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The floating microfluidic probe: Distance control between probe and sample using hydrodynamic levitation

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  • IBM Research Europe - Zurich

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Microfluidic probes (MFPs) are an emerging class of non-contact scanning devices used to perform local chemical reactions on surfaces covered with liquid. Typically, the probe is scanned at a distance between 10 μm and 50 μm over the surface. For proper functioning, the distance between the probe and the surface needs to be kept stable. Here, we present a self-regulating distance control for a microfluidic probe based on hydrodynamic levitation, and we call the device the “floating MFP.” By injecting a liquid between the probe head and the surface (flow rates: 5–500 μl min−1), we were able to achieve levitation heights up to 15 μm without perturbation of the probe function. We provide an analytical solution describing the levitation, which fits well with the experimental data. This work helps in the design and implementation of distance control in MFPs for a broad range of applications.
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The floating microfluidic probe: Distance control between probe and sample using
hydrodynamic levitation
Martina Hitzbleck, Govind V. Kaigala, Emmanuel Delamarche, and Robert D. Lovchik
Citation: Applied Physics Letters 104, 263501 (2014); doi: 10.1063/1.4886117
View online: http://dx.doi.org/10.1063/1.4886117
View Table of Contents: http://scitation.aip.org/content/aip/journal/apl/104/26?ver=pdfcov
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The floating microfluidic probe: Distance control between probe and sample
using hydrodynamic levitation
Martina Hitzbleck, Govind V. Kaigala, Emmanuel Delamarche, and Robert D. Lovchik
a)
IBM Research-Zurich, S
aumerstrasse 4, CH-8803 R
uschlikon, Switzerland
(Received 28 May 2014; accepted 17 June 2014; published online 30 June 2014)
Microfluidic probes (MFPs) are an emerging class of non-contact scanning devices used to perform
local chemical reactions on surfaces covered with liquid. Typically, the probe is scanned at a dis-
tance between 10 lm and 50 lm over the surface. For proper functioning, the distance between the
probe and the surface needs to be kept stable. Here, we present a self-regulating distance control
for a microfluidic probe based on hydrodynamic levitation, and we call the device the “floating
MFP.” By injecting a liquid between the probe head and the surface (flow rates: 5–500 ll min
1
),
we were able to achieve levitation heights up to 15 lm without perturbation of the probe function.
We provide an analytical solution describing the levitation, which fits well with the experimental
data. This work helps in the design and implementation of distance control in MFPs for a broad
range of applications. V
C2014 AIP Publishing LLC.[http://dx.doi.org/10.1063/1.4886117]
There is a class of microfluidic devices that are based on
the concept of having a probe dispensing liquids locally to
biological samples, tissues, or on surfaces.
1
These devices
are well-suited for localized, low-volume, and precision
processing of biological samples typically placed on stand-
ard glass slides or Petri dishes. We are interested in the
microfluidic probe (MFP), which is highly versatile in its
operation and its range of applications. The MFP has been
used for several applications, such as microscale staining of
tissue sections,
2
biochemical patterning of surfaces,
3
and
single-cell electroporation.
4
Central to the MFP is a micro-
fluidic chip (MFP head) comprising at least two channels for
liquids that terminate at an apex. The apex is aligned parallel
to the sample surface, and a processing liquid is simultane-
ously injected and aspirated resulting in a hydrodynamically
confined volume of liquid (flow confinement) on the surface,
(Fig. 1). MFPs operate at distances between 10 lm and
50 lm from the surface within a liquid environment, making
the distance regulation challenging for the following reasons:
(1) the liquid can vary in its composition, e.g., pH, ion con-
tent, and turbidity, (2) compatibility with standard biological
substrates is required, and (3) direct contact with the sample
should be avoided. MFP heads used to be leveled manually
with a reference slide and the distance was set using a motor-
ized stage. This worked well for applications involving flat
and transparent microscope slides, for example, creating an
array of proteins.
3
However, for surfaces with topographical
variations, a manual and continuous intervention was
required during operation that limited the technology to be
used with transparent substrates.
Controlling the probe-to-sample distance is critical not
only in the MFP
5,6
but also in other scanning technologies
such as nanopipettes
7
and atomic force microscopy-based
approaches.
