0.7 sccm (Sample C1). Here, the contact angle of the polymer was 120:7 0:8
,
similar to the homopolymer poly(PFDA) film. To confirm that samples C1-C3
were cross-linked, the solubility of the cross-linked films was compared to the
35
p!
Figure 8: FITR absorption spectra for (top) a poly(PFDA) film and then increasing cross-
linker ratios (top-bottom) and finally (bottom) a poly(EGDA) film.
36
homopolymer films in the fluorinated solvent hexafluoroisopropanol (HFIP). As
expected, the uncross-linked poly(PFDA) films dissolved in HFIP, while the cross-
linked poly(PFDA) films were insoluble in HFIP after soaking for more than a
week. The high contact angle indicates that the fluorinated groups are present in a
higher concentration than the cross-linker molecules at the surface.
100
Fourier transform infrared spectroscopy (FTIR) was used to examine the changing
composition of the films. A higher cross-linker flow rate resulted in a polymer film
with a lower ratio of PFDA:EGDA. This was revealed in the infrared absorption
spectra seen in Figure 8. The sharp peaks in the poly(PFDA) spectra at 1246 and
1207 cm
1
were caused by the asymmetric and symmetric stretching of the -CF
2
-
moiety, respectively. The sharp peak at 1153 cm
1
is caused by the -CF
2
-CF
3
- end
group.
159
The intensity of these peaks clearly decreases as the cross-linker flow rate
increases. Ultimately, the spectra become dominated by the EGDA contribution.
The FTIR spectra show a changing composition and the solubility experiments
prove the films were cross-linked.
3.5 Coating Limitations
Looking at the limits of the coating conditions, we attempted to coat small channels
with poly(PFDA-co-EGDA) using the reaction conditions for Sample C1 described
in Table 1. Devices with the same channel widths as the experimentally tested
device and a decreased height of 200mm are represented in Figure 9a. Additionally,
devices with a channel width of 200 mm throughout the device and channel heights
230, 95, and 50 mm were coated, as pictured in Figure 9b-d. After 40 minutes
37
Figure 9: Silicon wafers with a deposited poly(PFDA-co-EGDA) coating in (a) a channel
with 200 and 1000 mm wide sections and a height of 200 mm, and channels with a constant
width of 200 mm and heights of (b) 230 mm, (c) 100 mm, and (d) 50 mm. Image taken from
reference
127
38
of deposition, there was a continuous film in the unmasked region of the silicon
wafer for heights greater than 50 mm; whereas, there was no coating in the center
of the main channel when the height was 50 mm. Film thicknesses on silicon were
measured by profilometry (Dektak IIA) on at least three separate samples for each
geometry (Table 2).
Table 2: Thicknesses measured by profilometry of the poly(PFDA-co-EGDA) coatings at
different locations of the channels in Figure 9
main channel width (mm) channel height (mm)
film thickness (nm10%)
I II (center) III IV V
(a) 1000 200 350 225 300 310 350
(b) 200 200 150 100 120 150 160
(c) 200 100 130 45 55 65 130
(d) 200 50 100 0 40 60 100
3.6 Measuring Barrier Properties
The ability to use the fluoropolymer coatings to prevent absorption of low-
molecular-weight molecules and resist swelling in the presence of organic solvents
was investigated. Rhodamine B was chosen as the low-molecular-weight molecule
because it has been shown to isotropically diffuse through unmodified PDMS. The
diffusion was tracked by measuring the fluorescence intensity as a function of the
distance from the channel wall (Figure 10). To analyze PDMS swelling, hexane
droplets were injected into a continuous aqueous stream. The change in the size
of the droplets was measured; larger size reductions indicated that more hexane
partitioned into the PDMS (Figure 11).
39
Figure 10: The Rhodamine B fluorescence intensity was measured at one-hour intervals
over 3 hours. Image taken from reference
127
After 3 hours of continuous flow, the fluorescence intensity of Rhodamine B was
measured 20 mm from the wall of the unmodified channel (Sample A) as 1.18
0.06 (a.u.). This compares to a value of 0.26 0.02 for a channel modified with
poly(PFDA) (Sample B). Although the fluorescence intensity decreased, there was
still isotropic diffusion, indicating that Rhodamine B was still partitioning into the
channel walls. The hexane droplet decreased in size by 66 3% and 29 3%
in Samples A and B respectively. Since hexane does not swell the poly(PFDA)
polymer, the reduction in size can be attributed to hexane swelling the PDMS.
140
Cross-linking the PFDA stabilizes the coating by overcoming the weak
40
Figure 11: Lengths of the hexane droplets were measured at (a) the point of formation and
(b) the end of the channel. Image taken from reference
127
cohesive forces that are known to exist between linear chains with fluoroalkyl
moieties.
6, 99, 162
Analysis of Sample C1 showed no significant diffusion of
Rhodamine B into the PDMS after 3 hours and no swelling due to hexane
absorption. The fluorescence intensity 20 m from the channel wall and the
hexane droplet size both remained unchanged to within experimental error. Films
with higher cross-linking densities (Samples C2 and C3) were not as effective at
preventing diffusion and swelling due to the increased concentration of EGDA.
C1 acts as an ideal barrier due to both a molecular sieving effect and its high
fluorocarbon content. Sample C2 outperformed the homopolymer poly(PFDA)
coating, indicating that the benefits of cross-linking outweighed the loss of
fluorocarbon concentration. However, in Sample C3, the EGDA concentration was
too high and the decreased relative fluorocarbon concentration led to loss in barrier
performance. Therefore, there is a trade-off between film stabilization due to cross-
41
linking and solvent exclusion optimized at high fluorocarbon concentrations.
The ability to deposit continuous coatings into smaller devices was investigated
by decreasing the heights and widths of the channels. At the reaction conditions
described in Table 1 for our optimal coating, C1, and a deposition time of 40
minutes, devices with a uniform channel width of 200 mm and a height of 95 mm
were successfully coated throughout, while devices with a height of 50 mm were
not coated at the midpoint of the longest channel. It is important to note that these
smaller channels could be coated using iCVD by changing the reaction conditions
(decreasing the pressure or increasing the deposition time). Under the reported
conditions, the largest length:height aspect ratio at which the interior surfaces of the
channels were uniformly coated was 3.5 cm:95 mm. This is higher than achieved
with previously reported vapor-phase surface modification techniques.
21
3.7 Conclusion
The interior surfaces of multiple pre-assembled PDMS microfluidic devices can
be easily and reproducibly modified inside a single reaction chamber using iCVD.
Through tuning of the reaction parameters, a continuous cross-linked fluoropolymer
barrier coating that enables PDMS to resist absorption and swelling can be achieved
throughout the confined geometry. These barrier coatings will allow the devices to
be used as continuous flow reactors for reaction synthesis.
The coating method described here can be extended to other confined channel
geometries and to a variety of other commercially available vinyl monomers
to achieve a patterned surface,
46
a hydrophillic channel,
14
a thermo-responsive
42
channel,
3, 97
and create a click-active surface.
62
In addition, the approach is not
dependent on the substrate chemistry and can therefore be used to functionalize
other materials commonly used in microfluidic devices including polycarbonate,
silicon, glass, and poly(methyl methacrylate).
43
4 Ionic Liquid Droplet Formation
This work has been published
78
4.1 Motivation
Reactor miniaturization via microfluidic technology has enabled the continuous
flow synthesis of a large number of molecules and nanomaterials.
151
Microfluidic
reactors offer several advantages over traditional batch scale syntheses; namely,
improved heat and mass transport in high surface area-to-volume microchannels,
continuous throughput, superior reaction control, and minimal solvent waste and
by-product generation.
29, 151
These features make microfluidic reactors uniquely
suitable for producing tailor-made nanomaterials in high throughput with high
fidelity.
65, 150, 184
Various continuous-flow configurations have been reported for
the fabrication of metal nanoparticles including cobalt,
147
copper,
149
platinum,
palladium,
137
gold, silver,
175
and core-shell particles.
71
Previously, it has been demonstrated that gold nanoparticles can be synthesized in
a microfluidic reactor by the flow-focused mixing of HAuCl
4
and NaBH
4
in the
ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF
4
).
80
ILs,
such as those based on dialkylimidazolium cations (e.g., BMIM
+
), have shown
promise as dual-function solvents and stabilizing ligands for metal nanoparticles.
They are nonflammable, possess negligible vapor pressures, are chemically stable,
and have low interfacial tensions that can result in high nucleation rates, all of which
make them attractive solvents for nanoparticle synthesis. ILs also have the ability to
stabilize metal nanoparticles as a result of their high ionic charge and high dielectric
44
constant. Moreover, ILs are fully compatible with poly(dimethylsiloxane) (PDMS)
based microfluidic devices, unlike many traditional organic solvents.
81
Water-soluble acidic by-products produced during synthesis can be a challenge
to extract from water-miscible ILs such as BMIMBF
4
. Some evidence also
suggests BF
4
is prone to hydrolysis in the presence of water. For our current
work, we chose 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide
BMIMTf
2
N for the greater stability of the bistrflimide anion compared to
tetrafluoroborate and for its hydrophobicity, making it easier to obtain in purer form.
Substituting 1-butyl-3-methylimidazolium borohydride BMIMBH
4
for NaBH
4
also provides an improved reducing agent solubility in the IL without the possibility
of forming sodium-containing by-products.
Previous work was based on reactions in narrow flow-focused laminar streams
of reactants. Although more controlled than mixing in a macroscale batch
reactor, flow-focused laminar mixing within microchannels is diffusion-limited,
and concentration gradients can lead to polydispersity in nanoparticle syntheses.
One solution to this problem is the use of droplet flows. Droplet flow microfluidic
reactors allow for the generation of discrete droplets that are separated from
one another by an inert, immiscible carrier phase. In this configuration, mixing
within the droplet is rapid and can be precisely controlled, unlike in conventional
macroscale batch reactors where mixing is almost always turbulent and not well-
defined. Droplet flows can eliminate concentration dispersion and maintain a
constant ratio of reagents in all droplets. Convective mixing within these droplets
has been shown to decrease the mixing time by two orders of magnitude as
45
compared to diffusive mixing between co-flowing laminar streams. Despite these
favorable conditions, very few droplet-based syntheses of metal nanoparticles have
been reported to date and until now, small (i.e., <5 nm in diameter), monodisperse
metal nanoparticles have not yet been achieved in droplet microreactors. We have
attempted to fill this niche through the use of an IL microfluidic droplet reactor
4.2 Materials and Methods
4.2.1 Chemicals
Hydrogen tetrachloroaurate(III) hydrate (HAuCl
4
xH
2
O, 99.999%), silver(I)
tetrafluoroborate (AgBF
4
, 98%), sodium borohydride (NaBH
4
, 99%), trioctylamine
(98%), and
1-butyl-3-methylimidazolium bromide (BMIMBr,97%) were purchased from
Sigma-Aldrich. 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide
(BMIMTf
2
N, 99%) was purchased from IOLITEC Inc. (Tuscaloosa, AL).
The as-purchased BMIMTf
2
N was analyzed and found to contain <9 ppm
chloride and <161 ppm water by suppressed ion chromatography and Karl Fischer
titration methods, respectively (Galbraith Laboratories, Inc.; Knoxville, TN). 1-
Methylimidazole (99%) and 1-dodecanethiol (98%) were purchased from Alfa-
Aesar. Inert poly(chlorotrifluoroethylene) oil (Halocarbon 6.3) was purchased from
Halocarbon (River Edge, NJ). All chemicals were used as received without further
purification.
46
4.2.2 Synthesis of 1-butyl-3-methylimidazolium borohydride (BMIMBH
4
)
BMIMBH
4
was synthesized following a literature procedure.
176
Briefly, BMIM-
Br (5.14 g, 23.5 mmol) and NaBH
4
(1.07 g, 28.1 mmol) were stirred in dry
acetonitrile for 24 h at 25
C under an atmosphere of nitrogen. The colorless solution
was separated from the NaBr by-product via annula filtration and then dried in
vacuo to yield the BMIMBH
4
product (3.53 g, 97.4% isolated yield) as a low-
melting solid. The product appears to be stable for long periods of time when
stored under nitrogen.
1
H NMR (500 MHz, DMSO-d
6
, d): 9.15 (s, 1H), 7.78 (s,
1H), 7.71 (s, 1H), 4.17 (t, 2H), 3.85 (s, 3H), 1.80-1.74 (m, 2H), 1.30-1.22 (m, 2H),
0.90 (t, 3H), -0.06-0.55 (BH
4
).
13
C NMR (125 MHz, DMSO-d
6
, d): 136.4, 123.5,
122.2, 48.4, 35.6, 31.2, 18.7, 13.2.
4.2.3 Microfluidic Device Fabrication
Standard photolithography techniques were used to create a SU-8 50 photoresist
(MicroChem) mold on a silicon wafer from an emulsion transparency
mask (CAD/Art Services, Inc.). The completed mold was exposed to
trichloro(1H,1H,2H,2H-perfluorooctyl)silane (Sigma-Aldrich) in a desiccator for
20 min. A 5 mm thick layer of Sylgard
R
184 (10:1 base/cross-linker ratio, Dow
Corning) was cast onto the mold and cured in an oven at 65
C for 4 h. 2 mm holes
were punched at the ends of the channels. The devices were assembled by oxidizing
both the patterned surface and a 5 mm thick slab of blank PDMS with a corona
generator (BD20-AC, Electro-Technic Products, Inc.), pressing the layers together,
and curing the device in an oven at 65
C for 4 h. A typical device measured 2 x
4 cm overall and the channel depth, main channel width, and channel width at the
47
branched inlets were 450, 1000, and 200 mm, respectively.
4.2.4 Vapor Phase Polymerization onto Microfluidic Devices
The pre-assembled microfluidic devices were modified via iCVD in a custom-
designed reaction chamber (GVD Corporation). Monomer and initiator molecules
were continuously flowed into the chamber where a heated wire array thermally
decomposed initiator molecules into free radicals. These radicals and the monomer
molecules diffused into the channels via the channel inlets, adsorbed to the cooled
PDMS surfaces, and polymerized via a free radical chain mechanism. In order to
ensure that the coating penetrated the entire channel, the reactor pressure was kept at
65 mTorr, the stage temperature was kept at 30
C, and the wire filament temperature
was kept at 200
C. The di-tert-butyl peroxide initiator (Sigma-Aldrich, 98%),
1H,1H,2H,2H-perfluorodecyl acrylate monomer (SynQuest, 97%), and ethylene
glycol diacrylate cross-linker (Sigma-Aldrich, 90%) were all used as received. The
flow rates of the three gases were 2.6, 0.2, and 0.7 standard cm
3
min
1
, respectively.
4.2.5 Microfluidic Synthesis of Gold Nanoparticles
Solutions of HAuCl
4
(10 mM), 1-methylimidazole (5 M), and BMIMBH
4
(0.1 M)
were prepared in BMIMTf
2
N with stirring at 25
C. Equal volumes of HAuCl
4
and 1-methylimidazole solutions were thoroughly mixed before being introduced
on device via syringe pump. Syringes and outlet tubing interfaced with the
microfluidic device via PEEK tubing (I.D. = 0.762 mm) and exited the device via
silicon tubing (I.D. = 1.02 mm). Reagent solutions of HAuCl
4
/1-methylimidazole
and BMIMBH
4
were injected through inlets 2 and 4, respectively (Figure 12). A
48
pure BMIMTf
2
N buffer stream was injected between the two reagent streams via
inlet 3. All dispersed phase reagents had a flow rate of 0.5 mL h
1
. The immiscible
carrier oil, PCTFE was injected into the main channel with a flow rate of 10 mL
h
1
via inlet 1. The samples exited the microfluidic device and were collected for
30 min in an empty collection tube (residence time = 60 s) where they separated
into two distinct phases and the oil phase was removed prior to work up. The
AuNPs were precipitated by centrifugation after the addition of ethanol (4 mL). The
colorless supernatant was replaced with fresh ethanol and the mixture was sonicated
for 2 min using a probe sonicator fitted with a microtip at 50% duty cycle (Sonifier
S-450A analog ultrasonic processor, Branson). The AuNPs were again isolated by
centrifugation and finally redispersed in hexanes and 1-dodecanethiol (10-20 mL
mL
1
hexanes) with probe sonication for 1 min.
