K.-U. Kirstein

Switch-Matrix-Based High-Density Microelectrode Array in CMOS Technology

We report on a CMOS-based microelectrode array (MEA) featuring 11, 011 metal electrodes and 126 channels, each of which comprises recording and stimulation electronics, for extracellular bidirectional communication with electrogenic cells, such as neurons or cardiomyocytes. The important features include: (i) high spatial resolution at (sub)cellular level with 3150 electrodes per mm2 (electrode diameter 7 ¿m, electrode pitch 18 ¿m); (ii) a reconflgurable routing of the recording sites to the 126 channels; and (iii) low noise levels.

Resonant Magnetic Field Sensor With Frequency Output

This paper presents a novel type of resonant magnetic field sensor exploiting the Lorentz force and providing a frequency output. The mechanical resonator, a cantilever structure, is embedded as the frequency-determining element in an electrical oscillator. By generating an electrical current proportional to the position of the cantilever, a Lorentz force acting like an additional equivalent spring is exerted on the cantilever in the presence of a magnetic field. Thus, the oscillation frequency of the system, which is a function of the resonators equivalent spring constant, is modulated by the magnetic field to be measured. The resonant magnetic field sensor is fabricated using an industrial CMOS process, followed by a two-mask micromachining sequence to release the cantilever structure. The characterized devices show a sensitivity of 60 kHz/Tesla at their resonance frequency f0 =175 kHz and a short-term frequency stability of 0.025 Hz, which corresponds to a resolution below 1 muT. The devices can thus be used for Earth magnetic field applications, such as an electronic compass. The novel resonant magnetic field sensor benefits from an efficient continuous offset cancellation technique, which consist in evaluating the frequency difference measured with and without excitation current as output signal

An 11k-Electrode 126-Channel High-Density Microelectrode Array to Interact with Electrogenic Cells

A microelectrode array allows an arbitrary group of 126 electrodes to be selected from a total of 11,016 in order to do cell or neural recordings from areas of interest with 18 mum spatial resolution and 2.4 muv input-referred noise. Signals are amplified by 0 to 80dB, bandpass filtered (0.3 to 4kHz), and finally digitized (20kS/s, 8b). Example recordings from acute brain slices are shown

Monolithic Resonant-Cantilever-Based CMOS Microsystem for Biochemical Sensing

A resonant cantilever-based microsystem aimed at biochemical sensing is presented. The sensor system comprises a magnetically actuated resonant cantilever sensor array integrated with the feedback circuitry, digital control circuitry and a serial interface on a single chip in 0.8 mum CMOS technology. The sensor system shows a frequency stability of better than 3 Hz in water corresponding to a detection limit of about 30 pg mass loading. The system has been used for the detection of antibody-antigen interaction on the cantilever surface. The possibility to actuate and operate cantilever arrays in a liquid environment opens up a variety of new applications for bio-chemical sensing.

Cantilever-Based Biosensors in CMOS Technology

Single-chip CMOS-based biosensors that feature microcantilevers as transducer elements are presented. The cantilevers are functionalized to capture specific analytes, e.g., proteins or DNA. The binding of the analyte changes the mechanical properties of the cantilevers such as surface stress and resonant frequency, which can be detected by an integrated Wheatstone bridge. The monolithic integrated readout allows for a high signal-to-noise ratio, lowers the sensitivity to external interference and enables autonomous device operation.

A digital CMOS micro-hotplate array for analysis of environmentally relevant gases

A monolithic gas sensor array fabricated in industrial CMOS-technology combined with post-CMOS micromachining is presented. The device comprises an array of three metal-oxide-coated micro-hotplates with integrated MOS-transistor heaters and the needed driving and signal-conditioning circuitry. The operating temperature of the SnO/sub 2/ metal oxide resistors varies between 200 and 350/spl deg/C. Three digital PID controllers enable individual temperature regulation. Interface and temperature control are implemented digitally, making a power-saving mode and temperature modulation, to enhance the analyte discrimination, applicable. Emphasis was placed on a modular system with the required analog circuitry reduced to a minimum.

