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Multi-Physics Analysis of Microfluidic Devices With Hydrodynamic Focusing and Dielectrophoresis
Multi-Physics Analysis of Microfluidic Devices With Hydrodynamic Focusing and Dielectrophoresis
Introduction
As microfluidic devices become smaller and more complex, fewer options are available for modeling the
behavior these devices. Analytic solutions that provided scoping results when the devices were simple fail
to provide adequate assurance when the devices become complex. And if more than one physics
environment is involved, complexity will be present for the degrees of freedom as well as the geometry.
As a result, the only viable alternative is to use finite element simulation. One of the strengths of the
ANSYS finite element program is its ability to simulate multi-physics systems in both the macro and micro
scale domains. This paper presents some preliminary models for a microfluidic device to demonstrate some
of these abilities for a micromachined dielectrophoretic flow cytometer.
The behavior of the cells as they flow through the system undergoing hydrodynamic focusing can be
determined using Flotran for a fluidic model of the system. The dielectrophoretic behavior of cells present
in the fluid can be found as a result the electric fields generated between the submerged electrodes in the
flow. The Joule heating created by those electrodes and the subsequent temperature rise can be determined
by modeling the thermal behavior of the system. Optical detection methods, device fabrication and
packaging, and the performance of the electrodes and of the device as a whole will not be discussed.
The Phenomena
Flow Cytometry
Flow cytometry is defined as “a technique for identifying and sorting cells and their components (as DNA)
by staining with a fluorescent dye and detecting the fluorescence usually by laser beam illumination.”1 In
the simplest type of device, cells flow past an optical detector in a single file line and a count of cells is
made. If the device is a cell sorter, the output signal from the detector may be used to decide what direction
the cell should take. A secondary signal is then be sent to the sorting mechanism to change the path of the
cell, if necessary. Finally, cells flow out of the device through one of the two outlet channels. In this
example, hydrodynamic focusing uses the addition of a sheath fluid as the pipe narrows to focus the sample
flow into a single file line of cells before they enter the detection region.
Dielectrophoresis
Dielectrophoresis is the movement of dipole particles as a result of the “mechanical forces exerted by a
field on a suspended particle, through interaction with its induced dipole moment.”2 This can be useful for
manipulating polymer particles like latex spheres, as well as with living cells. Cells can experience positive
or negative dielectrophoresis depending on the properties of the cells and their surrounding medium. Those
experiencing negative electrophoresis migrate towards regions of low field strength. Depending on the
strength of the field, the cells are then either trapped at the field minima or they are deflected slightly from
their original course of travel.
In flow cytometers, electrodes can be placed near or in a fluid stream to exert a force on the cells as they
pass the electrodes. If the dielectrophoretic force is sufficient to overcome the drag force on the cell, the
cell will be pushed away from the electrodes. In this way, cells can be moved from the center of the
channel to one side or the other, effectively sorting them into separate output channels (figure 1).
Cytological Constraints
It is important that the living cells in the fluid sample are not permanently damaged or killed in the process
of being manipulated. Mammalian cells should be subjected to no more than 1 Pa shear stress, no more
than 70 mV across the cell membrane and a maximum temperature of no more than 39 degrees C. (Body
temperature is 37 C.) It is also preferable to keep the cells in a biologically compatible medium like a
physiological saline solution or a well regulated sucrose solution.
Hydrodynamic Focusing
The use of a sheath flow for hydrodynamic focusing is described in detail by Lee et al.3 Since the geometry
of the focusing region was not given, it was chosen using the velocity and shear stress requirements.
The behavior of the fluid in the focusing region of the microfluidic device is dependent on shear stress,
velocity profile and conversation of mass. The velocity profile at a radius r for a single fluid flowing
through a cylindrical pipe is given by:
r2
v(r ) = vmax (1 − ) Eq 1
R2
where r is the radial distance from the centerline of a pipe of inner radius R with a maximum fluid velocity
of vmax found at the center of the pipe. The shear stress on a cell in the flow is given by:
du
τ =µ Eq 2
dy
where τ is the shear stress, µ is the viscosity of the liquid, and du is the change in fluid velocity over the
distance dy. The allowable shear stress over the cell, cell diameter and the velocity of the cells are givens,
so equation (2) is solved for du which is then substituted into equation (1) to solve for the minimum inner
radius of the pipe in the detection region.