4.2.6 Microfluidic Synthesis of Silver Nanoparticles
Solutions of AgBF
4
(40 mM), 1-methylimidazole (1.2 M), and BMIMBH
4
(200 mM) were prepared in BMIMTf
2
N with stirring at 25
C. Equal
volumes of AgBF
4
and 1-methylimidazole solutions were thoroughly mixed
before being introduced on device via syringe pump. Reagent solutions of
AgBF
4
/1-methylimidazole and BMIMBH
4
were injected through inlets 2 and
4, respectively. Solutions containing the AgBF
4
were protected from light until
before the reaction. A pure BMIMTf
2
N buffer stream was injected between the
two reagent streams via inlet 3. All dispersed phase inlets had a flow rate of 0.5 mL
h
1
. The immiscible carrier oil was injected into the main channel with a flow rate
of 10 mL h
1
via inlet 1. The AgNPs were isolated by phase transfer whereby the
49
AgNP dispersion in BMIMTf
2
N was collected into an organic phase containing
hexanes (2 mL), ethanol (2 mL), 1-dodecanethiol (50 mL), and trioctylamine (25
mL). The samples were collected for 30 min (residence time = 2 min 45 s) and
the colored organic layer containing AgNPs was transferred to a new centrifuge
tube. The AgNPs were precipitated by centrifugation after the addition of methanol
(3 mL). The colorless supernatant was replaced with ethanol and the mixture was
sonicated for 2 min using a probe sonicator fitted with a microtip at 50% duty cycle.
The AgNPs were again isolated by centrifugation and finally redispersed in hexanes
(1-2 mL) with probe sonication for 1 min.
4.2.7 Batch Synthesis of Gold and Silver Nanoparticles
Solutions of HAuCl
4
(10 mM), 1-methylimidazole (5 M), and BMIMBH
4
(0.1 M)
were prepared in BMIMTf
2
N with stirring at 25
C. Solutions of HAuCl
4
(0.25
mL) and 1-methylimidazole (0.25 mL) were thoroughly mixed. Thereafter, 0.5 mL
of the BMIMBH
4
solution was rapidly injected, resulting in an immediate color
change. After stirring for 1 min the AuNPs were precipitated by centrifugation with
the addition of ethanol (4 mL). The colorless supernatant was replaced with fresh
ethanol and the mixture was sonicated for 2 min using a probe sonicator fitted with
a microtip at 50% duty cycle. The AuNPs were again isolated by centrifugation and
finally redispersed in hexanes and 1-dodecanethiol (10-20 mL mL
1
hexanes) with
probe sonication for 1 min.
For the synthesis of AgNPs, solutions of AgBF
4
(40 mM), 1-methylimidazole (1.2
M), and BMIMBH
4
(200 mM) were prepared in BMIMTf
2
N with stirring
at 25
C. Solutions of AgBF
4
(0.25 mL) and 1-methylimidazole (0.25 mL) in
50
BMIMTf
2
N were thoroughly mixed in the absence of light. Thereafter, a solution
of BMIMBH
4
in BMIMTf
2
N (0.5 mL) was rapidly injected resulting in a
color change after 10 s. The AgNPs were isolated by phase transfer whereby the
AgNP containing hexanes (2 mL), ethanol (2 mL), 1-dodecanethiol (50 mL), and
trioctylamine (25 mL). The colored organic phase containing AgNPs was separated
and the AgNPs precipitated by centrifugation with the addition of methanol (3 mL).
The colorless supernatant was replaced with ethanol and the mixture was sonicated
for 2 min using a probe sonicator fitted with a microtip at 50% duty cycle. The
AgNPs were again isolated by centrifugation and finally redispersed in hexanes (1-
2 mL) with probe sonication for 1 min.
4.3 Results and Discussion
4.3.1 Ionic Liquid Droplet Formation
Two-phase droplet flows offer ideal platforms for performing controlled synthesis
of nanomaterials. The rate of mixing and type of mixing in discrete droplets
separated by an immiscible carrier phase can be systematically tuned by varying
the flow rates of both phases. Breakup of an aqueous phase in a continuous oil
phase has been well characterized; however, studies on the breakup of highly
viscous dispersed phases in microfluidic channels are limited.
40, 164, 165
Stable
droplet formation of the viscous BMIMTf
2
N IL within a continuous fluorocarbon
oil phase, poly(chlorotrifluoroethylene) (PCTFE), was achieved by modifying the
interior surfaces of pre-assembled PDMS devices with a fluoropolymer coating
via iCVD.
127
Briefly, the poly(1H,1H,2H,2H-perfluorodecyl acrylate-co-ethylene
glycol diacrylate) coating is deposited in a vapor phase polymerization process
51
where monomer molecules and initiator radicals polymerize via a free-radical chain
mechanism on the interior surfaces of the pre-assembled channels. Vapor phase
polymerization improves upon previous methods for modifying pre-assembled
channels by allowing for the modification of multiple devices simultaneously
without the possibility of clogging channels, as can occur in liquid-phase
processing. Additionally, the polymer film creates a barrier that completely prevents
hydrophobic recovery due to the low glass transition temperature of PDMS.
185
Coated devices performed with no signs of degradation or delamination for at least
24 h.
The fluoropolymer film allows the PCTFE carrier oil to preferentially wet the
channel walls and provide a thin lubricating layer that prevents the IL droplets from
directly contacting the channel walls. On native PDMS, BMIMTf
2
N has a static
contact angle of 75
, which is well below the experimentally determined limit for
droplet formation. IL droplets do not form at any of the tested flow conditions
in bare PDMS channels. After coating the PDMS with the fluoropolymer film,
the contact angle increases to 110
as a results of the decreased surface energy
of the fluoropolymer film compared to native PDMS. As a result of the complex
interfacial properties of ILs, the contact angle is difficult to predict a priori and
varies significantly for different ILs interacting with PDMS.
The droplet flow of two immiscible fluid phases in a multiple inlet T-junction device
(Figure 12) was characterized to determine the optimal operating conditions for
synthesizing monodisperse nanoparticles. IL solutions of the metal salt precursor
and the reductant were injected via inlets 2 and 4, respectively. To prevent diffuse
52
Figure 12: Schematic representation of the multiple inlet T-junction microfluidic device
used to synthesize AuNPs and AgNPs. The carrier oil was injected via inlet 1 while the
reagent streams were introduced via inlets 2 and 4. A pure BMIMTf
2
N stream was
injected via inlet 3 to prevent diffusive mixing between reagent streams before droplet
formation could occur. The arrow in the channel indicates the direction of droplet flow.
Image taken from reference
78
mixing between reagent streams prior to droplet formation, we injected a pure
BMIMTf
2
N stream between the two reagent streams via inlet 3. Convective
mixing commenced once droplet formation occurred at the intersection of the
dispersed phase and the immiscible oil. A phase diagram, constructed from images
taken under different operating conditions, illustrates the dependence of the droplet
formation process on the PCTFE oil flow rate and the ratio of the reagent flow rate
(dispersed phase) to the oil flow rate (continuous phase) (Figure 13). All flows
were allowed to stabilize and each outlined set of micrographs depicts the breakup
53
Figure 13: Phase diagram indicating dependence of droplet formation on the relationship
between carrier oil flow rate and flow rate ratio of the dispersed phase (DF) and continuous
phase (CF). Each panel shows three time points in the formation and break-off of a single
droplet at the indicated conditions. Dripping regime conditions are outlined in green, jetting
regime conditions in blue, and nondroplet-forming conditions in red. Image taken from
reference
78
process for a single droplet at the indicated conditions. In the dripping regime,
droplet breakup occurs within a channel width of the injection point (outlined in
green).
10
At higher carrier flow rates and higher flow rate ratios (6 mL h
1
and
1/5, respectively), droplets pinch off further downstream at the end of an extended
strand, a phenomenon known as jetting.
54
4.3.2 Droplet Mixing
A combination of convective and diffusive mixing occurs within each droplet. With
jetting, or at even higher flow rates where droplets could not be formed, diffusive
mixing dominates, leading to an inhomogeneous distribution of reagents within
each droplet. This prolongs the nucleation burst and produces more polydisperse
nanoparticles.
148
It is preferable to operate in the dripping regime, where droplets
form at the channel junction and droplet sizes are more controllable and uniform.
24
In this regime, convective mixing - induced by recirculating streamlines caused
by the no-slip boundary conditions at the channel wall - results in fluid layering
within each droplet. Layering effectively reduces the distance over which species
are required to diffuse in order to mix. Decreasing the lengths over which diffusion
occurs leads to more rapid homogenization of reagents in each droplet. The time
scale for diffusive transport is inversely proportional to the diffusivity of the desired
species, and the time scale for convective mixing is inversely proportional to the
velocity of the droplet.
48
Consequently, the dominant form of mixing can be
estimated from the droplet velocity and the diffusivity of droplet species. The self-
diffusion of BMIMTf
2
N is an estimate of the upper limit for diffusivity at 1*10
7
cm
2
s
1
.
130
For this value and our channel geometry, the critical interlayering
velocity (defined as the limit at which convective mixing begins to dominate) would
be below the droplet velocity for all of the flow conditions tested. Also, operating
at the higher PCTFE flow rates would shift mixing further into the convection-
dominated regime. A larger flow rate ratio increases throughput; therefore, we
chose an oil flow rate of 10 mL h
1
and reagent flow rates of 0.5 mL h
1
(total
dispersed phase flow rate = 1.5 mL h
1
). Additionally, conditions were chosen
55
such that the emerging interface filled less than half the width of the main channel
before breaking off into droplets. This avoids significant droplet/wall interaction
as well as perturbations in the flow as shear stress drives droplet formation in this
regime, not pressure accumulating upstream from the emerging droplet.
The size of each droplet was measured a third of the way down the channel for
conditions shown to produce stable droplet formation. Droplet lengths varied
by3% in all cases, indicating that the syringe pumps were operating properly
and syringes were adequately sized. Trends in droplet size correlated well with
those reported for aqueous streams where droplet length was shown to decrease
with increasing capillary number and viscous force.
24
The dimensionless capillary
number (Ca) is a ratio of viscous stress to interfacial tension
Ca=
Vm
g
where m is the viscosity of the dispersed phase, V is the linear velocity, andg is the
interfacial tension.
18
The viscosity of the dispersed phase reaction mixture (39.09
0.65 mPa s for AuNP reagent droplets) was used to calculate Ca since this allows
for future comparison of viscous dispersed phases (i.e. various ionic liquids) with
different viscosities using the same carrier fluid. Altering the precursor solutions
for various syntheses will affect the dispersed phase viscosity. For example, the
AgNP reagent droplets contain less 1-methylimidazole, resulting in a small shift to
a higher viscosity. Overall, the range of stable droplet formation is shifted to higher
values of Ca when compared with the breakup process for aqueous phases. The
jump in droplet size for a flow rate ratio of 1/3 can be attributed to a transition from
56
the dripping to jetting regime, as indicated in the phase diagram. This transition
occurs at Ca 0.02 for a flow rate ratio of 1/3 and at Ca 0.07 for a flow rate
ratio of 1/5. For a given Ca, higher flow rate ratios resulted in larger droplets, as
expected from the droplet growing faster at a higher dispersed phase flow rate.
4.3.3 Synthesis and Characterization of Gold Nanoparticles
Under optimal droplet flow conditions, each of the 3-branched inlet streams had
flow rates of 0.5 mL h
1
, whereas the continuous phase (inlet 1) was injected at
10 mL h
1
. AuNPs were synthesized on device by first preparing BMIMTf
2
N
solutions of the metal salt HAuCl
4
xH
2
O, 1-methylimidazole, and BMIMBH
4
at
the aforementioned concentrations. The BMIMBH
4
reducing agent rapidly forms
a homogeneous solution in BMIMTf
2
N, circumventing solubility issues associ-
ated with NaBH
4
solutions in IL solvents. The HAuCl
4
solutions in BMIMTf
2
N
were thoroughly mixed with an equal volume of 1-methylimidazole solution in
BMIMTf
2
N prior to injection on device via inlet 2 (Figure 12). The addition of
1-methylimidazole was necessary to achieve nonagglomerated nanoparticles with
homogeneous morphologies. A common impurity in ILs, 1-methylimidazole, has
been shown to bind to metal surfaces and can serve as an acid scavenger, prevent-
ing the build up of acidic by-products that may destabilize nanoparticles and pro-
mote aggregation.
27, 123
The BMIMBH
4
solution was introduced via inlet 4 and a
pure BMIMTf
2
N buffer stream was injected via inlet 3 to prevent diffusive mix-
ing between reagents before droplet formation occurred. Synthesized AuNPs were
washed thoroughly with ethanol to remove excess BMIMTf
2
N and BMIMBH
4
and redispersed in hexane and 1-dodecanethiol. For comparison, batch reactions
57
were performed by stirring the above solutions in the same reagent ratios with re-
action times that matched the residence times on device.
The formation of AuNPs was confirmed by the observance of characteristic local-
ized surface plasmon resonances (LSPR) in their absorption spectra as measured on
a dual beam spectrophotometer (Shimadzu UV-1800) using quartz cuvettes with 1
cm path lengths from nanoparticle dispersions in hexane. Red colored suspensions
of AuNPs synthesized on device exhibited relatively narrow LSPR bands centered
at l = 519 nm (FWHM = 172 nm), typical of nonagglomerated, spherical AuNPs
(Figure 14).
41
The AuNPs produced in an analogous batch reaction displayed a
broadened and red-shifted LSPR band centered atl = 523 nm (FWHM = 197 nm),
indicative of larger and more polydisperse nanoparticles. The size, morphology,
and size distribution of resulting nanoparticles were characterized by transmission
electron microscopy (TEM). TEM micrographs were processed in Matlab to an-
alyze nanoparticle size and shape statistics. Nanoparticle diameters were calcu-
lated based on the projected area, in a manner consistent with NIST protocol.
115
Grayscale images were converted to binary images with discrete nanoparticles on
a uniform background, using a consistent thresholding technique for an accurate
comparison of separate samples.
The AuNPs synthesized on device under optimal droplet flow conditions were
spherical and monodisperse with a mean diameter of 4.28 0.84 nm (n = 54,684),
with average major and minor axis lengths of 4.78 and 4.13 nm, respectively
(Figure 15). The nanoparticles exhibited an ellipticity of 1.16, defined as the
major axis length/minor axis length. The AuNPs produced in an analogous batch
58
Figure 14: Normalized UV-vis spectra of AuNPs produced on device (black) and in an
analogous batch reaction (red).
reaction were larger with a mean diameter of 5.52 0.98 nm (n = 57,732)
and average major and minor axis lengths of 6.09 and 5.18 nm, respectively
(Figure 15). The AuNPs produced in the batch reaction possessed an ellipticity
of 1.18. We statistically analyzed the populations of AuNPs synthesized on
device and in batch. A Kolmogorov-Smirnov test
25
revealed the diameters were
not normally distributed all groups (p
device
= 0;p
batch
= 0). Therefore, a non-
parametric Wilcoxon rank sum test
23
was used to demonstrate that the diameters
of the AuNPs produced in batch were significantly larger than the diameters of the
nanoparticles produced on device (z= 196;p= 0). The AuNPs synthesized in batch
59
Figure 15: TEM micrographs of AuNPs produced in a) a droplet-based microfluidic device
and b) in an analogous batch reaction. Scale bars are 50 nm. Histograms of AuNP diameters
show that the nanoparticles produced c) on the device were smaller with a narrower size
distribution compared to d) those produced in batch. Image taken from reference
78
were 29% larger than those produced in the microfluidic device. In addition, the
major and minor axes of the AuNPs produced on device were statistically smaller
than their analogues synthesized in the batch reaction. Fast and efficient mixing
within droplets promotes a short nucleation burst and a more homogeneous reaction
environment, as compared with batch scale mixing with a magnetic stir bar where
homogenization takes more than a minute.
45
60
Figure 16: TEM micrographs of AgNPs produced a) in a droplet-based microfluidic device
and b) in an analogous batch reaction. Scale bars are 50 nm. UV-vis spectra of AgNPs
produced on device (black) and in a batch reaction (red). Image taken from reference
78
4.3.4 Synthesis and Characterization of Silver Nanoparticles
The same general procedure was used to synthesize small AgNPs. The AgNPs pro-
duced on device exhibited distinctive LSPR bands centered at l = 436 nm with
a small shoulder centered at l = 346 nm (Figure 16c).
53
In the analogous batch
reaction, the absorption spectra of the resulting AgNPs is dominated by the band
centered at l = 343 nm, with a less intense, broadened, and slightly blue-shifted
LSPR band centered at l = 431 nm, as compared to the AgNPs made on device. It
is worthwhile to note that for reactions on device and in batch, the absorbance band
observed around 350 nm increased in intensity with increasing 1-methylimidazole
concentration (Figure 17) and the reactions were perceived to slow, as qualitatively
judged by color. The intensity of this peak was also observed to increase with
decreasing residence time on device (Figure 18). This band has previously been at-
tributed to magic-sized silver clusters of different sizes.
70, 89, 106, 183
It is likely that
the absorbance band we observe around 350 nm is similarly due to silver clusters
of less than 10 atoms that serve as intermediates to AgNPs, and that rapid mix-
61
ing in the droplet flow accounts for the differences in the two products achieved
via the microfluidic reaction versus the analogous batch reaction (with identical 1-
methylimidazole concentrations).
