Low-noise low-power CMOS preamplifier for multisite extracellular neuronal recordings

This paper reports the design and the experimental results of a fully integrated, low-noise, low-power standard CMOS preamplifier circuit used to record the extracellular electrophysiological activity of in vitro biological neuronal cultures. Our goal is to use the preamplifier in a fully integrated, multi-channel, bi-directional neuro-electronic interface.Among others, two main requirements must be addressed when designing such kind of integrated recording systems: noise performance and very low frequency disturbance rejection. These two requirements need to be satisfied together with a small silicon area design, to be able to integrate a large number of recording channels (i.e. up to thousands) onto a single die. A prototype preamplifier circuit has been designed and implemented; in this paper we report the experimental results.While satisfying the above requirements, our circuit offers state-of-the-art smallest area occupation (0.13 mm2) and consumes 4.5 μW. Sub-threshold-biased lateral pnp transistors, used to implement very high resistance value integrated resistors, have been characterized to determine the resistance spread.The fabricated prototype, coupled with a commercial Micro-Electrode Array (MEA), has been successfully employed to record the extracellular electrophysiological spontaneous activity, both of muscular cardiac cells (cardiomyocytes) and of spinal cord neurons from murines.