Meinhard Knoll

A disposable biosensor for urea determination in blood based on an ammonium-sensitive transducer

A potentiometric urea-sensitive biosensor using a NH4(+)-sensitive disposable electrode in double matrix membrane (DMM) technology as transducer is described. The ion-sensitive polymer matrix membrane was formed in the presence of an additional electrochemical inert filter paper matrix to improve the reproducibility in sensor production. The electrodes were prepared from one-side silver-coated filter paper, which is encapsulated for insulation by a heat-sealing film. A defined volume of the NH4(+)-sensitive polymer matrix membrane cocktail was deposited on this filter paper. To obtain the urea-biosensor a layer of urease was cast onto the ion-sensitive membrane. Poly (carbamoylsulfonate) hydrogel, produced from a hydrophilic polyurethane prepolymer blocked with bisulfite, served as immobilisation material. The disposable urea sensitive electrode was combined with a disposable Ag/AgCl reference electrode to obtain the disposable urea biosensor. The sensor responded rapidly and in a stable manner to changes in urea concentrations between 7.2 x 10(-5) and 2.1 x 10(-2)mol/l. The detection limit was 2 x 10(-5) mol/l urea and the slope in the linear range 52 mV/decade. By taking into consideration the influence of the interfering K(+)- and Na(+)-ions the sensor can be used for the determination of urea in human blood and serum samples (diluted or undiluted). A good correlation was found with the data obtained by the spectrophotometric routine method.

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.

Generation of Oxide Charge and Interface States by Ionizing Radiation and by Tunnel Injection Experiments

Results of irradiation and high field tunnel injection experiments on MOS capacitors are discussed. The midgap voltage shift as a function of dose is caused by hole trapping only. In the case of tunnel injection, the generation of electron-hole pairs by impact ionization requires a much larger electron density and high fields. Thus a model of charge build-up is established which takes into account the hole trapping in neutral oxide states, the subsequent electron trapping in now positively charged states and detrapping of captured electrons. By means of this model, the prediction of the radiation hardness of MOS devices is feasible, provided that the impact ionization coefficient a is known accurately. If this is not the case, the combined techniques of ionizing irradiation and tunnel injection can be utilized to determine ¿ = ¿o exp(-H¿/F) as a function of the electrical field F. Electron capture and detrapping crosssections ¿n and ßn, resp., can be deduced by fitting the model to the experimental results. An F-3 dependency for ¿n and an exp(-Hß/F) dependency for ßn are found. Only a weak dependence on different processing parameters is observed. The proposed model is verified by a sequence of irradiation and injection steps. The generation of oxide charge is accompanied by an increase in interface state density Dit with a distribution, which peaks at about 0.15 eV above midgap, in both experiments. The results indicate that the generation of interface states is proportional to the amount of trapped holes.

Comparative studies of tunnel injection and irradiation on metal oxide semiconductor structures

Tunnel injection and irradiation experiments on metal oxide semiconductor (MOS) structures are performed in order to compare the results of both experiments and to check the feasibility of radiation hardness prediction of MOS devices. The comparison is based on the fact that in both hot electron and ionizing irradiation experiments electron‐hole pairs are generated in the SiO2. Due to an applied electrical field, these pairs are separated. The fraction of holes, trapped by neutral centers and the number of subsequently captured electrons by these now positively charged traps depend on the amount of available carriers, the magnitude of the respective capture cross sections for electrons and holes, and the number of hole traps. In the case of the tunnel injection experiment the number of the available carriers is a strong function of the field dependent ionization coefficient α. Up to now, its magnitude has not been accurately known. For this reason, a new method is presented which yields additional and rel...

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.

Bias‐temperature stress on metal‐oxide‐semiconductor structures as compared to ionizing irradiation and tunnel injection

This paper presents the change of the midgap voltage ΔVMG and the surface state density Dit caused by bias temperature (BT) stress, ionizing irradiation, and tunnel injection experiments on metal‐oxide‐semiconductor capacitors. The irradiation tests and the tunnel injection experiments are carried out to find correlations of the degradation mechanisms among the three stress procedures. The BT stress is performed on n‐ and p‐type samples with applied positive and negative fields (1–5 MV/cm). The stress temperatures are 100, 150, and 200 °C; the maximum aging time is 30 h. After BT stress, n‐ and p‐type samples exhibit the same degradations of the midgap voltage VMG and of the interface state density Dit, respectively. The increase of ‖VMG‖ and Dit for negative BT stress is significantly larger than in the case of positive BT stress. An analytical expression which describes the changes of VMG and Dit for negative BT stress is developed. Drastic changes of VMG and Dit are observed after switching the stress ...

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.

Reproducible attachment of micrometer sized particles to atomic force microscopy cantilevers

We present a method, which allows attaching micrometer sized spheres to an atomic force microscope cantilever in a reproducible manner. Spheres of different size with a minimum amount of glue are attached to a predefined position on the cantilever. This is performed by using an optical microscope and a laser-pulled micropipette, which guarantees nondestructive handling of the delicate cantilever beams. The method employs a simple setup consisting of a stereomicroscope and a micromanipulator. Images of the modified cantilevers were taken with a scanning electron microscope to clarify the position of the glued spheres on the cantilever. Electron dispersive x-ray analysis reveals that the surface of the microsphere is not covered with the glue, except at the contact area to the cantilever.