8
In order to sense distance at the sub-millimeter
scale, there are numerous feedback mechanisms based on
force,
9
current,
7
voltage, or frequency. As precise and fast
these sensing approaches may be, they are not suitable for
measuring the probe-to-sample distance during operation of
MFPs.
10
A MFP that allows processing of surfaces with to-
pographical variations and also on opaque substrates, with-
out the need for manual intervention, will significantly
broaden the range of applications.
Inspired by granite sphere fountains,
11
we hypothesized
that a “floating” mechanism could allow for probe-to-sample
distance control in a stable and self-sustained manner at the
micrometer length scale. We therefore implemented the
hydrodynamic levitation on the MFP and established key pa-
rameters for design considerations, which support the imple-
mentation of such a distance control. We call this particular
implementation of hydrodynamic levitation the “floating
MFP” (fMFP).
In contrast to the vertical MFP, wherein the head is
mounted to a motorized Z-stage, the fMFP is not constrained
along the Z-direction. Our approach was to clamp the head
onto a tone arm of a standard record player mounted to an
inverted light microscope ensuring the fMFP head is aligned
to the optics (Fig. 1(a)). The vertical movement during oper-
ation generally is between 10 lm and 50 lm, and the tilt vari-
ation caused by the 200 mm long tone arm was therefore
neglected (0.01for 50 lm height difference). The weight
of the head was by design adjusted using the counter weight
of the tone arm. A precise balance, embedded in the micro-
scope stage, allowed the weight of the head to be set to 0.1 g.
As shown in Figs. 1(b) and 1(c), the fMFP head comprises 4
microchannels. The two inner processing channels were used
to sustain a hydrodynamic flow confinement (Fig. 1(d)), and
the two outer floating channels were used to inject a floating
liquid that generated a lifting force (F
lift
). This force depends
on factors such as the gap height h, the geometry of the head,
and the weight of the head. In addition, the capillary force
F
capillary
, the viscosity lof the floating liquid, as well as the
momentum of the injected liquid are to be taken into account
to characterize the system. The key principle of the fMFP is
to use a stream of incompressible fluid flowing in a slit-like
confinement inducing a pressure due to the hydrodynamic re-
sistance exerted on the sidewalls of the system. The resulting
a)
yrl@zurich.ibm.com
0003-6951/2014/104(26)/263501/4/$30.00 V
C2014 AIP Publishing LLC104, 263501-1
APPLIED PHYSICS LETTERS 104, 263501 (2014)
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F
lift
counteracts with the above mentioned forces and reaches
a steady state at height h, which in practice is important for
functioning of the fMFP.
First, we looked at the hydrodynamic levitation of a
fMFP head having a circular apex with a radius Rand a sin-
gle circular floating channel of radius r0in the center. This
head has a cylindrical symmetry in which the partial differ-
ential equations of the Navier stokes equation decouple and
an analytical solution under approximation of creeping flow
can be established. At steady state and on account of the
cylindrical symmetry, the radial component of the velocity
vector is independent from the angle hand the only compo-
nent that is not equal to zero ðu¼uðr;zÞ~
erÞ. We assume a
parabolic flow profile in the Z-direction (no-slip condition)
and describe the velocity vector as ~
uðr;zÞ¼AðrÞzðhzÞ~
er.
