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 Paradomics正在开发高数据速率脑机接口技术，作为医疗平台 设备应用程序。在我们的第一阶段SBIR中，我们设计、构建并测试了一个基于 绑定到cmos读出电子设备的大规模平行微线电极阵列。该系统支持UP 至65,536个有效电极通道，同时以超过32,000赫兹的频率采样。我们用这个系统记录了 大鼠最多1200个微电极阵列的动作电位(穿透，1 mm深度)和局部野 绵羊(表面)30,000个微电极的电位。这是微丝的演示-- 这将构成我们下一个设备的核心--医疗植入物。 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 电极阵列制作。这种方法通过放电产生更有序、规则的阵列 加工(EDM)，从而改进了从第一阶段开始的捆绑体系结构的随机连接 按GMP要求生产的能力。继NIH SBIR之后，还开发了一种新的定制cmos传感器 第一阶段工作，执行神经数据的压缩感测，以减少 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，广泛测试 不同阵列设计的插入可靠性，以便产生最适合插入和 正在录音。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， 目的：为临床翻译寻找最佳的电极阵列设计。我们将测试能够可靠地 插入绵羊皮质，确认术中(在IRB下)将该阵列插入人体组织， 并评估该阵列在长达6个月的时间内对绵羊长期植入的组织响应。 未来阵列的总体目标是确保我们可以可靠地插入具有最小柄的阵列 在适当的螺距(100-400μm)和长度(即1 Mm)适用于人类皮质。 此外，这些数据对于设计经过认证的GLP研究以及规划与 FDA的IDE前会议，在那里我们需要一个最终的阵列设计和测试计划到位。 这项直接至第二阶段研究的目的如下： 特定目标(SA)1：确定最佳微电极阵列设计并验证植入绵羊体内 以及术中使用400-1600个电极的被动阵列的人体皮质组织。我们的目标是做得更好 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 在羊(羊)模型体内植入皮质组织(SA 1.1)，术中植入精细几何结构 进入人脑皮质(SA 1.2)。 具体目标2：确定在绵羊体内植入的被动阵列的长期生存能力。。我们将决定 通过将被动阵列长期植入绵羊体内，验证了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。将比较神经胶质瘢痕形成的程度和神经元丢失的程度。 在这些时间点上，高密度阵列和商用阵列之间的电极周围。