The geometry of the sheath flow region is entirely dictated by the principle of conservation of mass which
says that the total mass flow rate of all fluid streams entering a control volume must equal the total mass
flow rate of all fluid streams exiting the control volume. Since concentric sheath flow cannot be achieved,
two dimension sheath flow is used. In two dimensional sheath flow, the sample fluid enters the system with
a channel of sheath fluid on either side. These three streams converge and the total width of the channel is
decreased. It is assumed that the same incompressible fluid will be used for the sheath and sample fluids.
Using conservation of mass, the following relationship can be found between the required diameter of the
focused core (which must be the same as the diameter of the cells) and the geometry and initial velocities of
the core and sheath fluids as they enter the system4:
v2 Da
d= Ds = Eq. 3
vcore vD vD
1.5( 1 1 + 3 3 )
v2 D2 v2 D2
where d is the diameter of the focused core, vc is the velocity of the focused core (and also the maximum
velocity of the focused stream), Da is the diameter of the focused stream, v1 is the initial velocity of the top
sheath fluid, v2 is the initial velocity of the sample fluid, v3 is the initial velocity of the bottom sheath fluid
and D1, D2 and D3 are their respective diameters (figure 2). This method of focusing works because the
flow is in the laminar regime (Reynold’s number ~ 45). The streams will converge but will not mix since
diffusion across those boundaries is very slow. Therefore, the cells in the focused stream will stay in their
separate streamlines through the device.
Horizontal Focusing
A fully parameterized two dimensional finite element model was created using Flotran to demonstrate the
fluid focusing in the horizontal direction. Units for all models in this paper are in the micro MKS system
and the fluid is assumed to be physiological saline. The L2TAN command was used to create the narrowing
region between the inlet and outlet channels of the horizontal focuser; rectangles formed the other areas of
the focuser. FLUID141 elements were used with no slip boundary conditions specified on all fluid channel
walls. The velocities of all three fluid inlets were set as initial conditions and the pressure was set equal to
zero at the outlet. Meshing was done with the automatic meshing tool using a SMRTSIZE of 1.
A velocity vector plot of the horizontal focusing region is shown in Figure 3. The flow becomes fully
developed very quickly after the streams converge and a parabolic velocity profile can be seen at the outlet.
The maximum velocity is approximately 0.06 m/s. This is lower than the expected maximum velocity of
the system because the flow requires one more focusing step (vertical focusing) to achieve a maximum
velocity of 0.1 m/s before entering the detection region.
F = 2πε m r 3∇ E 2 Re(u * ) Eq 4
where u* is the Clausius-Mossotti (CM) ratio:
(ε *particle − ε medium
*
)
u* = Eq 5
(ε *particle + 2ε medium
*
)
and the complex permittivity is defined as ε = ε − jσ / w . Since the CM ratio for the example system is
*
negative, the cells are pushed away from fields of high concentration.
A two dimensional model of the electrodes in the fluid flow was created using PLANE67 (2D Thermal
Electric Solid) elements to model the behavior of the system in the electrical domain. The electrodes were
assumed to be gold rectangular boxes 3 microns wide and 15 microns deep with a 6 micron gap between
the top and bottom electrode (figure 15). A voltage of +5 V was applied to the nodes of the top line of the
top electrode. A voltage of -5 V was applied to the nodes of the bottom line of the bottom electrode. A
convection to bulk temperature was also applied at the right side of the model to allow the solution to
converge. (In the actual system, the dominant thermal initial condition is the temperature of the fluid as it
enters the electrode region while the thermal resistances of the walls and the device packaging will have
almost no impact. For this reason, the two dimensional model cannot be used for calculating temperature
increases and is presented only to demonstrate the shape of the electric fields generated.) In this model, DC
current was used for simplicity. Either AC or DC may used, but DC has the disadvantage of generating
electrolysis, which may be a concern for applications with biological specimens.
