Langmuir 2010, 26(14), 12465–12471Published on Web 06/24/2010
©2010 American Chemical Society
Dead-End Filling of SlipChip Evaluated Theoretically and Experimentally
as a Function of the Surface Chemistry and the Gap Size between the
Plates for Lubricated and Dry SlipChips
Liang Li, Mikhail A. Karymov, Kevin P. Nichols, and Rustem F. Ismagilov*
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago,
929 East 57th Street, Chicago, Illinois 60637
Received April 13, 2010. Revised Manuscript Received June 10, 2010
In this paper, we describe a method to load a microfluidic device, the SlipChip, via dead-end filling. In dead-end
filling, the lubricating fluid that fills the SlipChip after assembly is dissipated through the gap between the two plates of
the SlipChip instead of flowing through an outlet at the end of the fluidic path. We describe a theoretical model and
plates of SlipChips. In this method, filling is controlled by the balance of pressures: for filling to occur without leaking,
the inlet pressure must be greater than the capillary pressure but less than the maximum sealing pressure. We evaluated
our prediction with experiments, and our empirical results agreed well with theory. Internal reservoirs were designed to
prevent evaporation during loading of multiple solutions. Solutions were first loaded one at a time into inlet reservoirs;
The SlipChip design was also modified to enable ease of filling by using multiple access holes to the inlet reservoir.
This paper describes a robust method to fill a SlipChip with
aqueous solutions, called dead-end filling, that relies on the sur-
face chemistry and gap size of the SlipChip and is applicable to
both lubricated and dry SlipChips. SlipChip1-6is an emerging
microfluidic platform that enables simple, equipment-free mani-
made of two plates that move;or slip;relative to one another.
into the patterns of wells and ducts. Almost any program can be
encoded into the SlipChip, and the program is executed by slip-
ping, which disconnects or connects wells from ducts, and brings
lications of SlipChip include protein crystallization,1-3immuno-
assays,4and polymerase chain reactions (PCR).5,6For the Slip-
toindividual wellsthroughfluidicpaths. Animbalanceinpressure
fluidic path to balance pressure.1Applications performed in Slip-
Chip require quantification, and quantification relies on precise
metering of fluid volumes. Fluid volumes are defined by the well
racy of metered volumes. In addition, filling of multiple wells in
parallelisdesirable, toincrease the throughputand compatibility
with existing automation. Previously, the SlipChip was filled by
pipetting the solution into the fluidic path while allowing the
prefilled lubricating fluid to escape through an outlet.
This paper describes and characterizes, both theoretically and
experimentally, an alternative method to fill SlipChips. As the
sample solution fills the fluidic path, it displaces the lubricating
fluid or air that fills the SlipChip after assembly, and instead of
allowing the lubricating fluid or air filling the fluidic path to
escape through the outlet, the fluid originally in the fluidic path
is dissipated through the gap between the plates. We refer to this
process as “dead-end filling”,8because the chip design does not
contain outlets for each fluidic path. In this method of dead-end
purchased from commercial sources and used without additional
purification. Spectrum food dyes were purchased from August
amine) was obtained from 3M (St. Paul, MN). (Tridecafluoro-
1,1,2,2 -tetrahydrooctyl) trichlorosilane (Gelest Inc., Morrisville,
PA) was used to silianize and render surfaces fluorophilic. 1H,
1H,2H,2H-Perfluoro-1-octanol was obtained from Sigma-Aldrich
(St. Louis, MO). Soda-lime glass plates coated with chromium
and photoresist were purchased from Telic Company (Valencia,
CA). Photomasks were purchased from CAD/Art Services, Inc.
*To whom correspondence should be addressed. E-mail: r-ismagilov@
(2) Li, L.; Du, W.; Ismagilov, R. F. J. Am. Chem. Soc. 2010, 132, 106–111.
(3) Li, L.; Du, W.; Ismagilov, R. F. J. Am. Chem. Soc. 2010, 132, 112–119.
(4) Liu, W.; Chen, D.; Du, W.; Nichols, K. P.; Ismagilov, R. F. Anal. Chem.
2010, 82, 3276–3282.
(5) Shen, F.; Du, W.; Davydova, E.; Karymov, M.; Pandey, J.; Ismagilov, R. F.
Anal. Chem. 2010, 82, 4606–4612.
