DEVELOPMENT AND EVALUATION OF AN ON-CHIP
POTENTIOSTAT FOR BIOMEDICAL APPLICATIONS
C. Mc Caffrey, J. Doyle, V. I. Ogurtsov, K. Twomey and D. W. M. Arrigan
Tyndall National Institute, Lee Maltings, University College Cork, Cork, Ireland
Keywords: System on chip, Miniaturized, Electrochemical, Sensor electronics, Potentiostat.
Abstract: Potentiostat-based solutions are widely used as an instrumentation platform for electrochemical and
biochemical sensing systems, which are extensively used in areas as diverse as biomedical analysis, food
safety and monitoring of environmental pollutants. Biomedical diagnostics is a relatively new application
area of these systems, which can allow for in vivo, long-term patient investigation outside of the hospital
environment. It is expected that this emerging area will enable physicians to obtain radically new and
unique diagnostic information. The development of such an on-chip potentiostat-based sensing system
suitable for in vivo biomedical applications is the subject of the present study. The design is realized on a
mixed signal silicon breadboard substrate which allows for a low cost and time efficient progression from
concept to full integration on CMOS.
1 INTRODUCTION
Various electrochemical-based sensing systems play
an essential role in modern life, with increasing
demand for their use in biomedical analysis, food
safety, bioterrorism agent
detection and monitoring
of environmental pollutants (Zhang et al., 2007). In
general the techniques are performed using an
electrochemical cell. This cell typically consists of
three electrodes which are placed in an electroactive
solution. These electrodes are referred to as the
counter, reference and working electrodes. The
basis of an electrochemical analysis is the forcing of
a voltage across two of these electrodes (between
working and reference) and the measurement of the
resulting current between them, which is usually
provided through the counter electrode (Wang,
2000).
In systems of this type (Ogurtsov et al., 2009)
potentiostat-based electronic interfaces serve as the
instrumentation transduction platform. The
potentiostat circuit is at the core of a whole range of
analytical electrochemical techniques including
amperometry, voltammetry and impedance based
measurements. It is a key component in research in
corrosion, batteries, fuel cells, electro synthesis and
general electrochemistry.
In the majority of laboratory instrumentation the
device is implemented on PCB modules using
discrete electronic components since size or
detection limit is not an issue. However, in this
work, the size of the device is an issue and the
electronic interface must be incorporated in a
biomedical device which may be implanted. One
possible solution to meet this requirement is the use
of IC design techniques to develop an integrated
system on a chip. The advantages offered by this
solution, besides small size, include the potential for
reduction in noise and power and also a decrease of
electronic leakage current, which can lead to an
improvement of the detection limit.
2 POTENTIOSTAT TOPOLOGY
The function of the potentiostat circuit is two-fold
(Doelling, 2000). Firstly it has to force the voltage
across two electrodes in an electrochemical cell to a
controlled value, i.e. to create a potentiostatic
system. To accomplish this task the circuit forces a
current through the cell, often through a third
electrode. In its most basic form the potentiostat
consists of a single operational amplifier referred to
as a control amplifier (Ahmadi & Jullien, 2005). In
this configuration the current is forced from the
amplifier such as to drive the differential inputs to
the same value. This topology is at the core of all
potentiostats, however many developments have
103
Mc Caffrey C., Doyle J., I. Ogurtsov V., Twomey K. and W. M. Arrigan D. (2010).
DEVELOPMENT AND EVALUATION OF AN ON-CHIP POTENTIOSTAT FOR BIOMEDICAL APPLICATIONS.
In Proceedings of the Third International Conference on Biomedical Electronics and Devices, pages 103-107
DOI: 10.5220/0002728601030107
Copyright
c
SciTePress
improved on the basic design (Ayers et al., 2007;
Gore et al., 2006; Hasan, 2006).
A second but equally important function of the
potentiostat device is to provide for the measurement
of the current forced through the cell. A number of
approaches can be taken for the current
measurement but the use of a transimpedance
amplifier is widely accepted as the optimum
approach (Gamry Instruments, 2007). Another
example forces the cell current through a small
resistance and uses a differential amplifier to
measure the resulting voltage drop.
