Oximetry and Glucose Sensors

A SMART SENSOR FOR BIOMEDICAL APPLICATIONS W. Sansen, A. Claes, D. De Wachter, L. Callewaert, and M. Lambrechts Katholieke Universiteit Leuven Dep. Elektrotechniek ESAT-MICAS Kardinaal Mercierlaan, 94 B-3030 Heverlee Belgium Abstract Monolithic smart sensors for the voltammetric measurement of glucose or oxygen concentrations have been developed. Each smart sensor consists of a planar voltammetric sensor, a CMOS interface circuit and temperature sensor. The interface circuit and the temperature sensor are realised in a standard CMOS process. The sensor specific layers are added afterwards on the same chip with the CMOS compatible sensor technology developed for this purpose. Two versions of this smart sensor have been realised. The two electrode configuration with a Au working electrode has been implemented for the measurement of p02. The three electrode configuration with a Pt working electrode can measure glucose when an additional glucose oxidase membrane is applied on the electrodes. The interface circuit can apply voltages from +lV to -lV to the sensor and can handle sensor current ranges from 30 nA full scale to 1 pA full scale with a +/- 2.5 V supply voltage. The temperature sensor has a sensitivity of 154 pV/K. The total dimensions of this smart sensor are 0.75 mm by 5 mm.
2. Sensing principle The detection of oxygen or glucose is based on the voltammetric measurement with a two or three-electrode ) configuration in a potentiostatic configuration (Figure 1. At the positive input of the operational amplifier (opamp) the input potential (V,) is applied. The counter electrode (CE) injects a current in the solution so that the voltage of the reference electrode (RE) equals the applied voltage at every moment. The potential difference between the reference and working electrode (WEl) induces an oxidation or reduction reaction at the working electrode. This results in a current linearly proportional to the concentrations of the species involved in the reaction. In the two-electrode configuration the counter electrode is omitted and the output of the opamp is connected with its negative input. The current is injected in the solution via the reference electrode.

A two-electrode configuration has been implemented with a Ag/AgCl reference electrode and a Au working electrode for the measurement of p02. The output signal is a result of reduction of oxygen at the working electrode: for Vi, < -0.4 V vs. AgAgC1:

1. Introduction
This paper describes two smart sensors designed for the in vivo measurement of glucose or oxygen concentrations. The detection is based on a voltammetric measurement with a planar sensor. It is necessary that the dimensions of an in vivo sensor should be as small as possible. This implies that the current signal, directly proportional to the working electrode area, is very small too. Especially for current outputs in the nA range it is extremely important to minimize the length of the current path from the sensor to the interface circuit to reduce noise and interfering signals. The best solution for this problem is to place the interface circuit and the sensor on one chip. In our realisation the interface circuit contains an I-V convertor and an opamp as potentiostat. Dedicated CMOS compatible sensor technology has been developed and implemented for the realisation of such a monolithic smart sensor.
0 2

+ 2 H20 + 4 e- -> 4 OH-

The three-electrode configuration with an Ag/AgCl reference electrode and a Pt counter and working electrode measures glucose concentrations when an additional glucose oxidase (GOD) membrane is applied on the electrodes [ 11. in the membrane: GOD glucose + H20 + 0 2 -> gluconic acid + H202 for Vi, > 0.2 V vs. Ag/AgCl: H202->
2 e - + 2 H++ 0
2

Figure 1: Schematic representation of a smart sensor.

1088--IEEE ENGINEERING IN MEDICINE & BIOLOGY SOCIETY llTH ANNUAL INTERNATIONAL CONFERENCE CE2770-6/89/0000-l088 $01.00 C 1989 IEEE

Authorized licensed use limited to: Naval Science and Technological Laboratory. Downloaded on March 13, 2009 at 04:42 from IEEE Xplore. Restrictions apply.

3. Interface circuit and temperature sensor The interface electronics consist of an operational amplifier as potentiostat, a current-to-voltage convertor and a clock generator. A temperature sensor is integrated on the same chip to provide information for temperature compensation of the sensor. The circuit operates with a minimum supply voltage of +/-2.5 V. The potentiostat opamp is designed to drive the large capacitive loads of the double layer at the electrodes (about 10 nF). This opamp has a dynamic input range from +lV to - l V which complies with glucose as well as oxygen measurements. The I-V convertor consists of a switched capacitor current integrator followed by a sample-and-hold circuit. The input current range and the I/V conversion factor is controlled by the external clock frequency. Ranges from 30 nA full scale to 1 pA full scale are covered (Figure 2). The temperature sensor is based on the weak inversion characteristics of PMOS transistors. The output voltage of this circuit is proportional to absolute temperature with a sensitivity of 154 pV/K [2].(Figure 3 )
4. Sensor technology

necessary for the glucose sensor can be applied on wafer with lift-off and dry etching techniques. Because the complete sensor processing can be done on wafer, the described production technique delivers reproducible devices with a low cost if high volumes are produced. This implies that the smart sensors can be used as disposable sensors.
5. Conclusion A dedicated CMOS compatible sensor technology has been developed and implemented to realise smart sensors for the voltammetric measurement of oxygen and glucose. The signal processing unit produces a precise input voltage and a low noise signal output. The production technique yields low cost sensors with extremely small dimensions which can be used as disposable short time in vivo sensors.

The interface circuit of the smart sensor is realised in a standard 3 pm n-well CMOS technology. A silicon nitride passivation layer protects the circuit from the analyte. The polysilicon interconnection between interface circuit and the electrodes is provided during the standard processing. The sensor specific layers are added after the complete CMOS processing by the CMOS compatible sensor technology (Figure 4). The electrodes are sputtered or evaporated metal layers which are patterned with a CVDoxide assisted lift-off technique [3]. The membranes

References 1. M. Lambrechts, J. Suls, W.Sansen: "A thick film glucose sensor." Proc. of IEEEEMBS'87, Boston USA, November 1987, pp 789-799.

2. B.J. Hostica, J. Fickel and G . Zimmer: "Integrated monolithic temperature sensors for acquisition and regulation." Sensors and Actuators, 6, 1984, pp191-200.

3. M. Lambrechts, J. Suls, W.Sansen: "Planar voltammemc sensors using microelectronic and thick film technology." Proc. of Micro-technologie t.b.v. transducenten. Enschede NL. October 1986, pp 239-246.

290

300

310

320

330

340

350

temperature

[K]

Figure 2: Measured transfer characteristics of the I-V convertor.

Figure 3: Measured characteristics of the temperature sensor.

.-

Figure 4: Picture of the realised smart sensor ( Ag/AgCl RE and Pt WE and CE).

IEEE ENGINEERING IN MEDICINE h BIOLOGY SOCIETY llTH ANNUAL INTERNATIONAL CONFERENCE--1089

Authorized licensed use limited to: Naval Science and Technological Laboratory. Downloaded on March 13, 2009 at 04:42 from IEEE Xplore. Restrictions apply.