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IEEE JOURNAL OF SOLID-STATE CIRCUITS, VOL. 36, NO. 12, DECEMBER 2001

A CMOS Multiparameter Biochemical Microsensor With Temperature Control and Signal Interfacing
Erik Lauwers, Jan Suls, Walter Gumbrecht, David Maes, Georges Gielen, and Willy Sansen, Fellow, IEEE
Abstract—A fully integrated multiparameter microsensor chip is presented for continuous monitoring of concentrations of different blood gases (e.g., pH, pO2 , pCO2 ), ions, and biomolecules, and for conductometric measurements. The chip can monitor up to seven different chemical substances depending on the membranes deposited on the sensor units (on-chip ion-sensitive fieldeffect transistors (ISFETs), amperometric and conductometric cell). The sensors, which are positioned in a flow channel, are surrounded by on-chip interfacing and processing electronics so that external readout goes via a simple data acquisition card. In addition, temperature control of the measured fluids and a onetime-use security check have been provided for proper operation. Fabrication was done in a standard 1.2- m CMOS process to which extra postprocessing steps have been added for the chemical sensors and membranes. The chip operates at 5 V and the total die area is 25.7 mm2 . Full integration is obtained including the ISFETs and ISFET buffers, as well as a reference electrode structure, all integrated on the same chip in the same technology. Index Terms—Amperometric and conductometric cell, biochemical, CMOS microsensor, EPROM, ISFET, signal interfacing, temperature control.

for medical security reasons. The full system is processed in a 1.2- m single-metal single-poly CMOS technology and operates at 5 V. Extra postprocessing steps have been added to manufacture the sensor (interface) structures and a calibration system. The total chip area is 4.11 mm 6.25 mm. The process technology used was explained in detail in [1]. In this paper, the overall system and the electronic subblocks are explained in detail and measurements are presented. Minor additional details can be found in the visuals supplement of [2]. The paper is organized as follows. Section II presents an application for the microsensor chip and explains the global system setup. In Section III, the sensors are described, and in Section IV, the sensor interfacing electronics. Section V covers the heat regulation system, and Section VI explains the control electronics and the EPROM. In Section VII, chemical measurements are presented, and finally, in Section VIII, conclusions are drawn. II. TOTAL MICROSENSOR SYSTEM A typical use of the microsensor is measuring gas concentrations in blood. The chip is packaged such that the central part, where the sensors are aligned, is exposed to a flow channel where the blood and calibration solutions run through. This sensor alignment (centerline a–h along the long side) and the flow-channel perimeter around it (oval shape for O-ring to seal off the flow channel) can clearly be seen in Fig. 1. For a small moment during measurement, the flow is stopped such that a small blood sample is trapped at the sensor interface. After a short period needed to make sure that the sample acquires the correct temperature, measurement results are read in by a monitor. This monitor can be as simple as a laptop with a data acquisition card. Keeping the temperature of the measured samples constant is important for reproducibility of the results and for comparison with other measurements (eventually performed elsewhere). The main goal of the sensor development is twofold. First, the continuous monitoring of blood gasses must be possible with integrated sensors. Second, the system may only have a minimal amount of external connections in order to keep the wire connection to the monitor small. The minimal amount of external and ), connections is five: the power supply connections ( the clock signal, and the I/O connections. Three extra wires have been added so that a standard eight-wire connection is obtained (Fig. 2). The three extra wires are an external reference voltage for reasons of controllability, an external reference biasing current, and an extra ground connection to have a good analog reference even with currents up to 100 mA. Various versions of the system with different sensor configurations have been manufactured. Because from an electronic point of view, these ver-

I. INTRODUCTION ASS production, high yields, and low manufacturing costs are concepts readily associated with electronics integrated on a single piece of silicon. Other considerations such as low power, high speed, etc., are also motivations for silicon integration. Apart from these factors, small dimensions and portability are of great value in the field of medical healthcare. Analysis of blood gases in intensive-care units is common practice nowadays. For this analysis, many samples can be required every day, consuming a lot of blood, time, and resources. Continuous monitoring of blood gases is therefore a major improvement for critical-care patients and reduces the amount of blood samples needed. For many other applications, as for example, in bioreactors, the possibility to perform continuous measurements is also advantageous. This paper presents the implementation of a complete microsensor system for the continuous monitoring of ions, dissolved gases, and biomolecules. Even more functionality has been integrated on chip, such as a conductometric sensor, an on-chip absolute temperature control, and a one-bit EPROM
Manuscript received March 22, 2001; revised July 20, 2001. This work was supported by the Brite-Euram COMMONSENS project. E. Lauwers, J. Suls, G. Gielen, and W. Sansen are with the Katholieke Universiteit Leuven, ESAT-MICAS, 3001 Leuven-Heverlee, Belgium (e-mail: erik.lauwers@esat.kuleuven.ac.be). W. Gumbrecht is with Siemens AG, Erlangen, Germany. D. Maes is with IMEC, 3001 Heverlee, Belgium. Publisher Item Identifier S 0018-9200(01)09334-9.