(6) Shen, F.; Du, W.; Kreutz, J. E.; Fok, A.; Ismagilov, R. F. Lab Chip 2010,
(7) Adamson, D. N.; Mustafi, D.; Zhang, J. X.; Zheng, B.; Ismagilov, R. F.
Lab Chip 2006, 6, 1178–1186.
Sci. U.S.A. 2002, 99, 16531–16536.
DOI: 10.1021/la101460z Langmuir 2010, 26(14), 12465–12471
Article Li et al.
Device Fabrication. Glass devices were fabricated by glass
etching and sequential silanization to render the surface hydro-
phobic. Details can be found in the Supporting Information.
Plastic devices were fabricated by hot embossing. A glass mold
was used to emboss the chip pattern into 1/1600thick fluorinated
sed at 260 ?C, 400 lbs/in.2for 20 min in a Carver 3889 hot press.
The chips were rapidly cooled to room temperature before
pressure was removed. Fabrication of glass molds is detailed in
the Supporting Information.
Device Assembly. Each device consisted of two plates. App-
roximately300 μL ofthe lubricating fluid(LF) was pipettedonto
the bottom plate, and the top plate was slowly placed on top of
the bottom plate to avoid trapping air bubbles in channels. The
fixed by four paperclips. For the experiments with different gap
sizes, beads of 1.5 or 3.86 μm in diameter were suspended in LF.
These beads were silanized in 5% (v/v) (tridecafluoro-1,1,2,2-
tetrahydrooctyl) trichlorosilane in toluene. The measurement of
actual gap size is detailed in the Supporting Information. For
experiments with different interfacial tension, 10% (v/v) 1H,1H,
2H,2H-perfluoro-1-octanol (surfactant) was added to LF. Surface
Information. Contact angle and viscosity measurements are also
described in the Supporting Information.
Characterizing the Physical Model SlipChip (Figures 1
and 2). Inlet Pressure Control. Inlet pressure was provided
ends, one of which was connected to a barometer indicating the
output pressure in the system and the other was connected to the
Filling Solutions. A totalof4μL ofagreendye wasloadedby
from poly(dimethylsiloxane) (PDMS) and ∼5 mm in height, was
then sandwiched between the assembled device and a glass plate
and fixed by four paperclips. The glass plate bore a nanoport
assembly (Upchurch Scientific). The assembly was then connec-
ted to the pressure source, and solutions were pressurized and
observed in the LF-receiving channel (Figure 2C).
Characterization of Filling Speed. The channel between two
higher the flow rate, the faster the speed. The flow rate is defined
solution, and t (s) is the time recorded to fill the channel. Each
experiment was repeated three times.
Filling the Lubricated Device (Figure 3). Five solutions
used to fill the fluidic path for the sample; red, blue, orange, and
yellow dyes were used to fill the 16 fluidic paths for the reagents.
roximately 12.5 μm long, 12.5 μm wide, and 2.5 μm deep) with
Figure 1. ModelSlipChipusedtotestthephysicalmodelthatdes-
cribesthe process ofdead-endfilling.(A)Topviewof theSlipChip
with no leaking, showing that phase 1 (red) was filled (red arrows)
phase 2 (gray), which flowed (gray arrows) into the surrounding
receiving channels through the gap. (B) Zoom-in top view of the
(indicated bya thick arrow)>ΔPcapensures filling ofthe channel.
(C) Cross section of the SlipChip when in the regime of no leak
fines phase 1 in the filling channel. Phase 2 is dissipated through
the gap between the plates to the receiving channel. (D) Top view
was filled in a filling channel and also leaked (indicated by pink
arrows) into surrounding receiving channels. (E) Cross section of
(indicated by a thick arrow)>Psealpushes phase 1 through the gap
into the receiving channel, causing leaking. Parameters are des-
cribed in eqs 1-3.
Figure 2. Regimesofnoleak(regimeI)andleaking(regimeII)asa
function of both the applied pressure and the maximum sealing
of no leak (I) and leaking (II). Each point on the phase diagram
represents one experiment. Solid red diamonds represent experi-
experiments where leakage occurred. The white area in the phase
diagram indicates regime I (predicting no leak), and the shaded
area indicates regime II (predicting leaking). The two areas were
separated at the highest predicted pressures that did not induce
leaking. (B) A microphotograph of no leakage corresponds to
the diamond surrounded by a dashed square in (A). (C) A micro-
photograph of leaking corresponds to the triangle surrounded by
a dashed square in (A).
