F. Kohl

Miniaturized thin-film biosensors using covalently immobilized glucose oxidase☆

Abstract The production of a miniaturized glucose sensor by means of thin-film technology is reported. Two main problems related to miniaturization and device integration were solved: (1) the microminiaturization of a suitable electrochemical cell; (2) localized enzyme immobilization with a technology well suited for device integration. The well-known glucose oxidase/H 2 O 2 system was used to determine the glucose concentration. A miniaturized four-electrode arrangement was introduced to measure H 2 O 2 produced by the enzyme. A double working electrode array for reproducibility tests or differential measurements to suppress interferences is easily produced and can be placed on glass or flexible polymer substrates by means of thin-film technology. The enzyme was covalently coupled to a derivatized platinum thin-film working electrode by means of 1,2-arenequinones, which yield highly reproducible, fast and stable sensors. Measurement of a drop (5 μl) of physiological glucose solution is easily performed, giving a stable response after 40 s.

Miniaturized multi-enzyme biosensors integrated with pH sensors on flexible polymer carriers for in vivo applications

Abstract An electrochemical glucose sensor has been integrated, together with a pH sensor, on a flexible polyimide substrate for in vivo applications. The glucose sensor is based on the measurement of H 2 O 2 produced by the membrane-entrapped enzyme glucose oxidase (GOD). To minimize electrochemical interference, an electrode configuration was designed to perform differential measurements. The solid-state pH sensor employs a PVC-based neutral carrier membrane. The enzymes GOD and catalase were immobilized into two layers of photolithographically patterned hydrogels. The intended use of this device is the short-term monitoring of glucose and pH in intensive care units and operating theatres, especially for neurosurgical applications. The developed immobilization technique can also be used to create integrated multi-sensor chips for clinical analysers. The glucose and pH sensor exhibited excellent performance during tests in buffer solutions, serum and whole blood.

Wide range semiconductor flow sensors

Abstract Micromachined flow sensors based on thin film germanium thermistors offer high flow sensitivities and short response times. Using the controlled overtemperature scheme, the measurable air flow velocity ranges from ±0.01 to ±200 m/s and the response time to large step changes of the air velocity is less than 20 ms. In the constant power mode, a signal rise time of 1.6 ms has been demonstrated by the application of shock waves. An air flow measuring range from 0.6 ml/h to at least 150 l/h has been achieved, e.g. with a rectangular flow channel of 0.54 mm 2 cross-sectional area. Using a lookup table transformation, a linearized output signal can be obtained within 25 μs.

Development of miniaturized semiconductor flow sensors

Abstract Miniaturized flow sensors based on thin film germanium thermistors were developed offering high flow sensitivities and short response times. The thermistors are placed on a silicon nitride diaphragm carried by a silicon frame. Using the controlled overtemperature scheme the measurable airflow rate ranges from 0.6 to 150 000 cm 3 /h. In this paper we mainly report on the dynamic properties of the sensor. The response of the sensor to step changes of the heater power will be compared with its response to shock waves for both the constant power mode and the constant overtemperature operating mode. A simple arrangement for the generation of acoustic shock waves will be presented.

Thin-film Clark-type oxygen sensor based on novel polymer membrane systems for in vivo and biosensor applications

Abstract A planar miniaturized Clark-type oxygen sensor based on the Ross principle has been produced by means of thin-film technology. The use of a polarizable counter electrode in a three-electrode configuration allows the regeneration of the cathodically consumed oxygen, resulting in a zero-flux amperometric oxygen sensor. The platinum working and counter electrodes and the Ag/AgCl reference electrode were covered with a photostructured hydrogel layer, forming the electrolyte compartment, and a photostructured hydrophobic gas-permeable membrane. This arrangement exhibits no oxygen consumption and therefore the signal of the sensor shows almost no flow dependence. Additionally, this electrochemical feature leads to a dynamic equilibrium of the reaction products in the hydrogel layer, overcoming the lifetime limitations caused by buffer degradation in the classical Clark principle. The sensor was tested in buffer solutions and bovine serum, showing excellent performance and no effects of fouling on sensor response. This device can be scaled down and is best suited for integration with other sensors and as a basic transducer for biosensors.

