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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.

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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.

References

  1. Buzsaki, G. Large-scale recording of neuronal ensembles. Nat. Neurosci. 7, 446–451 (2004).

    CAS  PubMed  Google Scholar 

  2. Fernández-Ruiz, A. et al. Long-duration hippocampal sharp wave ripples improve memory. Science 364, 1082 (2019). 189–197.

    PubMed  PubMed Central  Google Scholar 

  3. Henze, D. A. et al. Intracellular features predicted by extracellular recordings in the hippocampus in vivo. J. Neurophysiol. 84, 390–400 (2000).

    CAS  PubMed  Google Scholar 

  4. Nakazono, T., Jun, H., Blurton-Jones, M., Green, K. N. & Igarashi, K. M. Gamma oscillations in the entorhinal-hippocampal circuit underlying memory and dementia. Neurosci. Res. 129, 40–46 (2018).

    PubMed  PubMed Central  Google Scholar 

  5. Hochberg, L. R. et al. Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature 485, 372–375 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Petrini, F. M. et al. Enhancing functional abilities and cognitive integration of the lower limb prosthesis. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.aav8939 (2019).

  7. Simmons, F. B. et al. Auditory nerve: electrical stimulation in man. Science 148, 104–106 (1965).

    CAS  PubMed  Google Scholar 

  8. Famm, K., Litt, B., Tracey, K. J., Boyden, E. S. & Slaoui, M. Drug discovery: a jump-start for electroceuticals. Nature 496, 159–161 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Wu, H., Gao, W. & Yin, Z. Materials, devices and systems of soft bioelectronics for precision therapy. Adv. Healthc. Mater. 6, 1700017 (2017).

    Google Scholar 

  10. Viswam, V., Obien, M. E. J., Franke, F., Frey, U. & Hierlemann, A. Optimal electrode size for multi-scale extracellular-potential recording from neuronal assemblies. Front. Neurosci. https://doi.org/10.3389/fnins.2019.00385 (2019).

  11. Negi, S., Bhandari, R., Rieth, L. & Solzbacher, F. In vitro comparison of sputtered iridium oxide and platinum-coated neural implantable microelectrode arrays. Biomed. Mater. 5, 15007 (2010).

    CAS  PubMed  Google Scholar 

  12. Boehler, C., Aqrawe, Z. & Asplund, M. Applications of PEDOT in bioelectronic medicine. Bioelectron. Med. 2, 89–99 (2019).

    Google Scholar 

  13. Carli, S. et al. Electrodeposited PEDOT:Nafion composite for neural recording and stimulation. Adv. Healthc. Mater. 8, 1900765 (2019).

    Google Scholar 

  14. Cogan, S. F. et al. Sputtered iridium oxide films for neural stimulation electrodes. J. Biomed. Mater. Res. 89, 353–361 (2009).

    Google Scholar 

  15. Gerwig, R. et al. PEDOT–CNT composite microelectrodes for recording and electrostimulation applications: fabrication, morphology, and electrical properties. Front. Neuroeng. https://doi.org/10.3389/fneng.2012.00008 (2012).

  16. Ludwig, K. A., Uram, J. D., Yang, J., Martin, D. C. & Kipke, D. R. Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) film. J. Neural Eng. 3, 59–70 (2006).

    PubMed  Google Scholar 

  17. Luo, X., Weaver, C. L., Zhou, D. D., Greenberg, R. & Cui, X. T. Highly stable carbon nanotube doped poly(3,4-ethylenedioxythiophene) for chronic neural stimulation. Biomaterials 32, 5551–5557 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Nimbalkar, S. et al. Ultra-capacitive carbon neural probe allows simultaneous long-term electrical stimulations and high-resolution neurotransmitter detection. Sci. Rep. 8, 6958 (2018).

    PubMed  PubMed Central  Google Scholar 

  19. Vomero, M. et al. Highly stable glassy carbon interfaces for long-term neural stimulation and low-noise recording of brain activity. Sci. Rep. 7, 40332 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Boehler, C., Stieglitz, T. & Asplund, M. Nanostructured platinum grass enables superior impedance reduction for neural microelectrodes. Biomaterials 67, 346–353 (2015).

    CAS  PubMed  Google Scholar 

  21. Boehler, C., Vieira, D. M., Egert, U. & Asplund, M. NanoPt – A nanostructured electrode coating for neural recording and microstimulation. ACS Appl. Mater. Interfaces https://doi.org/10.1021/acsami.9b22798 (2020).