(9) Roach, L. S.; Song, H.; Ismagilov, R. F. Anal. Chem. 2005, 77, 785–796.
Langmuir 2010, 26(14), 12465–12471
Li et al.Article
facilitate dissipation of the lubricating FC (Supporting Informa-
tion Figure S2). To load the sample and multiple reagents
simultaneously, the same sample filling procedure that was used
to test the physical model was used with the following modifica-
tions: all solutions were first loadedinto big reservoir wells ahead
ofthe fluidic paths.Thefillingprocesswascapturedusingacolor
digital camera under stereomicroscope Leica MZ16 as a series of
sequential images taken with 1 s time intervals (see Supporting
Information Movie S1). After filling, the top plate was slipped
relative to the bottom plate to bring reagent wells in contact with
sample wellsand to mix the solutionsinside. The slippingprocess
was facilitated by the lubricating FC even though the two plates
were clamped by paperclips.
Filling the Dry Device (Figure 4). The dead-end filling
method was adopted to load a dry FEP SlipChip with aqueous
solutions. Following the assembly of the FEP SlipChip in the
absence of any lubricating fluid, the SlipChip was sandwiched
between two glass slides. The top glass slide had access holes
aligned to the inlets of the SlipChip. The “sandwich” was fixed
with paper clips. A 1 μL volume of each solution was directly
loaded into the inlets using a pipet. The pipet tips were pushed
against the inlets through the access holes in the top glass slide.
The filling process spontaneously stopped when the solution
and 0.3 M KSCN was used as a sample. After loading, the top
plate of the SlipChip was slipped relative to the bottom plate
and solutions were combined while the SlipChip remained
sandwiched between the two glass slides throughout the pro-
cess. The reaction between Fe(NO3)3solution and KSCN solu-
tion produced a red solution of various complexes including
Filling the Multiaccess Hole Storage Reservoir in a Slip-
Chip (Figure 5). A 1.5 μL solution of a green food dye was
for less than 1 min to drive the solution from the reservoir to the
filling channel (Figure 5C,D).
Figure 3. Successful loading ofa SlipChipvia dead-endfilling.Green color representsthe sample, andpink,yellow,orange,and bluecolors
represent the reagents. Although the sample pathand reagent paths were filledat slightly different rates (see Supporting Information Movie
channels are LF receiving channels. (B) SlipChip was assembled under the lubricating fluid. (C) The reagent reservoir was loaded with
solution. All reagent reservoirs and the sample reservoir were loaded before filling any fluidic paths. (D) The SlipChip was slipped to form
through the receiving channels. (F) The SlipChip was slipped again to combine reagents with the sample. In (D-F), the microphotograph
micropatterned to facilitate LF dissipation.
DOI: 10.1021/la101460zLangmuir 2010, 26(14), 12465–12471
Article Li et al.
Results and Discussion
developed a physical model (Figure 1). In this model, we inves-
tigated dead-end filling of phase 1 in a single channel to replace a
prefilled phase 2. Phase 1 and phase 2 are immiscible, and the
contact angle of phase 1 on the channel surface in the presence of
phase 2 is larger than 90?; that is, phase 1 is the nonwetting fluid,
as follows: The nonwetting fluid (phase 1) is placed at the inlet.
Applied pressure drives the fluid into the fluidic path connected
to the inlet, pushing out an immiscible wetting fluid (phase 2).
Phase 2 is dissipated out through the gap (Figure 1C). Phase 1
stops flowing when it reaches the dead end.
Characterization of the Physical Model. To characterize
the physical model experimentally, we fabricated a simplified
model SlipChip (Figure 1). We designated a stained aqueous
solution to be phase 1 and a lubricating fluid (LF) to be phase 2.
The surface of the model SlipChip was modified to be preferen-
tially wetted by LF. Using the model SlipChip, we aimed to (1)
recognize the pressure range where robust filling can be achieved
without leaking and (2) determine parameters that affect filling
Inlet Pressure Has to Be Higher than Capillary Pressure.
Since the surface of the chip is wetted by LF (phase 2), the aque-
ous solution could not be loaded by capillary flow. Instead, the
pressure applied at the inlet (ΔPinlet, Pa) has to overcome a resis-
tant pressure, the capillary pressure (ΔPcap, Pa) at the interface
between the aqueous and LF (Figure 1B).
