Polymer Microfluidics Biomems Case Study: Ece/Me/Ie 485

Polymer Microfluidics BioMEMS
Case Study
ECE/ME/IE 485
Outline
• Introduction
• Modeling
• Fabrication –
bi i S f ih
Soft Lithography
h
• Cases
Polymer Microfluidic bioMEMS
Polymer Microfluidic bioMEMS
Cell Culture Cell Trapping
Patch Clamp
Electroporation
Courtesy of BioPOEMS Group@Berkeley
Microfluidic Cell Electrophysiology Chip
Microfluidic Cell Electrophysiology Chip
Microfluidic Particle Manipulation
Microfluidic Particle Manipulation
Microfluidic Cell Culture Chip
Microfluidic Cell Culture Chip
Microfluidic Tunable Imaging Lens on Chip
Microfluidic Tunable Imaging Lens on Chip
Self-aligned Integrated Microfluidic Optical
S t
Systems (SiMOS)
SiMOS Design SiMOS SMD set-up
Microfluidic
Detector channel Mirror Diode laser
Cylindrical lens
LED
Objective
j lens and filter
Planar Microlenses
Excitation light
Optical fiber
SiMOS
Self-aligned
Microlens with Avalanche photodiode
Microfluidics
100 m
Abstract: A portable device that can identify protein and peptides real time in
complex biological systems such as human bodily fluids reliably and accurately is in
high demand to properly diagnose and treat medical conditions.
conditions Recently,
Recently success
in isoelectric point (pI) based protein separation techniques utilizing a
microfluidics system has provided significant hope in developing such a device.
However, existing systems are cost prohibitive for the large‐scale, multiplexed
diagnostics required for complex diseases. Lynntech has developed an innovative
Polydimethylsiloxane (PDMS) based microfluidics system with a unique design
utilizing multi‐channel inlets and outlets for isoelectric point (pI) based separation
of proteins.
proteins The design of the microfluidics chip is optimized by performing
numerical simulations using COMSOL Multiphysics. The operating and design
parameters of the microfluidics device are optimized to maximize the pH range
and resolution in each chip for efficient separation. This work has provided basis
for developing a multi‐chip configuration that can achieve varying degrees of pI
resolution in each chip.
Microfluidic Protein Preconcentrator Using a Microchannel‐Integrated
Nafion Strip: Experiment and Modeling
M. Shen*, H. Yang, V. Sivagnanam, and M. A. M. Gijs
M Shen* H Yang V Sivagnanam and M A M Gijs
Laboratory of Microsystems, Ecole Polytechnique Fdrale de Lausanne, CH‐1015
Lausanne, Switzerland
Anal Chem Article ASAP
Anal. Chem., Article ASAP
Abstract: We propose a simple microfluidic device for protein preconcentration based on the electrokinetic
trapping principle. It comprises a narrow Nafion strip that is simply cut from a commercial membrane and is
integrated into a molded poly(dimethylsiloxane) (PDMS) microfluidic structure using a guiding channel.
Mechanically clamping the PDMS/Nafion assembly with a glass substrate results in a rapid prototypable,
leak‐tight, and easily disposable device. Our device preconcentrates negatively charged fluorescent proteins
located at the anodic microfluidic compartment side of the Nafion strip within a few minutes and up to a
concentration factor of 104. Moreover, we present a numerical study of the preconcentration effect by
solving the coupled Poisson, Nernst−Planck, and Navier−Stokes equations for our type of device, which
provides microscopic insight into the mechanism of preconcentration. The electrical field across the ion‐
permselective Nafion generates concentration polarization, i.e., ion depletion at the anodic side and ion
enrichment at the cathodic side for both types of ions, with a local excess of mobile positive ions in the
depleted concentration polarization zone, inducing a nonequilibrium electrical double layer in close
proximity to the Nafion membrane. A voltage difference applied over the anodic compartment is used to
generate the electrophoretic flow velocity of the negatively charged tracer biomolecules. This, in
combination with the electroosmotic flow in the opposite direction, which originates from the fixed charges
on the channel walls and the induced space charge near the membrane, provides the basis for the local
preconcentration of the negative tracer biomolecules.
Fluorescence micrographs captured
during preconcentration of a 6 nM
AF−BSA sample after application of a
voltage difference of 10 V (VH = 15 V, VL =
5 V) for 1, 5, 9, and 11 min. Both buffer
channel reservoirs (not shown) were
kept at 0 V.
(Left) Time dependence of the maximum fluorescence intensity of the preconcentrated plug for AF−BSA
concentrations of 60 nM, 6 nM, and 60 pM with the applied electrical potential difference of 10 V (VH = 15
V VL = 5 V). Also the fluorescence intensity from standard concentration samples (1, 3, and 6 μM) is shown.
V, 5 V) Al th fl i t it f t d d t ti l (1 3 d 6 M) i h
(Right) Maximum fluorescence intensity of the preconcentrated AF−BSA plug at a control time of 7 min for
initial concentrations of 60 nM and 600 pM as a function of the voltage difference applied over the anodic
compartment (keeping VL = 5 V).
Microfluidic Protein Preconcentrator Using a Microchannel‐
Integrated Nafion Strip: Experiment and Modeling
M. Shen
M Shen*, H. Yang, V. Sivagnanam, and M. A. M. Gijs
H Yang V Sivagnanam and M A M Gijs
Laboratory of Microsystems, Ecole Polytechnique Fdrale de Lausanne, CH‐
1015 Lausanne, Switzerland
,
The Nernst−Planck equation describes the conservation of mass for ionic species in a fluid medium in the presence of
an applied electrical field. In principle, the transport of positive (i = 1) and negative (i = 2) buffer ions and the
tracer molecules (i = 3) can be described by this equation:
where ci, Di, and zi are the molar concentration of ionic species i and its corresponding diffusion coefficient and

