Neural interface medical devices offer therapeutic potential for neurological disorders. To improve efficacy and broaden clinical applications, miniaturization to the micrometer scale is crucial. This allows for higher spatial resolution neural recordings and improved stimulation focality, potentially leading to better signal decoding and more natural neural activation patterns. Research into novel materials, including graphene-related materials, is ongoing to improve performance. Graphene's unique properties—capacitive interaction in aqueous media, mechanical flexibility, and wide potential window—make it an attractive candidate. However, single-layer graphene electrodes have limited electrochemical performance, while creating high-porosity, densely packed multilayer porous electrodes has proven challenging. This paper introduces a nanoporous graphene-based thin-film electrode material (EGNITE) and a wafer-scale fabrication process for high-resolution neural recording and stimulation.

Existing neural interfaces primarily use millimeter-scale metallic electrodes for recording or stimulating the nervous system. Miniaturization to the micrometer scale is suggested to improve spatial resolution in neural recordings, leading to better signal decoding. Smaller electrodes also improve stimulation focality and allow for the recapitulation of natural neural activation patterns. While noble metals like gold and platinum are classically used, research explores nanoengineered metals, metal oxides, conducting polymers, and carbon-based materials as alternatives. Graphene-related materials have emerged as attractive candidates due to their unique combination of properties, offering a capacitive interaction in aqueous media, mechanical flexibility, and a wide potential window. However, single-layer graphene's limited electrochemical performance constrains miniaturization. Multilayer porous electrodes show promise in improving performance by increasing surface area and reducing ion transport resistance, but their development has been challenging due to difficulties in achieving high porosity while maintaining dense layer packing. Current research focuses on miniaturized, implantable neural interfaces for chronic use.

The study developed a nanoporous graphene-based thin-film electrode material called EGNITE. EGNITE films were prepared via vacuum filtration of a graphene oxide (GO) solution, followed by transfer to a substrate and hydrothermal reduction. This process created a structure of horizontally stacked flakes with nano-scale pores between the planes. Characterization techniques included scanning electron microscopy (SEM), X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), atomic force microscopy (AFM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and electron energy-loss spectroscopy (EELS) to analyze the material's structure, porosity, and chemical composition. A wafer-scale fabrication process was developed to integrate EGNITE microelectrodes into flexible devices using polyimide (PI) as the substrate and insulation layer, and gold for the tracks. Two designs were created: a 64-channel microelectrocorticography (µECOG) array and a transverse intrafascicular multi-channel electrode (TIME) device. Electrochemical characterization involved cyclic voltammetry (CV) to assess electrochemical window, electrochemical impedance spectroscopy (EIS) to determine impedance and capacitance, and chronopotentiometry to evaluate charge injection limit (CIL) and stability under continuous stimulation. Mechanical stability was tested using ultrasound sonication and bending tests. In vivo testing involved acute epicortical recordings in rats using µECOG arrays to assess neural recording capabilities, focusing on local field potentials (LFPs) and multiunit activity (MUA). Acute intrafascicular stimulation in rats using TIME devices was performed to evaluate stimulation performance, focusing on compound muscle action potentials (CMAPs) and selectivity. Chronic biocompatibility was assessed via epicortical (12 weeks) and intraneural (8 weeks) implantation in rodents, followed by histological and immunohistochemical evaluations of tissue response.

EGNITE microelectrodes (25 µm diameter) exhibited low impedance (25.2 ± 0.7 kΩ at 1 kHz), high charge injection capacity (3–5 mC cm⁻²), and excellent stability during continuous stimulation (15 million pulses). The interfacial capacitance was estimated to be 13.9 mF cm², a significant increase compared to single-layer graphene. In vivo brain recordings in rats showed high-fidelity recordings with signal-to-noise ratios (SNRs) exceeding 10 dB for LFPs and significant MUA detection. Chronic intracortical recordings in mice (over 90 days) demonstrated long-term stability with the continued detection of auditory evoked potentials and single-unit activity. In vivo sciatic nerve stimulation showed low current thresholds (<100 µA) and high selectivity (>0.8) for activating specific muscle groups. Chronic biocompatibility studies showed minimal inflammatory responses in both cortical and peripheral nerve tissues after 12 and 8 weeks of implantation respectively. No significant differences in microglia activation levels were observed between EGNITE devices and controls. Minor increases in some inflammatory cytokines were observed at early time points but returned to baseline levels by 12 weeks. Functional studies in the peripheral nervous system revealed no significant damage to nerve fibers.

The study successfully demonstrated the potential of EGNITE thin-film microelectrodes for high-resolution neural interfacing. The achieved combination of low impedance, high charge injection capacity, and excellent stability makes EGNITE superior to existing graphene-based electrodes. The successful recording of high-fidelity neural signals, including LFPs, MUA, and SUA, in both acute and chronic in vivo studies highlights the technology's potential for advanced brain mapping and biomarker discovery. The results from the in vivo stimulation studies indicate the suitability of EGNITE electrodes for precise neuromodulation, particularly in applications requiring high selectivity. The favorable biocompatibility profile observed in both cortical and peripheral nerve tissue suggests excellent potential for chronic applications. The exceptional results with EGNITE microelectrodes provide strong evidence for this technology as a promising candidate for next-generation bidirectional neural interfaces.

The EGNITE technology offers a superior combination of properties for next-generation neural interfaces: high surface-to-volume ratio resulting in high capacitance, micro-scale miniaturization while retaining material properties, high yield and homogeneity, high charge density stimulation, and low intrinsic noise. High-fidelity recordings (high SNR) and low charge threshold stimulation, coupled with chronic tissue tolerance, demonstrates the technology's potential for bidirectional neural interfacing. Future research will focus on further improving electrochemical performance, investigating long-term stability in a therapeutic setting, and exploring alternative back-contacts to prevent corrosion.

While the study demonstrates excellent short-term and mid-term results, longer-term chronic studies are needed to fully assess the long-term stability and functionality of EGNITE electrodes. The impact of oxygen reduction reactions on charge injection capacity requires further investigation. Additional research is also needed to fully evaluate the degree of fibrotic capsule formation on chronic functional use and to explore alternative materials for back contacts to prevent long-term corrosion.