The end-result AgNPs synthesized on device have a mean diameter of 3.73 0.77
nm (n = 30;249) with major and minor axis lengths of 4.65 and 3.68 nm, respec-
tively (Figure 16a). Striking differences were observed for AgNPs synthesized in
batch. Whereas well-defined spherical AgNPs were produced on device, the same
conditions in batch produced large coral-like assemblies of very small AgNPs (<2
nm in diameter, Figure 16b). The presence of Moire fringes suggests short-range
order characteristic of nanoparticle superlattices.
?, 121, 146, 186
As in the synthesis of AuNPs, 1-methylimidazole provided an additional stabi-
lization effect that resulted in more uniform nanoparticle morphologies that were
largely nonagglomerated. However, unlike AuNP synthesis, much lower concentra-
tions of 1-methylimidazole were required to achieve well-defined spherical AgNPs.
It is likely that the acidic by-products formed in the reaction of HAuCl
4
xH
2
O ne-
cessitate higher concentrations of an acid-scavenger such as 1-methylimidazole for
stabilization of AuNPs compared to AgNPs.
4.3.5 Conclusion
Small, monodisperse Au and AgNPs were fabricated in an IL solvent using a sim-
ple droplet-based microfludic device. Various flow conditions were analyzed to
determine optimal flow rates for producing droplets whose contents were quickly
homogenized by convection-dominated mixing. Well dispersed spherical nanopar-
62
Figure 17: UV-vis spectra for AgNPs produced in a batch reaction with 0 (black), 10 (red),
50 (blue), and 80 (pink) equivalents of 1-methylimidazole added. The narrow band around
350 nm also increases in intensity with 1-methylimidazole concentration for reactions
performed on device.
ticles were obtained that were smaller and more monodisperse than those produced
in analogous batch reactions as a result of the rapid mixing and the homogeneous
reaction environment afforded by the discrete droplets within an immiscible car-
rier phase. Very few droplet-based microfluidic syntheses of metal nanoparticles
have been reported
33, 111, 152
and Au and AgNPs synthesized in microfluidic reac-
tors using aqueous or organic flows have resulted in nanoparticles that were larger
and more polydisperse or were produced under harsher reaction conditions (e.g.
elevated temperatures).
52, 88, 173, 174
Our work demonstrates that the combination
63
Figure 18: UV-vis spectra for AgNPs produced in the microfluidic device for various
residence times, 45 s (blue), 90 s (green), and 165 s (red).
of fast and controlled microfluidic mixing with IL solvents allows for the synthe-
sis of high-quality, small, monodisperse Au and AgNPs under very benign condi-
tions. This opens the possibility of such platforms being used for nanomanufac-
turing metal nanoparticles using inexpensive, rapid, and reproducible methods that
have minimal impact on the environment.
64
5 Organic Extraction and Droplet Manipulation
This work has been published
128
5.1 Motivation
Fluid flow in microfluidic devices is highly sensitive to the surface chemistry at the
walls of the channels due to characteristically high surface area-to-volume ratios.
Poly(dimethylsiloxane) (PDMS) has been a broadly applied material for microflu-
idic device fabrication due to its ease of mold replication and facile bonding.
4, 31
However, there are several disadvantages to working with PDMS, including its
tendency to swell in many organic solvents, its capacity to absorb low molecular
weight species from flowing streams, and its moderate hydrophobicity.
167
Many
schemes to alter the surface chemistry of PDMS microfluidic devices have been
proposed, but they generally present limitations and challenges that hinder their
widespread adoption. Modifying the PDMS prior to assembling the molded slabs
precludes bonding by silanol condensation
12, 51
and requires subsequent process-
ing to seal the device.
22, 67
Alternatively, coating pre-assembled devices can alter
the cross-sectional geometry of the channels and restrict flow.
2
Methods aimed
at constraining modification to the walls of the channels require pretreatments to
activate the surfaces
55
or UV exposure for photo-initiated reactions.
1, 56
Vapor
phase approaches to surface modification are inherently appealing because they are
adsorption-limited processes that only modify the channel surfaces.
144
Vapor phase
precursors diffuse into the channels, adsorb to the walls of the device, and sub-
sequently react. Pre-assembled channels have been coated with modified poly(p-
xylenes)
21
and we recently demonstrated that initiated chemical vapor deposition
65
(iCVD) can be used to deposit a multi-functional, cross-linked fluoropolymer coat-
ing.
127
This coating acted as a barrier to organic phase permeation into the PDMS
and reduced the surface energy of the channel walls to facilitate droplet breakup of
an ionic liquid phase.
79
In this paper, we have demonstrated that a vapor-deposited fluoropolymer coat-
ing facilitates aqueous droplet formation at a wide range of flow rates and can
be patterned to control the extraction of an organic phase for extraction-induced
droplet merger. Previously, patterned coatings within microfluidic channels had
been achieved by light exposure through masks or using flow patterns within the
device to control the location of surface modification.
1, 22, 38
We exploited the mass
transfer limitations of iCVD polymerization to create a discontinuous pattern within
pre-assembled microchannels without the use of a mask. In our system, reactants
enter the channels through holes at the inlets; therefore, their concentration in the
channel decreases with distance from the inlets until the concentration falls below
the threshold for polymerization.
We considered the formation of droplets in T-junction devices where the dispersed
phase was injected perpendicular to the continuous phase.
139
Previously, the two-
phase flow of immiscible fluids has been characterized as occurring in three regimes:
dripping, jetting, and co-flow.
?, ?, 24, 28
These categories describe droplets that form
at the intersection of the two phases, droplets that form downstream of the inter-
section, and the absence of droplets, respectively. The most stable and predictable
regime is dripping. These regimes have been characterized on the basis of channel
geometry, capillary number, flow rates, and fluid properties.
5, 40, 83, 135, 165, 166, 170, 171
66
The surface energy of channels also affects droplet formation. Given the proper flow
conditions, channels with an advancing water contact angle greater than 92
are ca-
pable of forming water-in-oil droplets due to preferential wetting of the oil phase
on the walls of the channels.
86
The native PDMS surface has a water contact angle
of 112 1
.
12
We decreased the surface energy of the channels by coating them
with the fluoropolymer and increased the water contact angle to 135 3
. The
decreased surface energy extended the range of accessible capillary numbers for
droplet formation, allowing droplets to be formed in the dripping regime at much
higher flow rates than were accessible in uncoated channels.
We also demonstrated that we could pattern the fluoropolymer coating to facili-
tate a new method for the controlled merger of droplets in microfluidic channels:
extraction-induced droplet merger. Droplet microfluidic platforms have been ex-
ploited as miniaturized reactors for synthesis,
49, 79
mixing,
169
and rapid fluid ex-
change.
17
However, these reactors typically produce one-step reaction products.
Multi-step reactions require merging droplets. Previously, droplet merger has been
achieved via pillar-induced droplet hold-up,
113
surface energy mediated droplet
hold-up,
38
and expansion channels to modulate droplet velocities.
16, 60, 160
The
merging within these devices was sensitive to flow rates, droplet sizes, fluid prop-
erties, and channel geometries. Merging times were hard-wired into the geometry
of the devices and could not be easily adjusted by varying the operating parame-
ters. Our method to merge droplets uses an organic droplet as a spacer between
two aqueous droplets. By using diffusion-restricted patterning to apply the fluo-
ropolymer only near the channel inlets, we can facilitate droplet formation there
while allowing for extraction downstream. Many hydrocarbons readily swell the
67
PDMS matrix and partition from flowing streams into the surrounding device.
81, 96
We have shown that coating the channels with a fluoropolymer creates a barrier to
prevent an organic phase from partitioning into the PDMS. However, the organic
spacer is extracted spontaneously in the uncoated downstream region of the chan-
nel, bringing the two aqueous droplets into contact. We can achieve a range of
merging times using a single device geometry by modulating flow rates or chang-
ing the composition of the organic phase. The merging times are insensitive to the
size of the merged droplets.
5.2 Materials and Methods
5.2.1 Photo- and Softlithography
Microfluidic devices were made in poly(dimethylsiloxane) (PDMS) using stan-
dard photolithography and polymer molding procedures. SU-8 50 negative pho-
toresist (MicroChem) was spun onto a silicon wafer (University Wafer) and ex-
posed through a patterned transparency mask (Output City). The unexposed re-
gions were developed and rinsed. The resulting molds were exposed to vapors of
trichloro(1H,1H,2H,2H-perfluorooctyl)silane (Aldrich) to prevent PDMS adhesion.
Subsequently, PDMS was mixed in a 1:10 (curing agent:base elastomer) ratio, de-
gassed, poured over the treated mold, and cured for 4 h at 65
C. A piece of PDMS
was also cured on a blank silicon wafer. Afterwards, both pieces of PDMS were
peeled off their respective wafers and a 2.5 mm diameter punch was used to create
holes in the slab with the channel pattern to form the inlets and outlets. The sur-
faces to be bonded were cleaned with packing tape (3M) and treated with a hand
held corona generator (BD20-AC, Electro-Technic Products, Inc.), and then placed
68
into intimate contact and lightly pressed together. The pre-assembled devices were
cured for 2 h at 65
C.
5.2.2 Vapor Phase Polymerization
Pre-assembled devices were then coated with a poly(1H,1H,2H,2H-perfluorodecyl
acrylate-co-ethylene glycol diacrylate) coating as previously described.14 We used
an initiated chemical vapor deposition process where the pre-assembled devices
were placed on a stainless steel stage that was maintained at 30
C within a pancake-
shaped vacuum chamber (GVD Corp., 250 mm diameter, 48 mm height). The vac-
uum chamber was maintained at 50 mTorr by a throttle valve (MKS Instruments).
Initiatordi-tert butyl peroxide (Sigma)and monomer1H,1H,2H,2H-perfluorodecyl
acrylate (SynQuest) and ethylene glycol diacrylate (Monomer-Polymer)vapors were
flown into the chamber and passed over a nichrome (Omega) wire array heated to
220
C where the thermally labile initiator molecules decomposed into free radi-
cals and the monomer molecules remained stable. The precursors diffused into the
pre-assembled channels via the holes punched at the inlets/outlets of the channels.
Precursor molecules diffused down the channels, adsorbed to the PDMS surface,
and polymerized via a free radical chain mechanism.
44, 144
The reaction was run for
60 minutes and then terminated by turning off the wire array, stopping the flow of
precursors, and pumping out any excess monomer and initiator molecules until the
chamber reached its original base pressure.
69
5.2.3 Droplet Formation
Microfluidic devices with a T-junction geometry were used to form aqueous droplets
within a fluorocarbon oil, poly(chlorotrifluoroethylene) (PCTFE) (Halocarbon). The
fluorinated oil is available in various viscosities; we blended Halocarbon 6.3 with
Halocarbon 95 to create a fluorous phase with a viscosity of 100 mPa*s. For droplet
formation experiments, we used T-junction devices with a 1.5 cm long channel, a
main channel width of 200 or 400 mm, inlet channel widths of either 50 or 100
mm, and channel heights of 400 mm. The PCTFE was injected via the continuous
phase inlet and the aqueous stream was injected via the dispersed phase inlet (Fig.
19b). The other inlets were plugged and the entire device was primed with PCTFE
before starting the aqueous flow. After both the dispersed and continuous phase
flow rates were set, the flow was allowed to stabilize for a few minutes before cap-
turing bright field images. Flow rates were modulated by syringe pumps (Harvard
Apparatus) and interfaced with the device using PEEK tubing (McMaster). Images
of droplets for size analysis were taken on a Nikon TI-E inverted microscope. Over
500 images (18 droplets per image) of discrete droplets were analyzed in Matlab
to determine the droplet lengths at each condition (ESI contains an explanation of
image analysis). High speed images of droplets (Fig. 20b) were captured on a
Phantom V711 camera (Vision Research) at 159250 frames per second with a 1.76
ms exposure time.
5.3 Organic Extraction
Organic phase extraction was performed in serpentine channels with a height of 130
mm and inlet widths of 50 and 400 mm. FC-40 (3M) was injected via the fluorous
70
phase inlet. Dyed aqueous streams were injected via the aqueous inlets and octanol,
dodecane, and hexane were injected via the organic phase inlet (Fig. 5c).
Fluids were injected using a solenoid valve-actuated control system.40 Each liquid
was contained within a reservoir that was connected, at the top, to a back pres-
sure of nitrogen (10 to 15 psi) and, at the bottom, to an inline solenoid valve (Lee).
Nitrogen displaced liquid from the reservoirs. This liquid flowed through LabView-
controlled solenoid valves. Each droplet in a given set of droplets was successively
injected such that the time each valve remained open determined the droplet size.
The FC-40 flow was stopped while the other liquids were injected. New sets of
droplets were not formed until the previous sets had exited the channel. The pres-
sure applied to the FC-40 reservoir determined the flow rate of the droplets. The
velocity was calculated by measuring the displacement of aqueous droplets for each
pressure applied to the fluorous phase. Three separate channels were tested at each
flow condition.
5.4 Results
5.4.1 Fluoropolymer coated droplet formation devices
Two sets of channel dimensions were examined, both with an inlet width to main
channel width ratio of 1:4. These PDMS channels were pre-assembled and then
coated with a fluorinated polymer, poly(1H,1H,2H,2H-perfluorodecyl acrylate-co-
ethylene glycol acrylate), using initiated chemical vapor deposition as previously
described.
127
The contact angle of a water droplet on the polymer film on a silicon
wafer was 120
, matching our previously reported value, which corresponded to
71
a cross-linked barrier film that was impermeable to organics.
127
These T-junction
devices were completely coated with the fluoropolymer. The combination of the
short channel length and the large cross-sectional area of the main channel, along
with the fact that both the inlets and outlets were left open during iCVD, allowed
the precursors to diffuse down the entire length of the channels. This was visualized
by sealing a slab of PDMS with the channel pattern to a silicon wafer, performing
iCVD polymerization, and peeling off the PDMS. This revealed a continuous coat-
ing on the silicon wafer (Fig. 19a). The polymer outline matched that of a device
filled with a solution of crystal violet (Fig. 19b).
Droplets formed better in coated channels than in uncoated channels. Surface en-
ergy and wetting have been shown to play a key role in controlling the conditions
under which droplets can be formed in two-phase flows in microchannels.
86
We
have previously demonstrated that fluoropolymer-coated channels can enable the
formation of droplets of ionic liquid that would otherwise wet the uncoated PDMS
walls. In that case, the static contact angle of the ionic liquid transitions from 75
on
bare PDMS to 110
on the fluoropolymer-coated PDMS, crossing the empirical 92
minimum for droplet formation to occur.
79, 86
In the case of an aqueous dispersed
phase, the static contact angle on PDMS was measured as 112 1
. This increased
to 135 3
on the fluoropolymer on PDMS due to the formation of a rough coat-
ing. The operating regime in which stable droplets formed was greatly extended
by coating the channels. We examined the formation of aqueous droplets (the dis-
persed phase) within an immiscible fluorocarbon oil, poly(chlorotrifluoroethylene)
(PCTFE) (the continuous phase).
72
Figure 19: (a) Silicon wafers were masked with a PDMS slab imprinted with the channel
pattern, coated with fluoropolymer using iCVD, and the PDMS was peeled off revealing
the polymer coating on the silicon wafer. (b) Devices made from the same channel patterns
were filled with a solution of crystal violet to elucidate the morphology of the channel.
Scale bars indicate 1 mm.
In the uncoated channels, at a flow rate ratio (water/oil) of 0.5, droplets formed by
a jetting mechanism where breakup occurred downstream from the intersection of
the dispersed and continuous phases (Fig. 20a, red/dashed outline). In uncoated
channels at a flow rate ratio of 0.05, droplet holdup events occurred where small
droplets, either satellite droplets or pieces of the main droplets, remained pinned
to the surface of the channel. These would then recombine with passing droplets
over time. This transfer of fluid between droplets is a mechanism for droplet cross-
talk which has been described as mass transfer between discrete droplet volumes.
17
The exchange of fluid creates issues when using the droplets as individual reaction
73
Figure 20: (a) Micrographs contrast the droplet formation process in uncoated (red/dashed
outline) and fluoropolymer coated (cyan/solid outline) channels. The continuous phase flow
rate was 10 mL/h and the channel widths were 200 or 400 mm. (b) Droplet formation was
imaged at a continuous phase flow rate (Qc) of 200 mL/h in coated channels with a width
of 400 mm. Scale bars indicate 200 mm.
74
vessels. Droplet formation was more stable in the fluoropolymer coated channels;
droplets formed in the stable dripping regime and we did not observe any droplet
holdup events (Fig. 20a, cyan/solid outline).