An increase in the cross-sectional dimension of the channel
decreases the resistant capillary pressure ΔPcap(Pa, eq 1) and
consequently facilitates filling. In eq 1, γ (N/m) is the surface
interface approximate curvatures in the horizontal (width w, m)
and vertical (height h, m) directions, respectively, and θ (?) is a
contact angle. Generally, it is difficult to determine the precise
shape ofthe interface even inrectangular channels,10,11especially
if this interface is formed partially by the solid surface and
partially by the liquid-liquid interface, as in this case. According
to the Young-Laplace equation, the approximate pressure
difference at the interface between the aqueous and LF phases
inlet channel(Figure1A) tobeequaltoorsmallerinsizethanthe
reservoir ata certain inlet pressure guarantees thatthe pressureis
high enough for filling of the main filling channel.
ΔPcap ¼ -γð1=Rwþ 1=RhÞ ¼ -2γ
The sealing pressure prevents the aqueous phase from leak-
ing out of the filling channel. Ina SlipChip,a gap exists between
the two plates andthe aqueous solutioncan leak out of the filling
channel (Figure 1E, cross-sectional view). The sealing pressure,
Pseal(Pa) (eq 2) prevents leakage.
Pseal ¼ -2γ cos θ=d
Here, γ (N/m) is the surface tension between the aqueous phase
and LF; θ (o) is the contact angle between the aqueous phase and
surface of the SlipChip in LF; d (m) is the gap distance between
the two plates of the SlipChip. The inlet pressure must be smaller
inlet pressure is higher, the aqueous phase will flow between the
plates, causing leaking.
simple model SlipChip contained multiple filling channels with
increasing size of the channel cross section. Each channel was
Figure 4. Performing a simple chemical reaction in a dry-loaded
FEP device. Schematics show features in the top plate (outlined in
red) and features in the bottom plate (outlined in dashed black
(A) The two plates of the SlipChip were aligned in the absence of
lubricating fluid to form the fluidic paths for the reagent and the
sample. (B) The reagent andsample solutions wereloadedintothe
bine the reagents with the sample. The reaction was accompanied
by the color change from clear to red.
Figure 5. DesigntoenablerapidloadingofsolutionsintoSlipChip
and an outlet) connected to a reservoir for solution storage in one
plate and a well of comparable size in the other plate to expand the
storage volume. (B) When loading a solution into the reservoir
through the inlet, lubricant escapes through the outlet with mini-
mum pressure resistance. (C) The loaded solution, surrounded by
lubricant, is stored in the reservoir without evaporation. Below are
the reservoir. (D) Applying pressure through both the inlet and the
outlet drives the stored solution into the filling channel with the
photographs at the same locations as in (C), to show the channel
being filled with the solution by dead-end filling.
(10) Ajaev, V. S.; Homsy, G. M. J. Colloid Interface Sci. 2001, 244, 180–189.
(11) Ajaev, V. S.; Homsy, G. M. J. Colloid Interface Sci. 2001, 240, 259–271.
Langmuir 2010, 26(14), 12465–12471
Li et al.Article
in the bottom plate, creating a symmetrical channel (Figure 1C,
E). The channel bore two circular reservoirs, one at the inlet and
filling. The dead-end reservoir helped visualize the end point of
filling. We also designed receiving channels alongside the filling
were open to ambient pressure and they were wide enough to
assume that the pressure inside the receiving channels were uni-
form. The receiving channels also helped visualization of leakage
because any leakage of phase 1 from the filling channel would
accumulate in the receiving channel (Figures 1D, E and 2C). We
measured the static contact angles of the stained aqueous solu-
tions on the SlipChip plate in the presence of LF; however, such
contact angles could be different from those within the device
(Figure1C), especiallyunder flow conditions.Therefore,tochar-
acterize the performance of the model SlipChip, we used the
upper limit of the allowed inlet pressure (eq 4). To vary the value
of the upper limit, we changed the maximum sealing pressure by
varying the interfacial tension (γ) and the gap between plates, by
adding fluorinated surfactants and monodispersed glass beads in
ded on inlet pressure and not on channel size (Figure 2). That is,
when the inlet pressure was lower than the maximum sealing
when the inlet pressure was higher than the maximum pressure,
leaking occurred in all channels (Figure 2C).
