A HYBRID BACTERIA AND MICROPARTICLE DETECTION
PLATFORM ON A CMOS CHIP: DESIGN, SIMULATION AND
TESTING CONSIDERATIONS
Zhao Lu1, Jaouad El-Fouladi 1, Sylvain Marte1 1 and Yvon Savaria 2
1
NanoRobotics Laboratory, Department of Computer and Software Engineering,
2
Department of Electric Engineering,
École Polytechnique de Montréal, Campus of the University of Montréal,
Montréal, QC, CANAD
Abstract- This paper presents a hybrid bacteria and
microparticles detection platform based on a CMOS technology.
Vertical face to face microelectrode arrays are implemented onto
CMOS chips by connecting the metal and via layers together. A
CMOS post-processing procedure based on Deep Reactive Ion
Etching (DRIE) is used to release the microelectrodes and to
construct microchannels in between. With medium flow of the
fluid, Bacteria and microparticles are allowed to pass through
the microchannels, where impedance variations are measured
using a microelectrode pair on the wall, and then detected by
electronic circuits embedded on the same chip. This
microelectronic/microfluidic hybrid system targets screening
individual bacterium or microparticle with high throughput and
accuracy. The system architecture is presented first, followed by
the detailed model, design, simulation and parameters of the
prototype. The CMOS post-processing, specific packaging and
testing procedures are also introduced in this paper. Finite
element analysis method (FEM) and circuit simulations confirm
that a single microparticle, 5 ȝm in diameter, can be detected by
the proposed microsystem. Based on preliminary etching results,
pairs of released electrodes 10 ȝm *2 ȝm *8 ȝm (L x W x H),
also contribute to validate the feasibility of the CMOS post-
processing procedure.
I. INTRODUCTION
Detecting bacteria or microparticles is becoming more
and more important in the field of biology, pharmaceutical
industry, bio-medicine and anti-bio-terrorism. In food- or
air-borne disease control, early detection of single
bacterium rather than later detection of larger
concentrations is critical for disease control. The current
most widely adopted technology for this type of task,
named flow cytometry [1], is based on fluorescent reactions
when the targeted particles pass through the detecting area.
Due to the required light source and the complexity of its
detector, fluorescent based flow cytometry with parallel
detection is very difficult to achieve. Furthermore, the
targeted particles or cells have to be prepared, generally by
coating them with a fluorescent label before detection. It
limits the application of this technology, and it also
increases the overall detection time. Thus the throughput is
low and the screening speed is relatively slow.
Another conventional bacteria detection technology is
based on electrochemical sensors [2~5], also referred to as
amperometric or impedimetric sensors. These sensors
detect changes in the electrical characteristics of the
medium containing the bacterial cells. Although the
electrochemical sensors offer advantages such as high
sensitivity, low cost and ease of integration onto a
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MEMS/NEMS device, long detection times (usually a 12
hours to 7 days process) are expected due to the long pre-
amplification period if the initial concentration of bacteria is
very low. Meanwhile, most bacteria and particles are not
motile, and the diffusion rate of the bacteria and particles is
very slow; especially under low Reynolds number laminar
conditions. It takes a long migration time for target bacteria
approaching the detection or sensing area where the
electrodes are implemented. The required signal processing
is another challenge for impedimetric sensors. Due to the
very small impedance signal, very precise and complex
signal processing circuits are needed.
With the recent development of MEMS and microfluidic
technology, especially bioMEMS or Lab-on-Chip,
combined with conventional microelectronic technology,
traditional biosensors can be integrated onto CMOS chips.
Although most of these systems need some post-processing
procedure or special package, their integration with a
CMOS chip not only significantly reduces the fabrication
cost and alleviates the requirements of signal processing,
but also greatly increases the sensitivity, throughput,
robustness, and reliability of this kind of system. Among
the benefits expected from the miniaturization of CMOS
based biosensors: we can cite a reduction in the required
bio-reagent and samples volume. Another benefit is that fast
detection and analysis can be performed. Moreover, high
density of biosensors with multiple functions can be
implemented onto a same substrate, which may greatly
increase the screening speed. Indeed, on-chip
microelectronic circuits make parallel signal processing and
production of real-time analysis reports possible. In the last
decade, different kinds of CMOS based biosensors have
been presented for bacteria detection, bio-analysis and
neuron activity monitoring [6-8]. For most of these
biosensors, the top metal layer or metal deposited with post-
processing is used to construct coplanar electrodes arrays
for electrical impedance spectroscopy. Highly integrated
microelectrode arrays and on-chip detection have also been
reported. However, confined by the size of the
microelectrode and the planar orientation, the sensitivity of
these devices is not sufficient to detect bacteria with very
low concentration. Meanwhile, the microelectrodes in these
biosensors have to be coated with some noble and
biocompatible material such as Gold and Platinum, which
not only increases cost, but also requires complicated
microfabrication procedures.
In this paper, we present a CMOS based
microfluidic/microelectronic system for faster single
 bacterium or microparticle detection. Metal and Via layers
of CMOS chip are used to construct vertical microelectrode
arrays. The microchannel between a pair of microelectrodes
allows a liquid medium containing the bacteria or
microparticles to flow from a microchamber on the surface
of a CMOS chip through the substrate down to the other
side of the chip. On-chip microelectronic circuits monitor
the impedance variations in the channel, when the measured
impedance is beyond some pre-defined threshold, the
existence of the target bacteria will be indicated and
counted. The real-time results can be collected and output to
a computer through I/O ports on the same chip. This system
aims at parallel, fast single bacterium detection with high
accuracy and screening speed. By re-configuring the
sensing circuits, this microsystem can also be used for
microparticle detection, bio-analysis, cell-culture and so on.
In this paper, the architecture and working principle of this
system is first presented. Then, its detailed design and
simulation results are introduced. The CMOS-post-
processing and related testing and packaging issues are also
discussed. Finally, the optimization, design consideration,
and potential applications of this system are also introduced.
II. PROPOSED ARCHITECTURE
A. High Level Overview
The proposed microelectrical/microfluidic hybrid
microsystem [9] consists of a microelectrode array,
microelectronic circuits, a top microchamber, an array of
microchannels, and outlets. As shown in Fig 1, the
microelectronic circuits and microelectrodes array are
implemented directly on a CMOS chip using standard 0.18