Coated devices formed droplets in the stable dripping regime
13, 24, 28
over a wide
range of continuous phase flow rates (0.25 to 200 mL/h) and dispersed-to-continuous-
phase flow rate ratios (0.05 to 2). This full range was achieved in the devices with
a main channel width of 400 mm. The 200 mm devices could not be operated at the
highest flow rates due to mechanical failure of PDMS bonding at high pressures.
In the coated 400 mm channels, aqueous droplets were formed at higher capillary
numbers (Ca1) than previously reported for multi-phase flows in PDMS devices
without surfactant stabilization (Fig. 20b). Typically, the upper limit for the drip-
ping regime is Ca5*10
2
here we report stable droplet formation at Ca of 0.8.
24, 28
At flow rate ratios of both 0.05 and 0.5 and the highest continuous phase flow rate
of 200 mL/h, uniformly sized droplets were formed that assumed a shape conform-
ing to the parabolic velocity profile of the carrier stream (Fig. 20b). The high
flow rate overcame the interfacial tension and deformed the liquid-liquid droplet
interface.
72, 168
The cross-section of these channels was square, allowing droplets
to adopt a more rounded geometry as compared to channels with a low aspect ra-
tio that forces droplets into a compressed, pancake shape. At the flow rate ratio of
0.05, the droplets did not contact the walls of the channel and exhibited a flat edge
on their upstream side. Droplets formed at a flow rate ratio of 0.5 were larger due
to the higher dispersed phase flow rate and their upstream sides were concave.
For Ca<5*10
2
, the size of droplets formed within the coated channels followed
75
Figure 21: Plot of droplet length as a function of capillary number for different flow rate
ratios as indicated in the legends in channels with inlet and main channel widths of (a) 50
and 200 mm and (b) 100 and 400 mm.
76
well studied trends as a function of the capillary number.
24
Droplet size was ap-
proximated by the length of the droplets imaged through the top of the transparent
PDMS. Droplet size could be tuned by changing the flow rate ratio. At a constant
capillary number, the droplet size increased with increasing flow rate ratio. Increas-
ing capillary number resulted in a decreased droplet size for flow rate ratios of 0.05,
0.25 and 0.5 (Fig. 21). At a constant flow rate ratio, the droplet size appeared
to plateau above Ca5*10
2
. Above this threshold, droplet formation remained
in the dripping regime in the coated channels. In the uncoated channels, droplet
formation was observed to transition to the jetting regime above Ca1*10
2
. At
lower capillary numbers in the uncoated channels, droplet formation shifted from
dripping to jetting over time as the dispersed phase began to wet the channel walls.
This transition was not observed in the coated channels.
In the coated channels, we observed that droplet formation was possible at flow rate
ratios of 1 and 2, such that the flow rate of the aqueous phase equaled or surpassed
that of the continuous phase. These droplets appeared stable within the channels
despite the short separation between droplets and without the use of any stabiliz-
ing surfactants. At these higher flow rate ratios, the droplet size increased above
Ca5*10
2
or Ca1*10
2
in the geometries with a main channel width of 200 or
400 mm, respectively. At the higher flow rate ratios and higher capillary numbers,
the size of the continuous phase segments separating the dispersed phase droplets
decreased, resulting in larger droplets. In the uncoated PDMS channel, droplets
were not observed at flow rate ratios of 1 or 2 for any of the capillary numbers we
tested; the two phases were observed as co-flowing streams with no jetting at any
point.
77
Figure 22: The deviation in the size of droplets in coated (cyan) and uncoated (red)
channels during an hour of operation at two different flow rate ratios and a continuous
flow rate of 10 mL/h and various dispersed phase flow rates (Qd) as indicated in the legend.
The deviations are calculated based on a constant, total mean.
As mentioned above, a key benefit of the low surface energy coating was more
stable droplet formation over extended periods of operation. We examined the size
distribution of droplets formed over the duration of an hour in coated and uncoated
channels at two different flow rate ratios (0.05 and 0.25) at a continuous phase flow
rate of 10 mL/h. A comparison at a higher flow rate ratio of 0.5 and continuous
phase flow rate of 10 mL/h was not possible because the uncoated devices did not
78
produce droplets. The distribution of sizes was noticeably wider in the uncoated
channels than in the fluoropolymer-coated devices. Comparing identical flow
conditions, the statistical F-test revealed that the standard deviation of droplet
lengths in the uncoated PDMS channels was larger than the standard deviation of
droplet lengths in the coated channels (p<0.01). This analysis examined the ratio
of variances of droplet sizes in the coated and uncoated channels. We represented
this graphically by plotting the cumulative deviation from the mean versus time
3600
å
t=1
jl
avg
l
t
j
where l is the droplet length (Fig. 22). The mean l was a constant value calculated
based on all droplets observed. We expect some deviation attributable to variation
in the syringe pumps. However, the deviation was larger in the uncoated channels
(red) than in the coated channels (cyan) under identical conditions.
5.4.2 Extraction-induced droplet merger
In addition to facilitating droplet formation, the fluoropolymer coating functioned
as a barrier to control where an organic phase partitioned into the PDMS for extraction-
induced merger of droplets. We utilized serpentine channels that were 40 cm long
with a main channel width of 400 mm, inlet widths of 50 mm, and a channel height
of 130 mm. We patterned the polymeric coating to restrict the fluoropolymer to the
vicinity of the inlets of the channel. To limit polymerization to only this region, the
outlet was sealed with tape. The inlets remained open for precursors to diffuse in
and polymerize on the luminal surfaces. At our operating pressure, the calculated
mean free path of the precursors was on the order of 100 mm. We achieved a pat-
terned coating by exploiting our previous work which showed that a channel with a
79
width of 200 mm and a height of 50 mm, had an extent of coating of approximately
1.5 cm.
127
The extent of coating is defined as the location where the polymer thick-
ness is greater than 10 nm. When a silicon wafer was used to seal the channels,
the extent of coating was observed to extend until the first turn in the channel (Fig.
23b). The combination of the winding channel and the distance from the inlets led
to a concentration gradient of precursors that ultimately decreased to a point below
which a thin film polymer coating could be observed. The full extent of the channel
can be seen when it is filled with a solution of crystal violet (Fig. 23c). Leaving the
outlet uncovered did not change the extent of polymer deposition near the inlets,
indicating that mass transfer of polymer precursors was via diffusion rather than
convective flow through the channel. Near the uncovered outlet, polymer deposited
within the channel. Increasing the deposition time resulted in a thicker polymer
film but it did not significantly change the extent of coating down the channel. This
result was consistent with previous work on vapor deposition of modified poly(p-
xylenes) where the polymer thickness within microchannels increased linearly with
time.
21
In this channel geometry, active control over the input streams was used to con-
trol droplet size. We controlled the size and frequency of droplets independent of
the continuous, fluorous phase flow rate. Thus, we could modulate the size of each
droplet independent of the flow conditions. We used solenoid valve-actuated control
on each stream to form discrete trains of droplets with two aqueous droplets sur-
rounding an organic spacer droplet. This active control of droplet size is useful in
designing reaction schemes because passive formation of droplets by shear breakup
produces a limited range of droplet sizes and frequencies. We merged the two aque-
80
Figure 23: (a) Cartoon of the extraction-induced process to merge two aqueous droplets
(navy and yellow) separated by an organic droplet (gray) within a fluorous phase (blue). (b)
Silicon wafers were masked with a PDMS slab imprinted with the channel pattern, coated
with fluoropolymer using iCVD, and the PDMS was peeled off revealing the polymer
coating on the silicon wafer. (c) Devices made from the same channel patterns were
filled with a solution of crystal violet to elucidate the morphology of the channel. (d/e)
Micrographs of two different sets of droplets (two dyed aqueous droplets surrounding a
transparent organic droplet). Each set is shown at different stages in the merger process
(1-4). Scale bars represent 400 mm.
81
ous droplets by extracting and eliminating the organic droplet (Fig. 23a,d,e). We
utilized an organic (i.e., dodecane, hexane, or octanol) spacer droplet to control the
timing of the merger event. The extraction occurred in the uncoated region of the
channel, downstream from the inlets. Sets of droplets flowed downstream under the
pressure of the fluorous phase. The PCTFE oil used for droplet formation experi-
ments proved inadequate for this work because it was miscible with a wide range
of organics tested. Therefore, we used FC-40 (a tertiary amine with three perflouo-
ralkane substituents) as the fluorous phase. This fluorinated oil was immiscible with
hexane, dodecane, and octanol. The pressure drop across the length of the channel
exerted a force on the organic droplet that drove the organic phase into the walls of
the channel. Typical of low Reynolds number flows in microfluidic channels, the
pressure drop across the channel was proportional to the flow rate.
172
At higher
flow rates, the pressure drop across the device increased and the pressure on the
organic droplet was greater. Therefore, there was a higher driving force for extrac-
tion at high flow rates. For an organic droplet of constant size, the time to merge
the outer aqueous droplets decreased with increasing velocity (Fig. 24a). We tested
four different flow rates resulting in droplet velocities of 1.0 to 2.0 mm/s. The time
to merge two droplets increased as the length of the organic phase droplet increased
for a constant flow rate. This trend was consistently observed for all four flow rates.
In these experiments, the size of the aqueous droplets remained approximately con-
stant.
The composition of the organic droplet also affected the time to merge droplets.
Generally, liquids with a solubility parameter similar to that of PDMS (14.9 MPa
0:5
)
will partition into the PDMS more quickly due to an ability to swell the PDMS to
82
Figure 24: The relation between the time to merge two aqueous droplets and the length of
the organic droplet (a) for different droplet velocities and an organic phase of dodecane and
(b) for different organics at a constant droplet velocity of 1.7 mm/s.
83
a higher degree.
81
We examined three organics: octanol, dodecane, and hexane.
These three liquids form a series with solubility parameters increasingly approach-
ing that of PDMS.
81
As expected, we observed that the merger time for a given
droplet length decreased as the solubility parameter of the organic phase approached
that of PDMS (Fig. 24b). Each droplet train was flowed down the channel at the
same flow rate, thus the same pressure drop existed in all three cases. The droplet
velocity was 1.7 mm/s and the dodecane data is the same as that shown in Fig. 24a.
The PDMS was not saturated with the organic phase during the course of these ex-
periments.
Finally, we showed the merger times in this system were insensitive to the size of
the aqueous droplets. We injected an aqueous droplet of varying length, followed
by an organic droplet of constant length, and finally an aqueous droplet of constant
length. The time to merge the two aqueous droplets depended only on the initial
size of the organic droplet (Fig. 25). We showed various sized droplets merging in
the same channel geometry (Fig. 23d,e). Previous techniques for merging droplets
have relied on decreasing the velocity of a lead droplet to allow a second to catch up
and merge; however, they are sensitive to droplet size and fluid properties.
16, 38, 113
However, in our extraction-induced merging, the merging was only dependent on
the organic phase composition and the flow rate. Neither of these depends on the
properties of the merged droplets.
84
Figure 25: The relation between the time to merge two aqueous droplets and the length of
one of the aqueous droplets for a droplet velocity of 2.0 mm/s.
5.5 Conclusion
We have demonstrated a robust extraction-induced droplet merging technique that
works with a wide range of droplet sizes and flow rates. In contrast to previously
demonstrated methods for droplet merger, our extraction-induced method is not tied
to the device geometry. We patterned a cross-linked fluoropolymer coating using
a solventless, maskless process to facilitate droplet formation. The polymer was
85
deposited near the inlets of serpentine channels while leaving the downstream re-
gion unmodified. The time to merge droplets depended on the composition of the
organic phase and the velocity of the droplets. The organic phase could be changed
to a wide range of fluids because the fluorous phase, FC-40, is immiscible with
various organics. Additionally, the aqueous droplets could be replaced with an-
other liquid phase that is immiscible with both the organic droplet and the fluorous
phase. Extraction-induced merger could be used in translating many multi-step
reactions onto microfluidic platforms. Additionally, in fully coated channels, we
formed droplets at unusually high continuous phase flow rates up to 200 mL/h and
dispersed-to-continuous-phase flow rate ratios up to 1 and 2. This allows for high
density and high frequency droplet generation and greatly increases droplet device
throughput beyond what has previously been demonstrated.
86
6 Three Dimensional Droplet Formation Exhibiting
Flow Invariance for Parallel Processing
6.1 Motivation
Continuous flow microfluidic reactors are powerful tools for synthesizing chemicals
and materials.
79, 80, 112, 142, 143
Microreactors allow for efficient heat transfer, excel-
lent control of local mixing conditions, and provide an ideal format for studying
reaction kinetics on a small scale.
49
Microfluidic systems also offer a clear and ap-
pealing route to scale-up via massively parallel operation. Scaling by parallelization
has clear advantages over traditional scale-up approaches. In contrast to a scale-up
approach that relies on increasing the size of a single batch reactor, scale-up by
parallelization does not change the local reaction conditions in terms of mixing
uniformity and temperature distribution, which are critically sensitive variables for
certain chemistries. For example, the scale up of colloidal inorganic nanoparticle
syntheses to yield kg quantities is difficult to execute in conventional batch reactors
because higher reagent concentrations or increased reaction volumes affect mass
and thermal transport, which in turn affect nucleation and growth, leading to loss
of particle quality and poor process reproducibility.
119
Microfluidic parallelization
can circumvent these issues and enable a simplified and more predictable scale-up
route.
One major challenge in implementing parallel microreactor systems is developing
control and design strategies that guarantee uniform fluidic behavior across an en-
semble of reactors.
26, 50
Here, we address this issue by presenting a fluidic design
87
that allows for geometrically controlled two-phase liquid-in-liquid droplet forma-
tion that is robust to fluctuations in driving pressure and flow rate. Microfluidic
liquid-in-liquid droplets flows are characterized by rapid homogenization of reac-
tants in the droplets.
148
They are therefore ideal for reactions that are sensitive to
concentration gradients and local mixing conditions. Droplets are isolated from
each other and the channel walls to eliminate dispersion effects and prevent device
fouling.
17
The design presented here enables an ensemble of parallel reactors with
consistent droplet formation behavior regardless of inconsistencies in the feed pres-
sure or flow rate across the reactor bank. In contrast, prior attempts at nanoparticle
synthesis scale-up using continuous flow have focused on modifying single channel
devices to employ larger droplets and increased operating flow rates.
93, 182
While
these approaches produce good quality nanoparticles, this strategy cannot be scaled
indefinitely.
An additional advantage of the droplet formation geometry we present here is that it
can be rapidly reconfigured to produce a variety of droplet sizes spanning three or-
ders of magnitude. This range of droplet sizes is used in many applications includ-
ing biomimetic vesicle formation, cell encapsulation, and millifluidic platforms.
94
In traditional T-junction and flow-focusing droplet formation devices, the operating
parameters (i.e. flow rates) allow for a relatively narrow range of droplet sizes to
be accessed by a single device geometry.
161
Switching to a different droplet size
regime requires redesigning (and refabricating) the device. In the device geometry
we present here, droplet size is set by the diameter of an easily interchangeable out-
let component. Different droplet sizes are accessible by swapping out this modular
component. This control mechanism is in contrast to upstream geometrical con-
88
trol exhibited in planar droplet formation devices where the inlet geometry governs
droplet size. Coupled with the relative insensitivity of droplet formation to flow
rates, this design represents an important innovation in microfluidic droplet forma-
tion.
In addition to demonstrating the robust operation of this droplet formation geometry
in a parallel system, we show it operating as the key element of a droplet
microreactor applied to the synthesis of metal nanoparticles. In this paper, we
demonstrate the first platinum nanoparticle (PtNP) synthesis using a continuous
flow droplet microreactor. A key aspect of our continuous flow synthesis is the use
of ionic liquid droplets as the dispersed phase and reaction medium. Ionic liquids
are gaining interest as solvents for precious metal nanoparticle synthesis because
of their ability to colloidally stabilize nanoparticles and induce high nucleation
rates resulting in more monodisperse nanoparticle ensembles.
32
This, coupled with
their environmental health, safety, and sustainability advantages over volatile and
flammable organic solvents,
177
makes ionic liquids promising solvents for large
scale nanofabrication reactions. Herein, the synthesis of PtNPs is performed in
ionic liquid droplets that are successfully recycled and reused to produce PtNPs
over multiple runs in high fidelity.
6.2 Materials and Methods
6.2.1 Device Fabrication
Microfluidic chips were designed in ProEngineer, exported as sterolithography files,
and printed in Somos Watershed XC 11122 by FineLine Prototyping using high res-
olution stereolithographic printing technology. Devices were used as received. Inlet
89
and outlets interfaced with O.D.=1/16” tubing. The channel dimensions are defined
in 29b. The height of the channel was 1 mm, inlet and outlet holes were 1.59 mm
in diameter, the length of the main channel was 5 mm, and the width of the main
channel was 4 mm.
