Peter Fromherz

A 128 128 CMOS Biosensor Array for Extracellular Recording of Neural Activity

Sensor arrays are a key tool in the field of neuroscience for noninvasive recording of the activity of biological networks, such as dissociated neurons or neural tissue. A high-density sensor array complementary metal–oxide–semiconductor chip is presented with 16 K pixels, a frame rate of 2 kiloframes per second, and a pitch of 7.8 m 7.8 m for imaging of neural activity. The related circuit and system issues as well as process aspects are discussed. A mismatch-canceling calibration circuitry with current mode signal representation is used. Results from first biological experiments are presented, which prove full functionality of the chip.

Noninvasive neuroelectronic interfacing with synaptically connected snail neurons immobilized on a semiconductor chip

A hybrid circuit of a semiconductor chip and synaptically connected neurons was implemented and characterized. Individual nerve cells from the snail Lymnaea stagnalis were immobilized on a silicon chip by microscopic picket fences of polyimide. The cells formed a network with electrical synapses after outgrowth in brain conditioned medium. Pairs of neurons were electronically interfaced for noninvasive stimulation and recording. Voltage pulses were applied to a capacitive stimulator on the chip to excite the attached neuron. Signals were transmitted in the neuronal net and elicited an action potential in a second neuron. The postsynaptic excitation modulated the current of a transistor on the chip. The implementation of the silicon-neuron-neuron-silicon circuit constitutes a proof-of-principle experiment for the development of neuroelectronic systems to be used in studies on neuronal signal processing, neurocomputation, and neuroprosthetics.

A 128 /spl times/ 128 CMOS bio-sensor array for extracellular recording of neural activity

A CMOS sensor array for monitoring neural signals of living cells with 128 /spl times/ 128 pixels in a 1 mm/sup 2/ area is described. A standard 0.5 /spl mu/m, 5 V CMOS process extended by top electrodes covered by a relatively thin bio-compatible dielectric is used. Detection circuitry is based on a sensor-MOSFET mismatch-compensating current-mode technique.

Instrumentation for handling monomolecular films at an air–water interface

A monolayer trough with two movable barriers and several compartments is described. In addition, a precision multilayer depositing lift, a simplified Langmuir trough, and a technique for isolating monolayers remaining in contact with water are discussed. Various applications of this combined instrumentation in the study of monomolecular films are presented.

Fluorescence interference-contrast microscopy on oxidized silicon using a monomolecular dye layer

A silicon chip is covered by a monomolecular film of a fluorescence dye with silicon dioxide used as a spacer. The fluorescence depends on the distance of the dye from the silicon. The modulation of the intensity is described quantitatively by an optical theory which accounts for interference of the exciting light and of the emitted light. The effect is used to obtain a microscopic picture of the surface profile with a precision of a few Angströms. The perspectives for an application in wet systems such as neuron-silicon junctions and lipid membranes on silicon are pointed out.

Electrical Interfacing of Nerve Cells and Semiconductor Chips

The electrical interfacing of individual nerve cells and silicon microstructures is considered, as well as the assembly of elementary hybrid systems made of neuronal networks and semiconductor microelectronics. Without electrochemical processes, coupling of the electron-conducting semiconductor and the ion-conducting neurons relies on a close contact of cell membrane and oxidised silicon with a high resistance of the junction and a high conductance of the attached membrane. Neuronal excitation can be elicited and recorded from the chip by capacitive contacts and by field-effect transistors with an open gate. Integrated iono-electronic system are obtained by the outgrowth of neuronal networks on the surface of the silicon chip, by implementing electrical circuits in the chip and by two-way interfacing of the neuronal and the electronic components.

Lipid-vesicle structure: Size control by edge-active agents

Abstract Fragments of planar lipid bilayers bifurcate into closed vesicles near a critical vesiculation index as determined by their size and by their edge tension. Gradual modulation by edge-active agents — as described in analogy to the Gibbs adsorption equation — leads to the formation of monodisperse vesicles of controlled size.

A new technique for investigating lipid protein films

Abstract A technique is described which permits independent investigation of (1), the adsorption of protein on lipid monolayers, and (2) the penetration of the adsorbed protein into the lipid film. Some results on the interaction of hemiglobin with arachidic acid and stearic acid methyl ester as model substances are presented, indicating that the adsorbed protein is not decoiled. The technique is suited as well to the investigation of the enzymatic activity of adsorbed enzymes as shown qualitatively with catalase.

Recombinant maxi-K channels on transistor, a prototype of iono-electronic interfacing

We report on the direct electrical interfacing of a recombinant ion channel to a field-effect transistor on a silicon chip. The ion current through activated maxi-KCa channels in human embryonic kidney (HEK293) cells gives rise to an extracellular voltage between cell and chip that controls the electronic source–drain current. A comparison with patch-clamp recording shows that the channels at the cell/chip interface are fully functional and that they are significantly accumulated there. The direct coupling of potassium channels to a semiconductor on the level of an individual cell is the prototype for an iono-electronic interface of ligand-gated or G protein-coupled ion channels and the development of screening biosensors with many transfected cells on a chip with a large array of transistors.

Micelle structure: a surfactant-block model

Abstract A structure of spheroidal micelles is developed by model building. It is a hybrid of two classical micelle models, the compact droplet and the bilayer fragment : droplet-like in overall shape and bilaver-like in local configuration. The micelle appears as a tiny isometric liquid crystal with particular architecture and dynamics.