ΔPinlet< Pseal;max ¼ 2γ=d
Dissipation of LF Limits the Filling Speed. The equations
predicted that changing related parameters affects filling speed
while changing unrelated parameters does not. In the simple
to flow resistance of the aqueous phase (phase 1) in the filling
LF (phase 2) in the filling channel; and ΔP3(Pa), the pressure
ses the pressure difference along the system. The pressure differ-
the viscosity of the corresponding fluid i (μ1is the viscosity of the
aqueous phase, μ2and μ3are the same, the viscosity of the lubri-
cating phase) and Li(m) is the average length of the fluid path.
Qi(m3/s) is the flow rate of discharge. Due to conservation of
mass, Q1, Q2, and Q3are the same. hiis the height of the fluidic
path; therefore, h1and h2are the same and equal to the height of
the channel. h3is the gap between the two plates of the SlipChip.
wi(m) is the width of the fluidic path. w1and w2are the same,
the flow rate (Q), which describes the filling speed.
ΔPflow ¼ ΔPinlet- ΔPcap
ΔPflow ¼ ΔP1þ ΔP2þ ΔP3
ΔPinlet ¼ ΔP1þ ΔP2þ ΔP3þ ΔPcap
8hi3wi 1 -2hi
We characterized the filling speed in the model SlipChip. We
assumed thatL1and L2were the same,equal to halfthe length of
ing channel and the large receiving channel. We assumed w3was
half the length of the filling channel. In the model SlipChip, the
ratio increased (height decreases and/or width of the channel
increases); and the pressure drop ΔPiin the channel changed
much larger than ΔPcapin order to fill the channel (eq 5). There-
ous solution, at a fixed inlet pressure, was determined by the rate
by its viscosity and the gap size.
Q ¼ Q3 ¼8h33w3ΔPinlet
keeping w3, L3, and ΔPinletconstant at 1 ? 104μm, 2 ? 103μm,
and 5.3 ? 103Pa respectively. We used beads of defined sizes to
control the gap (see Experimental Section in the Supporting
Information). We confirmed qualitatively that the filling rate
not sensitive to change of other parameters related to ΔP1, ΔP2,
and ΔPcap(Table 2, n=3 for all experiments).
Filling a More Complex SlipChip by Dead-End Filling.
We used the physical model and designed a system to use dead-
(Figure 3). We used a previously reported design, similar to the
user-loaded SlipChip screening conditions for protein crystal-
lization with 16 different precipitants and 11 mixing ratios for
each precipitant.2We made the following modifications to simp-
lify the design: Straight ducts were fabricated without turns, and
no narrow channels were used to balance the pressure. In addi-
tion, we added an inlet reservoir for each solution. The inlet
the simple model SlipChip, but also for storage and to prevent
Table 1. Effects of SlipChip gap and Viscosity of Lubricating Fluid on Filling Rates
w1= w2= 141 μm
w1= w2= 562 μmpredicted Q (nL/s)
(12) Ichikawa, N.; Hosokawa, K.; Maeda, R. J. Colloid Interface Sci. 2004, 280,
DOI: 10.1021/la101460z Langmuir 2010, 26(14), 12465–12471
ArticleLi et al.
evaporation. Solutions were first loaded into the inlet reservoirs
(Figure 3C), before applying pressure to fill the fluidic paths
(Figure 3D-F). We also designed smaller outlet reservoirs to
prevent undesirable back flow. To minimize the flow pressure
generated by dissipation of lubricating fluid between plates while
maintaining the same sealing pressure, receiving channels were
fabricatednearthefluidic pathsothatthe flowing distanceofthe
in depth) on the contacting surface of the SlipChip to further
lowertheflowpressure between plates(SeeExperimental Section
and Figure S2 in the Supporting Information). The similarity
between this chip and the user-loaded SlipChip2makes applica-
tions to crystallization straightforward. This SlipChip design can
also perform multiplexed screening of crystallization conditions
by loading multiple reagents at multiple mixing ratios. Loading
reagents at multiple mixing ratios allows for on-chip titrations.