ȝm CMOS technology. After the microchannels are created
passing between a pair of microelectrodes, the change of
impedance will be measured by sensing circuits integrated
on the CMOS chip. The presence of a bacterium will be
identified when the measured impedance is beyond some
predetermined threshold. Because the microchannels go
through the substrate, a small pressure difference between
the top microchamber and the bottom outlet will force the
fluid medium to pass through the device. The waste sample
is collected on the back side of the device. The flow rate has
to be calibrated according to the dynamic response
(frequency) of the sensing circuits. The sample can be
injected by either top outlet shown in Fig 1. When sample
injection is performed through one outlet, the other outlet is
blocked. Consequently, the liquid sample can only flow
through the device by the microchannels. Both top outlets
are functional only when a microchamber cleaning
procedure is required. A very thin layer of silicon oxide is
left during the post-processing procedure, to protect the
microelectrodes from corrosion/erosion. Such a layer is
biocompatible.
B. Specific parameters of a first implementation
A cut of the proposed electrode structure that we are
implementing is illustrated in Fig 2. The vertical
microelectrode structure is created by stacking the Metal
and Via layers of a 0.18 ȝm standard CMOS chip.





using a post-processing procedure based on DRIE 
  
technology, the microchamber and outlets are constructed
with epoxy as explained in the sequel.
Fig. 1. Schematic of the proposed hybrid microsystem.
The proposed system works as follows. First, a liquid
medium containing the bacteria is injected into the
microchamber above the microelectrode array. Then, the
medium enters into the microchannels. Controlled electrical
currents are injected through the microelectrodes embedded
on the wall of the microchannels. If there is a bacterium
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b.
Fig. 2. a) Cross-sectional view. b) 3-D view of the microchannel and
microelectrode based on a typical 0.18ȝm CMOS technology.
The height of the microelectrodes is around 8.05 ȝm
after connecting 6 Metal layers and 5 Via layers. The
microelectrodes are defined by stacking metal rectangles.
For instance, in a typical design, 10 ȝm x 2 ȝm (L x W)
stacked metal rectangles are separated by 10 ȝm. In order to
avoid the potential cross-talk among pairs of
microelectrodes, the distance between the microelectrode
pairs is kept at 80 ȝm. A total of 80 microelectrode pairs are
implemented on the first prototype. The die has a total area
 of around 2700 ȝm x 1300 ȝm (W x H). Metal wires
connect the microelectrodes to adjacent sensing circuits.
The silicon oxide between each pair of microelectrodes is
removed during the post-processing procedure using DRIE-
ICP dry etching technology. A through-wafer microchannel
is created between each electrode pair by etching through
the silicon substrate. After the post-processing procedure,
the microfluidic component is covered with transparent,
dielectric polymer, to protect bonding pads and wires on the
top of the CMOS chip and to avoid electrical shorts while
providing outlets for test sample injection. The planned
height of the microchamber is 1 mm, which provides a
volume of 15 ȝL for each test. microchamber. The bottom
microchamber used to collect the waste sample is fabricated
separately and bonded to the bottom of the chip. The
microchamber is constructed with Polydimethylsiloxane
(PDMS) using conventional soft lithography technology.
III. DESIGN AND SIMULATION
In this section we present some design constraints of the
sensing microelectronic circuit. It is designed to be robust
and flexible to meet various potential applications related to
the proposed microsystem.
As this experimental system is designed to prove
