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

第二阶段SBIR进一步开发和测试了采用超声波振动的系统，以改善 多通道穿透电极阵列的插入机构。本提案是对PA-18-871的回应 大脑计划：新工具和技术的开发、优化和验证 神经科学研究--包括与最终用户对这些工具和技术进行迭代改进 “社区”。Actuated Medical，Inc.的长期目标是开发能够实现准确 将穿透性神经电极阵列放置在组织损伤最小的靶点位置 置换，最终为神经植入物的临床应用铺平了道路。 穿透性神经植入物提供直接访问细胞外神经信号的中央和 具有高时间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，将力施加到神经 导致显著压缩(凹陷)的组织，阻止均匀的小腿插入，并增加 植入部位有受伤、出血和发炎的风险。这些问题会增加慢性外来者 身体反应(FBR)导致神经细胞死亡、神经胶质细胞惊吓和设备故障。第一阶段演示了 能够可释放地夹持并向一系列商业可获得的植入物类型传递超声波振动， 包括浮动式阵列，从而减少了插入力和表面凹陷的台架研究 对于大多数测试的植入物，高达80%-90%。在体内，超声波振动显著减少了大脑表面的凹陷 (~50%，p&lt；0.01)，并显示出血减少的证据，同时保留了装置的功能，如以下所示 植入后的神经记录。此外，初步工作表明，超声波具有很大的潜力 振动以改进超细(8-15微米)微线阵列以及NeuroNexus的矩阵平台的插入 阵列，最精致和复杂的商业植入物之一。此第二阶段SBIR扩展 使用NeuralGlider插入器插入复杂、脆弱和灵活的穿透性神经电极阵列 使用超声波振动来减少插入力、脑表面凹陷、组织损伤和出血。这个 该项目使用独特的多机构协作来获取科学数据，支持 NeuralGlider插入技术。阶段II假设：超声波微振动提高插入精度 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。具体目标：目标1-通过双光子评估植入创伤和炎症反应 成像和磁共振成像。目标2-演示NeuralGlider插入方法的有效性 用于超精细、超高密度的电极阵列设计。目标3-整合最终用户反馈、设计升级 用于联轴器选项，并进行验证和确认。目标4-展示更好的结果 微振动插入。

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.