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Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology

  1. Charles M. Liebera,b,2
  1. aDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138;
  2. bJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138
  1. Contributed by Charles M. Lieber, October 19, 2017 (sent for review October 10, 2017; reviewed by Dae-Hyeong Kim and Bozhi Tian)

Significance

Implantable electrical probes have led to fundamental neuroscience advances and treatment of neurological diseases, yet are unable to stably track the long-term evolution of large numbers of individual neurons critical to brain functions. Here, we demonstrate a scalable scheme for highly multiplexed mesh electronics probes that overcomes this long-standing challenge. We illustrate this scheme through fabrication of 32 to 128 channel probes with macroporous neural network-like structure and flexibility comparable to the brain. Following implantation into rodent brains, we demonstrate chronic 128-channel recordings with single-neuron-level stability from multiple brain regions over 4 mo. These scalable mesh electronics probes represent an ideal platform for mapping, tracking, and modulating the single-neuron-level circuit changes associated with learning, aging, and neurodegenerative diseases.

Abstract

Implantable electrical probes have led to advances in neuroscience, brain?machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution of these neurons over the entire course of study. Silicon probes based on microfabrication can yield large-scale, high-density recording but face challenges of chronic gliosis and instability due to mechanical and structural mismatch with the brain. Ultraflexible mesh electronics, on the other hand, have demonstrated negligible chronic immune response and stable long-term brain monitoring at single-neuron level, although, to date, it has been limited to 16 channels. Here, we present a scalable scheme for highly multiplexed mesh electronics probes to bridge the gap between scalability and flexibility, where 32 to 128 channels per probe were implemented while the crucial brain-like structure and mechanics were maintained. Combining this mesh design with multisite injection, we demonstrate stable 128-channel local field potential and single-unit recordings from multiple brain regions in awake restrained mice over 4 mo. In addition, the newly integrated mesh is used to validate stable chronic recordings in freely behaving mice. This scalable scheme for mesh electronics together with demonstrated long-term stability represent important progress toward the realization of ideal implantable electrical probes allowing for mapping and tracking single-neuron level circuit changes associated with learning, aging, and neurodegenerative diseases.

Footnotes

  • ?1T.-M.F. and G.H. contributed equally to this work.

  • ?2To whom correspondence should be addressed. Email: cml{at}cmliris.harvard.edu.
  • Author contributions: T.-M.F., G.H., and C.M.L. designed research; T.-M.F., G.H., R.D.V., and T.Z. performed research; T.-M.F., G.H., and C.M.L. analyzed data; T.-M.F., G.H., and C.M.L. wrote the paper; and R.D.V. and T.Z. discussed results and manuscript.

  • Reviewers: D.-H.K., Seoul National University; and B.T., The University of Chicago.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1717695114/-/DCSupplemental.

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