Online proceedings - EDA Publishing Association

11-13 May 2011, Aix-en-Provence, France
A Dielectrophoretic Preconcentrator with Circular
Microelectrodes for Biological Cells in Stepping
Electric Fields
Chun-Ping Jen and Ho-Hsien Chang
Department of Mechanical Engineering,
National Chung Cheng University,
Abstract- The ability to enrich rare cells, e.g. circulating tumor
cells (CTC), circulating fetal cells, and stem cells, has been an
important issue in medical diagnostics and characterization. The
main purpose of this investigation was to develop a handheld
microdevice capable of the effective preconcentration of rare cells.
Circular microelectrodes were designed to generate the stepping
electric field by switching the electric field to an adjacent electrode
pair by relays. The cancerous cells with positive dielectrophoretic
response were not only conveyed but also concentrated toward the
center of the circular microelectrodes because the
high-electric-field region between the adjacent electrodes was
gradually decreased in the direction of the stepping electric field.
Numerical simulations of the electric fields were performed to
demonstrate the concept of the proposed design. Moreover,
enrichment of cervical cancer cells was successfully achieved and
took about 160 seconds in the experiment with an approximate
efficiency of 75%, when the peak-to-peak voltage of 16 volts, a
frequency of 600 kHz and the time interval of relay switching with
20 seconds were applied.
Keywords: handheld; dielectrophoresis; enrichment; stepping
electric field.
I. INTRODUCTION
Biological manipulation is essential to numerous
biomedical applications, such as: the isolation and detection
of rare cancer cells, concentration of cells from dilute
suspensions, separation of cells according to specific
properties, and trapping or positioning of individual cells for
characterization. Among these applications, concentrating
rare cells, such as circulating tumor cells (CTC), circulating
fetal cells, and stem cells, has been an important technique in
biological and clinical studies [1,2]. A highly sensitive and
specific identification of CTC could prove helpful in the
early diagnosis of invasive cancers [3]. The methods of CTC
detection are generally divided into cytometric- and
nucleic-acid-based techniques; however, both of these
techniques require an enrichment and detection procedure
[1,4]. Numerous methods for concentrating biological cells
have been addressed in the relevant literature [5], such as
immuno-affinity, filtration (ISET, Isolation by Size of
Epithelial Tumor cells), fluorescent- (FACS,
fluorescence-activated cell sorting) and magnetic-activated
cell sorting (MACS, magnetic activated cell sorting), cell
surface markers, optical tweezers, and dielectrophoresis.
Dielectrophoresis (DEP) is achieved under a non-uniform
Chia Yi, Taiwan, R.O.C.
electric field generated by various electrode patterns.
Previous studies on dielectrophoretic response adopted large
electrodes, such as needles, pins, wires and sheets [6, 7].
Microfabrication technology has been employed to create the
microelectrode patterns in the studies on electrophoresis;
thereby, sufficiently large DEP forces were generated to
manipulate particles with small applied voltages. The
different patterns of microelectrodes used for DEP have been
reviewed in the relevant literature [8, 9]. The contactless and
gentle forces on cells are produced by dielectrophoresis;
therefore, it is particularly suitable for cell manipulation in a
microchip [9]. The main aim of this study was to design a
handheld device providing the stepping electric fields and a
dielectrophoretic microchip with circular microelectrode for
cellular preconcentration. Moreover, the preliminary
experiment also aimed to demonstrate the feasibility of
enriching cells with the proposed device.
II. THEORY AND DESIGN
The DEP force (F DEP ) acting on a spherical particle of
radius R suspended in a fluid of permittivity ε , is given as:
m
3
2
DEP
= 2 επ
m
Re(
CM
) ∇EfRF
(1)
where Re( f CM
) is the real part of the Clausius-Mossotti
factor; the magnitude of the electric field, E, may be replaced
by E rms , which is the root-mean-square of the external field,
in an alternating field. The Clausius-Mossotti factor (f CM ) is
a parameter of the effective polarizability of the particle; it
varies as a function of the frequency of the applied field (ω)
and the dielectric properties of the particle and the
surrounding medium. The Clausius-Mossotti factor for a
spherical particle is represented as:
**
⎡ − εε ⎤
mp
f = ⎢ * * ⎥
(2)
CM
⎣ p
+ 2εε
m ⎦
*
*
where ε and
p
ε are the complex permittivity of the
m
particle and the medium, respectively. The complex
permittivity is related to the conductivity σ and angular
frequency ω through the formula:
σ
* εε j−≡
ω
( j 1−= ) (3)
Therefore, the DEP force is dependent upon the dielectric
properties of the particles and the medium solution, particle
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