concepts in spite of a great deal of uncertainty, in our first
prototype, different sizes of microelectrodes are
implemented. This will be invaluable for evaluating the
performance of the circuit and to guide us toward the
selection of the best parameters that will allow to meet
requirements of different applications. Specifically, 5 µm x
5 µm, 6 µm x 6 µm, 8 µm x 8 µm, 10 µm x 10 µm, 12 µm x
12 µm, 15 µm x 15 µm and 20 µm x 20 µm (microelectrode
length x microchannel width) are chosen for this design.
In a first considered design of the stimulation and
sensing circuits, the fluid medium containing the
bacteria/microparticles to be detected is assumed to be an
electrolyte having a conductivity ranging from 0.5 to 5 S/m.
We also consider that the bacteria/microparticles to be
detected are essentially non-conducting, with a conductivity
much lower than that of the electrolyte. Based on available
information, the expected conductivity can be around 0.1
pS/m.
Based on various studies with COMSOLTM finite
element models of the physical structure, combined with
detailed circuit simulations, the preferred solution that was
retained for our experimental system isolates the
microelectrodes from the fluid media with thin dielectric
layers. To form these layers, the electrodes are coated with
a thin layer of a dielectric material (either silicon oxide or
Parylene) which results in the formation of a relatively high
value capacitance at the interface between each
microelectrode and the electrolyte. Based on material
properties, microelectrode dimensions and target dielectric
thickness, the value of this capacitance ranges from 2pF to
15pF. The resulting electrical model for each
microelectrode pair is shown in Fig 3.
The resistance Rsol reflects the finite conductivity of the
electrolyte. The value of Rsol is greater when a
nonconductive bacterium/microparticle is passing through
the microchannel between the electrodes. The C_ox
capacitors are due to the thin dielectric layers on the surface
of the electrodes. For a given electrode pair, as their
geometry is the same and the means of producing the
dielectric is equivalent, both capacitance values should be
almost equal. However, some slight variations on these
values should be considered. They can be caused by
variations of the process of the microelectrodes that creates
the structure.
With our previous observations, we can conclude that it
is very important for the circuit we design to be robust to
many uncertainties related to the design parameters of this
experimental device. For instance, we expect variations of
the conductivity of the electrolyte due to biological
activities. As mentioned earlier, the electrolyte conductivity
is ranging from 0.5 to 5 S/m. The nature and dimensions of
the bacteria/microparticles to detect can also change. For
instance, one may want to detect polythene beads of 3 µm,
5 µm or 6 µm diameter or bacterium with diameters that can
range from 1 µm to 3 µm. At last, variations of the
parameters controlling microelectrodes fabrication and
coating could have a significant incidence. These
considerations are capital issues in order to get a working
circuit.
To design the detection circuit, we took advantage of the
presence of the relatively large capacitance C_ox that can
integrate a DC current. In that case, the resulting circuit can
reduce to Fig 4, for which Equations (1), (2) and (3) apply.
Fig. 4. The equivalent circuit when injecting a DC current into a
microelectrode pair.
Thus if we inject a reference current “I”, the voltage
across a microelectrode pair is given by equation (3). It is a
linear relationship with a slope inversely proportional to
C_ox, and a value at the origin is directly proportional to
Rsol. If, for instance, C_ox is a constant, a change in Rsol
results in a vertical translation of the voltage created across
an electrode pair.
(1)