6.2.2 Droplet Visualization
Water-in-oil droplets were formed using an aqueous phase of Fe(SCN)
x
(3x)+
com-
plexes in deionized water, prepared by mixing 0.2 M KSCN (Sigma) with 0.067
M Fe(NO
3
)
3
9H
2
O (Sigma) in a 1:1 volumetric ratio. The oil phase was 1% w/v
Span80 (Sigma) in hexanes (Sigma). Fluids were driven by syringe pumps (Har-
vard Apparatus). Droplets were collected in a glass bottom petri dish (MatTex)
containing 1 mL of the 1% w/v Span80 in hexanes solution and imaged on an in-
verted Zeiss microscope using a 20x objective. At least 60 images of the collected
droplets were captured for each flow condition. Droplet sizes were analyzed using
custom image processing code in Matlab, primarily using the imfindcircles func-
tion.
Droplet formation was monitored in-situ using a Phantom V711 camera (Vision Re-
search). Images were captured at 4000 frames per second with a 240 ms exposure.
6.2.3 Platinum Nanoparticle Synthesis in Microfluidic Device
Potassium tetrachloroplatinate(II) (K
2
PtCl
4
, 99.%); Strem), poly(vinylpyrrolidone)
(PVP, MW = 55,000; Aldrich), ethylene glycol (99.8%; Sigma Aldrich), and 1-
butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMIMTf
2
N, 99%;
IoLiTec Lot K00219.1.4.) were used as received. In a typical procedure, K
2
PtCl
4
90
(39.0 mg) was added to ethylene glycol (2.5 mL) in a 23 mL vial and bath soni-
cated until dissolved, affording a brown-red mixture. Separately, PVP (213.1 mg)
was dissolved in BMIMTf
2
N (7.5 mL) by heating at 130
C for 10 min to give a
clear solution.
Platinum nanoparticles (PtNPs) were synthesized using our 3D droplet forming de-
vice by modifying the original design to incorporate three inlets (Supplementary
Fig. S1). Two inlets supplied the K
2
PtCl
4
in ethylene glycol at 2.5 mL/h and the
PVP in BMIMTf
2
N at 7.5 mL/h. The third inlet supplied a continuous phase of
FC-40 (Sigma) at 20 mL/h. The outlet PEEK (I.D. = 0.03 mm) fed into 50 feet
of perfluoroalkoxy (PFA) tubing (McMaster-Carr) that was placed in a convection
oven set to 150
C. The effluent was collected into a receiving flask cooled in an ice
bath to quench the reaction.
The PtNPs were transferred to two 50-mL centrifuge tubes and precipitated with
acetone (30 mL) to afford a black suspension, which was briefly vortex stirred ( 1
min), bath sonicated (3 min), and collected by centrifugation (6,000 rpm; 5 min).
The colorless supernatant was decanted and saved in order to wash the ionic liquid
for further syntheses. The black nanoparticulate solid was redispersed in ethanol
(10 mL), bath sonicated (3 min), precipitated with hexanes (30 mL), and centrifuged
(6,000 rpm; 5 min). This process was repeated 3x in order to remove any residual
organics (i.e., PVP, BMIMTf
2
N, ethylene glycol). The purified PtNPs were re-
dispersed in ethanol (5 mL) and remained colloidally stable for at least five months.
91
6.2.4 Recycling the Ionic Liquid
Equal amounts of hexanes, with respect to the ionic liquid, were added and vor-
texed before centrifugation (6,000 rpm; 10 min). Upon phase separation, the hex-
anes layer was removed and additional hexanes were added; this was repeated three
times. The ionic liquid was then heated under vacuum at 125
C for ca. 7 h and
then under flowing N
2
at 125
C for ca. 15 h to remove contaminants. The washed
ionic liquids purity was confirmed by
1
H and
19
F NMR.
6.2.5 Characterization
Transmission electron microscopy (TEM) images were obtained using a JEOL
JEM2100F (Joel Ltd.) microscope operating at 200 kV . Samples were prepared
on 400 mesh Cu grid coated with a lacey carbon film (Ted Pella, Inc.) by drop-
casting a dilute suspension of PtNPs in ethanol. The size distribution of the PtNPs
was determined by analyzing 500 unique nanoparticles. Powder X-ray diffraction
(PXRD) patterns were collected on a Rigaku Ultima IV diffractometer functioning
at 40 mA and 40 kV with a Cu K x-ray source (l=1.5406
˚
A). The step size and
collection time were 0.05 and 1 s per step, respectively.
1
H and
19
F NMR spectra
were obtained on Varian 600 spectrometer (600 MHz) with chemical shifts reported
in ppm.
6.3 Results
6.3.1 3D-printed microfluidic droplet generators
This microfluidic droplet generator was designed to be an easy-to-operate device
that formed consistent droplet sizes across a broad range of inlet pressures or flow
92
rates. The 3D geometry was fully replicated using stereolithographic (SLA) print-
ing technologies. This geometry was designed to interface with commercially avail-
able tubing (O.D. = 1/16”) to create a droplet generating chip that does not require
any fabrication steps in a clean room facility and can passively form droplet vol-
umes spanning four orders of magnitude. Tubing connections form an elastomeric
seal that resist leaking for flow rates up to 500 mL/h. The chip delivers the lami-
nated dispersed and continuous phases to the outlet in a perpendicular orientation
(Fig. 29a). The two flows alternately enter and fill the opening of the vertical cav-
ity created by the outlet tubing, causing the dispersed phase to pinch off and form
droplets (Fig. 29b). Droplets are formed at the interface between the outlet tubing
and the horizontal flow.
The basic 3D-printed device shown here can be used to form a broad range of
droplets sizes by interfacing it with outlet tubing of various inner diameters. The
size of the outlet tubing determines the droplet size such that the droplet sizes were
similar to the inner diameter of the outlet tubing (Fig. 30a). In comparison, a planar
T-junction geometry produces droplets with a size governed by the geometry of the
dispersed phase inlet.
24
Regardless of the outlet tubing size, the droplet population
was monodisperse, which allowed for the collected droplets to self-assemble into
hexagonally close packed arrays (Figs. 262728).
We also designed a droplet generator where the vertical cavity was integrated into
the SLA manufactured device. The breakup process was imaged in fully printed
devices with cylindrical sizes of I.D. = 250 and 500 mm. We observed droplets
forming at the point where the horizontal flow turned vertical, as in the droplet
93
Figure 26: 60 micrographs of droplets produced using PEEK tubing in the outlet (I.D. =
178 mm). Scale bar represents 500 mm
94
Figure 27: 60 micrographs of droplets produced using PEEK tubing in the outlet (I.D. =
254 mm). Scale bar represents 500 mm
95
Figure 28: 60 micrographs of droplets produced using PEEK tubing in the outlet (I.D. =
508 mm). Scale bar represents 500 mm
96
generators with externally connected tubing acting as the vertical cavity. As the
dispersed and continuous phases entered the vertically oriented cylinder, the dis-
persed phase segmented into droplets. This 250mm cylinder is the smallest channel
reported using the SLA process (FineLine Prototyping).
8
Post printing, FineLine
Prototyping cleared unreacted resin from the vertical cavity and the devices were
used as received.
While the technology is quickly advancing to create higher resolution features, a
major concern is that the smallest channel feature that has been replicated in the
commonly used Watershed material is 400mm. Herein, we have overcome this bar-
rier by (1) designing a device with a 250 mm feature and (2) developing a droplet
generator that uses the printed device as a fluidic manifold while relying on higher
resolution extruded tubing to control droplet size. The 250 mm channel was possi-
ble because it was designed to be accessible for manual clearing of uncured resin.
The latter is capable of manufacturing tubing (I.D. = 25 mm) on the same scale as
microfabrication techniques.
6.3.2 Flow invariant droplet formation
The defining characteristic of this droplet forming device is that uniform droplets
can be formed while varying the flow rate ratio. We demonstrated flow invariant
droplet formation for six different commercially available sizes of outlet tubing.
The smallest and largest inner diameters were 25 mm and 762 mm, respectively.
For each tubing size, flow-invariant droplet formation was observed up to an upper
limit flow rate (Fig 30b). By analyzing the sizes of collected droplets, we deter-
mined the upper limit of the flow invariant regime for each tubing size. Below this
97
Figure 29: (a) CAD rendering of a droplet generator with two inlets for the dispersed
and continuous phases and a single outlet that accepts tubing (O.D. = 1/16”) with various
I.D.s to control the droplet size (b) CAD rendering of a droplet generator fully constructed
by stereolithography (c) Micrographs depicting different views of the device during the
droplet breakup process (d) Micrographs of the droplet breakup process in fully SLA droplet
generators with an outlet size of 250 or 500 mm
98
upper limit, the droplet size was approximately the same as the diameter of the out-
let tubing (Fig 30c).
The upper limit of the flow-invariant regime can be expressed in terms of the cap-
illary number (Ca) of the system. For all outlet tubing sizes, this value (calculated
using outlet inner diameter as characteristic length and continuous phase flow rate
as characteristic velocity) was about 10
3
. Below this capillary number, the droplet
size was independent of the flow rate ratio for values from 1:20 up to 1:2 (Fig 30b).
We also observed a consistent droplet size for intermediate flow rate ratios.
The output of the droplet generator was dependent on the geometry of the
outlet tubing and not dependent on the surface chemistry of the channel prior
to the outlet. We modified the internal channel surfaces by depositing a
hydrophilic (poly(ethylene glycol diacylate)) or hydrophobic (poly(1H,1H,2H,2H
perfluorodecylarcylate-co-ethylene glycol diacrylate)) polymeric film via initiated
chemical vapor deposition. The two coatings have water contact angles of 60 and
120
, respectively. With the same outlet tubing (I.D.=254 mm), the coated devices
produced the same size droplets as the unmodified device (Fig. 2d).
6.3.3 Device parallelization
The droplet forming device can be used as a single unit in a highly parallelized
system of n units to linearly create n-fold droplets and n-fold throughput using the
same number of feed streams. A parallelized system of single droplet generators
would be designed to have an equal pressure drop and resistance over each channel
to create identical flow conditions in each droplet generator. However, feedback
between channels can arise due to unequal numbers of droplets flowing in each
99
Figure 30: (a) Micrographs of the droplets formed using the six different sizes of outlet
tubing listed (a) Plot of the droplet diameter vs. fractional droplet number for various outlet
tubing sizes. The solid lines represent the average droplet sizes for a single outlet size and
flow rate ratios of 1:2 and 1:20 (dispersed to continuous phase - shown as semi-transparent
points) (c) Droplet diameter versus outlet tubing inner diameter for flow rate ratios of 0.05
(left, diamond) and 0.5 (right, circle) (d) Boxplot of the droplet size produced droplet
generators with the same outlet tubing (I.D. = 254 mm) and different surface chemistries on
the channels, as modified by initiated chemical vapor deposition.
100
channel.
87
For this reason, our droplet generator is uniquely suited for use in a par-
allelized network. The effect of small flow rate fluctuations on the final droplet size
are naturally suppressed by the droplet generators.
To demonstrate this point, we constructed a parallel network (n=4) of droplet gen-
erators that delivered different flow rates to each branch (Fig. 31a). We printed a
manifold to equally distribute the dispersed and continuous phases to four droplet
generators. The manifold was connected to four independent droplet generators by
jumper cables (i.e., sections of PEEK tubing). The jumper cables connecting the
dispersed phases had lengths of 10, 12.5, 15, and 17.5 mm, resulting in relative
resistances of 1x, 1.25x, 1.5x, and 1.75x, respectively, because the resistance is lin-
early proportional to the length of cylindrical tubing. The network was assembled
to create the largest pressure drop over the dispersed phase jumper cables so there
would be a minimal feedback affecting the continuous phase jumper cables or the
outlets. The I.D. of the jumper cables were 127, 762, and 254 mm for the dispersed
phase, continuous phase, and outlets, respectively.
The network successfully delivered the same continuous phase flow rate to each
branch and different dispersed phase flow rates. When operating outside the flow
invariant regime, the droplet size produced was dependent on the branch location
and dispersed phase flow rate (Fig. 33b). At a dispersed and continuous phase flow
rate of 210 and 30 mL/h, droplet size decreased with increasing resistance over the
dispersed phase branch. As expected, the droplet size was smaller in branches with
a lower dispersed phase flow rate. In contrast, when operating within the flow in-
variant regime, the droplet size was independent of the branch location, despite a
101
different dispersed phase flow rate being delivered to each channel (Fig. 33b).
6.3.4 PtNP synthesis
The droplet generator presented here is suitable for chemical synthesis in dispersed
phases with a wide range of solvent properties. As a proof-of-concept, we demon-
strated the synthesis of PtNPs by a polyol reduction in droplet flows of 1-butyl-3-
methylimidazolium bis(trifluoromethylsulfonyl)imide (BMIMTf
2
N) ionic liquid
solvent. There are few examples of droplet flows of ionic liquids because they
represent an exceptional case of droplet flow behavior as a result of their complex
interfacial properties and high viscosity.
9, 37, 79
Here, BMIMTf
2
N ionic liquid
droplets are formed trivially in a modified droplet generator with three inlets so as
to accommodate two reagent/dispersed phase streams (Fig. 32). The two reagent
inlets supplied (1) the K
2
PtCl
4
precursor and the reducing agent (ethylene glycol),
and (2) poly(vinylpyrrolidone) (PVP) in BMIMTf
2
N. Droplets of the combined
reagents were formed using PEEK tubing (I.D. = 762 mm) in the outlet. The re-
action was initiated by flowing the droplets into a convection oven at 150
C to
quickly nucleate the PtNPs. The temperature in the tubing equilibrated in less than
a second to trigger the nucleation event. Likewise, an abrupt cooling step was used
to quickly quench the reaction and arrest nanoparticle growth.
Powder X-ray diffraction analysis confirmed the resulting nanoparti8cles crystal-
lized in the face centered cubic (fcc) structure expected for Pt metal. An average
lattice parameter of a = 3.89
˚
Awas calculated for the PtNPs, which is in close agree-
ment with bulk Pt metal (PDF 00-004-0802). Moreover, the diffraction peaks are
broadened, suggesting the presence of small nanoparticles on the order of3 nm
102
Figure 31: (a) Schematic of the parallel network assembled by connecting a distribution
manifold to four droplet generators. The continuous phase was linked using low resistance
jumper tubing (I.D. = 762 mm) and the dispersed phase was linked using various lengths
of tubing (I.D. = 127 mm) to create a gradient of resistances across the four branches. (b)
Droplet diameters produced by the four branches of the parallel network (top) by dispersed
and continuous phase flow rates of 10 and 70 mL/h (purple circles) and 30 and 210 mL/h
(black triangles) while operating in and beyond the flow invariant regime, respectively.
Figure 32: Rendering of the device geometry used for the synthesis of platinum
nanoparticles. It contains one inlet for the continuous and two inlets for the dispersed
phases and one outlet. Each port accepts O.D.=1/16” tubing.
103
by the Scherrer equation (Fig. 33b). We synthesized three rounds of PtNPs and
recycled the BMIMTf
2
N ionic liquid solvent between rounds. To recycle the
ionic liquid solvent, the PtNPs were harvested from the ionic liquid and then it was
washed to remove excess ethylene glycol and PVP. The purity of the BMIMTf
2
N
was unchanged, as evidenced by
1
H and
19
F NMR, upon recycling (Fig. 33c,d).
TEM images reveal that the PtNPs appear spherical and uniform in morphology
across each reuse of the ionic liquid (Fig. 33a). Their average size was 3.14
0.49 nm. The combined use of our droplet generator in a parallel network and a
reusable solvent system provide an ideal platform for manufacturing large quanti-
ties of nanomaterial product.
6.4 Discussion
We have introduced a novel droplet generator that uses a 3D geometry to form
droplets of controlled size. A key feature of this droplet formation geometry is that
there is a broad regime of inlet flow rate ratios over which resulting droplet size is
invariant to flow rate. Another advantage of this droplet formation format is that
its inherent modularity makes it simple to select the size of droplets that will be
formed. The size can easily be tuned by changing the size of the outlet tubing to
achieve a different I.D. The ease of operation and device setup lowers the barrier-to-
entry for first time users of microfluidic devices. The droplet size depends primarily
on the inner diameter of the outlet tubing and can be operated to be independent of
the dispersed phase flow rate. Therefore, an end user need not have an extensive
fluid mechanics understanding to operate the device to achieve the desired droplet
sizes.
104
Figure 33: (a) TEM images of PtNPs produced using the microfluidic droplet generator
using new, 1x recycled, and 2x recycled BMIMTf
2
N ionic liquid. (b) XRD of the PtNPs.
(c)
1
H NMR spectra of the BMIMTf
2
N ionic liquid (*indicates solvent peak), and (d)
19
F
NMR spectra of the BMIMTf
2
N ionic liquid. Scale bars represent 20 nm.
