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.

抽象的 该项目的目的是显着提高急性和半精神分子癫痫监测的领域 使用新型的高分辨率电视学（ECOG）记录/刺激网格（4096/256通道， 具有完整无线 数据和功率传输。该项目以我们先前的成功进行了有史以来的第一个人类试验的基础 具有数千个通道微电极网格的雄辩脑组织的急性映射。提出的系统 包括多种变革性的技术方法，包括：（1）利用高级薄膜 8英寸直径底物上的微结合化，因此允许数千个的长时间整合连接 频道； （2）利用新开发的白金纳米棒（PTNR）微电极技术 低阻抗，高电荷注射容量（4.4mc/cm2），稳定性和生物相容性； （3）使用薄 （〜10μm）parylene C底物，符合脑运动，符合脑曲率和 透明，允许在急性映射过程中更容易地可视化大脑解剖结构。此外，（4）网格 为该项目开发的是模块化的，可以修剪以适合不同尺寸的颅骨，（5） 系统提供新一代的微创Seeg电极，具有易于重新配置的微接触 在大脑的不同区域分发我们的拟议系统（6）员工最先进的收购 具有微型1024CH神经接口的电子设备，以及数据和功率的无线电传输， 启用完全无线监控，以消除电线外部化，（7）部署多屏和多屏 电生理活动整个曲目的窗户可视化，并可以选择显示和解释 标准方式的信号。 我们的目标是在半精神分子临床环境中展示传统和 新兴的临床生物标志物用于癫痫监测和治疗。为了实现这一目标，我们将追求目标 1来自FDA的监管输入，并根据优质实验室实践（GLP）扩展我们的网格，并执行 台式测试以及质量管理系统下的硬件和软件开发。在AIM 2中，我们 将在GLP下执行半复杂动物测试，以证明新的安全性，耐受性和效率 癫痫监测系统。在AIM 3中，我们将与 适当的IRB授权。我们将在AIM 4中追求FDA的清除，以实现AIM 4的半精神分子和过渡 目的5到具有顽固性癫痫患者的半复杂性癫痫监测。 在设备和系统开发，手术方法，电生理学和数据中进行的方法 分析不仅会提高功能和癫痫监测，还将对 在神经调节/治疗刺激，最小破坏性的脑机中的许多应用 接口和脊髓刺激。