  22. Zhao, Z., Gong, R., Zheng, L. & Wang, J. In vivo neural recording and electrochemical performance of microelectrode arrays modified by rough-surfaced aupt alloy nanoparticles with nanoporosity. Sensors 16, 1851 (2016).

    Google Scholar 

  23. U. S. P. C. USP Class VI in USP Biological Reactivity Tests In Vivo. US Pharmacopeia and National Formulary.

  24. International Organization for Standardization. 10993: Biological evaluation of medical devices.

  25. Hill, D. N., Mehta, S. B. & Kleinfeld, D. Quality metrics to accompany spike sorting of extracellular signals. J. Neurosci. 31, 8699 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Kimura, J. Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice (Oxford University Press, 2013).

  27. McCann, H., Pisano, G. & Beltrachini, L. Variation in reported human head tissue electrical conductivity values. Brain Topogr. 32, 825–858 (2019).

    PubMed  PubMed Central  Google Scholar 

  28. Baumann, S. B., Wozny, D. R., Kelly, S. K. & Meno, F. M. The electrical conductivity of human cerebrospinal fluid at body temperature. IEEE Trans. Biomed. Eng. 44, 220–223 (1997).

    CAS  PubMed  Google Scholar 

  29. Hladky, S. B. & Barrand, M. A. Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence. Fluids Barriers CNS 11, 26 (2014).

    PubMed  PubMed Central  Google Scholar 

  30. Levin, E., Muravchick, S. & Gold, M. I. Density of normal human cerebrospinal fluid and tetracaine solutions. Anesthesia Analgesia 60, 814–817 (1981).

    CAS  PubMed  Google Scholar 

  31. Franks, W., Schenker, I., Schmutz, P. & Hierlemann, A. Impedance characterization and modeling of electrodes for biomedical applications. IEEE Trans. Biomed. Eng. 52, 1295–1302 (2005).

    PubMed  Google Scholar 

  32. Woods, V. et al. Long-term recording reliability of liquid crystal polymer µECoG arrays. J. Neural Eng. 15, 066024 (2018).

    PubMed  PubMed Central  Google Scholar 

  33. Nelson, M. J., Pouget, P., Nilsen, E. A., Patten, C. D. & Schall, J. D. Review of signal distortion through metal microelectrode recording circuits and filters. J. Neurosci. Methods 169, 141–157 (2008).

    PubMed  PubMed Central  Google Scholar 

  34. Kumsa, D. W. et al. Electron transfer processes occurring on platinum neural stimulating electrodes: a tutorial on the i(V e) profile. J. Neural Eng. 13, 052001 (2016).

    PubMed  Google Scholar 

  35. Ivanovskaya, A. N. et al. Electrochemical roughening of thin-film platinum for neural probe arrays and biosensing applications. J. Electrochem. Soc. 165, G3125–G3132 (2018).

    CAS  Google Scholar 

  36. Marrese, C. A. Preparation of strongly adherent platinum black coatings. Anal. Chem. 59, 217–218 (1987).

    CAS  Google Scholar 

  37. Young, A. T., Cornwell, N. & Daniele, M. A. Neuro interfaces: neuro-nano interfaces: utilizing nano-coatings and nanoparticles to enable next-generation electrophysiological recording, neural stimulation, and biochemical modulation. Adv. Funct. Mater. 28, 1870079 (2018).

    Google Scholar 

  38. Doña Rodríguez, J. M., Herrera Melián, J. A. & Pérez Peña, J. Determination of the real surface area of Pt electrodes by hydrogen adsorption using cyclic voltammetry. J. Chem. Educ. 77, 1195 (2000).

    Google Scholar 

  39. Łukaszewski, M., Soszko, M. & Czerwiński, A. Electrochemical methods of real surface area determination of noble metal electrodes – an overview. Int. J. Electrochem. Sci. 11, 4442–4469 (2016).

    Google Scholar 

  40. Macdonald, J. R. Impedance spectroscopy. Ann. Biomed. Eng. 20, 289–305 (1992).

    CAS  PubMed  Google Scholar 

  41. Bobacka, J., Lewenstam, A. & Ivaska, A. Electrochemical impedance spectroscopy of oxidized poly(3,4-ethylenedioxythiophene) film electrodes in aqueous solutions. J. Electroanal. Chem. 489, 17–27 (2000).

