Thin, High-Density, High-Performance, Depth and Surface Microelectrodes for Diagnosis and Treatment of Epilepsy

摘要 该项目的目标是显著推进急性和半慢性癫痫监测领域。 使用新颖的高分辨率皮层脑电图仪(ECoG)记录/刺激栅格(4096/256通道， 分别)和具有全无线的立体脑电(SEEG)深度电极(120/8微米/微米) 数据和电源传输。这个项目建立在我们之前成功进行的第一次人体试验的基础上 使用数千通道微电极栅格对口才脑组织进行急性标测。拟议的系统 包含多种变革性的技术方法，包括：(1)利用先进的薄膜 在8英寸直径的基板上进行微制造，从而允许从数千个 (2)开发一种新开发的铂纳米棒(PTNR)微电极技术，具有优异的性能 低阻抗、高充电注入容量(4.4 mC/cm2)、稳定性和生物兼容性；以及(3)使用 (~10μm)对二甲苯C底物，顺应大脑运动，与脑曲率共形，以及 透明，在急性标测期间更容易显示大脑解剖结构。此外，(4)网格 为这个项目开发的是模块化的，可以进行修剪以适应不同大小的开颅手术，以及(5)这 系统提供新一代微创sEEG电极，具有易于重新配置的微接触 在大脑不同区域的分布我们建议的系统也使用了最先进的获取 带有微型1024ch片上神经接口系统的电子设备以及数据和电力的无线传输， 实现完全无线监控，消除有线外部化，并(7)部署多屏幕和多 整个电生理活动曲目的窗口可视化，可选择显示和解释 以标准的方式发出信号。 我们的目标是在半时间临床环境中展示传统和 用于癫痫监测和治疗的新兴临床生物标志物。为了实现这一目标，我们将在目标上追求 1来自FDA的法规输入，并根据高质量实验室实践(GLP)扩展我们的网格，并执行 在质量管理体系下进行台式测试和硬件和软件开发。在目标2中，我们 将在GLP下进行半慢性动物试验，以证明新的 癫痫监测系统。在目标3中，我们将执行临床前和人类手术中的记录 适当的IRB授权。我们将在Aim 4和过渡中寻求FDA批准半慢性植入物 目的5对难治性癫痫患者进行半时辰癫痫监测。 在设备和系统开发、外科手术方法、电生理学和数据方面所采用的方法 分析不仅将促进功能和癫痫监测，而且还将对 在神经调节/治疗性刺激、最小破坏性脑机中的大量应用 接口，和脊髓刺激。

ABSTRACT The goal of this project is to significantly advance the field of acute and semichronic epilepsy monitoring using novel, high-resolution electrocorticography (ECoG) record/stimulate grids (4096/256 channels, respectively) and stereoelectroencephalography (sEEG) depth electrodes (120/8 micro/macro) with full wireless data and power transfer. This project builds on our previous success in conducting the first-ever human trials for acute mapping of eloquent brain tissue with multi-thousand channel microelectrode grids. The proposed system encompasses multiple transformative technological approaches, including: (1) leveraging advanced thin-film microfabrication on 8” diameter substrates, thus permitting long integrated connectorization from thousands of channels; (2) exploiting a newly developed platinum nanorod (PtNR) microelectrode technology with excellent low impedance, high charge-injection-capacity (4.4mC/cm2), stability, and biocompatibility; and (3) using a thin (~10μm) parylene C substrate that is compliant to brain movements, conformal to brain curvature, and transparent, permitting easier visualization of brain anatomy during the acute mapping. Further, (4) the grids developed for this project are modular and can be trimmed to fit different sizes of craniotomies, and (5) this system offers a new generation of minimally invasive sEEG electrodes with easily reconfigurable microcontact distribution in different regions of the brain Our proposed system also (6) employs state-of-the-art acquisition electronics with a miniaturized 1024ch neural interface system-on-chip and radio transmission of data and power, enabling fully wireless monitoring that eliminates wire externalization, and (7) deploys multi-screen and multi- window visualization of the whole repertoire of electrophysiological activity, with the option to display and interpret signals in standard fashion. Our goal is to demonstrate in the semichronic clinical setting a high-definition display of traditional and emerging clinical biomarkers for epilepsy monitoring and treatment. To achieve this goal, we will pursue in Aim 1 regulatory input from the FDA and scale our grids under good quality laboratory practices (GLP), and perform benchtop testing and hardware and software development under a quality management system. In Aim 2, we will perform semichronic animal testing under GLP to demonstrate safety, tolerability, and efficacy of the new epilepsy-monitoring system. In Aim 3, we will will perform pre-clinical and human intraoperative recordings with appropriate IRB authorization. We will pursue FDA clearance for semichronic implants in Aim 4, and transition Aim 5 to semichronic epilepsy monitoring in patients with intractable epilepsy. The methods employed in device and system development, surgical approaches, electrophysiology, and data analysis will not only advance functional and epilepsy monitoring but will also have significant implications for numerous applications in neuromodulation/therapeutic stimulation, minimally destructive brain-machine interfaces, and spinal cord stimulation.