A. Jachimowicz

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.

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.

A suspended plate viscosity sensor featuring in-plane vibration and piezoresistive readout

Miniaturized viscosity sensors are often characterized by high-resonance frequencies and low-vibration amplitudes. The viscosity parameter obtained by such devices is therefore not always comparable to those probed by conventional laboratory equipment. We present a novel micromachined viscosity sensor with relatively low operating frequencies in the kHz range. The sensor utilizes Lorentz force excitation and piezoresistive readout. The resonating part consists of a rectangular plate suspended by four beam springs. The first mode of vibration is an in-plane mode. Thus, the contribution of the moving plate to the device damping is low, whereas the overall mass is high. This principle improves the quality factor and gives additional freedom to the device designer. This paper presents the device concept, the fabrication process and a prototype of the viscosity sensor. Measurement results demonstrate the feasibility of the device and show that the damping of the device is an appropriate measure for the viscosity.

High resolution flow characterization in Bio-MEMS

This paper introduces a micro-sensor compatible with Bio-MEMS applications for wide-range thermal flow rate measurements in liquids. Based on the applied materials and geometry, the sensor allows an outstanding resolution at minimum thermal cross-talk, enabling flow rate measurements down to 100 μg/h in water, i.e. 100 nl/h. Active and passive measuring principles, their respective applications, and the dynamic flow range coverage are 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.

New microminiaturized glucose sensors using covalent immobilization techniques

Abstract Glucose monitoring is at present the most widespread application of the GOD/H 2 O 2 system. This paper deals with a new technique for immobilizing onto electrochemical thin-film electrode cells based on this detection principle. The thin-film structure consists of a 100 nm thick titanium—platinum or —palladium sandwich layer on glass substrates isolated by a 3 μm silicon nitride film. A three-electrode miniaturized electrochemical cell with an outer diameter of 200 μm was produced by means of standard wet and dry etching procedures. The Ag/AgCl reference electrode was produced by depositing and structuring a 1 μm thick silver film which was subsequently chlorinated by FeCl 3 . The Pt or Pd surface was oxidized electrochemically in dilute aqueous oxidizing solutions. The modified surface was derivatized with amino-organic silylating agents. The covalent coupling of glucose oxidase was carried out by introducing a substituted bifunctional 1,4-benzoquinone group between the silylated electrode surface and the enzyme. A sulfonated polymer was used to protect the enzyme layer and to modify the diffusion characteristics of the electrode.

A micromachined doubly-clamped beam rheometer for the measurement of viscosity and concentration of silicon-dioxide-in-water suspensions

In this contribution we demonstrate the feasibility of a sensor system for viscosity and concentration measurement of complex liquids, in particular suspensions of silicon dioxide particles in water. The sensor system is based on a doubly clamped micromachined beam vibrating in the sample liquid, and an optical readout utilizing a DVD player pickup head. The vibrating beam features resonance frequencies in the range of several 10 kHz, and higher mechanical amplitudes than microacoustic sensors, e.g., quartz thickness shear mode (TSM) resonators or surface acoustic wave (SAW) devices. We show that the damping of the beam is dominated by the viscosity of the liquid, and that this relation also holds for the considered complex liquids, whereas a TSM resonator sensor fails to detect the steady state shear viscosity of the suspensions.

Dynamic thermal sensor - principles in MEMS for fluid characterization

Using thin-film technology with its characteristic low masses and high aspect ratios a new range of possibilities is made available for the use of dynamic thermal measuring principles. Based on this, a micromachined sensor was developed for the measurement of transient thermal signal responses leading to the thermal characterization of fluids at low sample volumes. The achieved resolution allowed the measurement of thermal parameters of the investigated fluids, i.e., thermal conductivity and specific heat, inside microfluidic systems at a high sensitivity, enabling the detection of inter-fluid boundaries, e.g., as found in micromixers and -reactors, making the sensor a useful tool for micro fluidic system characterization. This is achieved via the measurement of the frequency dependent thermal signal response.

Optimization of microfluidic particle sorters based on dielectrophoresis

In this paper, improved dielectrophoretic particle sorters are introduced for application in microfluidics. The optimal shape of the electrodes is briefly discussed and two new sorter topologies are introduced. Based on the theoretical considerations, four sorter configurations are analyzed in detail. The devices are modeled by calculating the particle trajectories from a combination of finite-element simulations and analytical calculations. The four sorter configurations have been realized in chips based on silicon, glass, and SU8 technology. The simulations and the experimental results are in very good agreement and confirm that with the new sorter configurations, much higher performance can be realized (+200%) compared to the classical line electrodes found in literature.