    CAS  Google Scholar 

  42. Barsoukov, E. & Macdonald, J. R. Impedance Spectroscopy: Theory, Experiment and Applications 3rd edn (John Wiley & Sons, 2018).

  43. Scholtz, F. Electroanalytical Methods: Guide to Experiments and Applications 2nd edn (Springer, 2010).

  44. Harris, K. D., Quiroga, R. Q., Freeman, J. & Smith, S. L. Improving data quality in neuronal population recordings. Nat. Neurosci. 19, 1165–1174 (2016).

    PubMed  PubMed Central  Google Scholar 

  45. Liu, X., Demosthenous, A. & Donaldson, N. Platinum electrode noise in the ENG spectrum. Med. Biol. Eng. Comput. 46, 997–1003 (2008).

    PubMed  Google Scholar 

  46. Buzsaki, G. Rhythms of the Brain (Oxford University Press, 2006).

  47. Neto, J. P. et al. Does impedance matter when recording spikes with polytrodes? Front. Neurosci. 12, 715 (2018).

    PubMed  PubMed Central  Google Scholar 

  48. Zijlmans, M. et al. How to record high-frequency oscillations in epilepsy: a practical guideline. Epilepsia 58, 1305–1315 (2017).

    PubMed  Google Scholar 

  49. Brummer, S. B. & Turner, M. J. Electrochemical considerations for safe electrical stimulation of the nervous system with platinum electrodes. IEEE Trans. Bio-med. Eng. 24, 59–63 (1977).

    CAS  Google Scholar 

  50. Hung, A., Zhou, D., Greenberg, R., Goldberg, I. B. & Judy, J. W. Pulse-clamp technique for characterizing neural-stimulating electrodes. J. Electrochem. Soc. 154, C479–C486 (2007).

    CAS  Google Scholar 

  51. Merrill, D. R., Bikson, M. & Jefferys, J. G. Electrical stimulation of excitable tissue: design of efficacious and safe protocols. J. Neurosci. Methods 141, 171–198 (2005).

    PubMed  Google Scholar 

  52. Rose, T. L. & Robblee, L. S. Electrical stimulation with Pt electrodes. VIII. Electrochemically safe charge injection limits with 0.2 ms pulses. IEEE Trans. Bio-med. Eng. 37, 1118–1120 (1990).

    CAS  Google Scholar 

  53. Janders, M., Egert, U., Stelzle, M. & Nisch, W. Novel thin film titanium nitride micro-electrodes with excellent charge transfer capability for cell stimulation and sensing applications. in Proceedings of 18th Annual International Conference of the IEEE Engineering in Medicine and Biology Society 245–247 (1996).

  54. Weiland, J. D., Anderson, D. J. & Humayun, M. S. In vitro electrical properties for iridium oxide versus titanium nitride stimulating electrodes. IEEE Trans. Bio-med. Eng. 49, 1574–1579 (2002).

    Google Scholar 

  55. Erdey-Grúz, T. & Volmer, M. Zur. Theor. der Wasserst. Überspannung 150A, 203 (1930).

    Google Scholar 

  56. Morton, S. L. The role of oxygen reduction in electrical stimulation of neural tissue. J. Electrochem. Soc. 141, 122 (1994).

    CAS  Google Scholar 

  57. Cogan, S. F., Ehrlich, J., Plante, T. D., Gingerich, M. D. & Shire, D. B. Contribution of oxygen reduction to charge injection on platinum and sputtered iridium oxide neural stimulation electrodes. IEEE Trans. Bio-med. Eng. 57, 2313–2321 (2010).

    Google Scholar 

  58. Cogan, S. F., Plante, T. D. & Ehrlich, J. Sputtered iridium oxide films (SIROFs) for low-impedance neural stimulation and recording electrodes. Conf. Proc. IEEE Eng. Med. Biol. Soc. 6, 4153–4156 (2004).

    PubMed Central  Google Scholar 

  59. Slavcheva, E., Vitushinsky, R., Mokwa, W. & Schnakenberg, U. Sputtered iridium oxide films as charge injection material for functional electrostimulation. J. Electrochem. Soc. 151, E226–E237 (2004).

