C. Sundermeier

Miniaturized real-time monitoring system for l-lactate and glucose using microfabricated multi-enzyme sensors

A miniaturized on-line monitoring system for the detection of L-lactate and glucose is presented. The system is based on a microfabricated multi-enzyme silicon sensor chip with flow channels integrated on the chip. The sensors were fabricated in containment technology. They were characterized in test solutions. The cross-talking behaviour was investigated and was found to be practically negligible. The linear measurement ranges of both glucose and lactate sensors were large enough for most practical applications. As a result of the miniaturization the analyte consumption could be reduced to a few nmol min(-1). The system was equipped with a microdialysis probe whose recovery was 45% for lactate and 37% for glucose in test solutions using a flow rate of 3 microl min(-1). Lower flow rates of 0.5 microl min(-1) resulted in recoveries of over 90%. The long-term stability of the system was acceptable. Initial measurements have also been performed in vitro using human blood serum.

Containment sensors for the determination of L-lactate and glucose

This paper reports some new results on enzyme based silicon containment sensors. For the first time an L-lactate sensor in containment technology is presented. Through optimization of the buffer system the stability of the lactate sensor was enhanced and the linear response of over 10 mM was achieved. The glucose sensor has also been optimized for a large linear measurement range exceeding 30 mM. A two-enzyme chip with glucose and lactate sensor elements which were integrated on one silicon chip is presented. The response behaviour of the two-enzyme chip was very similar to the single chip behaviour. No cross-talking effects could be observed. A fabrication process for mass-production is described.

Microdialysis system for continuous glucose monitoring

A microdialysis system for continuous glucose monitoring has been developed. The system has been optimized for in vivo applications. All the components have been miniaturized to get a small wearable device. It consists of a small gas driven syringe pump, a microdialysis sampling stage, a specially developed silicon flow-through sensor chip and the electronics. Integrated on the sensor chip are the glucose sensor elements together with a system of capillaries and flow channels. Each process step of the chip fabrication has been designed as a full wafer process to achieve mass-production compatibility. The total system performance is demonstrated by in vitro measurements taken from human serum and glucose standard solutions.

Micromachined glucose sensor

Abstract Until now the enzyme membrane in micro-enzyme sensors has been deposited on the top of the transducer. In such sensors problems are often caused by membrane adhesion and the mechanical stability of the membrane. Furthermore, a place-selective deposition of the membrane material, which is a precondition for the development of multi-functional sensors, is difficult to achieve. To overcome these problems a new device was designed. The enzyme membrane is deposited into the chip in pyramidal containments produced on silicon by anisotropic etching. Here we demonstrate the development of glucose sensors in containment technology. Containments with opening sizes towards the analyte solution side of between 120 μm and 480 μm were used. The enzyme membrane (gelatine gel with glucose oxidase) was deposited inside the containment. The sensitivity increased with increasing opening size. When the sensor was immersed continuously in undiluted human serum, it responded to changes in the glucose concentration for more than 2 days.

Multisensor array for pH, K+, Na+ and Ca2+ measurements based on coated-film electrodes

Abstract The construction of a multisensor array based on coated-film sensors is described. The pH, K+, Na+ and Ca2+ sensors studied so far show excellent electrode properties comparable to these of commercial ion-selective electrodes (ISE); the main attributes are the Nernst response over a wide concentration range, a good selectivity and short response times. They are similar, to coated-wire electrodes, but instead of a metal wire, a thin conductive metal layer manufactured in thin-film technology is used. It is shown that these transducers can be used for the development of a low-cost sensor for the determination of the ion activity in a simple way by potentiometric differential measurement. They can be applied to biomedical measurements, especially for blood analysis.

Potentiometric silicon microsensor for nitrate and ammonium

Abstract A new method of the integration of ion-sensitive membrane and silicon sensor chip has been developed. The ion-sensitive membrane is deposited into pyramidal containments produced on silicon by an anisotropic etching technique. Here we demonstrate the application of this method to the development of nitrate-sensitive sensors and ammonium-sensitive sensors. Acrylate and silicon matrix membranes was casted into the membrane containment. The sensors showed comparable response characteristics like sensors with PVC matrix membranes but had a considerably improved yield of sensor preparation.

Micromachined ion-selective electrodes with polymer matrix membranes

Abstract We have developed a new method for the integration of ion-sensitive membranes and silicon sensor chips. The ion-sensitive membrane is deposited in pyramidal containments produced on silicon by an anisotropic etching technique. Here we demonstrate the application of this method to the development of nitrate-sensitive sensors. PVC membranes are cast into the membrane containment. The sensors show an improved mechanical stability and lifetime compared to ISFETs. Slopes, detection limits and selectivities of the containment sensors are similar to those of ion-selective electrodes with internal electrolyte solution using the same membrane composition. The results of the drift and hysteresis measurements are sufficiently good for most practical applications.

Amperometric microelectrode array in containment technology

A new transducer concept for miniaturized amperometric sensor arrays is presented. A KCl-containing electrolyte for oxygen measurements is anchored inside the microcontainments of a silicon chip together with the working and reference electrodes. The fabrication process is planned as a full wafer process for low-cost mass production with a narrow variability. First measurements are presented and the problems and advantages of the containment concept discussed.

Microparticle detector for biosensor application

We report on the development of a high-sensitivity electrical biosensor that detects analyte molecules labelled by microparticles. Detection is achieved by measuring electrochemical current changes occurring when bead-labelled analyte molecules get specifically bound to microelectrodes. We present measurements with transducers that bear microelectrode arrays with a large number of microelectrodes connected in parallel as well as single addressable microelectrodes. These measurements reveal the very sensitive detection of even one single microparticle. By using magnetic microbeads a magnetic force can be applied to the beads to remove them from the electrodes. When this force exceeds the specific binding force of the analyte molecule the bound microparticles are removed and a signal is produced. We assume that the transducer could also be used for the determination of specific binding forces.

Potentiometric ion-selective silicon sensors for the on-line monitoring of blood electrolytes

A non-invasive on-line monitoring system for blood electrolytes has been developed on the basis of potentiometric ion-selective silicon sensors. The microsensors were fabricated in the patented containment technology owned by ICB. Additionally, multianalyte sensors with two and three containment sensor elements integrated on chip were realized. The new polysiloxane membrane functionalized with trifluoropropyl groups with improved adhesion on the silicon oxide surface were used as matrix membrane for all prepared solid state microsensors. The following containment sensors have been developed: potassium, calcium, sodium, and pH. They were characterized in physiological test solutions. The excellent reliability of the potassium sensors has been demonstrated successfully in clinical trials with real circulating whole blood samples and on extracorporal animal blood circulation. First simultaneous measurements of potassium, sodium and pH have also been performed in vitro using human blood samples.