Siddharth Shekar, Krishna Jayant, M Angeles Rabadan, Raju Tomer, Rafael Yuste and Kenneth L. Shepard “A miniaturized multi-clamp CMOS amplifier for intracellular neural recordingNature Electronics volume 2pages343–350 (2019)

Intracellular electrophysiology is a foundational method in neuroscience and uses electrolyte-filled glass electrodes and bench-top 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 mod-ules 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.