The simplified device topology used in this
design is illustrated in Figure 1. The control
amplifier forces the control voltage, V
control
, across
the reference and working electrode (which is held
at virtual ground). In order to hold this equality the
current, I
cell
, is forced through the cell and through
the resistor R. The transimpedance amplifier
measures this current and generates a voltage, V
out
,
which can conveniently be sampled by an ADC
device.
Figure 1: Standard potentiostat topology with inverting
control amplifier and transimpedance current
measurement.
3 INTEGRATED PROTOTYPING
PLATFORM
In general the development of any new mixed signal
circuit in the Tyndall fabrication facility, or indeed
any facility, would require the layout design and
fabrication of many layers (11 for the specified
process) and the purchase of a full mask set. To
justify a circuit fabrication a batch of 12 to 20
wafers would need to be done. The timescale
behind such a fabrication would be in the region of
three to four months and the cost could reach
€30,000. Even in the best cases with mixed signal
design, where the first prototypes are fully
functional, they will often not meet the target
specifications and will require additional tweaking
to fulfill the requirements. A second iteration is
more often than not required to reach the full
specification. In many cases three or more iterations
may be necessary. The timeframe and cost of these
multiple iterations can be prohibitive in many cases.
This is particularly true in a research environment.
The integrated circuit used in this work was a
prototyping platform based on a silicon breadboard
technology. This is an integrated component array
which supports a wide range of mixed signal
functionality. The motivation of the silicon
breadboard was to bring the advantages of gate array
technology to mixed signal circuit development.
The benefits are particularly relevant to the research
environment at Tyndall, where new concepts are
being explored and design requirements may change
significantly over the course of a project. In these
cases initial fabrications are required to obtain a
working prototype while a couple more may be
needed to meet the technical requirements.
The array, Figure 2, consisted of 1248 logic
gates (lower two thirds of die) and an analogue
section (upper third of die) consisting of 32
operational amplifiers, 1500 units of poly-poly
capacitors, 2M of resistance in 40 sticks of 6
segments and a range of more specialized
components including temperature and humidity
sensors. The device is fully customizable by the
application of a top layer metal interconnect which
requires just a single mask. This gives a cost of just
a few thousand Euro and a turn around time of just a
few weeks. Undoubtedly the breadboard platform
offers a huge advantage in respect of both time and
cost.
The breadboard is fabricated using a large
geometry (5 micron) on the C5P0 process, as this
Figure 2: Integrated prototyping platform (8x10mm).
BIODEVICES 2010 - International Conference on Biomedical Electronics and Devices
104
process has been proven and confirmed over a
substantial number of lots. The large geometry is
considered acceptable as speed is not an issue in
sensor applications and the process is more than
sufficient to push out the limits of sensitivity. The
fabricated die has 56 pads and a size of 8x10 mm.
However this is, after all, a development tool so this
should not be a major concern. Many of the larger
components will be redundant and trimming
techniques can be used to reduce the die size.
4 IMPLEMENTATION
The on-chip sensing system interfaces to a three-
electrode cell comprising a working electrode, a
reference electrode and a counter electrode, as
described above. The device was implemented on
the silicon breadboard described using four of the
amplifiers in the array along with a number of
resistive elements. The amplifiers are two-stage
devices using a P-input CMOS format. The design
provides a slew rate of 1V/µs, an open loop voltage
gain of 80 dB and a closed loop bandwidth of 10
kHz while maintaining an offset voltage of less than
±2.5mV. The resistive elements are created from a
combination of poly connect strips and the arrays
resistive segments.
A specific requirement is the necessity of an
enhanced dynamic range due to the differences in
concentrations of target analytes in biological
samples and the natural variations amongst patients
and samples, which results in a widely varying
sensor signal. The potentiostat, Figure 3, provides an
exact replication of the applied signal from the
digital to analogue converter (DAC) at the reference
electrode, due to the feedback via the conducting
biological sample solution.
Figure 3: Potentiostat sensor control circuit with input
stimulus voltage from DAC and connections to sensor.
The main problem in the design is to ensure
system stability under the conditions of a high
capacitive load from the working electrode. To
ensure a stable device a provision is made to add a
bandwidth reducing capacitance (C
ca
, dotted
interconnect) to the feedback path of the control
amplifier. Also a bias compensation resistance can
be added external to the IC. These components
could easily be integrated into the device once their
values are optimised.