The ability to titrate a reagent on-chip is important for protein
identity, can affect the outcome of crystallization.2
tion reached the end of the fluidic path even though the sample
fluidic path with more wells were still being filled (see Movie S1,
all the solutions can be loaded using a single pressure source.
whether the same approaches would work for a dry SlipChip, in
which no liquid is used to lubricate the plates. While lubricated
SlipChips prevent evaporation from wells and eliminate the air/
water interface that is undesirable in some applications, dry Slip-
Chips could be attractive for applications where the lubricating
be rapid because air has low viscosity and can escape rapidly bet-
ween the plates. The design of the device was the same as the
device shown in Figure 3, but this device was made from plastics
by hot embossing FEP using glass molds (see Figure S1 and
SlipChip was sandwiched between two glass plates and loaded in
the absence of any lubricating fluid. A simple chemical reaction
was used to demonstrate this dry-loading (Figure 4). Using this
method, the solutions filled the fluidic paths of the SlipChip
completely (Figure 4B), and slipping successfully combined the
solution (reagent) and the KSCN solution (sample) (Figure 4C).
This reaction produced a red solution of various complexes,
including Fe(SCN)3. No evidence of cross-contamination was
seen, and no red complex formed in the ducts.
Designing a SlipChip to Simplify Loading and Allowing
for Stable Storage of Solutions. We also developed a method
to easily load solution into a storage reservoir prior to dead-end
filling (Figure 5). Loading of the solution into the reservoir as
the gap, and, in some designs, this drainage may become rate
limiting, especially where dense arrays are loaded and lubricating
fluid from multiple reservoirs drains through the same paths. To
eliminate this potential problem, and to enable robust loading by
and the density of the reservoirs, we tested an additional simple
idea for creating a storage reservoir between the two plates into
design, each reservoir has an inlet and an outlet, creating a very
low resistance fluidic path for loading. The shape of the reservoir
is such that surface tension would drive the loaded solution into
the center of the storage reservoir (Figure 5C), where it would
occur when pressure is applied to both the inlet and outlet of the
surrounded by the lubricating fluid, allowing for stable storage
and preventing evaporation. We found that this idea is sound
(Figure5), and we recommendthatitbeincorporated into future
designs of dead-end loaded SlipChips.
to fill both lubricated (with fluorocarbons as lubricating fluids)
and dry (with air between the plates) SlipChips with aqueous
dard format, such as 96, 384, or 1536 well plates, or using such a
plate as one of the plates of the SlipChip. Standard equipment,
the plate; after pressurization, desired volumes would be formed
inside the SlipChip. In addition, a reservoir to store solutions at
the inlets can help prevent evaporation, a common problem for
protein crystallization,13and it would be useful for performing
immunoassays and PCR reactions. This paper provides a simple
method to control fluid flow in a microfluidic device to comple-
ment other creative ways in which flow has been generated and
controlled,14-19and SlipChip may find similar applications. The
concept of draining a fluid through a gap between plates can be
extended to other applications such as the separation of two
phases. For example,verysmall scaleliquid-liquidseparations20
could be accomplished by directing one phase to the gap while
filling could alsobeextended tosealed devices ifnarrowchannels
with high capillary pressureare used. A similarsystem21has been
described to facilitate merging of two sequential droplets. In this
by modifying the surface of the SlipChip to be hydrophilic, this
Table 2. Viscosity of Phase 1, Surface Tension between Phase 1 and Phase 2, and the Size of the Filling Channel Did Not Affect Loading Rate
w1= w2= 141 μm
w1= w2= 562 μm predicted Q (nL/s)
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Langmuir 2010, 26(14), 12465–12471
Li et al.Article
system could be extended to other systems where phase 1 is oil-
based and phase 2 is aqueous.
The “dry SlipChip” described here, operating without a lubri-
SlipChip. When aqueous solutions are used, the dry SlipChip
benefits from superhydrophobic surfaces with high contact angle
of the aqueous phase and low contact angle hysteresis. Such sur-
faces can be achieved by a number of approaches, including the
of block copolymers,24surface coatings,25surface roughness,26,27
and other approaches.28-32We believe that the dead-end filling
and dry SlipChip will play a role in a broad range of appli-
cations, including enabling diagnostics in resource-limited
Acknowledgment. This work was supported by the NIH
Protein Structure Initiative Specialized Centers Grant GM074961
(ATCG3D) and theNIH Director’s Pioneer AwardProgram, part
of the NIH Roadmap for Medical Research (1 DP1 OD003584).
Part of this work was performed at the Materials Research Science
and Engineering Centers microfluidic facility (funded by the Nati-
onal Science Foundation). We thank Heidi Park for contributions
to writing and editing this manuscript.
tal Section, tables, and figures and supporting movie. This
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