The continuity equation for incompressible fluids
ðr ~
u¼0Þrepresents the mass balance of the system and
requires that the flow rate of floating liquid entering the head
(Q
in
) equals the mass flow through the outlet, or any other cyl-
inderofradiusr0rRaround the inlet
Qin ¼ðh
0
dz ð2p
0
rdhAðrÞzðhzÞ;8rR;(1)
~
ur;z
ðÞ
¼3Qin
ph3rzhz
ðÞ
~
er:(2)
For a velocity field of Eq. (2), the left hand side of the
Navier Stokes equation (3) is identically zero, and in the ab-
sence of external forces acting on the head, the equation can
be simplified to rP¼lD~
u(creeping flow approximation)
q@~
u
@tþ~
ur
ðÞ
~
u

¼rPþlD~
uþ~
f:(3)
Furthermore, D~
u¼
r~
u¼0r ðr ~
uÞ)@P
@r¼l@2ur
@2z2
applies for the vector field in Eq. (2). As a boundary condition,
we set the pressure at the edge of the apex equal to 0, with
respect to the ambient pressure, or P(R)¼0. Integration
results in
Pr
ðÞ
¼6lQin
ph3ln r
R

:(4)
The pressure below the apex integrated over its
surface area generates a force acting on the head, which
we name lift force (F
lift
). Flif t ¼ÐR
rinlet dr Ð2p
0rdhPðrÞ
¼3lQin
2ph3ðR2r2
inletÞþ2r2
inletln rinlet
R

hi
:
Generally, the radius of the inlet is small with respect to
the radius of the apex ðrinlet RÞ
Flif t ¼3lQin
2ph3R2:(5)
There are mainly four forces acting on a levitating fMFP
head. These are: F
lift
,F
weight
,F
capillary
(from the pinning
forces of the liquid meniscus at the three-phase contact line
of the immersed head), and F
momentum
of the floating liquid
injected through the channels and redirected by the sample
surface (see Fig. 1).
We were interested to study the interplay of the above
forces at flow rates between 0 and 1000 llmin
1
with head
weights of 0.1–2 g to achieve levitation heights up to 20 lm.
Practical considerations suggested the above conditions to be
suitable for operating the fMFP. The range of F
weight
was
limited by the mechanical setup in Fig. 1(a).
Fig. 2shows the magnitudes of forces in relation to the
flow rate of the floating liquid for a circular fMFP. The capil-
lary action can be assumed to be constant since the length of
the three-phase contact line does not change during opera-
tion. For the highlighted flow rates and head weights shown
in Fig. 2, the momentum and the capillary force are small
compared to the weight and the lift force and therefore were
neglected in the analysis. Rearrangement of Eq. (5) results in
h¼3lQin
mnetgR2

1=3
:(6)
During levitation, the lift force counteracts the weight
and the fMFP head reaches equilibrium at height h.
We verified the analytical solution for h(6) by meas-
uring the lift heights of a circular fMFP at different flow
rates and with various head weights. In addition, we tested
the influence of the viscosity of the floating liquid on h. The
FIG. 1. Concept of a fMFP. (a) A modified tone arm was used to position a
fMFP head atop a glass slide placed on the stage of an inverted microscope.
The counter weight allowed adjusting F
weight
below 1 mN. (b) Injecting liquid
through floating channels generates a lifting force F
lift
resulting in hydrody-
namic levitation of the fMFP head at height habove the substrate. Processing
channels ending at the apex of the head are used to hydrodynamically confine
a liquid of interest on the substrate. (c) Photograph of a fMFP head compris-
ing microfabricated channels and vias for liquid interfacing. (d) Micrograph
showing the apex of a fMFP head levitating above a glass substrate. A flow
confinement was generated using a solution of fluorescein, and fluorescent
beads were added to the injected floating liquid as flow tracers.
263501-2 Hitzbleck et al. Appl. Phys. Lett. 104, 263501 (2014)
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vertical position of the head was determined with a resolu-
tion of 130 nm using an optical measuring device (STIL,
CHR 150-N, France). Figure 3shows the lifting measure-
ments with head weights of 125, 250, and 1000 mg plotted
together with the corresponding analytical solution. We find
that for flow rates higher than 100 llmin
1
the experimental
data are in good agreement with the analytical solution. For
lower flow rates, the analytical solution slightly deviates
from the experimental measurements, which is also observed
for hlower than 10 lm. Under these conditions, where the
resulting lift forces are low, the setup is more easily per-
turbed by the experimental conditions (e.g., mechanical re-
sistance, bending of capillary tubing, precision of pumps).
This is not the case if a solution of higher viscosity is used,
such as 30% glycerol in water, which results in higher levita-
tion heights already at flow rates below 10 llmin
1
.
Vertical MFP heads typically have a rectangular apex;
we therefore also studied the lifting behavior of such
geometries. The fabrication of vertical MFP heads is per-
formed by etching channels into a silicon wafer, sealing it
with a glass layer, and singulation of the head by dicing.