(2)

(3)

Fig. 3. Electrical model for each microelectrode pair.

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 Therefore the conceptual diagram of Fig 5 is proposed The Charge switch is implemented using a PMOS
to model the sensing mechanism associated with each transistor and the Discharge switch is implemented using a
electrode pair. NMOS transistor. Thus, as mutually exclusive conduction is
desired, only one control signal is needed for both switches.
The buffer is easily implemented with two simple CMOS
inverters.
In order to simulate the behaviour of this circuit, we
initially carried out simulations using COMSOL software in
order to find the expected range of Rsol. For these
simulations, we used non-conducting spherical beads of
5µm in diameter. The lengths of the electrodes were 6µm,
10µm and 20µm and the widths of the channels were of
6µm, 10µm and 20µm respectively (square channel section
assumed).The microbead is located at the centroid of the
volume defined by the microelectrodes pair. The
conductivity of the electrolyte is 1 S/m. Table 1 presents the
values of resistances found. It is obvious that smaller
Fig. 5. Conceptual diagram of the sensing mechanism.
microelectrodes with narrower channels provide better
When the Charge switch is on, the Discharge switch is discrimination. When the channel is much larger than the
forced off (mutually exclusive control) and the reference microbead, more reference current flows around the
current is injected in the upper microelectrode, generating a microbead, thus reducing the sensitivity of the circuits.
voltage modeled by equation (3). This voltage is fed to the
TABLE I
input of a buffer with a threshold voltage set to Vdd/2. After FEM SIMULATION RESULTS FOR Rsol WITH VARIOUS
some time, the Charge switch is turned off and The MICROELECTRODES, AND CHANNEL SIZES.
Discharge switch is turned on. The input of the buffer is
then grounded, and both capacitances are gradually Length of
Microelectrode Rsol with a Rsol without a Discrimination
discharged. After a suitable time, we can restart this process. bead (kȍ) bead (kȍ) ratio (%)
As a result a pulse train is created at the output of the circuit (µ m)
and the width of the pulses composing this train is related to
6 100.2 85.6 17
the value of Rsol. The greater is Rsol, the wider are the
pulses. Hence by analyzing this wave, the system can 10 92.1 83.2 10.7
automatically determine when a bacterium or microparticle
20 56.5 56.4 0.1
passed by.
The actual circuit that implements this detection concept
is shown in Fig 6. The reference current is provided from
outside the microchip and it is injected into the detection
circuit using a simple current mirror. This is necessary as
the design of the circuit proceeds in parallel with the
development of the post-processing microfabrication steps,
and different applications may require very different
stimulation currents. Ultimately, in a fixed application, with
well characterized post-processing steps targeting some
low-cost system, the current source would be on-chip. At
this stage, we expect that fully external control of the
injected current is essential for characterization tests.

Fig. 7. Simulation results of delay time according to the impedance

variations between the microelectrodes.

Based on those expected resistance values, it is possible

to simulate the behaviour of the designed circuit. Fig 7
shows a typical simulation result for a C_ox value of 5pF, a
charging time of 1.5µs, a discharging of 50 ns, and a
reference current of 1µA. The figure shows two simulations
Fig. 6. CMOS stimulus generation and detection circuit.

