This paper presents a chip-based electrophysiological platform enabling the study of micro- and macro-circuitry in in-vitro neuronal preparations. The approach is based on a 64x64 microelectrode array device providing extracellular electrophysiological activity recordings with high spatial (21 microm of electrode separation) and temporal resolution (from 0.13 ms for 4096 microelectrodes down to 8 micros for 64 microelectrodes). Applied to in-vitro neuronal preparations, we show how this approach enables neuronal signals to be acquired for investigating neuronal activity from single cells and microcircuits to large scale neuronal networks. The main elements of the platform are the metallic microelectrode array (MEA) implemented in Complementary Metal Oxide Semiconductor (CMOS) technology similar to a light imager, the in-pixel integrated low-noise amplifiers (11 microVrms) and the high-speed random addressing logic. The chip is combined with a real-time acquisition system providing the capability to record at 7.8 kHz/electrode the whole array and to process the acquired signals.
A voltammetric sensor developed for in situ trace metal
analysis in natural waters is presented. It consists of
an
array of 100 mercury-plated, iridium-based microdisk
electrodes, coated with a 300−600-μm-thick 1.5% agarose gel membrane. This membrane acts as a dialysis
membrane by allowing the diffusion of metal ions and
complexes and by hindering the diffusion of colloids and
macromolecules. Chronoamperometry and square wave
anodic stripping voltammetry (SWASV) have been used
to characterize the diffusion of hexacyanoferrate(III),
lead,
and cadmium in the agarose gel. For these species,
the
diffusion coefficients have been found to be half of the
diffusion coefficient in free solution, and the time
necessary for complete equilibration with the test solution
varied with the gel thickness in accordance with the
theory
and can be lowered to 5 min for a gel thickness of 300
μm. The same techniques have been used to
demonstrate
the efficiency of the membrane against fouling and convection. Pressures in the range 1−600 bar have been
found to have no effect on the sensor response. In
contrast, variations in temperature in the range 4−22
°C
considerably affected diffusion and charge-transfer kinetics, the resulting currents obeying a simple Arrhenius
equation. These results confirm the suitability of
the
voltammetric sensor for in situ analysis of heavy metals
in natural waters.
Neurons extracted from specific areas of the Central Nervous System (CNS), such as the hippocampus, the cortex and the spinal cord, can be cultured in vitro and coupled with a micro-electrode array (MEA) for months. After a few days, neurons connect each other with functionally active synapses, forming a random network and displaying spontaneous electrophysiological activity. In spite of their simplified level of organization, they represent an useful framework to study general information processing properties and specific basic learning mechanisms in the nervous system. These experimental preparations show patterns of collective rhythmic activity characterized by burst and spike firing. The patterns of electrophysiological activity may change as a consequence of external stimulation (i.e., chemical and/or electrical inputs) and by partly modifying the "randomness" of the network architecture (i.e., confining neuronal sub-populations in clusters with micro-machined barriers). In particular we investigated how the spontaneous rhythmic and synchronous activity can be modulated or drastically changed by focal electrical stimulation, pharmacological manipulation and network segregation. Our results show that burst firing and global synchronization can be enhanced or reduced; and that the degree of synchronous activity in the network can be characterized by simple parameters such as cross-correlation on burst events.
A platform for high spatial and temporal resolution electrophysiological recordings of in vitro electrogenic cell cultures handling 4096 electrodes at a full frame rate of 8 kHz is presented and validated by means of cardiomyocyte cultures. Based on an active pixel sensor device implementing an array of metallic electrodes, the system provides acquisitions at spatial resolutions of 42 microm on an active area of 2.67 mm x 2.67 mm, and in the zooming mode, temporal resolutions down to 8 micros on 64 randomly selected electrodes. The low-noise performances of the integrated amplifier (11 microV (rms)) combined with a hardware implementation inspired by image/video processing concepts enable high-resolution acquisitions with real-time preprocessing capabilities adapted to the handling of the large amount of acquired data.
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