A system reference voltage can be applied to the
control amplifier non-inverting terminal. Equally
the amplifier terminal can be grounded and an offset
voltage can be applied in adder configuration with
the DAC stimulus voltage. The value of the
resistance R is not critical so long as the three
resistors are well matched; 4.7 k was selected as it
was most convenient for the process. The function
of the buffer amplifier at the reference electrode was
to eliminate any current flowing through the
electrode resulting in a more stable reference for the
cell and a more accurate measurement (without
offset). The control amplifier can provide a sink or
source of 3.5mA for the cell.
The transimpedance amplifier element of the
device acquires the cell current from the working
electrode and converts it to a corresponding voltage,
V
out
, as illustrated in Figure 4. A significant
challenge for the current measurement is to meet the
wide range of cell currents encountered in practice.
Currents as high as a few mA to as low as a few 10s
nA need to be detectable, so the gain range of the
amplifier must be large. An integrated gain control
block consisting of resistors R
1
and R
2
and a PMOS
switch was included. With the switch opens the gain
contribution is just the resistance R
1
but when closed
the contribution is the parallel combination of R
1
and R
2
. This internal gain function was used in
conjunction with an external potentiometer (dotted
interconnect) which was first realised as a multiturn
variable resistor but later as a 256 tap digital
potentiometer for full gain control assuring the
required dynamic range.
Another important challenge for the
transimpedance amplifier design was to provide
uniformity of the frequency response, and to
eliminate possible oscillations in the transient
process, which can occur from a wide capacitance
range of the working electrode connected to the
amplifier input. This is a particular concern where
the device is controlled by a DAC which can only
approximate smooth waveforms with stepped
values. Again a provision was taken to connect a
bandwidth reducing capacitance across the stage
feedback path; that is between the working electrode
and V
out
pin.
DEVELOPMENT AND EVALUATION OF AN ON-CHIP POTENTIOSTAT FOR BIOMEDICAL APPLICATIONS
105
Figure 4: Transimpedance amplifier circuitry for
measurement of working electrode current including
external digital potentiometer.
5 EVALUATION
In order to evaluate the performance of the
developed potentiostat device a cyclic voltammetry
analysis was conducted with a gold working
electrode in an aqueous 0.5 M sulphuric acid
solution (H
2
SO
4
). For comparison a similar analysis
was carried out using a commercial CH Instruments
620B laboratory benchtop instrument. The
experiments were conducted in the potential window
0 to 1.5V. The voltammograms recorded for both
systems are shown in Figure 5. Using the custom-
built potentiostat, the voltammograms display an
oxidation peak at 1.3V and a reduction peak at 0.7V.
A similar response was seen using the commercial
version. The variances observed could be attributed
to the use of a different reference electrode for the
different systems, an industry standard silver silver-
chloride reference was used with the commercial
instrument while a plated platinum reference was
used for the miniaturised system. Furthermore the
developed system had limitations in the DAC
resolution of 12 bits while the commercial
instrument provides 16 bits waveform synthesiser
giving a closer approximation to the ideal analogue
signal resulting in a better accuracy. In any case the
systematic differences can be isolated from the
sample response through calibration. The
voltammograms obtained compare well with the
literature for gold oxidation and reduction in a
aqueous acid solution (Burke & Lee, 1992).
Cyclic Voltammograms in 0.5 M H2S04
-0.05
-0.04
-0.03
-0.02
-0.01
0
0.01
0.02
0.03
0.04
00.20.40.60.811.21.41.6
Voltage/V
Current (mA)
CHInstruments Potentiostat
Developed Potentiostat
Figure 5: Cyclic Voltammogram for the developed
potentiostat and a CHInstruments Potentiostat in 0.5M
H2S04.
Further evaluation was carried out to investigate
the response of the device when placed in an
embedded system. The application of the DAC
generated stimulus voltage was a particular concern,
since the required analogue signal could only be
approximated with a signal stepped between discrete
values. The response of the control amplifier and
current measurement amplifier to the stepped signal
had to be investigated. With sufficient bandwidth
reducing capacitances in place (100pF across
transimpedance amplifier, and 10pF across control
amplifier) the step response was found to be over
damped. An expected overshoot was observed in
response to a step, Figure 6, but this quickly decayed
within a few hundred micro seconds. Thus a stable
measurement can be assured so long as a sufficient
delay has elapsed between the signal step and
current sampling.