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 results. One is for a value of Rsol equal to 100kŸ and the
other is for a value of 140kŸ.
This simulation results confirm the expected linear
relationship described by equation (3) as well as the pulse
wave generated. It also shows that a large Rsol produces a
larger pulse width. Table 2 shows widths of the pulses in
the train for a value of C_ox of 8pF, a charging time of
3.5µ s, a discharging time 0.5µs, a reference current of 1µA
and Rsol values ranging from70kŸ to 150kŸ. This table
confirms the linear relation between the value of Rsol and
the pulse width.
TABLE II
WIDTH OF PULSE FOR VARIOUS Rsol VALUES
photoresist on top of the CMOS chip to provide an
additional protection layer. A typical photolithographic
process is used for this purpose. Then, the DRIE technology
is adopted to remove the silicon oxide between a pair of
microelectrodes and etch through the silicon substrate. In
Fig.8, an optical microscopy image illustrates part of the
microelectrode array and the scanning electron microscope
(SEM) image that depicts a pair of released microelectrodes.
Recall that the microchannel is to be etched through the dies
in between these electrodes.

Rsol (k) Pulses width (ns)

70 723

80 975

90 1230

100 1488

110 1742

120 1993

130 2247

140 2497

150 2755

To characterize the impact of possible process variations,

we performed a set of simulations with a C_ox value halved.
The variation of the pulse width with Rsol decreased. In
general, as the value of C_ox increases, the slope of the
voltage generated at the input of the inverters is smaller. A
larger time is then needed to reach the threshold of the
inverters in the proposed microelectronic circuit.
The circuit proposed was designed in a manner which
makes it flexible in multiple ways. Firstly, one can control
the injected current depending on the values of the
impedance to measure. It is then possible to vary the
charging and discharging time for the capacitors C_ox. Note
that the same circuit can be used for a wide range of C_ox
Fig. 8. Optical and SEM images of the released microelectrode and
and Rsol, making the circuit robust against inaccurate
microchannel after the silicon oxide is etched off.
knowledge of the device parameters and variations of these
values. B. Packaging
To avoid any electrical shorts caused by the liquid
IV. FABRICATION samples on the chip and to provide a microfluidic interface
for sample injection, a specific package is developed. As
A. CMOS Post-processing illustrated in Fig 9., the raw die is first mounted on a chip
The CMOS post-processing procedure includes two carrier for wire bonding. Then a special Epoxy is patterned
steps, passivation layer patterning and DRIE etching. On above the area of the microelectrode array by direct writing
the die received from the foundry (TSMC through CMC technology [10]. After that, liquid polymer is poured on the
Microsystems), the passivation layer on the microchannel surface of the CMOS chip to cover it completely, including
area is removed. So the silicon oxide between a pair of pads, wires and previously patterned Epoxy. After the liquid
microelectrodes is exposed and ready for the following polymer is fully cured, the whole device is set on a hot plate,
etching process. However, the thickness of the original when the temperature reaches about 70 oC, the Epoxy inside
passivation layer is not enough to protect the surrounding is melted and can be extracted through the outlets by
circuits and microelectrodes during the DRIE dry etching applying a vacuum. In order to remove the melted Epoxy
procedure. Thus, the first step is to pattern a layer of entering into microchannels during the heating procedure,