1. The calculation of the gradient requires that the nodes be sorted by coordinate in insure correct
calculation. (To understand this, imagine an ANSYS area meshed in the standard manner (lines
first and then the interior of the area). If the electric field distribution is cylindrical with a variation
in the X direction and no variation in the Y direction, calculation in the ANSYS vector along an
end line would result in a zero value when the actual value would be very steep.)
2. ANSYS does not permit the sorting of one vector based upon a second vector.
3. ANSYS does not permit calculating the DER1 for vector operations when the denominator vector
is not monotonically increasing. For 2 and 3 dimensional models, the denominator values are
likely to loop from minimum to maximum repeatedly. This will require a check on the
denominator values.
4. User calculation of the gradient will require *DO and *IF commands. The values for electric field
and for the node coordinates can be loaded into an ANSYS vector and the necessary calculations
performed. This calculation will be time consuming for large models and it may be more
convenient to export the data to another program, perform the calculations and return the force
values as loads for the subsequent calculation.
The best options to directly calculate the DEP forces on the cells in the fluid flow would be to export the
electric field and do the calculations in a separate program that was intended to do large scale linear algebra
or to write a custom macro that would calculate the gradient of the element electric energy (ETABLE,
SENE) distribution.
Joule Heating
One of the outputs of the electric domain analysis is the Joule heating that occurs as a result of the electric
current. The fluid between the electrodes acts as an electrical resistor. Some of the energy carried by the
current is passed from one electrode to the other, and some of it is dissipated as heat. The joule heating can
be combined with the fluid model to calculate the temperature rise and distribution in the fluid flow to
ensure that the cells will not go into thermal shock or be killed by the sorting process.
Since electrical conductivity (the reciprocal of resistivity) is a function of frequency, the joule heating is
also a function of frequency. Electrical conductivity is given by
σ = σ 0 + jwε
where σo is the base conductivity, j is equal to the square root of -1, w is electrode frequency, and ε is the
permittivity of the medium. The frequency dependence of the conductivity of saline at 1 MHz was found to
be at least two orders of magnitude smaller than the base conductivity, so for this example, the joule
heating will be approximately the same for AC and DC currents.
A three dimensional model of two electrode pairs in the fluid was created to display the Joule heating
between the electrodes. The Joule heating model uses SOLID69 elements and the same geometry and
initial conditions as the electric field model. Figure 18 shows a cut away view of the model. The area of
highest heat dissipation is in the area between the electrodes as expected but has a very limited range away
from the electrodes.
Conclusion
It has been shown that the behavior of microfluidic systems that operate in a number of physical domains
can be modeled and optimized using finite element methods. However, dielectrophoretic forces cannot be
modeled in ANSYS at this time without writing a custom macro to perform a direct calculation. The
creation of this macro will be the focus of future work.
Acknowledgements
The authors would like to thank the MIT Dept. of Chemical Engineering MicroChemical Systems
Technology Center for its support of this work, Prof. Alexander Slocum, Jason Kralj, Eddy Karat, Elena
Antonova and Dave Looman for their feedback, and the MIT 6.777 class for the Spring, 2003 for their
contributions to a similar project. M. K. Thompson would like to thank the National Science Foundation for
its support of her research through a Graduate Research Fellowship. The authors would also like to thank
ANSYS, Inc. for providing the software to make this analysis possible.
References
1. http://webster.com
2. Fiedler et al. Anal. Chem. 1998, 70, 1909-1915
3. Lee et al. Journal of Fluids Engineering, 2001, (123) 672-679
4. Lee et al. Journal of Fluids Engineering, 2001, (123) 672-679
5. Fiedler et al. Anal. Chem. 1998, 70, 1909-1915
6. Foster et al. Biophys. J. 1992,63,180-190.
7. Gimsa and Wachner. Biophys J, August 1998, 75, 1107-1116.