    CAS  Google Scholar 

  60. van Ooyen, A., Zagolla, V. G., Ulrich, C. & Schnakenberg, U. Pulse-clamp technique for single neuron stimulation electrode characterization. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 1635–1638 (2009).

    Google Scholar 

  61. Stefan, I. C. et al. Theoretical analysis of the pulse-clamp method as applied to neural stimulating electrodes. J. Electrochem. Soc. 148, E73–E78 (2001).

    CAS  Google Scholar 

  62. Suesserman, M. F., Spelman, F. A. & Rubinstein, J. T. In vitro measurement and characterization of current density profiles produced by non-recessed, simple recessed, and radially varying recessed stimulating electrodes. IEEE Trans. Bio-med. Eng. 38, 401–408 (1991).

    CAS  Google Scholar 

  63. Cogan, S. F., Troyk, P. R., Ehrlich, J., Gasbarro, C. M. & Plante, T. D. The influence of electrolyte composition on the in vitro charge-injection limits of activated iridium oxide (AIROF) stimulation electrodes. J. Neural Eng. 4, 79–86 (2007).

    PubMed  Google Scholar 

  64. Anderson, D. N., Duffley, G., Vorwerk, J., Dorval, A. D. & Butson, C. R. Anodic stimulation misunderstood: preferential activation of fiber orientations with anodic waveforms in deep brain stimulation. J. Neural Eng. 16, 016026 (2019).

    PubMed  Google Scholar 

  65. McIntyre, C. C. & Grill, W. M. Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output. J. Neurophysiol. 88, 1592–1604 (2002).

    PubMed  Google Scholar 

  66. Tehovnik, E. J. & Slocum, W. M. Depth-dependent detection of microampere currents delivered to monkey V1. Eur. J. Neurosci. 29, 1477–1489 (2009).

    PubMed  PubMed Central  Google Scholar 

  67. Bonner, M. D., Daroux, M., Crish, T. & Mortimer, J. T. The pulse‐clamp method for analyzing the electrochemistry on neural stimulating electrodes. J. Electrochem. Soc. 140, 2740–2744 (1993).

    CAS  Google Scholar 

  68. Abd Hamid, A. I., Gall, C., Speck, O., Antal, A. & Sabel, B. A. Effects of alternating current stimulation on the healthy and diseased brain. Front. Neurosci. 9, 391 (2015).

    PubMed  PubMed Central  Google Scholar 

  69. Goodman, J. H., Berger, R. E. & Tcheng, T. K. Preemptive low-frequency stimulation decreases the incidence of amygdala-kindled seizures. Epilepsia 46, 1–7 (2005).

    PubMed  Google Scholar 

  70. Boehler, C. & Asplund, M. PEDOT as a high charge injection material for low-frequency stimulation. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2018, 2202–2205 (2018).

    CAS  Google Scholar 

  71. Ghazavi, A. & Cogan, S. F. Electrochemical characterization of high frequency stimulation electrodes: role of electrode material and stimulation parameters on electrode polarization. J. Neural Eng. 15, 036023 (2018).

    PubMed  Google Scholar 

  72. Biegler, T., Rand, D. A. J. & Woods, R. Limiting oxygen coverage on platinized platinum; relevance to determination of real platinum area by hydrogen adsorption. J. Electroanal. Chem. Interfacial Electrochem. 29, 269–277 (1971).

    CAS  Google Scholar 

  73. Weltin, A. et al. New life for old wires: electrochemical sensor method for neural implants. J. Neural Eng. 17, 016007 (2019).

    PubMed  Google Scholar 

  74. Beebe, X. & Rose, T. L. Charge injection limits of activated iridium oxide electrodes with 0.2 ms pulses in bicarbonate buffered saline. IEEE Trans. Bio-med. Eng. 35, 494–495 (1988).

    CAS  Google Scholar 

  75. Hudak, E. M., Kumsa, D. W., Martin, H. B. & Mortimer, J. T. Electron transfer processes occurring on platinum neural stimulating electrodes: calculated charge-storage capacities are inaccessible during applied stimulation. J. Neural Eng. 14, 046012 (2017).

    PubMed  PubMed Central  Google Scholar 

  76. Kozai, T. D., Jaquins-Gerstl, A. S., Vazquez, A. L., Michael, A. C. & Cui, X. T. Brain tissue responses to neural implants impact signal sensitivity and intervention strategies. ACS Chem. Neurosci. 6, 48–67 (2015).