10
Typical apex dimensions are 1 2mm
2
. Two channels at
the locations (x
0
, 0), (x
0
, 0) are for injection of the floating
liquid. The other two channels for generating the flow con-
finement are disregarded for this analysis. We modified the
equation for a circular fMFP (4) to approximate the pressure
distribution of a vertical fMFP with rectangular apex.
In Eq. (7),f
x,y
is the minimal distance to the border of
the head in x and y direction, respectively, P
max
is the maxi-
mum pressure, i.e., the pressure at the borders of the inlet,
and K(a) a factor relating to the aspect ratio of the head.
Px;y
ðÞ
¼
0;8x6x0
ðÞ
2þy2>fx;y;
Pmax;8x6x0
ðÞ
2þy2winlet
2

2
;
6lQin
2ph3Ka
ðÞ
ln x6x0
fx

2
þy
fy

2
!
:
8
>
>
>
>
>
>
<
>
>
>
>
>
>
:
(7)
In addition to studying the interplay between flow rate,
head weight, and apex geometry (footprint and placement of
channels), we were also interested in establishing levitating
conditions that do not perturb the probe function.
Figures 4(a) and 4(b) show the results of a finite element
simulation and the analytical solution (7) of the pressure
FIG. 3. Lifting of a circular fMFP at different flow rates, various F
weight
and
viscosity l. Data points with error bars indicate experimental measurements,
and the curves represent the analytical solution based on Eq. (6). The inset
shows a stream of floating liquid spiked with fluorescent beads injected
through the central apertures of a circular fMFP.
FIG. 4. Hydrodynamic levitation of a vertical fMFP. (a) Simulated pressure
distribution within the floating liquid at a gap height of 10 lm and a flow
rate of 150 ll min
1
(left). Comparison between the simulated pressure dis-
tribution (dots) and the modified analytical solution (Eq. 7) along the two
indicated cross sectional views (right). (b) Experimental results (connected
black dots) showing the lifting behavior of an operational fMFP head having
a net weight of approximately 0.125 g. The color band visualizes simulated
lifting heights for different head weights (purple, m ¼0.3 g; dark red
m¼0.1 g). Stable flow confinements using red fluorescent processing liquid
were possible with floating liquid flow rates of more than 500 ll min
1
(flow
confinements shown in insets).
FIG. 2. Magnitudes of forces acting on a circular fMFP head. The area of
the circular apex is p(3 mm)
2
, the three-phase contact line p1.6 mm and the
radius of the central inlet channel 60 lm.
263501-3 Hitzbleck et al. Appl. Phys. Lett. 104, 263501 (2014)
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distribution in the gap between the fMFP head and the sur-
face. The simulation and the analytical solution of pressure
distribution corroborate. These solutions provide guidelines
for the placement of the processing channels relative to the
floating channels and the apex geometry.
Using the optical measuring approach, as employed
with the circular MFP, the lifting of a vertical fMFP at
125 mg 620 mg was monitored for different flow rates and
compared with the simulation results, Fig. 4(b). For each
flow rate, we performed a simulation to estimate the lifting
heights for head weights between 0.1 g (purple) and 0.3 g
(dark red). The influence of the head weight is more pro-
nounced at high flow rates, hence enabling better control of
h. This characteristic may further be leveraged by using a
higher viscous floating liquid. For the head weight of about
125 mg, the measured lifting behaviour is in agreement with
the simulation results.
While increased flow rates of the floating liquid allow
for precise distance control, a high flow rate, such as 1000 ll
min
1
, perturbs the flow confinement of a vertical fMFP (see
inset of Fig. 4(b)). From a practical standpoint, we operate at
hof 10–15 lm, which can readily be achieved at flow rates
lower than 500 llmin
1
where no distortion of the flow con-
finement was observed.
In conclusion, distance control using hydrodynamic lev-
itation allows for easy, rapid, and self-sustaining operation
of MFPs on surfaces covered with liquids. This approach is
applicable to both static and scanning mode of operation of
the MFP and does not need any additional active peripheral
devices other than the ones inherent to the MFP, while ensur-
ing compatibility to a standard inverted microscope. By
altering the flow rates and the head weights, the desired levi-
tation was readily achieved. Further control over the
levitation is possible using liquids with varying viscosities,
changing the apex geometry and surface properties of the
head. We believe that hydrodynamic levitation can more
generally be applicable to other probe-based devices, ena-
bling their use in liquid environments without complex
means of distance control.