corresponding valence, respectively. F is the Faraday constant, and Rand T represent the molar gas constant and
temperature, respectively. is the electrical potential, and u is the fluid velocity. This equation describes the flux of
ions under the influence of both an ionic concentration gradient ci(t) and an electrical field.
P i
Poisson’s equation is used to describe the relation of the electrical potential and the local concentration distribution
’ i i d d ib h l i f h l i l i l d h l l i di ib i
of buffer ions and charged tracer molecules:
where ρfix is the volumetric fixed charge density of the membrane and ε0 and εr are the vacuum permittivity and the

relative dielectric constant respectively
relative dielectric constant, respectively.
Moreover, the Navier−Stokes equation and the continuity equation for an incompressible fluid are incorporated into
the model, which describes the motion of the fluid:
wherep = 0 indicates the absence of external hydrostatic pressure and ρ and η are the density and viscosity of the
0 indicates the absence of external hydrostatic pressure and ρ and η are the density and viscosity of the
water‐based fluid. The Navier−Stokes equation should be employed with the electrical body force term to
incorporate the interaction between the local electrical field and ion concentration gradients, as indicated in the
third term on the right in eq 3.
M. Shen
,
(i) The Brinkman equation for the porous medium (for example, the Nafion membrane) in the absence of external
hydrostatic pressure was adopted for describing the flow inside the membrane, taking into account the electrical body
force from the mobile ions:
here 0 < εp < 1 is the porosity and κ the permeability of the membrane. The correction factorn originates from the reduced

