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

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正在开发高数据率脑机接口技术，作为医疗平台。 设备应用。在我们的第一阶段SBIR中，我们设计、构建并测试了一个基于 大规模平行微丝电极阵列键合到CMOS读出电子器件。该系统支持 至65，536个有效电极通道，以超过32，000 Hz的频率同时采样。我们用这个系统来记录 大鼠中多达1200个微电极阵列的动作电位（穿透，1 mm深度）和局部场 来自绵羊（表面）中> 30，000个微电极的电位。这是一个微型导线的示范 到CMOS键合架构，将形成我们的下一个设备，医疗植入的核心。 对于这种新的植入式医疗设备，我们已经开发了一种新的和实质性改进的方法， 电极阵列制造。该方法通过放电产生更有序、规则的阵列 加工（EDM），从而改善了第一阶段的束结构的随机连接， 能够按照GMP生产。一种新的定制CMOS传感器，也是在NIH SBIR之后开发的 第一阶段的努力，执行压缩感测的神经数据，以减少电力和数据的要求， 未来的设备 当我们准备制造这种植入式医疗设备并将其推向市场时， 不同阵列设计的插入可靠性，以便生产最佳插入优化的装置， 录制.在这里，我们建议使用400-1600个电极的无源阵列，比我们的第一阶段方法小， 以找到用于临床转化的最佳电极阵列设计。我们将测试阵列设计， 插入绵羊皮层，在手术中验证该阵列插入人体组织（在IRB下）， 并在长达6个月的时间内评价对阵列的组织反应，将其长期植入绵羊体内。 未来阵列的总体目标是确保我们能够用最小的柄可靠地插入阵列 在适当间距（100 - 400 μm）和长度（即1 mm）适合于人类皮层。 此外，这些数据对于设计经认证的GLP研究以及计划与 FDA的IDE前会议，我们将需要一个最终的阵列设计和测试计划到位。 本直接进入II期研究的目的如下： 特定目的（SA）1：确定最佳微电极阵列设计并确认绵羊体内植入 和手术中使用400-1600个电极的无源阵列的人皮质组织。我们的目标是更好地 了解高密度微丝电极阵列的几何参数如何影响插入可靠性 在绵羊模型（SA 1.1）中植入体内皮质组织，术中植入精细几何结构 进入人类皮层（SA 1.2）。 具体目标2：确定绵羊体内植入的无源阵列的长期生存能力。.我们将确定 我们的高密度阵列的长期生存能力，通过长期植入被动阵列在羊。动物 将在4、8、12和24周内植入。将比较神经胶质瘢痕形成和神经元丢失的程度 在这些时间点上，高密度和商业阵列之间的电极周围。