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A miniaturized multi-clamp CMOS amplifier for intracellular neural recording

Nature Electronics volume 2, pages 343–350 (2019)Cite this article

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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.

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Fig. 1: Miniaturized multi-clamp amplifier.
Fig. 2: Amplifier electrical characterization.
Fig. 3: In vitro recordings using sharp microelectrodes.
Fig. 4: In vitro recordings using patch pipettes.

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Data availability

The data that supports the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported in part by the National Institutes of Health under U01NS090596 and U01NS099697 to K.L.S.; UG3TR002151 to M.A.R. and R.T.; and R01MH101218, R01MH100561, DP1EY024503, R01EY011787 and R01NS110422 to R.Y. This work was also supported, in part, by the US Army Research Office under contract no. W911NF-12-1-0594 (MURI) and by DARPA under contract no. N66001-17-C-4002 to K.L.S. and R.Y. K.J. was supported in part by the Kavli Institute of Brain Science at Columbia.

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Authors and Affiliations

  1. Department of Electrical Engineering, Columbia University, New York, NY, USA

    Siddharth Shekar, Krishna Jayant & Kenneth L. Shepard

  2. Department of Biological Sciences, Columbia University, New York, NY, USA

    Krishna Jayant, M Angeles Rabadan, Raju Tomer & Rafael Yuste

  3. Kavli Institute for Brain Science, Columbia University, New York, NY, USA

    Krishna Jayant, Rafael Yuste & Kenneth L. Shepard

  4. NeuroTechnology Center, Columbia University, New York, NY, USA

    Krishna Jayant, M Angeles Rabadan, Raju Tomer, Rafael Yuste & Kenneth L. Shepard

Authors
  1. Siddharth Shekar
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  2. Krishna Jayant
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  3. M Angeles Rabadan
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  4. Raju Tomer
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  6. Kenneth L. Shepard
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Contributions

S.S. and K.J. conceptualized the study and performed the experiments and analysis. S.S. designed the circuits. M.A.R. and R.T. provided cell cultures. R.Y. and K.L.S. provided advice on the experiments. K.L.S. provided overall supervision and guidance. S.S., K.J. and K.L.S. edited the manuscript. All authors provided comments.

Corresponding authors

Correspondence to Krishna Jayant or Kenneth L. Shepard.

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Competing interests

S.S., K.J. and K.L.S. are listed as inventors on a provisional patent filed by Columbia University. The other authors declare no competing interests.

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Supplementary Information

Supplementary Sections 1–7 and Supplementary Table 1.

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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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