Microelectrode Array Insertion System using Ultrasonic Vibration to Improve Insertion Mechanics, Reduce Tissue Dimpling and Trauma, and Improve Placement Precision in the Neocortex

使用超声波振动的微电极阵列插入系统改善插入力学，减少组织凹陷和创伤，并提高新皮质的放置精度

• 批准号: 10268984
• 负责人: Maureen L. Mulvihill
• 金额: $ 142.35万
• 依托单位: ACTUATED MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10268984
• 关键词: Amputees; Animal Model; BRAIN initiative; Brain; Caliber; Cell Death; Chronic; Cicatrix; Clinical; Collaborations; Communication; Communities; Complex; Coupling; Data; Development; Devices; Dura Mater; Electrodes; Engineering; Equipment Malfunction; Exhibits; Feedback; Foreign Bodies; Frequencies; Goals; Hemorrhage; Human; Image; Implant; Implantation procedure; Implanted Electrodes; Incidence; Individual; Inflammation; Location; Magnetic Resonance Imaging; Manuals; Marketing; Mechanics; Medical; Medical Research; Methods; Microelectrodes; Motion; Neocortex; Neurologic; Neurons; Neurosciences Research; Operative Surgical Procedures; Outcome; Paraplegia; Patient Care; Penetration; Peripheral Nervous System; Phase; Polymers; Property; Proprioception; Prosthesis; Rattus; Resolution; Risk; Sales; Sensory; Shapes; Silicon; Site; Small Business Innovation Research Grant; Speed; Structure; Surface; System; Technology; Testing; Tissues; Trauma; Tungsten; Ultrafine; Ultrasonics; Validation; Work; base; brain machine interface; carbon fiber; commercialization; cranium; density; design; extracellular; flexibility; grasp; implantation; improved; improved outcome; in vivo; innovation; millimeter; minimally invasive; motor control; neural implant; neurotransmission; nonhuman primate; novel; pre-clinical; preservation; prosthesis control; relating to nervous system; response; success; tissue trauma; tool; two-photon; verification and validation; vibration

This Phase II SBIR further develops and tests a system that employs ultrasonic vibration to improve the insertion mechanics for multichannel penetrating electrode arrays. This proposal is in response to PA-18-871 BRAIN Initiative: Development, Optimization, and Validation of Novel Tools and Technologies for Neuroscience Research – including ‘Iterative refinement of such tools and technologies with the end-user community’. The long-term goal of Actuated Medical, Inc. is to develop technology enabling accurate placement of penetrating neural electrode arrays at target locations with minimal tissue trauma and displacement, ultimately paving the way for clinical use of neural implants. Penetrating neural implants provide direct access to extracellular neural signals across the central and peripheral nervous systems with both high temporal and spatial resolution. Unfortunately, the implantation of neural electrode arrays, commonly comprised of numerous closely spaced shanks, applies forces to neural tissue resulting in significant compression (dimpling), prohibiting uniform shank insertion, and increasing the risk of trauma, bleeding and inflammation at the implant site. These issues can increase the chronic foreign body response (FBR) leading to neural cell death, glial scaring, and device failure. Phase I demonstrated the ability to releasably grip and deliver ultrasonic vibration to a range of commercially available implant types, including floating-style arrays, resulting in reductions of insertion force and surface dimpling in bench studies of up to 80-90% for most implants tested. In vivo, ultrasonic vibration significantly reduced brain surface dimpling (~50%, p<0.01) and exhibited evidence of reduced bleeding, while preserving device function as evidenced by post implant neural recordings. Furthermore, preliminary work suggests significant potential for the ultrasonic vibration to improve insertion of ultrafine (8-15 µm) microwire arrays, as well as NeuroNexus’ Matrix platform arrays, one of the most delicate and complicated commercially-available implants. This Phase II SBIR expands use of the NeuralGlider inserter for inserting complex, fragile, and flexible penetrating neural electrode arrays using ultrasonic vibration to reduce insertion force, brain surface dimpling, tissue damage, and bleeding. The project uses a unique multi-institutional collaboration to obtain scientific data, supporting the benefits of the NeuralGlider insertion technology. Phase II hypothesis: Ultrasonic micro-vibration improves insertion accuracy and success, reduces insertion trauma, and improves recording outcomes for penetrating neural electrode arrays. Specific Aims: Aim 1 - Evaluate implantation trauma and inflammation response through 2-photon imaging and magnetic resonance imaging. Aim 2 - Demonstrate efficacy of NeuralGlider insertion approach for ultra-fine, ultra-high-density electrode array designs. Aim 3 - Integrate end user feedback, design upgrades for coupling options, and conduct Verification and Validation. Aim 4 - Demonstrate improved outcomes with micro-vibrated insertion.

这一第二阶段SBIR进一步开发并测试了一个员工超声振动以改善该系统的系统 多通道穿透电极阵列的插入力学。该建议是对PA-18-871的回应 大脑计划：开发，优化和验证新颖的工具和技术 神经科学研究 - 包括'与最终用户的迭代改进此类工具和技术 社区'。 Actisted Medical，Inc。的长期目标是开发技术，使其准确 将穿透性神经电极阵列放置在最小组织创伤的目标位置 位移，最终为神经神经的临床使用铺平了道路。 穿透性神经直接可直接访问中央和中央的细胞外神经信号 具有高临时和空间分辨率的外周神经系统。不幸的是，植入 神经电极阵列通常由许多紧密间隔的小腿组成，适用于神经元 组织导致明显的压缩（凹痕），禁止均匀的小腿插入，并增加 植入物部位的创伤，出血和炎症的风险。这些问题会增加慢性外国 身体反应（FBR）导致神经元细胞死亡，神经胶质恐惧和装置衰竭。第一阶段证明了 能够可靠地抓住和传递超声波振动到一系列市售植入物类型的能力， 包括浮动阵列，导致插入力和表面凹痕减少 大多数已测试的大多数人最多可达80-90％。在体内，超声振动显着降低了脑表面凹痕 （〜50％，p <0.01）并暴露了降低出血的证据，同时保留了设备功能。 植入后神经记录。此外，初步工作表明了超声波 振动以改善超细插入（8-15 µm）微孔阵列的插入，以及Neuronexus的矩阵平台 阵列，是最精致，最复杂的商业上可用的即兴。此II阶段SBIR扩展 使用神经手机插入器插入复合物，脆弱和柔性的穿透性神经电极阵列 使用超声振动减少插入力，脑表面凹痕，组织损伤和出血。这 项目使用独特的多机构合作来获取科学数据，并支持 神经插入技术。 II期假设：超声波微振动提高了插入精度 和成功，减少插入创伤并改善穿透神经电极的记录结果 数组。具体目的：目标1-通过2 -Photon评估植入创伤和炎症反应 成像和磁共振成像。目标2-证明神经插入方法的效率 用于超细的超高密度电极阵列设计。 AIM 3-整合最终用户反馈，设计升级 用于耦合选项，并进行验证和验证。 AIM 4-通过 微振动的插入。