A miniaturized multi-clamp CMOS amplifier for intracellular neural recording

Abstract

Intracellular electrophysiology is a foundational method in neuroscience and uses electrolyte-filled glass electrodes and benchtop amplifiers to measure and control transmembrane voltages and currents. Commercial amplifiers perform such recordings with high signal-to-noise ratios but are often expensive, bulky and not easily scalable to many channels due to reliance on board-level integration of discrete components. Here, we present a monolithic complementary metal–oxide–semiconductor multi-clamp amplifier integrated circuit capable of recording both voltages and currents with performance exceeding that of commercial benchtop instrumentation. Miniaturization enables high-bandwidth current mirroring, facilitating the synthesis of large-valued active resistors with lower noise than their passive equivalents. This enables the realization of compensation modules that can account for a wide range of electrode impedances. We validate the amplifier’s operation electrically, in primary neuronal cultures, and in acute slices, using both high-impedance sharp and patch electrodes. This work provides a solution for low-cost, high-performance and scalable multi-clamp amplifiers. An integrated circuit amplifier, which is fabricated in a commercial complementary metal–oxide–semiconductor (CMOS) process, can record both voltages and currents with performance that exceeds commercial benchtop instrumentation.

Cite this article

Shekar, S., Jayant, K., Rabadan, M.A. et al. A miniaturized multi-clamp CMOS amplifier for intracellular neural recording. Nat Electron 2, 343–350 (2019). https://doi.org/10.1038/s41928-019-0285-3

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