105
These droplet forming devices are uniquely suited to high-throughput processing
using microfluidics. They were used in a parallel configuration because they are
(1) insensitive to small changes in flow, that could arise due to feedback between
channels and (2) resist clogging that could affect droplet formation (Fig. 34). The
four-branched parallel network produced droplets of similar size despite having a
gradient of dispersed phase flow rates being delivered to each branch. We also
synthesized monodisperse PtNPs over multiple runs while using the same recycled
IL solvent. Using this device infrastructure along with the minimal waste chem-
istry provides a tandem platform for producing large quantities of precious metal
nanoparticles. This can be easily extended to other applications requiring high-
throughput synthesis in or of droplets.
Figure 34: Top down view of the droplet generating device from Fig. 32. It is held in
place by a custom clamp. The droplet generating device remains visually unchanged after
running the PtNP precursors. The CAD drawing shows the top-down view of the device.
Scale bar is the same for all images and represents 1 mm.
106
7 Conclusions and Outlook
Microuidics, low Reynolds number ow channels, and laminar ow devices have all
been used to describe similar types of ow congurations in which the surfaces and
interfaces are very important. They control the dynamics of the system due to
high surface area-to-volume ratios at the length scales typical of these channels.
Therefore, the surface chemistry of the device material plays a key role in determin-
ing ow patterns and ow stability. Many have attempted to address these issues by
developing new protocols for making devices from different device materials. Our
solution is more robust and widely applicable because using initiated chemi- cal
vapor deposition (iCVD) to modify surfaces works for any device material. A
large library of surface chemistries is available because the iCVD process does
not require solvents and proceeds via a generalized free-radical chain mechanism.
We leveraged the ability to make low surface energy channels to introduce two-
phase droplet ows of ionic liquids. The thermally stable, liquid salt is a unique sol-
vent and weakly coordinating ligand that facilitates the reduction of noble metal
nanoparticles and prevents aggregation. Combining this unique chemistry with our
three dimensional droplet generator, we have outlined a robust method for translat-
ing batch chemistries to continuous ow platforms. As the last piece in the puzzle,
we demonstrated parallelization of the droplet generators and their resistance to
ow perturbations as key requirements to scalable manufacturing of nanomaterials.
Looking ahead, we anticipate the integration of higher order droplet manipulation
and monitoring to create a truly standalone manufacturing system. Droplet coales-
ence and splitting are key in replicating multi-step syntheses. As we have integrated
our droplet generator with a commercial convection oven to achieve temperature
107
triggered nucleation, various modes of in-line monitoring can be built into the u-
idic cascade. UV-vis spectroscopy can be used to monitor the synthesis product in
real time. Rather than try to build a system around a microuidic channel, one could
use a ow module inserted into a standard cuvette slot. This is just one example of
streamlining innovation by adapting the more exible component.
108
References
[1] A. R. Abate, A. T. Krummel, D. Lee, M. Marquez, C. Holtze, and
D. A. Weitz. Photoreactive coating for high-contrast spatial patterning of
microfluidic device wettability. Lab Chip, 8(12):2157–60, 2008.
[2] A. R. Abate, D. Lee, T. Do, C. Holtze, and D. A. Weitz. Glass coating for
pdms microfluidic channels by sol-gel methods. Lab Chip, 8(4):516–8, 2008.
[3] M. E. Alf, P. D. Godfrin, T. A. Hatton, and K. K. Gleason. Sharp
hydrophilicity switching and conformality on nanostructured surfaces
prepared via initiated chemical vapor deposition (icvd) of a novel
thermally responsive copolymer. Macromolecular Rapid Communications,
31(24):2166–2172, 2010.
[4] J. R. Anderson, D. T. Chiu, R. J. Jackman, O. Cherniavskaya, J. C.
McDonald, H. Wu, S. H. Whitesides, and G. M. Whitesides. Fabrication
of topologically complex three-dimensional microfluidic systems in pdms
by rapid prototyping. Anal Chem, 72(14):3158–3164, 2000.
[5] S. L. Anna, N. Bontoux, and H. A. Stone. Formation of dispersions using
flow focusing? in microchannels. Applied Physics Letters, 82(3):364, 2003.
[6] D. Anton. Surface-fluorinated coatings. Advanced Materials, 10(15):1197–
1205, 1998.
[7] M. Antonietti, D. Kuang, B. Smarsly, and Y . Zhou. Ionic liquids for
the convenient synthesis of functional nanoparticles and other inorganic
nanostructures. Angew Chem Int Ed Engl, 43(38):4988–92, 2004.
[8] A. K. Au, W. Lee, and A. Folch. Mail-order microfluidics: evaluation
of stereolithography for the production of microfluidic devices. Lab Chip,
14(7):1294–301, 2014.
[9] Z. Barikbin, M. T. Rahman, P. Parthiban, A. S. Rane, V . Jain, S. Duraiswamy,
S. H. Lee, and S. A. Khan. Ionic liquid-based compound droplet
microfluidics for ’on-drop’ separations and sensing. Lab Chip, 10(18):2458–
63, 2010.
[10] C. N. Baroud, F. Gallaire, and R. Dangla. Dynamics of microfluidic droplets.
Lab Chip, 10(16):2032–45, 2010.
109
[11] S. Begolo, G. Colas, J. L. Viovy, and L. Malaquin. New family of fluorinated
polymer chips for droplet and organic solvent microfluidics. Lab Chip,
11:508–12, 2011.
[12] S. Bhattacharya, A. Datta, J. M. Berg, and S. Gangopadhyay. Studies
on surface wettability of poly(dimethyl) siloxane (pdms) and glass under
oxygen-plasma treatment and correlation with bond strength. Journal of
Microelectromechanical Systems, 14(3):590–597, 2005.
[13] K. W. Bong, S. C. Chapin, D. C. Pregibon, D. Baah, T. M. Floyd-Smith, and
P. S. Doyle. Compressed-air flow control system. Lab Chip, 11(4):743–7,
2011.
[14] R. K. Bose and K. K. S. Lau. Initiated cvd of poly(2-hydroxyethyl methacry-
late) hydrogels: Synthesis, characterization and in-vitro biocompatibility.
Chemical Vapor Deposition, 15(4-6):150–155, 2009.
[15] B. Boutevin, F. Guida-Pietrasanta, and A. Ratsimihety. Synthesis of
photocrosslinkable fluorinated polydimethylsiloxane: Direct introduction of
acrylic pendant groups vis hydrosilylation. J. of Polm. Sci.: Part A: Polym.
Chem., 38:3722–3728, 2000.
[16] N. Bremond, A. R. Thiam, and J. Bibette. Decompressing emulsion droplets
favors coalescence. Phys Rev Lett, 100(2):024501, 2008.
[17] X. Casadevall i Solvas and A. deMello. Droplet microfluidics: recent
developments and future applications. Chem Commun (Camb), 47(7):1936–
42, 2011.
[18] K. Chan and K. K. Gleason. Initiated chemical vapor deposition of linear
and cross-linked poly(2-hydroxyethyl methacrylate) for use as thin-film
hydrogels. Langmuir, 21(19):8930–8939, 2005.
[19] K.-Y . Chan, J. Ding, J. Ren, S. Cheng, and K. Y . Tsang. Supported mixed
metal nanoparticles as electrocatalysts in low temperature fuel cells. Journal
of Materials Chemistry, 14(4):505, 2004.
[20] G. Chen, F. Svec, and D. R. Knapp. Light-actuated high pressure-
resisting microvalve for on-chip flow control based on thermo-responsive
nanostructured polymer. Lab Chip, 8(7):1198–204, 2008.
[21] H. Y . Chen, Y . Elkasabi, and J. Lahann. Surface modification of confined
microgeometries via vapor-deposited polymer coatings. J Am Chem Soc,
128(1):374–80, 2006.
110
[22] H. Y . Chen and J. Lahann. Fabrication of discontinuous surface patterns
within microfluidic channels using photodefinable vapor-based polymer
coatings. Anal Chem, 77(21):6909–14, 2005.
[23] S. Choi. Introductory Applied Statistics in Science. Prentic-Hall, Inc.,
Englewood Cliffs, NJ, 1978.
[24] G. F. Christopher, N. N. Noharuddin, J. A. Taylor, and S. L. Anna.
Experimental observations of the squeezing-to-dripping transition in t-
shaped microfluidic junctions. Phys Rev E Stat Nonlin Soft Matter Phys,
78:036317, 2008.
[25] G. Clarke and D. Cooke. A Basic Course in Statistics. Arnold, New York,
4th edition, 1998.
[26] D. Conchouso, D. Castro, S. A. Khan, and I. G. Foulds. Three-dimensional
parallelization of microfluidic droplet generators for a litre per hour volume
production of single emulsions. Lab Chip, 14(16):3011–20, 2014.
[27] P. Dash and R. W. Scott. 1-methylimidazole stabilization of gold
nanoparticles in imidazolium ionic liquids. Chem Commun (Camb),
(7):812–4, 2009.
[28] M. De Menech, P. Garstecki, F. Jousse, and H. A. Stone. Transition from
squeezing to dripping in a microfluidic t-shaped junction. Journal of Fluid
Mechanics, 595:141–161, 2008.
[29] A. J. DeMello. Control and detection of chemical reactions in microfluidic
systems. Nature, 442(7101):394–402, 2006.
[30] K. M. Docherty, J. K. Dixon, and J. Kulpa, C. F. Biodegradability of
imidazolium and pyridinium ionic liquids by an activated sludge microbial
community. Biodegradation, 18(4):481–93, 2007.
[31] D. C. Duffy, J. C. McDonald, O. J. A. Schueller, and G. M. Whitesides.
Rapid prototyping of microfluidic systems in poly(dimethylsiloxane). Anal
Chem, 70(23):4974–4984, 1998.
[32] J. Dupont and J. D. Scholten. On the structural and surface properties of
transition-metal nanoparticles in ionic liquids. Chem Soc Rev, 39(5):1780–
804, 2010.
[33] S. Duraiswamy and S. A. Khan. Droplet-based microfluidic synthesis of
anisotropic metal nanocrystals. Small, 5(24):2828–34, 2009.
111
[34] M. J. Earle, C. M. Gordon, N. V . Plechkova, K. R. Seddon, and T. Welton.
Decolorization of ionic liquids for spectroscopy. Anal Chem, 79(2):758–64,
2007.
[35] J. El-Ali, P. K. Sorger, and K. F. Jensen. Cells on chips. Nature,
442(7101):403–11, 2006.
[36] I. H. El-Sayed, X. Huang, and M. A. El-Sayed. Selective laser photo-thermal
therapy of epithelial carcinoma using anti-egfr antibody conjugated gold
nanoparticles. Cancer Lett, 239(1):129–35, 2006.
[37] X. Feng, Y . Yi, X. Yu, D. W. Pang, and Z. L. Zhang. Generation of water-
ionic liquid droplet pairs in soybean oil on microfluidic chip. Lab Chip,
10(3):313–9, 2010. Feng, Xuan Yi, Ying Yu, Xu Pang, Dai-Wen Zhang,
Zhi-Ling England Lab Chip. 2010 Feb 7;10(3):313-9. Epub 2009 Nov 18.
[38] L. M. Fidalgo, C. Abell, and W. T. Huck. Surface-induced droplet fusion in
microfluidic devices. Lab Chip, 7(8):984–6, 2007.
[39] G. S. Fonseca, G. Machado, S. R. Teixeira, G. H. Fecher, J. Morais, M. C.
Alves, and J. Dupont. Synthesis and characterization of catalytic iridium
nanoparticles in imidazolium ionic liquids. J Colloid Interface Sci, 301:193–
204, 2006.
[40] P. Garstecki, M. J. Fuerstman, H. A. Stone, and G. M. Whitesides. Formation
of droplets and bubbles in a microfluidic t-junction-scaling and mechanism
of break-up. Lab Chip, 6(3):437–46, 2006.
[41] S. K. Ghosh and T. Pal. Interparticle coupling effect on the surface plasmon
resonance of gold nanoparticles: from theory to applications. Chem Rev,
107(11):4797–862, 2007.
[42] L. Goldstein, F. Glas, J. Y . Marzin, M. N. Charasse, and G. Le Roux. Growth
by molecular beam epitaxy and characterization of inas/gaas strained-layer
superlattices. Applied Physics Letters, 47(10):1099, 1985.
[43] A. C. Gossard, P. M. Petroff, W. Weigmann, R. Dingle, and A. Savage.
Epitaxial structures with alternate-atomic-layer composition modulation.
Applied Physics Letters, 29(6):323, 1976.
[44] M. Gupta and K. K. Gleason. Initiated chemical vapor deposition
of poly(1h,1h,2h,2h-perfluorodecyl acrylate) thin films. Langmuir,
22(24):10047–52, 2006.
112
[45] G. Halasz, B. Gyure, I. M. Janosi, K. G. Szabo, and T. Tel. V ortex flow
generated by a magnetic stirrer. American Journal of Physics, 75(12):1092,
2007.
[46] P. D. Haller, C. A. Flowers, and M. Gupta. Three-dimensional patterning of
porous materials using vapor phase polymerization. Soft Matter, 7(6):2428,
2011.
[47] J. P. Hallett and T. Welton. Room-temperature ionic liquids: solvents for
synthesis and catalysis. 2. Chem Rev, 111(5):3508–76, 2011.
[48] K. Handique, D. T. Burke, C. H. Mastrangelo, and M. A. Burns. On-
chip thermopneumatic pressure for discrete drop pumping. Anal Chem,
73(8):1831–1838, 2001.
[49] R. L. Hartman, J. P. McMullen, and K. F. Jensen. Deciding whether to go
with the flow: evaluating the merits of flow reactors for synthesis. Angew
Chem Int Ed Engl, 50(33):7502–19, 2011.
[50] M. Hashimoto, S. S. Shevkoplyas, B. Zasonska, T. Szymborski, P. Garstecki,
and G. M. Whitesides. Formation of bubbles and droplets in parallel, coupled
flow-focusing geometries. Small, 4(10):1795–805, 2008.
[51] K. Haubert, T. Drier, and D. Beebe. Pdms bonding by means of a portable,
low-cost corona system. Lab Chip, 6(12):1548–9, 2006.
[52] S. He, T. Kohira, M. Uehara, T. Kitamura, H. Nakamura, M. Miyazaki,
and H. Maeda. Effects of interior wall on continuous fabrication of silver
nanoparticles in microcapillary reactor. Chemistry Letters, 34(6):748–749,
2005.
[53] S. He, J. Yao, P. Jiang, D. Shi, H. Zhang, S. Xie, S. Pang, and H. Gao.
Formation of silver nanoparticles and self-assembled two-dimensional
ordered superlattice. Langmuir, 17(5):1571–1575, 2001.
[54] P. C. Hu, S. Li, and N. Malmstadt. Microfluidic fabrication of asymmetric
giant lipid vesicles. ACS Appl Mater Interfaces, 3(5):1434–40, 2011.
[55] S. Hu, X. Ren, M. Bachman, C. E. Sims, G. P. Li, and N. L. Allbritton.
Surface-directed, graft polymerization within microfluidic channels. Anal
Chem, 76(7):1865–70, 2004.
113
[56] S. Hu, X. Ren, M. Bachman, C. E. Sims, G. P. Li, and N. L. Allbritton.
Tailoring the surface properties of poly(dimethylsiloxane) microfluidic
devices. Langmuir, 20(13):5569–5574, 2004.
[57] H. Huang, C. He, Y . Zeng, X. Xia, X. Yu, P. Yi, and Z. Chen. Preparation
and optical properties of worm-like gold nanorods. J Colloid Interface Sci,
322(1):136–42, 2008.
[58] X. Huang, I. H. El-Sayed, W. Qian, and M. A. El-Sayed. Cancer cell imaging
and photothermal therapy in the near-infrared region by using gold nanorods.
J Am Chem Soc, 128(6):2115–20, 2006.
[59] X. Huang, S. Neretina, and M. A. El-Sayed. Gold nanorods: From
synthesis and properties to biological and biomedical applications. Advanced
Materials, 21(48):4880–4910, 2009.
[60] L. H. Hung, K. M. Choi, W. Y . Tseng, Y . C. Tan, K. J. Shea, and A. P.
Lee. Alternating droplet generation and controlled dynamic droplet fusion
in microfluidic device for cds nanoparticle synthesis. Lab Chip, 6(2):174–8,
2006.
[61] L. H. Hung, R. Lin, and A. P. Lee. Rapid microfabrication of solvent-
resistant biocompatible microfluidic devices. Lab Chip, 8(6):983–7, 2008.