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0018–9200/01$10.00 © 2001 IEEE

sions do not differ much. These different subsystems will be explained in Sections III–VI. however. a block diagram of the sensor chip is given. but uses blood samples to be placed in cartridges allowing nearly instantaneous measurements. 1. Seven sensors are located in the centerline and one is above the centerline (e). For example. The second part contains the extra functionalities: temperature control and an EPROM.: CMOS MULTIPARAMETER BIOCHEMICAL MICROSENSOR 2031 Fig. indicated by letters in Fig. Fig. 2. commercial biosensors exist that provide the same range of possible measurements. In Fig. They can all be operated in parallel if required by the user. only one is highlighted here and will be fully explained. The number of eight is determined by the available space in the flow channel. there are two important differences. 1. The third part contains all the electronics necessary to control the chip and the external communication as well as the biasing. Currently. The I-STAT does not allow for continuous measurements. The first part contains the sensors and their interfacing electronics. Layout of the total system. if the oxygen sensor output is made available only at the chip’s output by use of an EPROM similar to the security . whereas in this work.LAUWERS et al. This biosensor works mainly according to the same principles. A prominent commercially available biosensor is the I-STAT from the I-STAT Corporation. Block diagram of the sensor chip. The sensors are microfabricated thin-film electrodes. 2. It can roughly be divided in three parts. SENSORS The chip has eight integrated sensors. However. the idea is to make one standard chip to reduce manufacturing costs and then to program the chip according to the needs of the user. fully integrated sensors are used. III.

IV. and g in Fig. 5. i. DECEMBER 2001 Fig. The counter and working and reference electrodes are indicated by the letters . The sensor chip continuously monitors ions. The conductometric sensor. The adsorption of charged species at the solution–oxide interface is measured.b is cancelled out by making this effect equal for transistors T2a.. the applied voltage a way that the drain current remains constant. Traditionally. 3. and . pump one is off). The ISFETs can be used to measure the voltages between the conductometric electrodes. It was decided to integrate six ion-sensitive field-effect transistors (ISFETs) (b. f. 36. Also. oval structure around a and e) next to the flow channel. Here. respectively. . c. such as. To tackle this problem. which is a modified symmetrical OTA with pMOS source follower (Fig. Measurements on previous prototypes indicated that this design is very robust toward technology variations and can handle an input (output) voltage from about 2 V up to 5 V with a supply of 5 V. The ISFETs are biased in the correct linear operating point . Both operations are combined in an ISFET buffer with low offset. Different solutions for this reference problem have been published. one oxygen sensor (h). dissolved gases.b is kept constant. Transistor schematic of the ISFET buffer: a modified symmetrical OTA with pMOS source follower. which measures the electric conductivity of an electrolyte solution. a solution based on different pH-sensitive electrodes [5]. which in turn allowed an easier design for the controller. d. this calibration solution then remains in place while all the other ISFETs see the fluid being measured. The actual open sensor window is sketched by the circle around them. the drain–source voltages over transistors T1a. e. Other versions manufactured contain different sensor units such as an enzymatic or pCO sensor. 1. The (Fig. The operation is based on direct contact of the electrolyte with the gate oxide. and biomolecules. B. external reference electrodes are used for stable measurements [4]. Potentiostatic Setup In Fig. for correct operation the drain-to-source voltage of the ISFET has to be kept constant. as will be explained in Section VI. pump one is on). An ISFET is basically a field-effect transistor of which the gate metalization has been omitted. It was chosen to directly apply by an external connection this voltage to make sure that it is a well-controlled electrical signal. To prevent polarization of the reference due .2032 IEEE JOURNAL OF SOLID-STATE CIRCUITS. The size of the micropool in polyimide around the sensor’s active area is determined by the used selective-membrane dispensing technique. During a calibration cycle (pump two is on. 1). More information concerning the membrane dispensing is given in [3]. The pMOS source follower T5 is added to match the input and output voltage swing and also to lower the output impedance. a reference electrode with an Ag–AgCl interface has been integrated in a bypass structure (Fig. for example. the current is kept constant and the gate voltage of the ISFET is measured through a buffer and then sent to the monitor for analysis. The layout of this bypass structure is based on a previous design to monitor blood gasses [5]. ISFET Buffer Amplifier EPROM. stable potentials can only be obtained with a fixed chloride concentration in the sample solution. 3.b are kept constant. Fig. bypassing the (interface) impedances of the current providing electrodes.b and so the drain–source voltage of T1a. During measurement (pump two is off. ISFET calibration setup. and one conductometric sensor (a). The ISFET calibration setup is schematically shown in Fig. is built with two parallel sensors of which one electrode is shared (the middle one). The response of an ISFET can be measured in two ways. In addition. VOL. the bypass structure traps the calibration fluid on top of the reference ISFET. hence allowing a four-point conductometric measurement. However. NO. Dimensions of the individual sensors are determined by chemical considerations from previous prototypes. 4) can be held constant and the change applied voltage in the drain current is measured as a function of the ion activity. ions and their properties) of the solution. 12. The ISFET and its buffer are integrated in one process and on the same device to enable a more stable operation. a schematic of the potentiostatic setup is given for an amperometric measurement. is measured. INTERFACE ELECTRONICS A. can be changed in such Alternatively. 4.b using the same technology as T1a.b. The bulk effect of transistors T1a. By introducing the bootstrap transistors T2a. A sinusoidal input signal is applied at the electrodes and the current through the electrodes which is dependent on the composition (number of charged elements. this allowed having a face is indicated by 1:4 demultiplexer instead of a 1:5 demultiplexer. 4). a normal CMOS FET but with an oxide–nitride gate dielectric and a Pt gate. The actual measured voltage at the solution–oxide inter.e. then the user only has to pay for this reduced functionality.

