Journal
NATURE ELECTRONICS
Volume 2, Issue 8, Pages 343-350Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41928-019-0285-3
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Funding
- National Institutes of Health [U01NS090596, U01NS099697, UG3TR002151, R01MH101218, R01MH100561, DP1EY024503, R01EY011787, R01NS110422]
- US Army Research Office [W911NF-12-1-0594]
- DARPA [N6600117-C-4002]
- Kavli Institute of Brain Science at Columbia
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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.
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