As mentioned trimming techniques were used to
reduce the size of the die, since many of its
Figure 6: Time domain potentiostat response to a DAC
generated cyclic voltammetry signal.
BIODEVICES 2010 - International Conference on Biomedical Electronics and Devices
106
components were redundant in the application. In
particular the sensors included in the die could be
removed along with most of the logic gates and
operational amplifiers. The die was laser cut to a
length on 7.5mm giving a final overall size of
8x7.5mm. Some further optimisation of the die size
could be obtained with improved routing.
6 CONCLUSIONS & FUTURE
WORK
It is clear from the evaluation that the integrated
potentiostat developed in this work performed well
in comparison with a conventional commercially-
available benchtop instrument. Further tests showed
that when compared with a similar device assembled
with discrete components the integrated version
provided improved performance in a number of
respects. Obviously there were advantages in terms
of size but also the noise immunity and step
response was found to be superior for the integrated
device. In total the obtained technical characteristics
of the device allow us to conclude that the developed
chip is suited to the requirements of in-vivo
biomedical applications.
The success of the early investigations of this
device warrants one or two more iterations to
improve on the design. Additional components will
be integrated in the next iteration and consideration
is being given to the full integration of the
potentiometer with the gain control function.
Furthermore the DAC could be integrated giving a
full system on chip solution. In the longer term the
device will be proven and fully evaluated before a
full CMOS fabrication is considered. This will
dramatically reduce the size of the final product.
Using the integrated prototyping platform the road to
a full integration will be shortened, and the total cost
dramatically reduced.
ACKNOWLEDGEMENTS
Financial support of this work by Enterprise Ireland
(grants CFTD/04/112, CFTD/05/122 and
PC/2008/0184) and Science Foundation Ireland’s
National Access Program (project NAP68) is
gratefully acknowledged.
REFERENCES
Ahmadi, M. M., & Jullien, G. A. (2005). A very low power
CMOS potentiostat for bioimplantable applications.
Paper presented at the Proceedings of The Fifth
International Workshop on System-on-Chip for Real-
Time Applications.
Ayers, S., Gillis, K. D., Lindau, M., & Minch, B. A. A. M.
B. A. (2007). Design of a CMOS Potentiostat Circuit
for Electrochemical Detector Arrays. IEEE
Transactions on Circuits and Systems I: Fundamental
Theory and Applications, 54(4), 736-744.
Burke, L. D., & Lee, B. H. (1992). An Investigation of the
Electrocatalytic Behavior of Gold in Aqueous-Media.
[Article]. Journal of Electroanalytical Chemistry,
330(1-2), 637-661.
Doelling, R. (2000). Potentiostats An Introduction. A.
Retrieved from www.bank-
ic.de/encms/downloads/potstae2.pdf
Gamry Instruments. (2007). Application Note –
Potentiostat Primer. A. Retrieved from
www.gamry.com/App_Notes/Potentiostat_Primer.htm
Gore, A., Chakrabartty, S., Pal, S., & Alocilja, E. C. A. A.
E. C. (2006). A Multichannel Femtoampere-
Sensitivity Potentiostat Array for Biosensing
Applications. IEEE Transactions on Circuits and
Systems I: Fundamental Theory and Applications,
53(11), 2357-2363.
Hasan, S. M. R. (2006). Stability and Compensation
Technique for a CMOS Amperometric Potentiostat
Circuit for Redox Sensors. Paper presented at the
IEEE Asia Pacific Conference onCircuits and
Systems.
Ogurtsov, V. I., Twomey, K., Bakunine, N. V., Mc
Caffrey, C., Doyle, J., Beni, V., et al. (2009, Jan 14-
17). Miniaturized Electrochemical Sensing Systems for
in Vitro and in Vivo Biomedical Applications. Paper
presented at the 2nd International Conference on
Biomedical Electronics and Devices, Porto,
PORTUGAL.
Wang, J. (2000). Analytical Electrochemistry. In (pp. pp
28 – 74): Wiley-VCH.
Zhang, X., Ju, H., & Wang, J. (Eds.). (2007).
Electrochemical Sensors, Biosensors and their
Biomedical Applications ACADEMIC PRESS.
DEVELOPMENT AND EVALUATION OF AN ON-CHIP POTENTIOSTAT FOR BIOMEDICAL APPLICATIONS
107