HEAT REGULATION For reproducible blood-gas measurements. it can be seen that for every increase in temperature of drops about 2. Schematic view of the potentiostatic setup. The measurements in Fig. This means going transistor and then reading out from no heating power to full heating power and back. C. the heating device is turned on to generate enough heat to keep replacing connection is left open and . no measurable effect is caused on the feedback system. The feedback loop is designed with the first pole being the . as shown in Fig. however. This voltage (also referred to 1 . 1 is connected to the extra resistor branch and can easily be connected to the bondpad on its left during packaging. 5 is integrated on chip.0095 s and 0.15 s supporting this statement. This voltage is then sent to the output. This relatively low frequency originates from low offset specifications for the different building blocks. so that the heating feedback system has to be designed with the fastest of both time constants in mind. 8 yield time constants of 0. To keep the on-chip temperature constant. a heatregulating loop including a temperature-sensing device and a heating device have been integrated. nMOS transistor and is designed to be able to generate 0.25 W two possible output ranges were foreseen. 1(a)] is connected to an opamp and resistor structure (see left-hand side of Fig. The heating device is a normal of different chemical solutions with varying gas concentrations. Fig. The second exponential is very dependent on the chip package used. The driving (4) It is assumed that the thermal resistance of the silicon is small compared to the thermal resistance to the environment [7]. The currents are very small (typically nanoamperes) and must be amplified for further signal handling. varies according to a combination of two exponential functions: or one exponential that characterizes the heat resistance and heat (2) capacitance of the silicon. This current is then converted and amplified to a voltage through a feedback resistor . 2). an input current of 100 nA of 1 V. faradic current. Through the feedback loop. different fluids can only be compared validly if the temperature during different measurements is the same.LAUWERS et al. a difference in sensitivity factor of 4. is proportional to . From Fig. For a given input potential and chemical consets the maximal output range and centration. The voltage at the counter electrode is regulated such that the reference electrode is kept in the same as for the ISFETs. is the biasing (1) current of the transistor. the potential at the working electrode can be set to voltage induce an electrochemical. which necessitate large transistors and therefore limit the gain bandwidth (GBW). 7. as given by (3) to current drawn through it. Conductometric Sensor As explained above. then the voltage drop over the bipolar transistor. By changing the input operating point . This corresponds to an effective resistance of gives a 10 M . 6. 7). Also. .33 was taken. at 37 C) throughout different measurements. the size of conthus the sensitivity of the current-to-voltage converter ( verter). With the highest sensitivity selected. For fixed ) can now be used to control the chip temperature. 7.: CMOS MULTIPARAMETER BIOCHEMICAL MICROSENSOR 2033 electrode [Fig. then a new feedback resistance is obtained which is “Sensor in” pad in Fig. is proportional to the absolute temperature. The bondpad in the lower right corner of Fig. This was done by or 50 mA with a 5-V power supply. 