Free‐Standing Nanofilm Electrode Arrays for Long‐Term Stable Neural Interfacings

Abstract

relate neural activity with stimulus and action across multiple timescales-from millisecond-precise spiking patterns that represent sensory and motor information to longer-term neural plasticity that enables neural circuits to progressively adapt to changing environmental contingencies. [2,3] High-density silicon probes and microwire arrays [4][5][6][7] are valuable tools for large-scale recordings of neuronal activity at single-spike resolution and have been applied to show that perceptual learning involves distributed brain regions. [8,9] However, the mechanical mismatch between stiff probes and soft neural tissues can cause micromotion-related inflammatory responses and recording instabilities, [10][11][12] limiting their long-term use in basic and biomedical applications. Flexible probes, including injectable mesh electronics, [13] nano electronic thread, [14] and Neurotassel, [15] have been developed to reduce the mechanical mismatch between probes and tissues. These probes have shown greatly reduced micromotion and inflammatory responses in the brain, thus leading to improved long-term stability in neuronal recordings. However, the bending stiffness of micrometer-thick polymer substrates in these flexible probes is typically two orders of magnitude higher than that of nanofilm electrodes, making it a limiting factor in cellular-scale electrode-tissue interfacings. It is thus highly desirable to develop novel neural electrode technologies [13][14][15][16][17][18][19][20][21][22][23][24][25] that can enable intimate integration with neural tissues and stable tracking of neuronal activity over long terms.In this study, we develop free-standing nanofilm electrode arrays for intimate neural interfacings and stable neuronal activity tracking over long terms. To assist depth implantation into the brain, each NEA was encapsulated into a biodissolvable polymer carrier through elastocapillary selfassembly. After implantation into mouse brain, the high flexibility of free-standing gold nanofilms facilitated their intimate and innervated integration with neural tissues. As a result, chronically implanted NEAs could allow stable tracking of the same populations of neurons over months. This capability allowed us to study how the same neuronal populations in the dorsal striatum represent and update stimulus-outcome associations across multiple timescales during perceptual learning.Flexible neural electrodes integrated on micrometer-thick polymer substrates offer important opportunities for improving the stability of neuronal activity recordings during cognitive processes. However, the bending stiffness of micrometer-thick polymer substrates is typically two orders of magnitude higher than that of nanofilm electrodes, making it a limiting factor in electrode-tissue interfacings. Here, this limitation is overcome by developing self-assembled nanofilm electrode arrays (NEAs) that consist of high-density, free-standing gold nanofilm electrodes. Chronically implanted NEAs can form intimate and innervated interfaces with neural...

Electron Conductive and Transparent Hydrogels for Recording Brain Neural Signals and Neuromodulation

“…Although some achievements have been realized by scientists, materials used to make the implantable probes suffer from several challenges such as a mismatch in chemo-mechanical properties and a tradeoff between electron conduction and optical transparency. [21,22] Due to their inherently high electronic conductivity and electrochemical stability, traditional implantable probes are primarily fabricated using inorganic materials. However, the inorganic electrodes show an extremely high elasticity modulus, for instance, >100 MPa for platinum, which is much higher than that of human tissues (10-100 kPa).…”

Challenges and Opportunities of Implantable Neural Interfaces: From Material, Electrochemical and Biological Perspectives

“…Notably, functional nanomaterials such as graphene can be utilized as the free-standing candidate to enable wide-band brain activity recordings and also promote the scaling elastic adhesion radius of neural electrodes to a subcellular scale, therefore facilitating neuroscience and biomedical applications. [69,70] Shi et al [62] developed a clinically-friendly 49-channel silk fMEA (Figure 3F), applying ≈30 μm silk as the substrate and 2 μm thick PI as the supporting/isolating layers. When the silk layer is solved completely, the fMEA is biocompatible with the cortical surface and spontaneously conformal coupling to achieve in situ real-time and spatiotemporal ECoG detection/monitoring, neural stimulation/decoding the neural and/or brain activities of rats in a series of statues.…”

“…Notably, functional nanomaterials such as graphene can be utilized as the free‐standing candidate to enable wide‐band brain activity recordings and also promote the scaling elastic adhesion radius of neural electrodes to a subcellular scale, therefore facilitating neuroscience and biomedical applications. [ 69,70 ] Shi et al. [ 62 ] developed a clinically‐friendly 49‐channel silk fMEA (Figure 3F), applying ≈30 µm silk as the substrate and 2 µm thick PI as the supporting/isolating layers.…”

“…A thin chromium (Cr) and gold (Au) layer were deposited by e‐beam evaporation to prepare the electrode sites, interconnects, and bonding pads, while a thick PI layer of 0.75 µm was employed as the insulating layer. Their group [ 69 ] further developed free‐standing Au nanofilm electrode arrays (NEAs) that consist of 120 channels and are encapsulated into a biodissolvable polymer carrier through elastocapillary self‐assembly. Such neural electrodes based on free‐standing nanoscale materials offer opportunities to a variety of implantable and high‐density fMEAs.…”

Bioelectric Interface Technologies in Cells and Organoids

“…[21] A variety of nanostructured architectures with strategically designed layout of integrated electrodes or FETs have been developed to offer conformal and stable interfaces with diversely shaped cells/organoids, and to provide long-term, continuous recording of biophysiological signals with high sensitivity and high fidelity. [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] For example, many different forms of needle type architectures were developed for cell interfacing, ranging from nanoprobes, [57][58][59][60][61] nanopillars, [42,[62][63][64][65] nanotubes, [66] nanocrowns, [24] to nanovolcanos. [67] Aside from these 1D nanostructured configurations, 2D planar type, [68][69][70][71] as well as diverse 3D architectures have been devised to allow monitoring with higher spatial resolutions.…”