[62] S. G. Im, K. W. Bong, B. S. Kim, S. H. Baxamusa, P. T. Hammond,
P. S. Doyle, and K. K. Gleason. Patterning nanodomains with orthogonal
functionalities: solventless synthesis of self-sorting surfaces. J Am Chem
Soc, 130(44):14424–5, 2008.
[63] S. G. Im, K. W. Bong, C. H. Lee, P. S. Doyle, and K. K. Gleason.
A conformal nano-adhesive via initiated chemical vapor deposition for
microfluidic devices. Lab Chip, 9(3):411–6, 2009.
[64] S. G. Im, B.-S. Kim, L. H. Lee, W. E. Tenhaeff, P. T. Hammond, and
K. K. Gleason. A directly patternable, click-active polymer film via initiated
chemical vapor deposition. Macromolecular Rapid Communications,
29(20):1648–1654, 2008.
[65] A. Jahn, J. E. Reiner, W. N. Vreeland, D. L. DeV oe, L. E. Locascio, and
M. Gaitan. Preparation of nanoparticles by continuous-flow microfluidics.
Journal of Nanoparticle Research, 10(6):925–934, 2008.
114
[66] P. K. Jain, K. S. Lee, I. H. El-Sayed, and M. A. El-Sayed. Calculated
absorption and scattering properties of gold nanoparticles of different size,
shape, and composition: applications in biological imaging and biomedicine.
J Phys Chem B, 110(14):7238–48, 2006.
[67] J. M. Jeong, M. S. Oh, B. J. Kim, C. H. Choi, B. Lee, C. S. Lee, and
S. G. Im. reliable synthesis of monodisperse microparticles: Prevention of
oxygen diffusion and organic solvents using conformal polymeric coating
onto poly(dimethylsiloxane) micromold. Langmuir, 29(10):3474–81, 2013.
[68] X. Ji, X. Song, J. Li, Y . Bai, W. Yang, and X. Peng. Size control of gold
nanocrystals in citrate reduction: the third role of citrate. J Am Chem Soc,
129(45):13939–48, 2007.
[69] T. Kawaguchi, H. Iwasaka, K. Matsumoto, K. Toko, and N. Miura.
Prevention of nonspecific adsorption onto a poly(dimethylsiloxane)
microchannel in a microsensor chip by using a self-assembled monolayer.
Journal of Micro/Nanolithography, MEMS and MOEMS, 9(1):013012,
2010.
[70] S. A. Khan, D. Senapati, T. Senapati, P. Bonifassi, Z. Fan, A. K. Singh,
A. Neeley, G. Hill, and P. C. Ray. Size dependent nonlinear optical properties
of silver quantum clusters. Chemical Physics Letters, 512(1-3):92–95, 2011.
[71] A. Knauer, A. Thete, S. Li, H. Romanus, A. Cski, W. Fritzsche, and J. M.
Khler. Au/ag/au double shell nanoparticles with narrow size distribution
obtained by continuous micro segmented flow synthesis. Chemical
Engineering Journal, 166(3):1164–1169, 2011.
[72] M. T. Kreutzer, F. Kapteijn, J. A. Moulijn, C. R. Kleijn, and J. J. Heiszwolf.
Inertial and interfacial effects on pressure drop of taylor flow in capillaries.
AIChE Journal, 51(9):2428–2440, 2005.
[73] E. T. Lagally, I. Medintz, and R. A. Mathies. Single-molecule dna
amplification and analysis in an integrated microfluidic device. Analytical
Chemistry, 73(3):565–570, 2001.
[74] J. Lahann, M. Balcells, H. Lu, T. Rodon, K. F. Jensen, and R. Langer.
Reactive polymer coatings: a first step toward surface engineering of
microfluidic devices. Anal Chem, 75(9):2117–22, 2003.
115
[75] K. K. Lau and K. K. Gleason. All-dry synthesis and coating of methacrylic
acid copolymers for controlled release. Macromol Biosci, 7(4):429–34,
2007.
[76] K. K. S. Lau and K. K. Gleason. Initiated chemical vapor deposition (icvd) of
poly(alkyl acrylates): a kinetic model. Macromolecules, 39(10):3695–3703,
2006.
[77] K. K. S. Lau and K. K. Gleason. Initiated chemical vapor deposition (icvd) of
poly(alkyl acrylates): an experimental study. Macromolecules, 39(10):3688–
3694, 2006.
[78] L. L. Lazarus, C. T. Riche, N. Malmstadt, and R. L. Brutchey. Effect of ionic
liquid impurities on the synthesis of silver nanoparticles. Langmuir, 2012.
[79] L. L. Lazarus, C. T. Riche, B. C. Marin, M. Gupta, N. Malmstadt, and
R. L. Brutchey. Two-phase microfluidic droplet flows of ionic liquids for
the synthesis of gold and silver nanoparticles. ACS Appl Mater Interfaces,
4(6):3077–83, 2012.
[80] L. L. Lazarus, A. S. Yang, S. Chu, R. L. Brutchey, and N. Malmstadt. Flow-
focused synthesis of monodisperse gold nanoparticles using ionic liquids on
a microfluidic platform. Lab Chip, 10(24):3377–9, 2010.
[81] J. N. Lee, C. Park, and G. M. Whitesides. Solvent compatibility
of poly(dimethylsiloxane)-based microfluidic devices. Anal Chem,
75(23):6544–54, 2003.
[82] M. J. Lee, N. Y . Lee, J. R. Lim, J. B. Kim, M. Kim, H. K. Baik, and Y . S. Kim.
Antiadhesion surface treatments of molds for high-resolution unconventional
lithography. Advanced Materials, 18(23):3115–3119, 2006.
[83] W. Lee, L. M. Walker, and S. L. Anna. Role of geometry and fluid properties
in droplet and thread formation processes in planar flow focusing. Physics
of Fluids, 21(3):032103, 2009.
[84] S. Li, P. C. Hu, and N. Malmstadt. Imaging molecular transport across lipid
bilayers. Biophys J, 101(3):700–8, 2011.
[85] S. Li, J. Xu, Y . Wang, and G. Luo. Controllable preparation of nanoparticles
by drops and plugs flow in a microchannel device. Langmuir, 24(8):4194–9,
2008.
116
[86] W. Li, Z. Nie, H. Zhang, C. Paquet, M. Seo, P. Garstecki, and E. Kumacheva.
Screening of the effect of surface energy of microchannels on microfluidic
emulsification. Langmuir, 23(15):8010–8014, 2007.
[87] W. Li, E. W. K. Young, M. Seo, Z. Nie, P. Garstecki, C. A. Simmons,
and E. Kumacheva. Simultaneous generation of droplets with different
dimensions in parallel integrated microfluidic droplet generators. Soft
Matter, 4(2):258, 2008.
[88] X. Z. Lin, A. D. Terepka, and H. Yang. Synthesis of silver nanoparticles in a
continuous flow tubular microreactor. Nano Lett, 4(11):2227–2232, 2004.
[89] T. Linnert, P. Mulvaney, A. Henglein, and H. Weller. Long-lived nonmetallic
silver clusters in aqueous solution: preparation and photolysis. J Am Chem
Soc, 112(12):4657–4664, 1990.
[90] M. Liong, J. Lu, M. Kovochich, T. Xia, S. G. Ruehm, A. E. Nel, F. Tamanoi,
and J. I. Zink. Multifunctional inorganic nanoparticles for imaging, targeting,
and drug delivery. ACS Nano, 2(5):889–96, 2008.
[91] X. Liu, J. G. Worden, Q. Huo, and J. P. Brennan. Kinetic study of gold
nanoparticle growth in solution by brust-schiffrin reaction. Journal of
Nanoscience and Nanotechnology, 6(4):1054–1059, 2006.
[92] W. H. Lizcano-Valbuena, D. C. de Azevedo, and E. R. Gonzalez. Supported
metal nanoparticles as electrocatalysts for low-temperature fuel cells.
Electrochimica Acta, 49(8):1289–1295, 2004.
[93] S. E. Lohse, J. R. Eller, S. T. Sivapalan, M. R. Plews, and C. J. Murphy. A
simple millifluidic benchtop reactor system for the high-throughput synthesis
and functionalization of gold nanoparticles with different sizes and shapes.
ACS Nano, 2013.
[94] N. Lorber, F. Sarrazin, P. Guillot, P. Panizza, A. Colin, B. Pavageau, C. Hany,
P. Maestro, S. Marre, T. Delclos, C. Aymonier, P. Subra, L. Prat, C. Gourdon,
and E. Mignard. Some recent advances in the design and the use of
miniaturized droplet-based continuous process: applications in chemistry
and high-pressure microflows. Lab Chip, 11(5):779–87, 2011.
[95] X. Luo, A. Morrin, A. Killard, and M. Smyth. Application of nanoparticles
in electrochemical sensors and biosensors. Electroanalysis, 18(4):319–326,
2006.
117
[96] N. Malmstadt, M. A. Nash, R. F. Purnell, and J. J. Schmidt. Automated
formation of lipid-bilayer membranes in a microfluidic device. Nano Lett,
6(9):1961–5, 2006.
[97] N. Malmstadt, P. Yager, A. S. Hoffman, and P. S. Stayton. A
smart microfluidic affinity chromatography matrix composed of poly(n-
isopropylacrylamide)-coated beads. Analytical Chemistry, 75(13):2943–
2949, 2003.
[98] Y . Mao and K. K. Gleason. Hot filament chemical vapor deposition
of poly(glycidyl methacrylate) thin films usingtert-butyl peroxide as an
initiator. Langmuir, 20(6):2484–2488, 2004.
[99] Y . Mao and K. K. Gleason. Positive-tone nanopatterning of chemical vapor
deposited polyacrylic thin films. Langmuir, 22(4):1795–9, 2006.
[100] Y . Mao and K. K. Gleason. Vapor-deposited fluorinated glycidyl copolymer
thin films with low surface energy and improved mechanical properties.
Macromolecules, 39(11):3895–3900, 2006.
[101] S. Marre and K. F. Jensen. Synthesis of micro and nanostructures in
microfluidic systems. Chem Soc Rev, 39(3):1183–202, 2010.
[102] M. Matsumoto, K. Mochiduki, and K. Kondo. Toxicity of ionic liquids and
organic solvents to lactic acid-producing bacteria. Journal of Bioscience and
Bioengineering, 98(5):344–347, 2004.
[103] A. D. McFarland and R. P. Van Duyne. Single silver nanoparticles as real-
time optical sensors with zeptomole sensitivity. Nano Letters, 3(8):1057–
1062, 2003.
[104] T. C. Merkel, V . I. Bondar, K. Nagai, B. D. Freeman, and I. Pinnau. Gas
sorption, diffusion, and permeation in poly(dimethylsiloxane). Journal of
Polymer Science Part B: Polymer Physics, 38(3):415–434, 2000.
[105] S. Morrissey, B. Pegot, D. Coleman, M. T. Garcia, D. Ferguson, B. Quilty,
and N. Gathergood. Biodegradable, non-bactericidal oxygen-functionalised
imidazolium esters: A step towards greener ionic liquids. Green Chemistry,
11(4):475, 2009.
[106] M. Mostafavi, N. Keghouche, M.-O. Delcourt, and J. Belloni. Ultra-slow
aggregation process for silver clusters of a few atoms in solution. Chemical
Physics Letters, 167(3):193–197, 1990.
118
[107] C. J. Murphy, A. M. Gole, J. W. Stone, P. N. Sisco, A. M. Alkilany, E. C.
Goldsmith, and S. C. Baxter. Gold nanoparticles in biology: beyond toxicity
to cellular imaging. Acc Chem Res, 41(12):1721–30, 2008.
[108] S. K. Murthy and K. K. Gleason. Fluorocarbonorganosilicon copolymer
synthesis by hot filament chemical vapor deposition. Macromolecules,
35(5):1967–1972, 2002.
[109] M. Natali, S. Begolo, T. Carofiglio, and G. Mistura. Rapid prototyping of
multilayer thiolene microfluidic chips by photopolymerization and transfer
lamination. Lab Chip, 8(3):492–4, 2008.
[110] M.-A. Neouze. About the interactions between nanoparticles and
imidazolium moieties: emergence of original hybrid materials. Journal of
Materials Chemistry, 20(43):9593, 2010.
[111] A. M. Nightingale, S. H. Krishnadasan, D. Berhanu, X. Niu, C. Drury,
R. McIntyre, E. Valsami-Jones, and J. C. deMello. A stable droplet reactor
for high temperature nanocrystal synthesis. Lab Chip, 11(7):1221–7, 2011.
[112] A. M. Nightingale, T. W. Phillips, J. H. Bannock, and J. C. de Mello.
Controlled multistep synthesis in a three-phase droplet reactor. Nat
Commun, 5:3777, 2014.
[113] X. Niu, S. Gulati, J. B. Edel, and A. J. deMello. Pillar-induced droplet
merging in microfluidic circuits. Lab Chip, 8(11):1837–41, 2008.
[114] J. B. Orhan, V . K. Parashar, J. Flueckiger, and M. A. Gijs. Internal
modification of poly(dimethylsiloxane) microchannels with a borosilicate
glass coating. Langmuir, 24(16):9154–61, 2008.
[115] N. N. J. A. P. PCC-7. Nist - ncl joint assay protocol pcc-7. 2010.
[116] M. Petkovic, J. L. Ferguson, H. Q. N. Gunaratne, R. Ferreira, M. C.
Leito, K. R. Seddon, L. P. N. Rebelo, and C. S. Pereira. Novel
biocompatible cholinium-based ionic liquidstoxicity and biodegradability.
Green Chemistry, 12(4):643, 2010.
[117] H. Pfruender, M. Amidjojo, U. Kragl, and D. Weuster-Botz. Efficient whole-
cell biotransformation in a biphasic ionic liquid/water system. Angew Chem
Int Ed, 43(34):4529–31, 2004.
[118] H. Pfruender, R. Jones, and D. Weuster-Botz. Water immiscible ionic liquids
as solvents for whole cell biocatalysis. J Biotechnol, 124(1):182–90, 2006.
119
[119] T. W. Phillips, I. G. Lignos, R. M. Maceiczyk, A. J. deMello, and J. C.
deMello. Nanocrystal synthesis in microfluidic reactors: where next? Lab
Chip, 14(17):3172–80, 2014.
[120] J. Polte, T. T. Ahner, F. Delissen, S. Sokolov, F. Emmerling, A. F.
Thunemann, and R. Kraehnert. Mechanism of gold nanoparticle formation
in the classical citrate synthesis method derived from coupled in situ xanes
and saxs evaluation. J Am Chem Soc, 132(4):1296–301, 2010.
[121] B. L. V . Prasad, S. I. Stoeva, C. M. Sorensen, and K. J. Klabunde. Digestive
ripening of thiolated gold nanoparticles: the effect of alkyl chain length.
Langmuir, 18(20):7515–7520, 2002.
[122] J. Ranke, M. Cox, A. Mller, C. Schmidt, and D. Beyersmann. Sorption,
cellular distribution, and cytotoxicity of imidazolium ionic liquids in
mammalian cells influence of lipophilicity. Toxicological & Environmental
Chemistry, 88(2):273–285, 2006.
[123] E. Redel, R. Thomann, and C. Janiak. First correlation of nanoparticle size-
dependent formation with the ionic liquid anion molecular volume. Inorg
Chem, 47(1):14–6, 2008.
[124] H. X. Ren, X. Chen, X. J. Huang, M. Im, D. H. Kim, J. H. Lee,
J. B. Yoon, N. Gu, J. H. Liu, and Y . K. Choi. A conventional
route to scalable morphology-controlled regular structures and their
superhydrophobic/hydrophilic properties for biochips application. Lab Chip,
9(15):2140–4, 2009.
[125] K. Ren, Y . Zhao, J. Su, D. Ryan, and H. Wu. Convenient method
for modifying poly(dimethylsiloxane) to be airtight and resistive against
absorption of small molecules. Anal Chem, 82(14):5965–71, 2010.
[126] L. Ren, L. Meng, Q. Lu, Z. Fei, and P. J. Dyson. Fabrication of gold nano-
and microstructures in ionic liquids–a remarkable anion effect. J Colloid
Interface Sci, 323(2):260–6, 2008.
[127] C. T. Riche, B. C. Marin, N. Malmstadt, and M. Gupta. Vapor deposition of
cross-linked fluoropolymer barrier coatings onto pre-assembled microfluidic
devices. Lab Chip, 11(18):3049–52, 2011.
[128] C. T. Riche, C. Zhang, M. Gupta, and N. Malmstadt. Fluoropolymer surface
coatings to control droplets in microfluidic devices. Lab Chip, 14(11):1834–
41, 2014.
120
[129] J. P. Rolland, R. M. Van Dam, D. A. Schorzman, S. R. Quake, and
J. M. DeSimone. Solvent-resistant photocurable liquid fluoropolymers for
microfluidic device fabrication [corrected]. J Am Chem Soc, 126(8):2322–
3, 2004.