5. If or is the leakage current at zero biasing. The sensitivity is then increased: larger than The thermal time constant of the regulating loop was measured by externally applying a 5-V pulse to the gate of the heater (Fig. In this design. . If the current through the bipolar device is kept constant. which is the bondpad. as as and to allow a large range To allow large variations in indicated in the inset in Fig. the connection the feedback resistor is . and one that characterizes the heat loss to the environment [7]. V. The temperature is set through If the . then the on-chip temperature constant. This means that wherever both are put on the same chip. with a -resistor network. the on-chip temperature needs to be fixed (for example. which is connected as a diode (inset in Fig. signal frequencies up to 5 kHz can be applied. The complete setup of Fig. which is an input control voltage to the system (through the is applied. If. Limited by the individual blocks concerned (the ISFETs and the converter). The temperature-sensing device is a parasitic vertical p-n-p bipolar transistor.2 mV. 6) to convert the current into an output voltage. it is also possible to perform a complete four-point conductometric measurement on chip. an inert counter electrode is introduced to provide the current for the reduction (or oxidation) at the working electrode. and the absolute temperature. 8).

VOL. Temperature regulation: measured base–emitter voltage dependence of a bipolar transistor on the environment temperature and schematic of how this is used in the heat-regulating loop. the chip may only be used on one patient and this for a limited time. Also. is the current for the total system bipolar transistor. 36. During measurements of the temperature-control loop. DECEMBER 2001 Fig. . fastest thermal pole. between 33 C and 47 C ambient temperature. For health care reasons. Modified feedback impedance for two possible ranges of operation. A. In a fully mounted and packaged chip. the chip must be discarded. The difference between both to the resistance of the routing. A fully automated measurement was performed by automatically changing the thermochuck temperature. NO. through the power supply. 7. EPROM The sensor chip was primarily developed for (but not limited to) medical use. an electronically controllable thermochuck was used to set the ambient or environment temperature of the chip. This information is sufficient for designing the range of the temperature-control loop. Fig. is the voltage drop over the bipolar transistor that is in is the voltage over a second integrated the feedback loop. a measurement result of the temperature-control loop is given. VI. 2). With the given heating power. 8. Fig. 8 and is in . The temperature value was derived with an accuracy of values is due about 1 mV.4 mV. To make sure that two patients never use the same chip.2034 IEEE JOURNAL OF SOLID-STATE CIRCUITS. This is equal to 0. After use. because the heat loss to the environment will then be smaller. 12. which is almost a factor of ten smaller than without regulation. CONTROL ELECTRONICS The control electronics consist of an EPROM ( a controller. In Fig. T as a function of time when the heater gate voltage switches from 0 to 5 V and back. a single-bit EPROM is integrated on the microsensor chip. this value will be even better. and a line driver ( in Fig. the EPROM in Fig. 6. The result given is an average of ten measured values. 2). 9. The chemical measurements presented in Section VII are performed on a fully packaged device.24 mV/ C. the attenuation of the thermal path can be estimated by extrapolating the curves of Fig. The first time the sensor is used. the voltage over the bipolar transistors changes only with 3.