    CAS  PubMed  Google Scholar 

  77. Polikov, V. S., Tresco, P. A. & Reichert, W. M. Response of brain tissue to chronically implanted neural electrodes. J. Neurosci. Methods 148, 1–18 (2005).

    PubMed  Google Scholar 

  78. Prodanov, D. & Delbeke, J. Mechanical and biological interactions of implants with the brain and their impact on implant design. Front. Neurosci. 10, 11 (2016).

    PubMed  PubMed Central  Google Scholar 

  79. Salatino, J. W., Ludwig, K. A., Kozai, T. D. Y. & Purcell, E. K. Glial responses to implanted electrodes in the brain. Nat. Biomed. Eng. 1, 862–877 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Johnson, M. D., Kao, O. E. & Kipke, D. R. Spatiotemporal pH dynamics following insertion of neural microelectrode arrays. J. Neurosci. methods 160, 276–287 (2007).

    CAS  PubMed  Google Scholar 

  81. Halliwell, B. Reactive oxygen species and the central nervous system. J. Neurochem. 59, 1609–1623 (1992).

    CAS  PubMed  Google Scholar 

  82. Magnotta, V. A. et al. Detecting activity-evoked pH changes in human brain. Proc. Natl Acad. Sci. USA 109, 8270–8273 (2012).

    CAS  PubMed  Google Scholar 

  83. Hibbert, D. B., Weitzner, K., Tabor, B. & Carter, P. Mass changes and dissolution of platinum during electrical stimulation in artificial perilymph solution. Biomaterials 21, 2177–2182 (2000).

    CAS  PubMed  Google Scholar 

  84. Robblee, L. S., McHardy, J., Marston, J. M. & Brummer, S. B. Electrical stimulation with Pt electrodes. V. The effect of protein on Pt dissolution. Biomaterials 1, 135–139 (1980).

    CAS  PubMed  Google Scholar 

  85. Maas, A. I., Fleckenstein, W., de Jong, D. A. & van Santbrink, H. Monitoring cerebral oxygenation: experimental studies and preliminary clinical results of continuous monitoring of cerebrospinal fluid and brain tissue oxygen tension. Acta Neurochirurgica Supplementum 59, 50–57 (1993).

    CAS  PubMed  Google Scholar 

  86. Patrick, E., Orazem, M. E., Sanchez, J. C. & Nishida, T. Corrosion of tungsten microelectrodes used in neural recording applications. J. Neurosci. Methods 198, 158–171 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Cogan, S. F., Jones, G. S., Hills, D. V., Walter, J. S. & Riedy, L. W. Comparison of 316LVM and MP35N alloys as charge injection electrodes. J. Biomed. Mater. Res. 28, 233–240 (1994).

    CAS  PubMed  Google Scholar 

  88. Geddes, L. A. & Roeder, R. Criteria for the selection of materials for implanted electrodes. Ann. Biomed. Eng. 31, 879–890 (2003).

    CAS  PubMed  Google Scholar 

  89. Shepherd, R. K., Carter, P. M., Enke, Y. L., Wise, A. K. & Fallon, J. B. Chronic intracochlear electrical stimulation at high charge densities results in platinum dissolution but not neural loss or functional changes in vivo. J. Neural Eng. 16, 026009 (2019).

    PubMed  Google Scholar 

  90. Spiers, K. et al. An X-ray fluorescence microscopic analysis of the tissue surrounding the multi-channel cochlear implant electrode array. Cochl. Implants Int. 17, 129–131 (2016).

    Google Scholar 

  91. Percival, S. J., Dick, J. E. & Bard, A. J. Cathodically dissolved platinum resulting from the O2 and H2O2 reduction reactions on platinum ultramicroelectrodes. Anal. Chem. 89, 3087–3092 (2017).

    CAS  PubMed  Google Scholar 

  92. Pourbaix, M. Atlas of Electrochemical Equilibria in Aqueous Solutions (National Association of Corrosion Engineers, 1966).

  93. Williams, D. F. Corrosion of implant materials. Ann. Rev. Mater. Sci. 6, 237–266 (1976).

    CAS  Google Scholar 

  94. Asplund, M., Nyberg, T. & Inganäs, O. Electroactive polymers for neural interfaces. Polym. Chem. 1, 1374–1391 (2010).