A perforated CMOS microchip for immobilization and activity monitoring of electrogenic cells

CMOS-based microelectrode systems offer decisive advantages over conventional micro-electrode arrays, which include the possibility to perform on-chip signal conditioning or to efficiently use larger numbers of electrodes to obtain statistically relevant data, e.g., in pharmacological drug screening. A larger number of electrodes can only be realized with the help of on-chip multiplexing and readout schemes, which require integrated electronics. Another fundamental issue in performing high-fidelity recordings from electrogenic cells is a good electrical coupling between the cells and the microelectrodes, in particular, since the recorded extracellular signals are in the range of only 10–1000 µV. In this paper we present the first CMOS microelectrode system with integrated micromechanical cell-placement features fabricated in a commercial CMOS process with subsequent post-CMOS bulk micromachining. This new microdevice aims at enabling the precise placement of single cells in the center of the electrodes to ensure an efficient use of the available electrodes, even for low-density cell cultures. Small through-chip holes have been generated at the metal-electrode sites by using a combination of bulk micromachining and reactive-ion etching. These holes act as orifices so that cell immobilization can be achieved by means of pneumatic anchoring. The chip additionally hosts integrated circuitry, i.e., multiplexers to select the respective readout electrodes, an amplifier with selectable gain (2×, 10×, 100×), and a high-pass filter (100 Hz cut-off). In this paper we show that electrical signals from most of the electrodes can be recorded, even in low-density cultures of neonatal rat cardiomyocytes, by using perforated metal electrodes and by applying a small underpressure from the backside of the chip. The measurements evidenced that, in most cases, about 90% of the electrodes were covered with single cells, approximately 4% were covered with more than one cell due to clustering and approximately 6% were not covered with any cell, mostly as a consequence of orifice clogging. After 4 days of culturing, the cells were still in place on the electrodes so that the cell electrical activity could be measured using the on-chip circuitry. Measured signal amplitudes were in the range of 500–700 µV, while the input-referred noise of the readout was below 15 µVrms (100 Hz–4 kHz bandwidth). We report on the development and fabrication of this new cell-biological tool and present first results collected during the characterization and evaluation of the chip. The recordings of electrical potentials of neonatal rat cardiomyocytes after several days in vitro, which, on the one hand, were conventionally cultured (no pneumatic anchoring) and, on the other hand, were anchored and immobilized, will be detailed.

Digital systems architecture to accommodate wide range resistance changes of metal-oxide sensors

A monolithic gas sensor array fabricated in industrial CMOS technology combined with post-CMOS micromachining is presented. The device comprises an array of three metal-oxide-coated micro-hotplates with integrated MOS transistor heaters and the needed driving and signal-conditioning circuitry. Three digital PID controllers enable individual temperature regulation for each hotplate. The operating temperature of the SnO2 metal-oxide sensors may amount up to 350degC. A serial interface and the temperature control units have been implemented digitally. The mainly digital implementation offers the advantage to apply a power-saving mode and temperature modulation techniques to enhance the analyte discrimination capability.

CMOS monolithic atomic force microscope

A single-chip atomic force microscope fabricated in industrial CMOS-technology with post-CMOs micromachining is presented, which comprises an array of twelve cantilevers with integrated deflection sensors and actuators, digital proportional-integral-derivative (PID) deflection controllers, amplification stages, offset compensation circuitry, digital filters for sensor-actuator coupling compensation, A/D and D/A converters, dedicated serial lines (one per cantilever) for fast data transfer, and an I/sup 2/C serial interface for chip programming. Parallel scanning imaging evidenced a height resolution better than 10nm.

CMOS-Based Tactile Microsensor for Medical Instrumentation

This paper presents a novel tactile sensing device aimed at a variety of medical instrumentation applications, including extravascular blood pressure monitoring, distinguishing a coronary artery from a nearby running cardiac vein, and locating the site of a coronary occlusion. The monolithically integrated microsensor is fabricated using an industrial CMOS process with a limited number of postmicromachining steps. Using the tonometric principle, an array of membrane capacitors can detect and monitor the pulsatile pressure variations inside a blood vessel