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

 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, 2MΩ 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).

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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

, 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 kΩ 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,

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

and R

and a PMOS

switch was included. With the switch opens the gain

contribution is just the resistance R

but when closed

the contribution is the parallel combination of R

and R

. 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

). 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

0.01

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.

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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.

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