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: 10255795
• 负责人: Matthew R Angle
• 金额: $ 148.84万
• 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/10255795
• 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; 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; 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; 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.

项目摘要 Paradromics正在开发高数据速率大脑计算机接口技术作为医疗的平台 设备应用。在我们的第I阶段SBIR中，我们设计，建造和测试了基于的神经记录系统 大规模并行的微孔电子阵列粘合到CMOS读数电子设备。该系统支持 以超过32,000 Hz同时采样至65,536个活动电极通道。我们使用此系统记录 从大鼠（穿透，1mm深度）和局部田间的1200微电极阵列的动作电位 绵羊（表面）中> 30,000个微电极的电势。这是Microwire-的演示 TO-CMOS键合体系结构将构成我们下一个设备的核心，即医疗植入物。 对于这种新的可植入医疗设备，我们开发了一种新的且大大改进的方法 电极阵列制造。通过电气放电，此方法可产生更多有序的定期阵列 加工（EDM），从阶段I的捆绑结构的随机连接改善 在GMP下生产的能力。 NIH SBIR也开发了一种新的定制CMOS传感器 第一阶段的努力，对神经数据执行压缩敏感性，以降低功率和数据要求 未来设备。 当我们准备构建此植入医疗设备并将其登上市场时，至关重要的是进行广泛测试 不同阵列设计的插入可靠性，以生产最佳优化插入和 记录。在这里，我们建议使用400-1600个电极的被动阵列，比我们的阶段方法小， 找到用于临床翻译的最佳电极阵列设计。我们将测试可能是可靠性的阵列设计 插入绵羊皮质中，验证该阵列在术中（IRB下）中的人体组织中的插入， 并在长达6个月内评估组织对阵列的组织反应，长期植入绵羊。 未来阵列的总体目标是确保我们可以用最小的小腿可靠地插入阵列 宽度以在适当的音高（100-400μm）和长度（即1 mm）适用于人皮质。 此外，这些数据对于设计认证的GLP研究以及与与计划对话至关重要 FDA进行易于id的会议，我们将需要最终确定的阵列设计和测试计划。 该直接对第二阶段研究的目的如下： 特定目标（SA）1：确定最佳的微电极阵列设计并验证植入绵羊 术中人类皮质组织，被动阵列为400-1600个电极。我们的目标是更好 了解高密度微电极电极阵列的几何参数如何影响插入可靠性 在卵巢（SA 1.1）的体内进入皮质组织，并具有精制的几何形状术中植入术中的几何形状 进入人皮层（SA 1.2）。 特定目的2：确定植入绵羊的被动阵列的长期活力。 。我们将确定 通过长期在绵羊中实现被动阵列，我们的高密度阵列的长期生存能力。动物 将在4、8、12和24周内植入。将比较神经胶质疤痕和神经元丧失的程度 在这些时间点上的高密度和商业阵列之间的电子周围。