velocity due to the electric double layer overlap effect within the pores; we used a value of n = 0.1 in our simulations.
(ii) Because of the existence of the EDL due to the fixed charge on the interface between the microchannel and electrolyte
solution EOF of the first kind is generated by applying an electrical field over the microchannel However in the small
solution, EOF of the first kind is generated by applying an electrical field over the microchannel. However, in the small
region close to the membrane−microchannel interface, because of the CP phenomena, a secondary EDL due to the
induced space charge develops. To be more precise, near the membrane, the effective EDL, which generates locally an
EOF of the second kind, results from the secondary EDL, complemented by the primary (quasi‐equilibrium) EDL. To take
into account the two kinds of EOF simultaneously and to reduce the complexity of the calculation process, EOF of the
first kind was modeled as originating from an effective velocity slip of the liquid at the microchannel walls on the basis
of the thin EDL assumption. The slip velocity is given by the Helmholtz−Smoluchowski formula
where Et is the tangential electrical field just outside the double layer, ε and η are the permittivity and viscosity of the liquid
(both assumed constant), and ζ is the ζ potential. This approach permits avoidance of the use of a very fine mesh to
resolve EDL‐based effects in the anodic microchannel. Since the EOF of the first kind is implemented into the model in
the form of the boundary slip, the fixed surface charge on the microchannel walls is no longer considered.
M. Shen
,
diffusion coefficient of a
positive/negative ion in the
electrolyte 1 5 × 10−9m2/s
1.5
diffusion coefficient of a 2 × 10−10m2/s
positive/negative ion in the
membrane
membrane porosity, εp 0.28
membrane permeability, κ 10−18 m2
assumed ion concentration 1 mM
(positive and negative) in
the electrolyte solution, C0
assumed fixed volumetric 1 mM
charge concentration of the
membrane
M. Shen
,
(a) Simulated fluid velocity streamlines
(uniform density plot) with normalized
arrows indicating the flow direction after
g
application of the external voltage (VL = 5
V, VH = 15 V) for 15 min. A vortexlike flow
behavior is observed as a consequence
of the development of the EDL close to
p
the membrane−anodic compartment
interface. (b) Arrows representing the
electrical field strength, superimposed
on the velocity streamlines, in an area
y ,
indicated by the dashed rectangle in (a).
(c) Flow profile in the anodic
compartment along the solid line in (a)
pp g
after application of the external voltage
(VL = 5 V, VH = 15 V) for 1, 7, and 15 min.
M. Shen
,
(a) Distributions for monovalent positive (full lines) and negative (dashed curves) ions of the background
electrolyte after application of the external voltage (V
y pp g ( L = 5 V,, VH = 15 V) for 1, 7, and 15 min. The calculation
) , ,
was done along the solid line shown in the inset at the lower left. (b) Zoom on the ion distributions of the
background electrolyte in a region close to the membrane, showing charge imbalance and formation of the
EDL
Abstract: Joule heating in the electromagnetic cell sorting system is problematic. Our micro‐device was
fabricated for the rapid separation by high magnetic field gradients of electromagnet and dissipates the
Joule heat energy that causes unnecessary heat‐up in the device. By using a cooling channel embedded in
microfluidic channel, Joule heat can be reduced to dissipate thermal energy to an active area of a
microfluidic channel and maintain the temperature of device biocompatible, e.g. 37 C. We analyzed the
temperature distribution of the device using numerical model and compared with the experimental data.
Finally, we demonstrated the magnetic beads separation and obtained the separation efficiency of 97%.
Abstract: Microfluidics is able to provide many benefits to the fields of biology and chemistry through its
ability to use small amounts of fluid and to finely control the environment of the experiment, However, the
precision of the flow rate control at the microscale remains limited to either off‐chip variable‐flow‐rate
pumps or on‐chip valves. Here, we report an on‐chip pneumatic valve that allows for proportional, analog
control of the flow rate with the actuation pressure. FEM simulations were used to model the flow controller
to develop a tool to optimize the device design for linear dependence of the flow rate on the actuation
pressure. Microfluidic devices were manufactured in elastomeric material (PDMS) and experiments were
performed to compare the results from the FEM simulation. We found that both the simulations and the
experiments exhibited a linear relationship between flow rate and actuation pressure over 70% ± 5% of the
range from completely closed to completely open, with R2 ≥ 0.98. The close agreements between the
experiments and simulations indicate the utility of FEM to optimize the design of microfluidic components.
ABSTRACT: Electroporation is an efficient method of introducing foreign impermeant molecules such as
drugs and genes into cells. Conventional electroporation has been based on the application of short
electrical pulses (electropulsation). Electropulsation requires specialized equipment and cannot be
integrated easily with techniques such as electrophoresis which is based on constant voltage. Here we
demonstrate the delivery of small molecules and genes into cells, using a microfluidic electroporation
technique based on constant direct current (DC) voltage that we developed earlier. We demonstrate the
delivery of two molecules into Chinese hamster ovary (CHO‐K1) cells: a membrane impermeable nucleic acid
dye (SYTOX1 Green) and a plasmid vector carrying the gene for green fluorescent protein (pEGFP‐C1). Our
devices can exert field variations to flowing cells that are analogous to the application of single or multiple
pulses by having different geometries. We investigate the effects of the electrical parameters and different
geometries of the device on the transfection efficiency and cell viability. Our technique provides a simple
solution to electroporation‐based drug and gene delivery by eliminating the need for a pulse generator. We
envision that these simple microscale electroporation devices will have the potential to work in parallel on a
microchip platform and such technology will allow high‐throughput functional screening of drugs and genes.
ABSTRACT: High‐sensitivity microfluidic calorimeters raise the prospect of achieving high‐throughput
biochemical measurements with minimal sample consumption. However, it has been challenging to realize
microchip‐based calorimeters possessing both high sensitivity and precise sample‐manipulation capabilities.
Here, we report chip‐based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5‐nL
samples with 4.2‐nW resolution. Our approach, based on a combination of hard‐ and soft‐polymer
microfluidics, provides both exceptional thermal response and the physical strength necessary to construct
high‐sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures.
Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction
chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution
via on‐chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute
microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving
measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol.
The device structure can be adapted easily to enable a wide variety of other standard calorimeter
operations; one example, a flow calorimeter, is described.

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Polymer Microfluidics BioMEMS

where ci, Di, and zi are the molar concentration of ionic species i and its corresponding diffusion coefficient and

where ρfix is the volumetric fixed charge density of the membrane and ε0 and εr are the vacuum permittivity and the

here 0 < εp < 1 is the porosity and κ the permeability of the membrane. The correction factorn originates from the reduced

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