Active pixel sensor array for high spatio-temporal resolution electrophysiological recordings from single cell to large scale neuronal networks

Abstract

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.

Frequency-dependent signal transfer at the interface between electrogenic cells and nanocavity electrodes

“…Fields of application for in vitro MEA systems include pharmacological highthroughput screening, cell-based biosensors, and research on information processing in neuronal networks [7][8][9][10][11][12][13]. During the last years, the integration of complementary metal oxide semiconductor technology (CMOS) with MEAs has led to the development of very high-density recording units, opening up new opportunities for the investigation of communication in cellular networks [14,15]. Nevertheless, the simple fabrication of low-impedance and high-spatial-resolution electrodes still remains an experimental challenge.…”

Microchemistry- and MEMS-based Integrated Electrochemical Devices for Bioassay Applications

“…To overcome this problem and incorporate more sensors into a chip-based device, semiconductor technology has been employed. [59][60][61][62][63][64][65][66][67][68] For instance, Lindau and colleagues reported the development of a complementary metal oxide semiconductor (CMOS)-based chip containing 10 © 10 microelectrodes for use in the detection of dopamine. 68 We developed an LSI-based amperometric sensor for electrochemical imaging, [69][70][71][72] designated the Bio-LSI system, first reported by Inoue et al 69 The Bio-LSI system is based on CMOS technology and provides higher temporal resolution for the detection of electrochemical species at different locations on the chip.…”

Direct interfacing of neurons to highly integrated microsystems

“…CMOS (complementary metal oxide semiconductor) technology-based planar, high-density microelectrode arrays (HD-MEAs) feature several thousands of transducers at densities of > 3'000 transducers per mm 2 [4,18,[21][22][23][24][25][26] (Figure 1), which enables recordings from large neuronal networks at single-cell, or even subcellular-component resolution [27,28]. The integrated systems feature tightly-spaced transducers and the respective addressing and readout circuitry on a single chip [4,[21][22][23][24][25][26].…”

“…1a, have been pursued [21,22,24,26]. In the case of open-gate FET transducers, additional stimulation spots are needed and distributed between the electrodes.…”

“…The integrated systems feature tightly-spaced transducers and the respective addressing and readout circuitry on a single chip [4,[21][22][23][24][25][26].…”