Commercial translation of high-density carbon fiber electrode arrays for multi-modal analysis of neural microcircuits

摘要 测量和操纵活体动物局部脑回路活动的能力对于 了解大脑功能和功能障碍的复杂性。一种新型的穿透式高密度碳纤维 由柔性超薄导电碳微纤维组成的电极阵列是最近在 研究神经微电路动力学的大脑倡议。与传统的微电极阵列相比，碳 纤维阵列具有极佳的生物相容性，可产生极少的神经胶质疤痕，从而实现超乎寻常的接近 利用改进的电极实现前所未有的单单位记录产量的神经元记录电极 稳定性、高信噪比记录和高电荷注入能力(CIC)，以实现卓越的刺激。在……里面 此外，这些阵列可用于使用快速扫描来测量神经递质或其他生物化合物 循环伏安法(FSCV)。由微电极阵列的先驱和行业领先者BlackRock Neurotech领导 制造，这种直接到第二阶段的SBIR的目标是将新型的实验室制造的高密度 由密歇根大学Chestek实验室的碳纤维阵列(C-CFA)向最先进的商业 产品(BRN-CFA)，使这一强大而多功能的神经技术能够在 神经科学界。目标1：BRN-CFA的微制造和组装将显著提高 BRN-CFA中碳纤维硅支撑梭的去除微加工工艺 来自制造方案的职业危险材料和采用现代绝缘体上的硅 晶片制造工艺，以提高制造的安全性、效率和可靠性。阵列组件和 制造将在黑石的质量管理体系下进行。目标2：绩效验证和流程 转移到BlackRock Neurotech将评估优化的BRN-CFA电气特性、健壮性、 通过体外电学、电化学测试、加速老化和视觉测试的稳定性和寿命 检查。分析将与C-CFA进行交叉验证。经过验证的几何图形、制造和 组装过程将转移到BlackRock制造，以实现稳健和可重复的生产。 目的3.BRN-CFA的体内慢性性能验证将与C-CFA交叉验证 CFA在大鼠皮质进行了为期6个月的体内研究，以评估设备的可插入性和慢性性能。这个 该项目的成功成果将是第一个商业化的具有卓越性能的BRN-CFA 用于研究局部神经回路动力学。通过解决这一关键的、未得到满足的需求，BRN-CFA产品 承诺加快脑动力学的基础科学发现和下一代的发展 治疗。

ABSTRACT The ability to measure and manipulate local brain circuit activity in living, behaving animals is essential to understanding the complexities of brain function and dysfunction. A novel, penetrating high-density carbon fiber electrode array composed of flexible, ultrathin conductive carbon microfibers was recently developed under the BRAIN Initiative to study neural microcircuit dynamics. In contrast to conventional microelectrode arrays, carbon fiber arrays are exceptionally biocompatible and produce minimal glial scarring resulting in exceptional proximity of the recording electrodes to neurons for unprecedented single-unit recording yield with improved electrode stability, high signal-to-noise recording, and high charge injection capacity (CIC) for superior stimulation. In addition, these arrays can be used to measure neurotransmitter or other biological compounds using fast-scan cyclic voltammetry (FSCV). Led by Blackrock Neurotech, a pioneer and industry leader in microelectrode array fabrication, the goal of this Direct-to-Phase II SBIR is to translate the novel laboratory fabricated high-density carbon fiber array (C-CFA) by the Chestek lab at the University of Michigan to a state-of-the-art commercial product (BRN-CFA) to enable broad dissemination of this powerful and versatile neurotechnology across the neuroscience community. Aim 1: Microfabrication and assembly of the BRN-CFA will dramatically improve the microfabrication process for the silicon support shuttles of the carbon fibers in the BRN-CFA by removing occupationally hazardous materials from the fabrication scheme and adopting a modern silicon-on-insulator wafer fabrication process to improve manufacturing safety, efficiency, and reliability. Array assembly and fabrication will occur under Blackrock’s Quality Management System. Aim 2: Performance validation and process transfer to Blackrock Neurotech will assess the optimized BRN-CFA electrical characteristics, robustness, stability, and longevity through in-vitro electrical, electrochemical testing, accelerated aging, and visual inspection. Analyses will be cross-validated against the C-CFA. The validated geometry, fabrication, and assembly processes will be transferred to Blackrock manufacturing to enable robust and reproducible production. Aim 3. In-vivo chronic performance validation of the BRN-CFA will cross-validate the BRN-CFA against the C- CFA in a 6-month in-vivo study in rat cortex to assess insertability and chronic performance of the devices. The successful outcome of this project will be the first commercially available BRN-CFA with exceptional performance for the study of local neural circuit dynamics. By addressing this critical, unmet need, the BRN-CFA product promises to accelerate basic scientific discovery of brain dynamics and the development of next-generation therapies.