We acknowledge financial support by the European
Research Council (ERC) Starting Grant, under the 7th
Framework Program (Project No. 311122, BioProbe). We
thank Folkert Horst for his help with the optical distance
measurements and Marcel Buerge and Urs Kloter for the
support in building the experimental setup. Viola Vogel
(ETH Zurich), Urs Duerig, Bruno Michel, and Walter Riess
are acknowledged for their continuous support.
1
G. V. Kaigala, R. D. Lovchik, and E. Delamarche, Angew. Chem. Int. Ed.
51, 11224 (2012).
2
R. D. Lovchik, G. V. Kaigala, M. Georgiadis, and E. Delamarche, Lab
Chip 12, 1040 (2012).
3
D. Juncker, H. Schmid, and E. Delamarche, Nature Mater. 4, 622 (2005).
4
A. Ainla, S. Xu, N. Sanchez, G. D. M. Jeffries, and A. Jesorka, Lab Chip
12, 4605 (2012).
5
M. A. Qasaimeh, T. Gervais, and D. Juncker, Nat. Commun. 2, 464
(2011).
6
K. V. Christ and K. T. Turner, Lab Chip 11, 1491 (2011).
7
B. Babakinejad, P. Jnsson, A. Lpez Crdoba, P. Actis, P. Novak, Y.
Takahashi, A. Shevchuk, U. Anand, P. Anand, A. Drews, A. Ferrer-
Montiel, D. Klenerman, and Y. E. Korchev, Anal. Chem. 85, 9333 (2013).
8
A. Meister, M. Gabi, P. Behr, P. Studer, J. Vrs, P. Niedermann, J. Bitterli,
J. Polesel-Maris, M. Liley, H. Heinzelmann, and T. Zambelli, Nano Lett.
9, 2501 (2009).
9
K.-H. Kim, N. Moldovan, and H. Espinosa, Small 1, 632 (2005).
10
G. V. Kaigala, R. D. Lovchik, U. Drechsler, and E. Delamarche, Langmuir
27, 5686 (2011).
11
J. H. Snoeijer and K. van der Weele, “Physics of the granite sphere
fountain,” Am. J. Phys. (submitted).
263501-4 Hitzbleck et al. Appl. Phys. Lett. 104, 263501 (2014)
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... Remarkably, the roll-to-roll system integrated with a PCD was found to be insensitive on the gap and small angles between the PCD and the film. This resilience is due to the force equilibrium between the tension in the plastic film and the hydrodynamic pressure generated by the injections of fluids in the narrow gap (25). We implemented a second roll-to-roll process to print pure silver patterns on a different material: polyethylene terephthalate (PET). ...
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Significance Automated liquid handling is of utmost importance for life sciences, pharmaceutical research, and surface engineering. Despite its ubiquitous presence, the last decades’ advances in this domain have mainly consisted of the robotization of the human pipetting movement, with its intrinsic limitations. In this article, we lay the foundation for the pixelated chemical display (PCD), a liquid-handling system based on open-space microfluidics. This device uses the streaming of fluids through independent flow subunits to tessellate a surface with hundreds of reagents simultaneously. PCDs distinguish themselves from previous technology by offering a fast dilution-free reagent switching and a precise yet multiplexable spatiotemporal control of fluids on surfaces. PCDs will be of use in life sciences and for maskless surface processing.
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An increasing number of applications in biology, chemistry, and material sciences require fluid manipulation beyond what is possible with current automated pipette handlers, such as gradient generation, interface reactions, reagent streaming, and reconfigurability. In this article, we introduce the pixelated chemical display (PCD), a new scalable strategy to highly parallel, reconfigurable liquid handling on open surfaces. Microfluidic pixels are created when a fluid stream injected above a surface is confined by neighboring identical fluid streams, forming a repeatable flow unit that can be used to tesselate a surface. PCDs generating up to 144 pixels are fabricated and used to project chemical moving pictures made of several reagents over both immersed and dry surfaces, without any physical barrier or wall. Overall, this article sets the foundation for massively parallel surface processing using continuous flow streams and showcases new possibilities in both wet and dry surface patterning and roll-to-roll processes.