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 hot water is injected for cleaning the debris of Epoxy in the
microchamber and microchannels. Finally, the device is
installed on a dedicated PCB for testing.
Fig. 9. a) Wire bonding, b) Epoxy is patterned on the area of
microelectrode array by direct writing technology. c) Polymer is poured on
the surface of the CMOS chip to protect the pads and bonding wires. d)
After the epoxy is melted and removed, the microchamber and outlets are
formed by the surrounding transparent epoxy.
V. DISCUSSION
The ultimate goal of this project is to provide a portable
hand-held microsystem for on-site usage. By adopting a
standard CMOS technology, the task of fabricating high
density array of face to face microelectrodes can be
achieved easily and the on-chip detection circuit also
greatly increases the signal to noise level. As it is a first
prototype for validating the ideas and evaluating the
performance of the circuit and feasibility of the
microfabrication process, the parameters are chosen for
better understanding of challenges and leaving enough
space for further adjustment to meet requirements of
different applications. Based on our simulations and the
preliminary microfabrication results, single bacterium or
microparticle can be identified by the proposed
microsystem. However, there is always a balance between
the performance and cost of a design. For example, the
circuit simulation results suggest a narrow microchannel
compatible with the size of targeting bacteria or
microparticles for better sensitivity. However, producing
smaller microchannels, for example, less than 10 ȝm, will
significantly increase the complexity of the post-processing
procedure, thus increasing cost accordingly. Meanwhile, in
order to achieve higher screening speed and throughput,
higher density of the microelectrodes are needed, which
could raise the background noise and cross-talk of circuits
and reduce the performance of the system. With the concept
of design for test, this first prototype aims to develop a
uniform platform for validating the performance of the
circuits and microelectrodes under different conditions and
providing data for further optimization. The proposed
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testing scheme comprises the following steps. Firstly,
testing will be performed with different kinds of medium
such as electrolyte with different conductivity, deionised
water, PBS, and bacteria medium. The collected data can be
used not only to evaluate the function of the circuit, but
more importantly, to establish a reference database. The
anti-corrosion/erosion capability of microelectrodes and the
long-time permeability of the package will also be checked
at this stage. Then, microparticles with varied size will be
used to determine the sensitivity of the system and to
calibrate the circuits as well. Meanwhile, controlled
medium injection will used to investigate the relationship
between the flow rate of the sample injection and dynamic
response of the circuit. Finally, a diluted bacteria medium
will be used to demonstrate the function of the system and
then a concentrated bacteria medium will be used to
determine the maximum frequency/minimum response time
of the system in practical operating conditions. Moreover,
by collecting results corresponding to different species of
bacteria, microparticles or other bio-entities, a more precise
and wide database can be established for future on-site
detection. By adjusting the circuits’ parameter, this
microsystem can be reconfigured to fulfill detection tasks.
It should be stressed that the proposed microelectronic
circuit is designed to produce a high yield microchip.
Indeed, its simplicity and small size make it possible to
have an independent circuit for each microelectrodes pair.
Thus, a bug that appears in one cell doesn’t propagate to the
other cells. Moreover, the system is designed to be totally
self-referenced, making it very robust against variations of
any kind. This self-reference comes from the choice made
to create a pulse train. By comparing the widths of the
pulses independently for each cell, they become self-
referenced. The information about a problem in a cell is
then taken into account in the pulse train generated. Finally,
detection of a microparticle between two microelectrodes
only relies on comparisons of results generated by the same
cell.
VI. CONCLUSION AND FINAL REMARKS
This paper proposed a microfluidic/microelectronic
hybrid system based on CMOS technology. On this Lab-
on-Chip microsystem, face to face microelectrodes are
constructed by stacking Metal and Via layers of a CMOS
chip. CMOS post-processing with the DRIE technology is
used to release the microelectrode array and form the
microchannels in between. A dedicated package is
developed to integrate microchambers and outlets on top of
the CMOS chip and to isolate the circuits from the
microfluidic component as well. The liquid medium
containing bacteria or particles can be injected into the
mirochamber and microchannel, where the microelectrode
pairs are implemented on the wall. finite element modeling
and circuit simulations were used to confirm that single
bacterium or particles can be identified by the presented
detection circuits. The reported preliminary etching results
also partly validate the proposed post-processing procedure.
This microsystem is designed to detect pathogenic bacteria
or other micro-size bio-entities present in a diluted liquid
media in minutes.
 VII. ACKNOWLEDGEMENTS
This work was initially supported by a grant from the
Canadian Institute for Robotics and Intelligent Systems
(IRIS). It was recently supported in part by a Canada
Research Chair (CRC) in Development, Fabrication, and
Validation of Micro/Nanosystems, the Canada Foundation
for Innovation (CFI), the National Sciences and
Engineering Council of Canada (NSERC), and the
Government of Québec. The authors also thank CMC
Microsystems for access to various design tools and CMOS
fabrication technologies.

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