<italic>In Vitro</italic> Multi-Functional Microelectrode Array Featuring 59 760 Electrodes, 2048 Electrophysiology Channels, Stimulation, Impedance Measurement, and Neurotransmitter Detection Channels

Abstract

Biological cells are characterized by highly complex phenomena and processes that are, to a great extent, interdependent. To gain detailed insights, devices designed to study cellular phenomena need to enable tracking and manipulation of multiple cell parameters in parallel; they have to provide high signal quality and high-spatiotemporal resolution. To this end, we have developed a CMOS-based microelectrode array system for in vitro applications that integrates six measurement and stimulation functions, the largest number to date. Moreover, the system features the largest active electrode array area to date (4.48 × 2.43 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ) to accommodate 59760 electrodes, while its power consumption, noise characteristics, and spatial resolution (13.5-μm electrode pitch) are comparable to the best state-of-the-art devices. The system includes: 2048 action potential (AP, bandwidth: 300 Hz-10 kHz) recording units, 32 local-field-potential (LFP, bandwidth: 1 Hz-300 Hz) recording units, 32 current recording units, 32 impedance measurement units, and 28 neurotransmitter detection units, in addition to the 16 dual-mode voltage-only or current/voltage-controlled stimulation units. The electrode array architecture is based on a switch matrix, which allows for connecting any measurement/stimulation unit to any electrode in the array and for performing different measurement/stimulation functions in parallel.