High-resolution thin-film temperature sensor arrays for medical applications

Abstract Highly sensitive and fast temperature sensors with sensitive areas of 0.14 × 0.1 mm 2 have been arranged in arrays with interdistances of 0.4 mm consisting of thin films of amorphous germanium (a-Ge) to yield a high temperature coefficient of resistance of 2%/K at room temperature. The sensors are passivated by a 3-μm-thick silicon nitride layer and can be placed on glass, alumina and polymer substrates. The sensor noise limits the temperature resolution of 0.1 mK whereas the 90% response time is typically 3 ms. The electrical resistance of the sensor is in the range of 10 5 ohm. A measurement current of 1 μA causes selfheating of the sensor on glass substrates of less than 0.3 mK in water. This corresponds to a measured heat resistance of 3 × 10 3 K/W. Temperature distribution measurements in the cortex of rabbits and enzyme-calorimetric determinations have been accomplished with these devices.

Robust Precision Position Detection With an Optical MEMS Hybrid Device

For vibration and displacement sensors, robustness is one of the key requirements. Optical measurement concepts are among the most promising possibilities to achieve it. The presented microoptoelectromechanical system sensor modulates a light flux by means of two congruently placed aperture gratings: one etched into a seismic mass and the other fixed to the sensor package. Commercially available LED and photodetector components at the top and bottom of the sandwich structure generate and detect this modulated light flux and allow for a cost-effective implementation. The prototype used for experimental verification is actuated by inertial forces and exhibits a high sensitivity of 0.85 mV/nm for displacements of the seismic mass and a corresponding noise level of about 14 pm/√Hz. This sensitivity and noise level can be further improved, paving the way for small, lightweight, robust, and high-precision displacement sensors for a large variety of applications.

Deposition and properties of germanium-carbon alloy films produced from tetraethylgermanium in an R.F. discharge

Abstract Thin films of a relatively low concentration of germanium exhibiting electrical conductivities up to 7 × 10 -5 (ω cm) -1 were prepared by r.f. glow discharge decomposition of tetraethylgermanium in a stream of argon. Physical properties such as density, refractive index and electrical conductivity were determined over the range of r.f. power from 10 to 100 W. Power loads under 30 W yielded soft and transparent polymeric materials of low conductivities and low densities while films obtained at higher power loads were glassy in appearance, non-transparent, black, hard and dense (densities in the range 3.0–3.6 g cm -3 ). The conditions yielding optimum values of important physical parameters were established for depositions on the lower excited electrode. For a monomer flow rate of 0.44 standard cm 3 min -1 and an argon flow rate of 20 standard cm 3 min -1 the highest values of the electrical conductivity, density and refractive index were obtained at a power load of 50 W. In terms of energy input per unit mass of monomer, this corresponds to about 0.8 × 10 9 J kg -1 . The Auger spectroscopic measurements showed that the highest content of germanium was found in the films deposited on the lower electrode under these conditions. Pattern generation by means of photolithography and subsequent reactive ion etching was carried out with a lateral resolution of approximately 1 μm.

The construction of microcalorimetric biosensors by use of high resolution thin-film thermistors

Abstract A new calorimetric biosensor has been developed using thin-film thermistor arrays and immobilized enzymes. The miniaturized thermistors produced on glass substrates, exhibit a high sensitivity of 2%/K (TCR), a temperature resolution of 0·1 mK, a rise-time of 3 ms and high reproducibility of resistance and TCR. The life time in physiological solution is at least three months. Additionally this device can be miniaturized and integrated on different substrate materials. A Peltier thermostat with a temperature stability of 1 mK was built up containing two thermistor arrays which were inserted into a flow-through system to enable the detection of the heat produced by an enzyme reaction in a differential mode. Covalently immobilized glucose oxidase and catalase on controlled pore glass (CPG) were used to demonstrate the high sensitivity of the produced thermistor arrays.

An Optical In-Plane MEMS Vibration Sensor

This paper presents encouraging results of a novel optoelectronic conversion method for relative displacement. An optical modulator responding to acceleration and gravitation is used for characterization. The Si microelectromechanical system (MEMS) component comprise a spring suspended, in-plane oscillating mass carrying an array of optical apertures. Light flux modulation is achieved with a second array of complementary apertures that is fixed to the Si frame. The investigated device comprises a sandwich structure of an SMD LED, the MEMS aperture gratings, and a phototransistor. Relative displacements of the gratings generate a modulation of the LED light flux that is detected by the phototransistor. Depending on the aperture design, the relative displacement may extend over several tens of microns maintaining a sub-nm resolution. Thus, no closed-loop position control system is required, resulting in minimum complexity and energy consumption of the MEMS component. This setup simplifies the manufacturing process as much as possible, which is one of the significant advantages of the sensor principle. Furthermore, the presented prototype exhibits a promising high sensitivity of 60 nA/nm for displacement, featuring a noise level of about 8 pm/√Hz.