Tutorial: guidelines for standardized performance tests for electrodes intended for neural interfaces and bioelectronics

Abstract

Implantable neural interfaces advance the possibilities for neuroscientists to study the brain. They are also promising for use in a multitude of bioelectronic therapies. Electrode technology plays a central role in these developments, as the electrode surfaces form the physical interfaces between technology and the biological targets. Despite this, a common understanding of how electrodes should best be evaluated and compared with respect to their efficiency in recording and stimulation is currently lacking. Without broadly accepted performance tests, it is difficult to rank the many suggestions for electrode materials available in the literature, or to identify where efforts should be focused to advance the field most efficiently. This tutorial critically discusses the most relevant performance tests for characterization of neural interface electrodes and explains their implementation, interpretation and respective limitations. We propose a unified standard to facilitate transparent reporting on electrode performance, promote efficient scientific process and ultimately accelerate translation into clinical practice.

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Fig. 1: The electrode/tissue interface.
Fig. 2: Impedance in relation to electrode size.
Fig. 3: Impact of the measurement system.
Fig. 4: Charge-balanced stimulation.
Fig. 5: Voltage profile during charge injection.
Fig. 6: Pulse-clamp test.
Fig. 7: Typical CV of a Pt-electrode in PBS.
Fig. 8: Pourbaix diagram.
Fig. 9: Electrode types.
Fig. 10: Polarization during stimulation.
Fig. 11: A summary of the performance tests proposed in this tutorial.

Data availability

The experimental data supporting the findings of this study (Figs. 2, 3, 5, 7, 10 and Supplementary Fig. 1) are available from the corresponding author upon request.

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Acknowledgements

This work was partially supported by BrainLinks-BrainTools, Cluster of Excellence funded by the German Research Foundation (DFG, EXC 1086). M Asplund and C Boehler were supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 759655). L. Fadiga was supported by PRIN 2015. We acknowledge S. Shaner, University of Freiburg, for support in proofreading of the final manuscript.

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M.A. and C.B. wrote the main part of the manuscript with expert input from S.C., L.F. and T.S. C.B. was responsible for all experimental data included in the manuscript. S.C. wrote the section on spectroscopic analysis.

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Correspondence to Maria Asplund.

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The authors declare no competing interests.

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Peer review information Nature Protocols thanks Andreas Hierlemann, Jonathan Viventi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Key references using the performance tests described in this tutorial:

Boehler, C., Stieglitz, T. & Asplund, M. Biomaterials 67, 346–353 (2015): https://www.sciencedirect.com/science/article/pii/S0142961215006183

Boehler, C., Vieira, D. M., Egert, U. & Asplund, M. ACS Appl. Mater. Interfaces 12, 14855–14865 (2020): https://pubs.acs.org/doi/abs/10.1021/acsami.9b22798

Boehler, C., Oberueber, F., Schlabach, S., Stieglitz, T. & Asplund, M. ACS Appl. Mater. Interfaces 9, 189–197 (2017): https://pubs.acs.org/doi/abs/10.1021/acsami.6b13468

Vomero, M. et al. Materials 11, 2486 (2018): https://europepmc.org/article/med/30544545

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Boehler, C., Carli, S., Fadiga, L. et al. Tutorial: guidelines for standardized performance tests for electrodes intended for neural interfaces and bioelectronics. Nat Protoc 15, 3557–3578 (2020). https://doi.org/10.1038/s41596-020-0389-2

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