Development and evaluation of novel high-density intracortical microelectrode arrays for clinical applications

临床应用新型高密度皮质内微电极阵列的开发和评估

• 批准号: 10483140
• 负责人: Matthew R Angle
• 金额: $ 143.3万
• 依托单位: PARADROMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483140
• 关键词: Action Potentials; Animal Model; Animals; Architecture; Caliber; Cells; Chronic; Cicatrix; Clinical Research; Clinical Trials; Custom; Data; Development; Devices; Electrodes; Electronics; Ensure; Epilepsy; Evaluation; Excision; Feedback; Foreign Bodies; Freedom; Future; Geometry; Goals; Histology; Human; Implant; Implantation procedure; Institutional Review Boards; Investigation; Length; Locked-In Syndrome; Medical Device; Methods; Microelectrodes; Modeling; Monitor; Operative Surgical Procedures; Patients; Persons; Phase; Process; Rattus; Recovery; Sampling; Series; Sheep; Small Business Innovation Research Grant; Support System; Surface; System; Technology; Testing; Time; Tissues; Translations; United States National Institutes of Health; Width; base; brain computer interface; clinical application; clinical translation; cohort; density; design; good laboratory practice; human tissue; implantation; improved; in vivo; innovation; medical implant; meetings; neuron loss; novel; phase 2 study; preclinical study; relating to nervous system; response; safety study; sensor; sheep model; tool; translation to humans

PROJECT SUMMARY Paradromics is developing high data rate brain computer interface technologies as a platform for medical device applications. In our Phase I SBIR, we designed, built, and tested a neural recording system based on massively parallel microwire electrode arrays bonded to CMOS readout electronics. That system supports up to 65,536 active electrode channels sampled simultaneously at over 32,000 Hz. We used this system to record action potentials from arrays of up to 1200 microelectrodes in rats (penetrating, 1mm depth) and local field potentials from >30,000 microelectrodes in sheep (surface). This serves as a demonstration of the microwire- to-CMOS bonding architecture that will form the core of our next device, a medical implant. For this new implantable medical device, we have developed a new and substantially improved method of electrode array fabrication. This method produces more ordered, regular arrays through Electrical Discharge Machining (EDM), thus improving on the stochastic connections of the bundle architecture from Phase I with the ability to be produced under GMP. A new, custom CMOS sensor, also developed following the NIH SBIR Phase I effort, performs compressive sensing of neural data to reduce power and data requirements in the future device. As we prepare to build this implantable medical device and take it to market, it is critical to extensively test the insertion reliability of different arrays designs in order to produce a device best optimized for insertion and recording. Here we propose to use passive arrays of 400-1600 electrodes, smaller than our Phase I approach, to find the optimal electrode array design for clinical translation. We will test array designs that can reliably insert into the sheep cortex, validate the insertion of that array in human tissue intraoperatively (under IRB), and evaluate the tissue response to the array over a period of up to 6 months, implanted chronically in sheep. The overall goal for the future array is to ensure that we can reliably insert the array with the smallest shank width to mitigate the chronic foreign body response at an appropriate pitch (100 - 400 μm) and length (i.e. 1 mm) suitable for the human cortex. Moreover, this data will also be critical for designing certified GLP studies, and for planning conversations with the FDA for pre-IDE meetings, where we will need a finalized array design and testing plan in place. The aims of this Direct to Phase II study are as follows: Specific Aim (SA) 1: Determine optimal microelectrode array design and validate implantation in sheep and human cortical tissue intraoperatively with passive arrays of 400-1600 electrodes. We aim to better understand how the geometric parameters of high density microwire electrode arrays impact insertion reliability into cortical tissue in vivo in an ovine (sheep) model (SA 1.1), with refined geometries implanted intraoperatively into human cortex (SA 1.2). Specific Aim 2: Determine long-term viability of implanted, passive arrays in sheep. . We will determine the long-term viability of our high-density array by chronically implanting the passive arrays in sheep. Animals will be implanted over 4, 8, 12, and 24 weeks. The degree of glial scarring and neuron loss will be compared around electrodes between high-density and commercial arrays over these timepoints.

项目总结