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: 10477274
• 负责人: Shadi Dayeh
• 金额: $ 250.01万
• 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/10477274
• 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; animal safety; base; biomaterial compatibility; brain machine interface; brain tissue; clinical biomarkers; cranium; data exchange; density; efficacy testing; electric impedance; ergonomics; integrated circuit; 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; wireless; wireless sensor

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