and hence provide an extra check to see if the electronics work properly. M2 needs a has been taken. In order to generate this 8 V. the EPROM could be programmed to indicate the kind of sensor configuration that is available on this particular chip. and a security margin of 25%.5 V. If the CGV is now increased to 8 V during write mode. The sizing of transistors M1 and M2 can be explained as follows. The W/L of M1 has been . a charge pump was also integrated. The controller can intrinsically be clocked at 1 MHz according to simulations. while only a small current flows if the FGT has been programmed. The output voltage (8 V in this design) can be varied easily by resizing the output capacitor. a large current flows through M1. If it has not been used. so that with a control-gate voltage (CGV) of 1.5 and 8 V. To this end. When the CGV is now brought back to 1. larger W/L. If more than one bit is integrated and some logic is added.: CMOS MULTIPARAMETER BIOCHEMICAL MICROSENSOR 2035 Fig. In order not to load this output capacitance too much. Hence. 9. Three wires have been added so that a standard eight-wire connection is obtained: an external for reasons of controllability. A schematic of the total EPROM is given in Fig. This value was calculated from the chosen specifications for minimal clock frequency of the system. the clock signal. an external reference voltage reference biasing current. The synchronization is done by including three analog biasing voltages in the chain of 16 multiplexer inputs. which induce an upward threshold voltage shift. then M2 taken as is on and has to conduct a lot of current without lowering the drain–source voltage of the FGT too much. This current is measured and an output bit is sent to the monitor. then the current increases drastically. Assuming that a low R/W signal means “read. Then the monitor can read this and automatically set the correct parameters.LAUWERS et al. the controller (part 3 of Fig. the same demultiplexer input is selected. but much less than a second decoder would. If the R/W signal is in write mode. Schematic view of the complete EPROM. TABLE I OVERVIEW OF THE EPROM FUNCTION large drain–source on-resistance. Controller The minimal amount of external connections is five: the and . The functioning of the EPROM is summarized in Table I. The charge pump is a three-stage bootstrap structure. This can easily be achieved by taking a 1:16 demultiplexer instead of a 1:4 and connecting every fourth output together. only a small current of the order of 10 pA flows through the FGT. Before programming. The core of the EPROM is a floating-gate nMOS transistor (FGT) to which a control gate is capacitively coupled. then the chip can be used and the EPROM is programmed to avoid future use. M3 has a channel length of 20 m and M4 of 40 m. In case the FGT has not been programmed.5 V. 2) has to redirect 16 outputs to one output line and redirect one input line to four different inputs. If a minimal frequency of 5 kHz and a maximal droop of 1 mV are taken. Use of an EPROM can even be further exploited in future versions. This increases the used area a little. 10. every fourth clock cycle. and a value of B. and both have a width of 2 m. Fully automated chip temperature measurement.” then in read mode. the output is high (low) when the FGT has (not) been programmed. Fig. and every 16th clock cycle. then leakage current F (5) is read. This means that if M1 has a The decoder and gray counter are well-known digital building blocks and will not be further explained. 10. transistors M3 and M4 need to have a high drain–source resistance. The schematics of the multiplexer and demultiplexer are identical. a hold capacitance of 40 pF has been placed to temporarily store the input voltages while the other ports are being refreshed. Hence. and an extra ground connection to have a good analog reference even with currents up to 100 mA. This control gate can have two different voltages: 1. the same multiplexer input is selected. It is not a standard EPROM circuit solution. and power supply connections the I/O connections. This is a nonreversible operation and therefore provides a valid security check. creating hot electrons that are trapped in the gate oxide of the FGT. transistor M1 is on and M2 is off. This necessitates the use of a 16:1 multiplexer and a 1:4 demultiplexer. but the chip’s speed is limited by the analog electronics which have . At each demultiplexer output. Analog voltages eliminate the possibility of still having hard faults in the hardware without noticing. Only one decoder is needed if. the threshold voltage of the FGT is small. maximal voltage droop. a current of the order of 10 A flows through it.