... A measurement of electrical current between electrodes, as employed in SECM, imposes conditions on the applied buffer systems and requires the implementation of electrodes, which also limits the types of compatible applications [17]- [19]. A measurement of the hydraulic resistance of the gap between the probe and the sample requires a relatively high flow rate (above 100 µl/min) to obtain a quantifiable signal [20]. The sample surface thus is exposed to significant shear stress, which is incompatible with e.g. ...
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Objective: We aim to improve operational robustness of liquid scanning probes. Two main failure modes to be addressed are an obstruction of the flow path of the processing liquid and a deviation from the desired gap distance between probe and sample. Methods: We introduce a multi-functional design element, a microfluidic bypass channel, which can be operated in dc and in ac mode, each preventing one of the two main failure modes. Results: In dc mode, the bypass channel is filled with liquid and exhibits resistive behavior, enabling the probe to passively react to an obstruction. In the case of an obstruction of the flow path, the processing liquid is passively diverted through the bypass to prevent its leakage and to limit the build-up of high pressure levels. In ac mode, the bypass is filled with gas and has capacitive characteristics, allowing the gap distance between the probe and the sample to be monitored by observing a phase shift in the motion of two gas-liquid interfaces. For a modulation of the input pressure at 4 Hz, significant changes of the phase shift were observed up to a gap distance of 25 {\mu}m. Conclusion: The presented passive design element counters both failure modes in a simple and highly compatible manner. Significance: Liquid scanning probes enabling targeted interfacing with biological surfaces are compatible with a wide range of workflows and bioanalytical applications. An improved operational robustness would facilitate rapid and widespread adoption of liquid scanning probes in research as well as in diagnostics.
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Article
Objective: We aim to improve operational robustness of liquid scanning probes. Two main failure modes to be addressed are an obstruction of the flow path of the processing liquid and a deviation from the desired gap distance between probe and sample. Methods: We introduce a multi-functional design element, a microfluidic bypass channel, which can be operated in dc and in ac mode, each preventing one of the two main failure modes. Results: In dc mode, the bypass channel is filled with liquid and exhibits resistive behavior, enabling the probe to passively react to an obstruction. In the case of an obstruction of the flow path, the processing liquid is passively diverted through the bypass to prevent its leakage and to limit the build-up of high pressure levels. In ac mode, the bypass is filled with gas and has capacitive characteristics, allowing the gap distance between the probe and the sample to be monitored by observing a phase shift in the motion of two gas-liquid interfaces. For a modulation of the input pressure at 4 Hz, significant changes of the phase shift were observed up to a gap distance of 25 μm. Conclusion: The presented passive design element counters both failure modes in a simple and highly compatible manner. Significance: Liquid scanning probes enabling targeted interfacing with biological surfaces are compatible with a wide range of workflows and bioanalytical applications. An improved operational robustness would facilitate rapid and widespread adoption of liquid scanning probes in research as well as in diagnostics.
Chapter
Microfluidic Quadrupoles (MQs), in analogy to electrical and magnetic quadrupoles, have been recently introduced and analyzed both theoretically and experimentally. Typically, the MQ is generated in a narrow gap formed between a four-aperture Microfluidic Probe (MFP) and a bottom substrate. Unique to the MQ is its ability to generate a dynamic floating concentration gradient and a stagnation point, which have prospective applications in biology and life sciences. In this chapter, we consider the concept behind the MQ, describe the various forms of the MQ, and highlight their key features. Experimental setups, procedures and techniques of measuring the characteristics of the MQ are then presented. The chapter concludes with a review of applications available in the literature and our perspectives of the future of this field.
Chapter
This chapter describes the approximations under which the classical Navier-Stokes equation reduces to the Hele-Shaw problem. It discusses the validity of the point source approximation in Hele-Shaw cells and how they relate to experimental results. The limit and validity of these approximations provide design and operation criteria to ensure that the probes will behave as predicted by the Hele-Shaw theory. The chapter establishes the microfluidic dipole and quadrupole problems using Hele-Shaw flows. It provides the key approximations to extract scaling laws and accurate 1D models to quantify diffusive transport under microfluidic probes. The chapter also presents a brief overview of how these models can be practically applied to optimize probe design, guide experiments, and automate probe operation. It describes the limits of the Hele-Shaw flow approximation and illustrate the basic features of this kind of quasi-2D flow profile.