[130] A. L. Rollet, P. Porion, M. Vaultier, I. Billard, M. Deschamps, C. Bessada,
and L. Jouvensal. Anomalous diffusion of water in [bmim][tfsi] room-
temperature ionic liquid. J Phys Chem B, 111(41):11888–91, 2007.
[131] G. T. Roman, T. Hlaus, K. J. Bass, T. G. Seelhammer, and C. T. Culbertson.
Sol-gel modified poly(dimethylsiloxane) microfluidic devices with high
electroosmotic mobilities and hydrophilic channel wall characteristics. Anal
Chem, 77(5):1414–22, 2005.
[132] M. B. Romanowsky, A. R. Abate, A. Rotem, C. Holtze, and D. A. Weitz.
High throughput production of single core double emulsions in a parallelized
microfluidic device. Lab Chip, 2012.
[133] A. Romero, A. Santos, J. Tojo, and A. Rodriguez. Toxicity and
biodegradability of imidazolium ionic liquids. J Hazard Mater, 151(1):268–
73, 2008.
[134] L. M. Rossi, G. Machado, P. F. P. Fichtner, S. R. Teixeira, and J. Dupont.
On the use of ruthenium dioxide in 1-n-butyl-3-methylimidazolium ionic
liquids as catalyst precursor for hydrogenation reactions. Catalysis Letters,
92(3/4):149–155, 2004.
[135] A. Rotem, A. R. Abate, A. S. Utada, V . Van Steijn, and D. A. Weitz. Drop
formation in non-planar microfluidic devices. Lab Chip, 12(21):4263–8,
2012.
[136] A. E. Saunders, M. B. Sigman, and B. A. Korgel. Growth kinetics and
metastability of monodisperse tetraoctylammonium bromide capped gold
nanocrystals. The Journal of Physical Chemistry B, 108(1):193–199, 2004.
[137] C. W. Scheeren, G. Machado, S. R. Teixeira, J. Morais, J. B. Domingos,
and J. Dupont. Synthesis and characterization of pt0 nanoparticles in
imidazolium ionic liquids. J Phys Chem B, 110(26):13011–20, 2006.
[138] M. H. Schneider, Y . Tran, and P. Tabeling. Benzophenone absorption
and diffusion in poly(dimethylsiloxane) and its role in graft photo-
polymerization for surface modification. Langmuir, 27(3):1232–40, 2011.
121
[139] T. Schneider, D. R. Burnham, J. VanOrden, and D. T. Chiu. Systematic
investigation of droplet generation at t-junctions. Lab Chip, 11(12):2055–9,
2011.
[140] U. Schreiber, B. Hosemann, and S. Beuermann. 1h,1h,2h,2h-perfluorodecyl-
acrylate-containing block copolymers from arget atrp. Macromolecular
Chemistry and Physics, 212(2):168–179, 2011.
[141] H. S. Schrekker, M. A. Gelesky, M. P. Stracke, C. M. Schrekker, G. Machado,
S. R. Teixeira, J. C. Rubim, and J. Dupont. Disclosure of the imidazolium
cation coordination and stabilization mode in ionic liquid stabilized gold(0)
nanoparticles. J Colloid Interface Sci, 316(1):189–95, 2007.
[142] V . Sebastian, S. K. Lee, C. Zhou, M. F. Kraus, J. G. Fujimoto, and K. F.
Jensen. One-step continuous synthesis of biocompatible gold nanorods for
optical coherence tomography. Chem Commun (Camb), 48(53):6654–6,
2012.
[143] V . Sebastian Cabeza, S. Kuhn, A. A. Kulkarni, and K. F. Jensen. Size
controlled flow synthesis of gold nanoparticles using a segmented flow
microfluidic platform. Langmuir, 2012.
[144] S. Seidel, C. Riche, and M. Gupta. Chemical vapor deposition of polymer
films. 2011.
[145] E. T. Silveira, A. P. Umpierre, L. M. Rossi, G. Machado, J. Morais, G. V .
Soares, I. J. Baumvol, S. R. Teixeira, P. F. Fichtner, and J. Dupont. The partial
hydrogenation of benzene to cyclohexene by nanoscale ruthenium catalysts
in imidazolium ionic liquids. Chemistry, 10(15):3734–40, 2004.
[146] A. B. Smetana, K. J. Klabunde, and C. M. Sorensen. Synthesis of spherical
silver nanoparticles by digestive ripening, stabilization with various agents,
and their 3-d and 2-d superlattice formation. J Colloid Interface Sci,
284(2):521–6, 2005.
[147] H. Song, D. L. Chen, and R. F. Ismagilov. Reactions in droplets in
microfluidic channels. Angew Chem Int Ed Engl, 45(44):7336–56, 2006.
[148] H. Song, J. D. Tice, and R. F. Ismagilov. A microfluidic system for
controlling reaction networks in time. Angewandte Chemie, 115(7):792–
796, 2003.
122
[149] Y . Song, E. E. Doomes, J. Prindle, R. Tittsworth, J. Hormes, and C. S. Kumar.
Investigations into sulfobetaine-stabilized cu nanoparticle formation: toward
development of a microfluidic synthesis. J Phys Chem B, 109(19):9330–8,
2005.
[150] Y . Song, J. Hormes, and C. S. Kumar. Microfluidic synthesis of
nanomaterials. Small, 4(6):698–711, 2008.
[151] Y . Song, H. Modrow, L. L. Henry, C. K. Saw, E. E. Doomes, V . Palshin,
J. Hormes, and C. S. S. R. Kumar. Microfluidic synthesis of cobalt
nanoparticles. Chemistry of Materials, 18(12):2817–2827, 2006.
[152] K. I. Sotowa, K. Irie, T. Fukumori, K. Kusakabe, and S. Sugiyama. Droplet
formation by the collision of two aqueous solutions in a microchannel and
application to particle synthesis. Chemical Engineering & Technology,
30(3):383–388, 2007.
[153] A. Stark and K. R. Seddon. Ionic liquids. Kirk-Othmer encyclopedia of
chemical technology.
[154] M. Stasiewicz, E. Mulkiewicz, R. Tomczak-Wandzel, J. Kumirska, E. M.
Siedlecka, M. Golebiowski, J. Gajdus, M. Czerwicka, and P. Stepnowski.
Assessing toxicity and biodegradation of novel, environmentally benign
ionic liquids (1-alkoxymethyl-3-hydroxypyridinium chloride, saccharinate
and acesulfamates) on cellular and molecular level. Ecotoxicol Environ Saf,
71(1):157–65, 2008.
[155] H. F. Sterling and R. C. G. Swann. Chemical vapour deposition promoted by
r.f. discharge. Solid-State Electronics, 8(8):653–654, 1965.
[156] S. Stolte, S. Abdulkarim, J. Arning, A.-K. Blomeyer-Nienstedt, U. Bottin-
Weber, M. Matzke, J. Ranke, B. Jastorff, and J. Thming. Primary
biodegradation of ionic liquid cations, identification of degradation products
of 1-methyl-3-octylimidazolium chloride and electrochemical wastewater
treatment of poorly biodegradable compounds. Green Chemistry, 10(2):214,
2008.
[157] S. Stolte, J. r. Arning, U. Bottin-Weber, M. Matzke, F. Stock, K. Thiele,
M. Uerdingen, U. Welz-Biermann, B. Jastorff, and J. Ranke. Anion effects
on the cytotoxicity of ionic liquids. Green Chemistry, 8(7):621, 2006.
[158] S. Stolte, M. Matzke, J. Arning, A. Bschen, W.-R. Pitner, U. Welz-Biermann,
B. Jastorff, and J. Ranke. Effects of different head groups and functionalised
123
side chains on the aquatic toxicity of ionic liquids. Green Chemistry,
9(11):1170, 2007.
[159] H. A. Szymanski and R. E. Erickson. Infrared band handbook. IFI/Plenum,
New York, 2nd rev. and enl. edition edition, 1970.
[160] Y .-C. Tan, Y . L. Ho, and A. P. Lee. Droplet coalescence by geometrically
mediated flow in microfluidic channels. Microfluidics and Nanofluidics,
3(4):495–499, 2006.
[161] S. Y . Teh, R. Lin, L. H. Hung, and A. P. Lee. Droplet microfluidics. Lab
Chip, 8(2):198–220, 2008.
[162] R. R. Thomas, D. R. Anton, W. F. Graham, M. J. Darmon, B. B. Sauer, K. M.
Stika, and D. G. Swartzfager. Preparation and surface properties of acrylic
polymers containing fluorinated monomers. Macromolecules, 30(10):2883–
2890, 1997.
[163] T. Thorsen, S. J. Maerkl, and S. R. Quake. Microfluidic large-scale
integration. Science, 298:580–4, 2002.
[164] T. Thorsen, R. W. Roberts, F. H. Arnold, and S. R. Quake. Dynamic
pattern formation in a vesicle-generating microfluidic device. Phys Rev Lett,
86(18):4163–4166, 2001.
[165] J. D. Tice, A. D. Lyon, and R. F. Ismagilov. Effects of viscosity on droplet
formation and mixing in microfluidic channels. Anal Chim Acta, 507(1):73–
77, 2004. Anal Chim Acta. 2004 Apr 1;507(1):73-77.
[166] J. D. Tice, H. Song, A. D. Lyon, and R. F. Ismagilov. Formation of droplets
and mixing in multiphase microfluidics at low values of the reynolds and the
capillary numbers. Langmuir, 19(22):9127–9133, 2003.
[167] M. W. Toepke and D. J. Beebe. Pdms absorption of small molecules and
consequences in microfluidic applications. Lab Chip, 6(12):1484–6, 2006.
[168] C. P. Tostado, J. Xu, and G. Luo. The effects of hydrophilic surfactant
concentration and flow ratio on dynamic wetting in a t-junction microfluidic
device. Chemical Engineering Journal, 171(3):1340–1347, 2011.
[169] E. Um, M. E. Rogers, and H. A. Stone. Combinatorial generation of droplets
by controlled assembly and coalescence. Lab Chip, 13(23):4674–80, 2013.
124
[170] S. van der Graaf, T. Nisisako, C. G. Schroen, R. G. van der Sman, and R. M.
Boom. Lattice boltzmann simulations of droplet formation in a t-shaped
microchannel. Langmuir, 22(9):4144–52, 2006.
[171] V . van Steijn, M. T. Kreutzer, and C. R. Kleijn. -piv study of the formation of
segmented flow in microfluidic t-junctions. Chemical Engineering Science,
62(24):7505–7514, 2007.
[172] S. A. Vanapalli, A. G. Banpurkar, D. van den Ende, M. H. Duits, and
F. Mugele. Hydrodynamic resistance of single confined moving drops in
rectangular microchannels. Lab Chip, 9(7):982–90, 2009.
[173] J. Wagner, T. Kirner, G. Mayer, J. Albert, and J. M. Khler. Generation
of metal nanoparticles in a microchannel reactor. Chemical Engineering
Journal, 101(1-3):251–260, 2004.
[174] J. Wagner and J. M. Kohler. Continuous synthesis of gold nanoparticles in a
microreactor. Nano Lett, 5(4):685–91, 2005.
[175] J. Wagner, T. Tshikhudo, and J. Kohler. Microfluidic generation of metal
nanoparticles by borohydride reduction. Chemical Engineering Journal,
135:S104–S109, 2008.
[176] D. Wang, V . Goel, R. D. Oleschuk, and J. H. Horton. Surface modification
of poly(dimethylsiloxane) with a perfluorinated alkoxysilane for selectivity
toward fluorous tagged peptides. Langmuir, 24(3):1080–6, 2008.
[177] T. Welton. Room-temperature ionic liquids. solvents for synthesis and
catalysis. Chem Rev, 99(8):2071–2084, 1999.
[178] J. S. Wilkes. A short history of ionic liquidsfrom molten salts to neoteric
solvents. Green Chemistry, 4(2):73–80, 2002.
[179] J. Xu, A. Asatekin, and K. K. Gleason. The design and synthesis of hard
and impermeable, yet flexible, conformal organic coatings. Adv Mater,
24(27):3692–6, 2012.
[180] J. Xu and K. K. Gleason. Conformal, amine-functionalized thin films
by initiated chemical vapor deposition (icvd) for hydrolytically stable
microfluidic devices. Chemistry of Materials, 22(5):1732–1738, 2010.
[181] J. T. Yoke, J. F. Weiss, and G. Tollin. Reactions of triethylamine with
copper(i) and copper(ii) halides. Inorganic Chemistry, 2(6):1210–1216,
1963.
125
[182] L. Zhang, G. Niu, N. Lu, J. Wang, L. Tong, L. Wang, M. J. Kim, and
Y . Xia. Continuous and scalable production of well-controlled noble-metal
nanocrystals in milliliter-sized droplet reactors. Nano Lett, 14(11):6626–31,
2014.
[183] Z. Zhang, R. C. Patel, R. Kothari, C. P. Johnson, S. E. Friberg, and P. A.
Aikens. Stable silver clusters and nanoparticles prepared in polyacrylate
and inverse micellar solutions. The Journal of Physical Chemistry B,
104(6):1176–1182, 2000.
[184] C.-X. Zhao, L. He, S. Z. Qiao, and A. P. J. Middelberg. Nanoparticle
synthesis in microreactors. Chemical Engineering Science, 66(7):1463–
1479, 2011.
[185] F. Zhou, D. Xing, B. Wu, S. Wu, Z. Ou, and W. R. Chen. New insights
of transmembranal mechanism and subcellular localization of noncovalently
modified single-walled carbon nanotubes. Nano Lett, 10(5):1677–81, 2010.
[186] J. Zhuang, H. Wu, Y . Yang, and Y . C. Cao. Controlling colloidal superparticle
growth through solvophobic interactions. Angew Chem Int Ed Engl,
47(12):2208–12, 2008.
126
Abstract (if available)
Abstract
While microfluidic research has been a thoroughly investigated field, there are a couple key holes that we have investigated and attempted to fill with innovative and practical solutions. The issues can be grouped into two categores: surface chemistry tuning and high throughput scale-up. In general, we address these issues using initiated chemical vapor deposition to modify device materials and we address the second issue in the context of the synthesis of noble metal nanoparticles. These research efforts span and integrate fluid dynamics, surface chemistry modification, and nanoparticle synthesis. In an academic pursuit of fundamental understanding of these concepts, we have also developed practical solutions that can be employed by others to advance the field. ❧ This report begins with chapter 1, a general introduction covering topics that are not addressed in as much detail in the following chapters. In the following four chapters, the development, optimization, and execution of microreactor systems is investigated. In chapter 2, the chemical modification of pre-assembled microfluidic devices by initiated chemical vapor deposition, is presented as a robust means of modifying channels after their fabrication. The technique is expandable to any device materials and the coating efficacy is demonstrated using two different flow assays. In chapter 3, the synthesis of gold and silver nanoparticles using an ionic liquid solvent is discussed. These are only possible because of the surface modification to lower the surface energy of the channels and facilitate droplet formation of the ionic liquid. The ionic liquid solvent system allows gold nanoparticles to be synthesized at room temperature, contrary to typical synthetic protocols requiring elevated temperatures. The silver nanoparticle synthesis requires a carefully timed reaction that is achieved by changing the residence time of the reaction droplets. In chapter 4, a new method to merge droplets is presented. Using a spacer droplet that is selectively extracted, two bookend droplets merge and their the time between formation and merger can be tuned using several parameters, spacer droplet size, spacer composition, or flow rate. In chapter 5, a new geometry for producing droplets is presented. The three dimensional configuration is possible by the stereolithography (SLA) process, a 3D printing technology. The droplet generating geometry is convertible to produce a wide range of droplet volumes, spanning three orders of magnitude. Droplet size is controlled by the size of the chosen outlet tubing. When operating at lower capillary numbers, the droplet sizes are independent of the flow rate ratio. Incorporating these devices into a parallel network, a general scheme for scaling-up microfluidic throughput is presented. The synthesis of platinum nanoparticles, a timed and heat triggered reaction, is performed using the droplet generating devices. Final remarks are included that examine the current state of the art and an outlook for future directions.
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Asset Metadata
Creator
Riche, Carson T.
(author)
Core Title
Synthesis of high-quality nanoparticles using microfluidic platforms
School
Viterbi School of Engineering
Degree
Doctor of Philosophy
Degree Program
Chemical Engineering
Publication Date
05/12/2016
Defense Date
05/07/2015
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Malmstadt, Noah (
committee chair
), Brutchey, Richard (
committee member
), Gupta, Malancha (
committee member
)
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ctriche88@gmail.com,riche@usc.edu
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https://doi.org/10.25549/usctheses-c40-199317
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199317
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Tags
microfluidics
nanoparticles