    CAS  Google Scholar 

  95. Boehler, C., Oberueber, F., Schlabach, S., Stieglitz, T. & Asplund, M. Long-term stable adhesion for conducting polymers in biomedical applications: IrOx and nanostructured platinum solve the chronic challenge. ACS Appl. Mater. Interfaces 9, 189–197 (2016).

    PubMed  Google Scholar 

  96. Schander, A. et al. In-vitro evaluation of the long-term stability of PEDOT:PSS coated microelectrodes for chronic recording and electrical stimulation of neurons. in 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) 6174–6177 (2016).

  97. Thaning, E. M., Asplund, M. L., Nyberg, T. A., Inganas, O. W. & von Holst, H. Stability of poly(3,4-ethylene dioxythiophene) materials intended for implants. J. Biomed. Mater. Res. 93, 407–415 (2010).

    Google Scholar 

  98. Ordonez, J., Schuettler, M., Boehler, C., Boretius, T. & Stieglitz, T. Thin films and microelectrode arrays for neuroprosthetics. MRS Bull. 37, 590–598 (2012).

    CAS  Google Scholar 

  99. Čvančara, P. et al. On the reliability of chronically implanted thin-film electrodes in human arm nerves for neuroprosthetic applications. Preprint at bioRxiv https://doi.org/10.1101/653964 (2019).

  100. Jorfi, M., Skousen, J. L., Weder, C. & Capadona, J. R. Progress towards biocompatible intracortical microelectrodes for neural interfacing applications. J. Neural Eng. 12, 011001–011001 (2015).

    PubMed  Google Scholar 

  101. Sohal, H. S., Vassilevski, K., Jackson, A., Baker, S. N. & O’Neill, A. Design and microfabrication considerations for reliable flexible intracortical implants. Front. Mech. Eng. https://doi.org/10.3389/fmech.2016.00005 (2016).

  102. Yasuda, H., Yu, Q. S. & Chen, M. Interfacial factors in corrosion protection: an EIS study of model systems. Prog. Org. Coat. 41, 273–279 (2001).

    CAS  Google Scholar 

  103. Schmitt, G. et al. Passivation and corrosion of microelectrode arrays. Electrochim. Acta 44, 3865–3883 (1999).

    CAS  Google Scholar 

  104. Vanhoestenberghe, A. & Donaldson, N. Corrosion of silicon integrated circuits and lifetime predictions in implantable electronic devices. J. Neural Eng. 10, 031002 (2013).

    CAS  PubMed  Google Scholar 

  105. Hemmerich, K. J. General aging theory and simplified protocol for accelerated aging of medical devices. Med. Plastics Biomater. 16–23 (1998).

  106. Hukins, D. W., Mahomed, A. & Kukureka, S. N. Accelerated aging for testing polymeric biomaterials and medical devices. Med. Eng. Phys. 30, 1270–1274 (2008).

    CAS  PubMed  Google Scholar 

  107. Mazzucco, D. C., Dumbleton, J. & Kurtz, S. M. Can accelerated aqueous aging simulate in vivo oxidation of gamma-sterilized UHMWPE? J. Biomed. Mater. Res. 79, 79–85 (2006).

    Google Scholar 

  108. Takmakov, P. et al. Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species. J. Neural Eng. 12, 026003 (2015).

    PubMed  PubMed Central  Google Scholar 

  109. Street, M. G., Welle, C. G. & Takmakov, P. A. Automated reactive accelerated aging for rapid in vitro evaluation of neural implant performance. Rev. Sci. Instrum. 89, 094301 (2018).

    PubMed  Google Scholar 

  110. Rubehn, B. & Stieglitz, T. In vitro evaluation of the long-term stability of polyimide as a material for neural implants. Biomaterials 31, 3449–3458 (2010).

    CAS  PubMed  Google Scholar 

  111. Jerkiewicz, G., Vatankhah, G., Lessard, J., Soriaga, M. P. & Park, Y.-S. Surface-oxide growth at platinum electrodes in aqueous H2SO4: Reexamination of its mechanism through combined cyclic-voltammetry, electrochemical quartz-crystal nanobalance, and Auger electron spectroscopy measurements. Electrochim. Acta 49, 1451–1459 (2004).

    CAS  Google Scholar 

  112. Butz, N., Kuhl, M. & Manoli, Y. Charge balancing circuit, stimulator circuit and method for charge balancing. US Patent 20190111249 (2019).

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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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