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Photolithography reached an extraordinary level of sophistication for producing microelectronic components reaching sub-20 nm dimensions on a massive manufacturing scale with extremely high yields. This chapter describes the microfluidic probe (MFP) technology in general terms, and explains how to design and fabricate MFP heads for implementing hydrodynamic flow confinement (HFC) of a liquid on a surface. HFC of a particular liquid on a surface using an MFP is a powerful concept. The first implementation of HFC using an MFP relied on hybrid heads made from a patterned Si chip bonded to a polydimethylsiloxane (PDMS) layer. In the examples of MFP heads, through-wafer etching had to be performed to ensure the connection of apertures with larger channel structureslocated on the other face of the head onto which fluidic ports could be established. The chapter also presents an overview of key concepts discussed in the subsequent chapters of the book.
Article
The microfluidic probe (MFP) is a noncontact technology that applies the concept of hydrodynamic flow confinement (HFC) within a small gap to eliminate the need for closed microfluidic conduits and, therefore, overcome the conventional closed-system microfluidic limitation. Since its invention, the concept has experienced continuing advancement with several applications, ranging from manipulating mammalian cells and printing protein arrays to performing microfabrication. One of the recent developments of the MFP technology is the microfluidic quadrupole (MQ)-a microfluidic analogy of the electrostatic quadrupoles-that is capable of generating a stagnation point (SP) and floating concentration gradients. These distinct features combined with the open-channel concept make the MFP and MQ potentially suitable tools for studying cell dynamics or diagnostic cell trapping and manipulation (using the SP).
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A striking example of levitation is encountered in the "kugel fountain" where a granite sphere, sometimes weighing over a ton, is kept aloft by a thin film of flowing water. In this paper, we explain the working principle behind this levitation. We show that the fountain can be viewed as a giant ball bearing and thus forms a prime example of lubrication theory. It is demonstrated how the viscosity and flow rate of the fluid determine (i) the remarkably small thickness of the film supporting the sphere and (ii) the surprisingly long time it takes for rotations to damp out. The theoretical results compare well with measurements on a fountain holding a granite sphere of one meter in diameter. We close by discussing several related cases of levitation by lubrication.
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We present here a novel platform combination, using a multifunctional pipette to individually electroporate single-cells and to locally deliver an analyte, while in their culture environment. We demonstrate a method to fabricate low-resistance metallic electrodes into a PDMS pipette, followed by characterization of its effectiveness, benefits and limits in comparison with an external carbon microelectrode.
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A flexible method to extract more high-quality information from tissue sections is critically needed for both drug discovery and clinical pathology. Here, we present micro-immunohistochemistry (μIHC), a method for staining tissue sections at the micrometre scale. Nanolitres of antibody solutions are confined over micrometre-sized areas of tissue sections using a vertical microfluidic probe (vMFP) for their incubation with primary antibodies, the key step in conventional IHC. The vMFP operates several micrometres above the tissue section, can be interactively positioned on it, and even enables the staining of individual cores of tissue microarrays with multiple antigens. μIHC using such a microfluidic probe is preservative of tissue samples and reagents, alleviates antibody cross-reactivity issues, and allows a wide range of staining conditions to be applied on a single tissue section. This method may therefore find broad use in tissue-based diagnostics and in research.
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The concept of fluidic multipoles, in analogy to electrostatics, has long been known as a particular class of solutions of the Navier-Stokes equation in potential flows; however, experimental observations of fluidic multipoles and of their characteristics have not been reported yet. Here we present a two-dimensional microfluidic quadrupole and a theoretical analysis consistent with the experimental observations. The microfluidic quadrupole was formed by simultaneously injecting and aspirating fluids from two pairs of opposing apertures in a narrow gap formed between a microfluidic probe and a substrate. A stagnation point was formed at the centre of the microfluidic quadrupole, and its position could be rapidly adjusted hydrodynamically. Following the injection of a solute through one of the poles, a stationary, tunable, and movable-that is, 'floating'-concentration gradient was formed at the stagnation point. Our results lay the foundation for future combined experimental and theoretical exploration of microfluidic planar multipoles including convective-diffusive phenomena.