Therefore. to drive large loads with a reasonable power consumption. 36. Measurement results are plotted in Fig. enabling a solution with regulated oxygen concentration to be pumped over the sensor array. The amperometric measurement is done using the potentiostatic setup (IV-OTA and Pot-OTA). First. In this application. a linear relation of about . The total dynamic linearity error or offset variation is less than 15 mV. a line driver is needed. Offset (or total nonlinearity) of the rail-to-rail line driver.5 and 0. The output stage is a modified Miller-compensated opamp stage [8]. 12. 12.4 to 0. the open-loop gain reduces because the output transistors work in their linear region.6 V versus the reference electrode. reducing the gain. because the read-out software and not the hardware is the main speed-limiting factor. In these regions of operation. The two diodes. 12 the result of an input voltage sweep is given. Through and O inputs.5 V as well as high voltages up to 5 V.7-V input voltage. In simulation. However.46 mW.7 V. This limits the speed for the prototype system to maximally about 20 kHz. shift the positive zero. the flow channel is connected to an artificial patient. CHEMICAL MEASUREMENTS The chip microphotograph is shown in Fig. Signals that need a higher accuracy than 15 mV and with an expected output voltage range that contains this transition region must be compensated. On a 5-V scale. Once above 0. there is a shift in offset due to the nMOS differential pair that starts to operate in its active region. The transistor schematic of the line driver design is given in Fig. This line driver must be able to drive loads up to 300 pF. it is varinot necessary to add a special structure to keep the ation small. so that the open-loop variation is divided by the loop gain. Rail-to-rail line driver (biasing circuit not drawn). this is not a problem here. This limits the frequency range of the opamp but. The current of the two complementary input-differential pairs is summed and amplified. Clearly. located next to the compensation capacitance .2036 IEEE JOURNAL OF SOLID-STATE CIRCUITS. it is important to keep the total transconductance variation (when the input varies over the full scale) small. 11. when designing a rail-to-rail opamp. the working electrode is set at a the voltage of 0. however. Line Driver To bring the analog signals off chip. The total system speed is limited by the DAC card used in the monitor and the software. VOL. 12.6 V (throughout different batches and runs). the difference stays well within this 1-mV accuracy (or 12 bits) and not within a 15-mV accuracy that is relevant for full-swing signals only. For this purpose. it can be seen that the difference between input and output stays smaller than 1 mV for an input from 0. DECEMBER 2001 Fig. the amplification was chosen to be higher than 60 dB. the absolute accuracy can be higher.6 dB and a GBW of 300 kHz for a load of 300 pF and a power consumption of 5. The buffer must have a unity gain and must be able to drive low voltages from about 0. Thus. Large transistors are used where appropriate to provide low offsets. also for the temperature information range. Then the oxygen concentration in the fluid is varied. The driver was also integrated separately as a test structure. In Fig. this means that the absolute accuracy equals dB bits (6) Fig. and in Fig. an amperometric oxygen measurement performed on two different packaged sensors is presented. C. to higher frequencies. This means that if the gain is made large enough. 13. if the absolute temperature information is considered. locally for one signal. as mentioned earlier. the driver has a gain of 61. the opamp has unity feedback. VII. For the measurement. 14. that is common in two-stage Miller amplifiers. 11. NO. the voltage range is always between 0. Fig. a rail-to-rail opamp was designed. Only at the two extremities is a little increase seen. 13. Sensor chip die microphotograph. Normally. For example.

