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Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces

Abstract

Implantable neural microelectrodes that can record extracellular biopotentials from small, targeted groups of neurons are critical for neuroscience research and emerging clinical applications including brain-controlled prosthetic devices. The crucial material-dependent problem is developing microelectrodes that record neural activity from the same neurons for years with high fidelity and reliability. Here, we report the development of an integrated composite electrode consisting of a carbon-fibre core, a poly(p-xylylene)-based thin-film coating that acts as a dielectric barrier and that is functionalized to control intrinsic biological processes, and a poly(thiophene)-based recording pad. The resulting implants are an order of magnitude smaller than traditional recording electrodes, and more mechanically compliant with brain tissue. They were found to elicit much reduced chronic reactive tissue responses and enabled single-neuron recording in acute and early chronic experiments in rats. This technology, taking advantage of new composites, makes possible highly selective and stealthy neural interface devices towards realizing long-lasting implants.

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Figure 1: Microthread electrodes.
Figure 2: In vitro electrical characterization of MTEs.
Figure 3: Physical characteristics of the MTEs.
Figure 4: In vivo single-unit recording capabilities.
Figure 5: Chronic in vivo recording capabilities of MTEs.
Figure 6: Histological comparison of tissue reaction to chronically implanted microthread and silicon probes.

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Acknowledgements

This work was financially supported by a National Institutes of Health Challenge Grant in Health and Science Research from the National Institute of Neurological Disorders and Stroke (1RC1NS068396-0110) and the Center for Neural Communication Technology, a P41 Resource Center funded by the National Institute of Biomedical Imaging and Bioengineering (P41 EB002030). A. Agarwal and F. S. Midani assisted in chronic probe assembly/packaging, chronic surgery and chronic electrophysiological recordings. A. L. Ryan and S. Saha conducted ATRP. H-Y. Chen carried out Raman spectroscopy. Multiphoton imaging of chronically implanted tissue was conducted by Wadsworth Center Advanced Light Microscopy & Image Analysis Core. L. Hains cut the tissue and conducted preliminary immunohistochemistry. Confocal images were collected on the Zeiss LSM510 at the University of Michigan Microscopy and Image Analysis Laboratory. N.A.K. and D.R.K. acknowledge partial financial support of this work from a DARPA STTR grant (W31P4Q-08-C-0426).

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T.D.Y.K., N.B.L., J.L., N.A.K. and D.R.K. planned the project. Carbon fibres were provided by H.Z. MTEs were assembled by T.D.Y.K. and P.R.P. CVD parameters were designed by X.D., and CVD was carried out by X.D. and T.D.Y.K. PEGMA coatings and biofouling testing were carried out by X.D. Raman spectroscopy data were analysed by X.D. PEDOT deposition parameters were designed by N.B.L. and T.D.Y.K. and carried out by P.R.P. and T.D.Y.K. P.R.P. and T.D.Y.K. also conducted in vitro characterization of the devices. SEM imaging and energy-dispersive X-ray analysis was carried out by H.Z. In vivo recordings were carried out by N.B.L. and T.D.Y.K. Chronic in vivo experiments were planned, carried out and analysed by T.D.Y.K. Data analysis was carried out by N.B.L. and T.D.Y.K. K.L.S. led and carried out the two-photon immunohistochemistry and imaging for the chronic implant. Cryo-immunohistochemistry was planned by P.R.P. and T.D.Y.K. and conducted by T.D.Y.K. T.D.Y.K. and D.R.K. wrote the manuscript. All authors discussed the results.

Corresponding authors

Correspondence to Takashi D. Yoshida Kozai, Nicholas A. Kotov or Daryl R. Kipke.

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Competing interests

D.R. Kipke has a significant financial and leadership interest in NeuroNexus Technologies, a company specializing in neural interface devices. At the time of this study, N.B. Langhals was a consultant for NeuroNexus Technologies.

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Kozai, T., Langhals, N., Patel, P. et al. Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces. Nature Mater 11, 1065–1073 (2012). https://doi.org/10.1038/nmat3468

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