CMOS-based Microelectrode Arrays (MEAs)

Microelectrode arrays (MEAs) are arrangements of usually 60 electrodes that are used for multisite extracellular recordings from electrogenic cells, such as neurons, heart cells, retinal cells, or muscle cells. They are used in the fields of neuroscience and biosensing, to study fundamentals of learning processes of aging and mental diseases, or to assess the behavior of cultured electrogenic cells upon exposure to pharmacological agents or hazardous substances.

The use of CMOS-based devices can overcome some limitations of passive MEAs, in particular in performing measurements at high spatial and temporal resolution.
Several CMOS-based MEAs have been developed at our lab during the past years: a device with 128 bidirectional channels (250 μm electrode pitch, 10 - 30 μm electrode diameter) for information processing with natural neuronal networks; a microchip with 16 perforated electrodes for pneumatic anchoring of cells; and a high-density electrode array for electrophysiological recordings at subcellular resolution.

The high-density CMOS-based microelectrode array features 11,011 metal electrodes and 126 channels, each of which comprises recording and stimulation electronics, for extracellular bidirectional communication with electrogenic cells.
The important features include:

(i) high spatial resolution at (sub)cellular level with 3,150 electrodes per mm² (electrode diameter 7 μm, electrode pitch 18 μm)
(ii) a reconfigurable routing of the recording sites to the 126 channels;
(iii) low noise levels

The overall chip size of the high-resolution array is 7.5 mm by 6.1 mm, the active area featuring the electrodes is 2.0 mm by 1.75 mm.

Publications

• P. Livi, F. Heer, U. Frey, D. J. Bakkum, and A. Hierlemann, “Compact Voltage and Current Stimulation Buffer for High-Density Microelectrode Arrays,” Proceedings of the IEEE International Solid-State Circuits Conference, ISSCC, San Francisco, USA, 2010,  pp. 240 – 241, 2010, ISBN 978-1-4244-6034-2.
• U. Frey, J. Sedivy, F. Heer, R. Pedron, M. Ballini, J. Mueller, D. Bakkum, S. Hafizovic, F. D. Faraci, F. Greve, K.-U. Kirstein, and A. Hierlemann, “Switch-matrix-based high-density microelectrode array in CMOS technology,” IEEE Journal of Solid-State Circuits, Vol. 45, no. 2, pp. 467–482, 2010.
• U. Frey, U. Egert, F. Heer, S. Hafizovic, and A. Hierlemann, “Microelectronic System for High-Resolution Mapping of Extracellular Electric Fields Applied to Brain Slices,” Biosensors and Bioelectronics, vol. 24, no. 7, pp. 2191-2198, 2009.
• C. D. Sanchez-Bustamante, U. Frey, J. M. Kelm, A. Hierlemann, and M. Fussenegger, “Modulation of Cardiomyocyte Electrical Properties Using Regulated Bone Morphogenetic Protein-2 Expression,” Tissue Engineering Part A, vol. 14, no. 12, pp. 1969-1988, 2008.
• F. Heer, S. Hafizovic, T. Ugniwenko, U. Frey, W. Franks, E. Perriard, J.-C. Perriard, A. Blau, C. Ziegler, A. Hierlemann, “Single-chip microelectronic system to interface with living cells“, Biosensors and Bioelectronics 22 (2007), p. 2546-2553.

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Collaborations

Groups at ETH Zurich and the University of Zurich; University of Freiburg, Germany; RIKEN, Kobe, Japan; Friedrich-Miescher Institute, Basel, Switzerland; University of Berne, Switzerland, University of Tokyo, Japan.

Contact

Dr. Douglas Bakkum