13. 16. It can clearly be seen that the output voltage follows the potassium concentration according to (7) This is close to the theoretical slope of 59 mV. Fig. and built-in security EPROM. the same microsystem allows up to seven different measurements. Also. Amperometric measurement of oxygen. which makes it a difficult to reproduce process. “A CMOS multiparameter biochemical microsensor with temperature control and signal interfacing. pp. including the interfacing electronics. Arquint. SPIE. and N. A difference in thickness of the membrane can easily induce such large differences in the output slope because of the high amplification factor of the IV-OTA. The difference in slope between both measurements is explained by slight differences in the selective membranes deposited on top of the sensor (Clarck-type O sensor). 207–214. Lauwers et al. Kunnecke. H. 1188–1190. 3857. typically within one minute.: CMOS MULTIPARAMETER BIOCHEMICAL MICROSENSOR 2037 Fig. 244–245. pp. van den Berg. Also. on-chip integrated ISFETs and ISFET buffers. 1999. REFERENCES [1] F. Next.” in Transducers’99. 15. CONCLUSION A fully integrated multiparameter sensor chip has been presented. a conductometric measurement result is presented in Fig. In total. 1993. for cm specific resistance. Feb. vol. Jorgensen and W.LAUWERS et al. Finally. In Fig. Hence. The resistance is calculated using (8) In Fig. the absence of an absolute voltage level in this figure.. temperature control. Measured resistance versus specific resistance of buffer solution. pp.. 15. pCO and pH. which is in the expected range. vol.” Sensors and Actuators B. [4] Ph. Experimental measurement results have been presented that prove the functionality of the system and the feasibility of the integration of multiple chemical sensors on one chip. “A biochemical CMOS integrated multiparameter microsensor. Those membranes are deposited manually on the prototype devices. For example. [2] E. 16. pp. Sept. the theoretical a fluid with a 100value is spec resistance distance cm area electrode cm k (9) The difference with the measured value in Fig. the buffer fluid is plotted. 2001. Fig. Strong points of the system chip include low pin count. nonideal etching) and the nonideally parallel layout. 1999. van der Schoot. Solid-State Circuits Conf. The input is a 1-kHz signal with a 100-mV amplitude and the feedback resistance of the IV-OTA is 100 k . 14. de Rooij. Van Steenkiste et al. F. The measured resistance versus specific resistance of . VIII. the measurement of the potassium concentration using an ISFET with a potassium-selective membrane is described. the output of the ISFET buffer connected directly to a plotter (bypassing the multiplexer) is shown. 340–344. “Integrated bloodgas sensor for pO . (ISSCC). “Fully automated membrane dispensing in nanoliter scale and its application in sensor manufacturing. IEEE Int.” Proc. the output voltage amplitude thus varies between 143 and 400 mV. 16 can be readily expected for a chemical sensor as a result of the condition of the electrodes (oxidation. B. the response time is fairly rapid. [3] C. 25 mV/10%[O ] full scale is observed between the oxygen concentration and the output voltage of the IV-OTA. Measured output voltage of a fully packaged K sensor. A.” in Proc. 16. a conductometric sensor and oxygen sensor are integrated on-chip with their interfacing electronics.

