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

用于癫痫诊断和治疗的薄型、高密度、高性能、深度和表面微电极

• 批准号: 10294893
• 负责人: Shadi Dayeh
• 金额: $ 236.48万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10294893
• 关键词: Acute; Anatomy; Animal Model; Animal Testing; Animals; Area; Authorization documentation; Biological Markers; Biophysics; Brain; Brain imaging; Brain region; Caliber; Charge; Chronic; Clinical; Clinical Trials; Computer software; Craniotomy; Data; Data Analyses; Development; Device or Instrument Development; Devices; Diagnosis; Diagnostic; Electrocorticogram; Electrodes; Electronics; Electrophysiology (science); Epilepsy; Excision; Family suidae; Feasibility Studies; Film; Generations; Goals; Gold; Grant; High Frequency Oscillation; Histologic; Human; Impairment; Implant; Incidence; Injections; Institutional Review Boards; Intractable Epilepsy; Laboratories; Language; Maps; Measures; Medical Device; Methods; Microelectrodes; Microfabrication; Monitor; Motor; Movement; Neurostimulation procedures of spinal cord tissue; Operative Surgical Procedures; Outcome; Pathologic; Patients; Performance; Phase; Platinum; Preclinical Testing; Procedures; Protocols documentation; Radio; Reaction; Research; Resolution; Safety; Seizures; Signal Transduction; Source; Structure; Surface; System; Systems Development; Systems Integration; Technology; Testing; Therapeutic; Therapeutic procedure; Thinness; Tissues; Vision; Visualization; Wireless Technology; animal safety; base; biomaterial compatibility; brain machine interface; brain tissue; clinical biomarkers; cranium; data exchange; density; efficacy testing; electric impedance; ergonomics; manufacturing process; meetings; miniaturize; minimally invasive; nanorod; neuroregulation; novel; parylene C; phase 2 testing; pre-clinical; preservation; relating to nervous system; safety testing; software development; success; transmission process

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.

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电图（ECoG）记录/刺激网格（4096/256通道， 和立体脑电图（sEEG）深度电极（120/8微/宏），具有全无线 数据和能量传输该项目建立在我们之前成功进行首次人体试验的基础上， 使用数千通道微电极网格对功能脑组织进行急性标测。所提出的系统 包含多种变革性技术方法，包括：（1）利用先进的薄膜 在8”直径的基板上进行微加工，从而允许从数千个 （2）利用新开发的铂纳米棒（PtNR）微电极技术， 低阻抗、高电荷注入容量（4.4mC/cm 2）、稳定性和生物相容性;和（3）使用薄的 （~10μm）聚对二甲苯基片，符合大脑运动，符合大脑曲率，以及 透明，允许在急性标测期间更容易地可视化脑解剖结构。此外，（4）网格 为这个项目开发的是模块化的，可以修剪，以适应不同大小的开颅手术，和（5）这 系统提供了新一代微创sEEG电极，具有易于重新配置的微触点 我们提出的系统还（6）采用了最先进的采集技术， 具有小型化的1024 ch神经接口片上系统以及数据和功率的无线电传输的电子器件， 实现完全无线监控，消除有线外部化，以及（7）部署多屏幕和多 整个电生理活动库的窗口可视化，可选择显示和解释 以标准方式发送信号。 我们的目标是在半慢性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Aim 1来自FDA的监管输入，并根据良好质量实验室规范（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及软件开发。在目标2中， 将在GLP下进行半慢性动物试验，以证明新药物的安全性、耐受性和疗效。 癫痫监测系统在目标3中，我们将进行临床前和人类术中记录， 适当的IRB授权。我们将在目标4中寻求FDA对半慢性植入物的批准， 目的5对难治性癫痫患者进行半慢性癫痫监测。 器械和系统开发、手术入路、电生理学和数据中采用的方法 分析不仅将促进功能和癫痫监测，而且还将对 在神经调节/治疗刺激、最小破坏性脑机 接口和脊髓刺激。