Bioinspired flexible electronics for seamless neural interfacing and chronic recording

Abstract

Implantable neural probes are among the most widely applied tools for the understanding of neural circuit functions and the treatment of neurological disorders. Despite remarkable progress in recent years, it is still challenging for conventional rigid probes to achieve stable neural recording over long periods of time. Recently, flexible electronics with biomimetic structures and mechanical properties have been demonstrated for the formation of seamless probe-neural interfaces, enabling long-term recording stability. In this review, we provide an overview of bioinspired flexible electronics, from their structural design to probe-brain interfaces and chronic neural recording applications. Opportunities of bioinspired flexible electronics in fundamental neuroscience and clinical studies are also discussed.

Fig. 1. Interfaces between bioinspired flexible electronics and synthetic tissues. (a) Morphology of a highly curvilinear and porous nanoES. (b) The intimate nanoES–neural interface with an interpenetrating neurite. (c) Multiplexed LFP recording with the nanoES/neural hybrids. (a)–(c) have been reproduced from ref. 27 with permission from Nature Publishing Group, copyright 2012. (d and e) Hybrids of cardiac tissues and multilayer silicon nanowire FET array scaffolds. (f) Multiplexed action potential recording with the silicon nanowire FET array. (g) Mapping of the action propagation through a 3D cardiac tissue. (d)–(g) have been reproduced from ref. 30 with permission from Nature Publishing Group, copyright 2016. (h) Schematic of the microelectronic cardiac hybrids and their applications in tissue function sensing and regulation. (i) A recording/stimulating electrode covered with polymers. (j) Stromal cell-derived factor-1 releasing induced cell migration promotion. (h)–(j) have been reproduced from ref. 31 with permission from Nature Publishing Group, copyright 2016.

Fig. 2. Bioinspired flexible electronics interfacing spheroids and organoids. (a) A CM spheroid encapsulated by the microelectrode array. (b) Microelectrode array for multiplexed LFP recording of the CM spheroid. (a) and (b) have been reproduced from ref. 34 with permission from American Association for the Advancement of Science, copyright 2019. (c) Integration of mesh electronics into organoids through organogenesis. (d) Mesh electronics distributed uniformly in a human cardiac organoid with seamless device–tissue interfaces. (e) Evolution of LFPs of cardiomyocyte cells during organogenesis. (c)–(e) have been reproduced from ref. 35 with permission from American Chemical Society, copyright 2019.

Fig. 3. Carbon-based fibre microelectrodes for in vivo neural interfacing. (a) Scanning electron microscopy image of the ultrasmall carbon fibre microelectrode. (b) Optical image of two carbon fibre microelectrodes implanted into the rat cortex. (c) Comparison of bleeding caused by MTE probes and silicon probes. (a)–(c) have been reproduced from ref. 41 with permission from Nature Publishing Group, copyright 2012. (d) A four-channel CNT fibre microelectrode array. (e) Comparison of the tissue inflammatory responses to CNT fibre microelectrodes and PtIr electrodes. (f) Stable single-unit neural recording from day 1 to day 117 with an electrode made of a 15 μm diameter CNT fibre. (d)–(f) have been reproduced from ref. 50 with permission from American Chemical Society, copyright 2019.

Fig. 4. Polymer based-fibre microelectrodes for in vivo neural interfacing. (a) Structures of NET-50 and NET-10 probes. (b) A knotted NET-50 probe with high flexibility and robustness (left), and schematic of the NET engaging mechanism (right). (c) The intact microvessels around a NET-10 probe. (a)–(c) have been reproduced from ref. 21 with permission from American Association for the Advancement of Science, copyright 2017. (d) Schematic of the self-assembly of Neurotassel in molten PEG and an assembled Neurotassel/PEG composite fibre with 16 electrodes. Scale bar, 500 μm. (e) Scanning electron microscopy image of the Neurotassel/PEG fibre with 1024 electrodes. (f) Stable tracking of the same neuron from 3 to 6 weeks. Scale bars, 100 μm (vertical), 1 ms (horizontal). (d)–(f) have been reproduced from ref. 22 with permission from American Association for the Advancement of Science, copyright 2019.

Fig. 5. Mesh electronics for in vivo neural interfacing. (a) Structure of mesh electronics. (b) Unfolding of mesh electronics after the injection. (a) and (b) have been reproduced from ref. 55 with permission from Nature Publishing Group, copyright 2015. (c) The interface between injected mesh electronics and brain tissue after 2 week, 4 week and 3 month postimplantation. (d) Mesh electronics for stable LFP recording 2 months and 4 months postimplantation. (c) and (d) have been reproduced from ref. 59 with permission from Nature Publishing Group, copyright 2016. (e) NeuE with neuron-mimetic structures. (f) 3D interfaces between NeuE and neurons 2 day, 2 week, and 3 month postimplantation. (g) Stable single-unit activity recording with NeuE over 3 month postimplantation. (h) The migration of neural progenitor cells along NeuE. (e)–(h) have been reproduced from ref. 62 with permission from Nature Publishing Group, copyright 2019.

Fig. 6. Epidermal grid electrodes for in vivo neural interfacing. (a and b) The Neurogrid conformably attaches on an orchid petal and a rat cortical surface. (c) Extracellular action potential recording in cortex (left) and hippocampus (right) of a rat with the Neurogrid. Scale bars (top): 10 ms, 50 μV. Scale bars (bottom): 1.5 ms, 50 μV. (a)–(c) have been reproduced from ref. 24 with permission from Nature Publishing Group, copyright 2015. (d) A 240-channel Neurogrid conformably adheres to the cortical surface of an epilepsy patient. (e) Comparison of the performance between the Neurogrid and clinical strips. Scale bars: 1 s, 500 μV. (d) and (e) have been reproduced from ref. 65 with permission from American Association for the Advancement of Science, copyright 2016.

Hongbian Li

Jinfen Wang

Ying Fang