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Microfluidic systems allow (bio)chemical processes to be miniaturized with the benefit of shorter time-to-result, parallelism, reduced sample consumption, laminar flow, and increased control and efficiency. However, such miniaturization inherently limits the size of the solid objects that can be processed and entails new challenges such as the interfacing of macroscopic samples with microscopic conduits. Here, we report a microfluidic probe (MFP) that overcomes these problems by combining the concepts of 'microfluidics' and of 'scanning probes'. Here, liquid boundaries formed by hydrodynamic forces underneath the MFP confine a flow of processing solution and replace the solid walls of closed microchannels. The MFP is therefore mobile and can be used to process large surfaces and objects by scanning across them. We illustrate the versatility of this concept with several examples including protein microarraying, complex gradient-formation, multiphase laminar-flow patterning, erasing, localized staining of cells and the contact-free detachment of a single cell. Many constraints imposed by the monolithic construction of microfluidic channels can now be circumvented using an MFP, opening up new avenues for microfluidic processing.
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Using nanopipettes to locally deliver molecules to the surface of living cells could potentially open up studies of biological processes down to the level of single molecules. However, in order to achieve precise and quantitative local delivery it is essential to be able to determine the amount and distribution of the molecules being delivered. In this work, we investigate how the size of the nanopipette, the magnitude of the applied pressure or voltage, which drives the delivery, and the distance to the underlying surface influences the number and spatial distribution of the delivered molecules. Analytical expressions describing the delivery are derived and compared with the results from finite element simulations and experiments on delivery from a 100 nm nanopipette in bulk solution and to the surface of sensory neurons. We then developed a setup for rapid and quantitative delivery to multiple subcellular areas, delivering the molecule capsaicin to stimulate opening of Transient Receptor Potential Vanilloid subfamily member 1 (TRPV1) channels, membrane receptors involved in pain sensation, in different neuritis. Overall, precise and quantitative delivery of molecules from nanopipettes has been demonstrated, opening up many applications in biology such as locally stimulating and mapping receptors on the surface of live cells.
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Local interactions between (bio)chemicals and biological interfaces play an important role in fields ranging from surface patterning to cell toxicology. These interactions can be studied using microfluidic systems that operate in the "open space", that is, without the need for the sealed channels and chambers commonly used in microfluidics. This emerging class of techniques localizes chemical reactions on biological interfaces or specimens without imposing significant "constraints" on samples, such as encapsulation, pre-processing steps, or the need for scaffolds. They therefore provide new opportunities for handling, analyzing, and interacting with biological samples. The motivation for performing localized chemistry is discussed, as are the requirements imposed on localization techniques. Three classes of microfluidic systems operating in the open space, based on microelectrochemistry, multiphase transport, and hydrodynamic flow confinement of liquids are presented.
Article
Non-contact scanning microfluidic technologies such as the microfluidic probe (MFP) are of great interest for microscale (bio)chemical and biological applications on surfaces, which cannot be processed in closed microfluidic systems. Here we present a new type of MFP heads that have their main axis normal to the processed surface. Vertical MFP heads have in-plane-fabricated microchannels and are assembled by anodically bonding a microfabricated Si chip with a glass layer. These heads are easier to fabricate, package and position than standard MFP heads that are operated parallel to a surface.
Article
Closed-channel microfluidic devices are widely used in a number of chemical and biological applications; however, it is often difficult to interact with samples, such as cells, that are enclosed inside them. Hydrodynamically confined microflows (HCMs) allow microfluidic-type flows to be generated in open liquid environments, such as Petri dishes, thus greatly increasing the flexibility of microfluidic approaches. HCMs have previously been used for protein patterning and selective cell treatment applications, but the underlying fluid mechanics is not fully understood. Here, we examine the effect of device geometry and flow parameters on the properties of the flow envelope and pressure drop of several two-port HCM devices using a combination of experiments and modeling. A three-port device, which allows for different flow envelope shapes to be generated, is also analyzed. The experimental results agree well with the 3-D computational fluid dynamics simulations, with the majority of the measurements within 10% of the simulations. The results presented provide a framework for understanding the fluid mechanics of HCMs and will aid in the design of HCM devices for a broad range of applications.