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Electrochemical impedance spectroscopy in vivo for neurotechnology and bioelectronics

Nature Reviews Electrical Engineering volume 2, pages 110–124 (2025)Cite this article

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Abstract

Electrochemical impedance spectroscopy (EIS) is a well‐established electrochemical technique that provides invaluable information regarding the properties and functionality of electrodes within bioelectronic devices. EIS is the primary technique that reports on electrode properties in vivo using the implanted device itself. Nevertheless, there are many inconsistencies in the way this technique is implemented and reported on. Without a clear understanding of the experiment and experimental set‐up, it is challenging to draw meaningful conclusions and for results to be extrapolated across studies to benefit and advance the field. This Review discusses in vivo EIS experiments, specifically focusing on challenges in the experimental set‐up, the equipment used, data presentation and circuit modelling for neural interfaces. We propose guidelines for methodical reporting and a consistent, standardized use of terminology, paramount in understanding the performance of electrodes functioning at neural interfaces and promoting the transferability of findings across studies.

Key points

  • Electrochemical impedance spectroscopy is a valuable tool for evaluating the stability of electrodes at a neural interface.

  • Consideration of the equipment limitations and electrochemical set-up (electrode configuration and locations) is critical for meaningful interpretation of impedance measurements.

  • Caution is advised when drawing conclusions from a single frequency measurement. It is recommended that the linearity assumption is supported by an accompanying full-spectrum measurement or a Lissajous plot.

  • Models used in the electrical circuit modelling of impedance spectra should be validated and all elements should represent physical properties at the electrode interface.

  • The development of an on-the-probe reference electrode would enable more robust in vivo measurements and the ability to separate electrode surface changes from tissue impedance.

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Fig. 1: The relationship between the Nyquist and Bode representations of impedance spectra.
Fig. 2: Circuit modelling of impedance spectroscopy.
Fig. 3: Overview of two-electrode and three-electrode set-ups for recording impedance spectra in vitro and in vivo.
Fig. 4: Considerations in the equipment used to collect electrochemical impedance spectroscopy data, presented as Lissajous plots and accuracy contour plots.
Fig. 5: Interpretation of impedance data.
Fig. 6: Impedance spectra as Nyquist plots representing changes in tissue impedance.

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Acknowledgements

This work was supported by the CatWalk Spinal Cord Injury Trust and the Health Research Council of New Zealand (project grant and HRC/Catwalk Partnership 19/895). This work was also supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense (US $534,258) through the Spinal Cord Injury Research Program (award HT9425-23-1-0492). Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. B. Hazelgrove was supported by a University of Auckland Doctoral Scholarship. B.R. was supported by the Neurological Foundation First Fellowship (1952 FF). M.A. and L.M were supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation programme (grant agreement 101113487 ‘ProBER‘), the European Innovation Council H2020 programme (grant agreements 899287 ‘NeuraViper’ and 101099366 ‘BioFINE’), and the Chalmers Gender Initiative for Excellence (GENIE).

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  1. School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

    Brittany Hazelgrove, Brad Raos, Bruce Harland & Darren Svirskis

  2. Department of Microtechnology and Nanoscience, Chalmers University of Technology, Gothenburg, Sweden

    Lukas Matter & Maria Asplund

  3. Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand

    Leo Cheng

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B. Hazelgrove and L.M. researched data for the article. All authors substantially contributed to the discussion of the content, wrote the manuscript, and reviewed and edited the manuscript before submission.

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Nature Reviews Electrical Engineering thanks Alexandra Joshi-Imre, who co-reviewed with Yupeng Wu, Katarzyna Krukiewicz and Mark E. Orazem for their contribution to the peer review of this work.

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Hazelgrove, B., Matter, L., Raos, B. et al. Electrochemical impedance spectroscopy in vivo for neurotechnology and bioelectronics. Nat Rev Electr Eng 2, 110–124 (2025). https://doi.org/10.1038/s44287-024-00126-6

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