His research interests include design and computer-aided design (simulation. degrees in electrical engineering from the Katholieke Universiteit Leuven. Schelter. ESAT. 1994. “A high-dynamic-range CMOS opamp with low-distortion output structure. Sansen. U. Erik Lauwers was born in Leuven. He has been involved in design automation and in numerous analogue integrated circuit designs for telecom.D. He is working on the development of semiconductorbased chemical and biochemical sensors and microsystems for medical applications.W. and test) of analog and mixed-signal integrated circuits. 704–708. Until 1983. He is cofounder and organizer of the workshops on Advances in Analog Circuit Design in Europe.” Sensors and Actuators B. degree in electrical engineering in 1997 from the Katholieke Universiteit Leuven. vol. Belgium. in 1984. He received the M. Mar. pp. in 1996. Wong and M. 29. Belgium. 1987.D. 1204–1207. W. He received the M. He is a member of several editorial and program committees of journals and conferences. Since 1984. and in 1994 at the T. He is a member of several boards of directors. Solid-State Circuits. in 1973. His research interests are mainly in mixed-signal and analog base-band integrated circuits. he received a BAEF fellowship. Willy Sansen (M’72–SM’86–F’95) received the M. Geeraerts.2038 IEEE JOURNAL OF SOLID-STATE CIRCUITS. “Electrothermal simulation and design of integrated circuits. theses in these fields. pp. 36. vol. and B. synthesis. he has been working toward the Ph. Dec. 8–19. 143–146. where he is currently a Professor. degree as a Research Assistant at the ESAT-MICAS Laboratories of the Katholieke Universiteit Leuven. Belgium.L. in 1985 at the University of Pennsylvania. he joined IMEC as a Process Engineer to work on the CMOS integration of chemical sensors and of ferroelectric memories. VOL. degree in electrical engineering from the Katholieke Universiteit Leuven (K. and sensors. White.” IEEE Trans. Erlangen. [7] W.Sc. Graindourze. consumer electronics. pH sensor system for online blood monitoring. H. CA. In 1972 he was appointed by the National Fund of Scientific Research (Belgium) at the ESAT laboratory of the K. Nurnberg. After being a Postdoctoral Research Assistant and Visiting Lecturer at the University of California. In 1978. degree in electronics from the University of California. 12. he returned to the Department of Electrical Engineering of the Katholieke Universiteit Leuven. 36. He is a member of the executive and program committees of the IEEE ISSCC conference. Walter Gumbrecht received the Ph. and W. Berkeley. SolidState Circuits. Belgium. Electron Devices. [6] H. David Maes received the degree in electrical engineering from the University of Leuven. 1989. which includes about fifty members and which is active in research projects with industry. “A CMOS-integrated “ISFET-operational amplifier” chemical sensor employing differential sensing. in 1972. . degree in physical chemistry in 1983 from the University of Erlangen. Belgium. 22.D. Philadelphia. In 1969. in 1986 and 1990. During 1984–1990. 479–487. D. Georges Gielen was born in Heist-op-den-Berg. respectively. Leuven) in 1967 and the Ph. layout. he has headed the ESAT-MICAS Laboratory on analog design. fellowship. B. Steyaert and W. Belgium. Ulm. He joined the Corporate Technology Department of the Siemens AG. Van Petegem. Germany. H. He has authored and coauthored eleven books and more than 550 papers in international journals and conference proceedings. he studied the photochemical reaction mechanism of transition metal complexes after pulsed laser excitation under an I. and Ph. Stanford. pp. Peters. he has been a Delegate Scientist from IMEC at the KULeuven. where he has been a full Professor since 1980. Since 1984. U. His interests are in the integration of biomembranes and biorecognition systems in planar chemical sensor applications. in 1981 at the EPFL Lausanne.” IEEE J.Sc. He serves regularly on the program committees of international conferences and is an associate editor for several journals.Sc. and has supervised over forty Ph. Gumbrecht. Electrotechnical Department. DECEMBER 2001 [5] W. The work involved the modeling of the ground state of Co(II)N4 Schiffs Base complexes. medical applications. he was the head of the Electrical Engineering Department. Since 1997. pCO . Feb. modeling. In 1996. vol. Sansen. Leuven.O. Jan Suls received the Master’s degree in chemistry in 1979 from the Katholieke Universiteit Leuven (KULeuven).N. and is the program chair of the ISSCC 2002 conference. Germany. vol. Berkeley.” IEEE J. he was a Visiting Professor at Stanford University. pp.D. 1994. “Integrated pO . NO. [8] M.D.

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