Development of an Acoustic Implant Protection System to Improve Performance and Longevity of Neural Interfaces

开发声学植入保护系统以提高神经接口的性能和寿命

• 批准号: 10763996
• 负责人: Maureen L. Mulvihill
• 金额: $ 120.42万
• 依托单位: ACTUATED MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-05 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10763996
• 关键词: Development; Acoustic; Implant; Protection; System

This SBIR Fast-track finalizes, tests, and commercializes the Acoustic Implant Protection (AIP) system, which uses the application of precision acoustic fields to penetrating neural implants to prevent electrode impedance rise and improve implant longevity. This submission is in response to: Notice of Special Interest (NOSI): NOT- MH-21-125 Translation of BRAIN Initiative Technologies to the Marketplace. Problem to be solved: Chronic neural implants hold great potential for illuminating features of neural function, treating neurological disorders, and enabling the next generation of brain-machine interface-based neuroprosthetics. Penetrating microelectrode arrays provide direct access to neural signals with high temporospatial resolution. However, their preclinical and clinical viability are limited by their poor longevity and variability in functionality due to the immune response or foreign body response (FBR). The FBR can cause glial scarring and neural cell loss near the electrode sites of penetrating arrays over a period of several weeks, which are leading causes of signal recording losses through both electrical isolation and spatial distancing effects. The FBR begins with electrode insertion, when damage to the blood brain barrier activates astrocytes and microglia. Although ‘soft’ electrode materials, thinner shanks, and floating arrays have been developed to minimize the mismatch between brain and implant, none of these have demonstrated sufficient recording life and immunity to the FBR. Exogenous chemical means have been used to directly suppress the FBR, and have yielded positive results to varying degrees, but limitations of effectiveness, high costs, and/or undesirable side-effects still exist. A simple approach is needed to mitigate FBR for both preclinical and clinical use. Solution: Sub-threshold therapeutic ultrasound has recently been shown to have protective and healing effects in models of cerebral disease and injury, through promotion of neurotrophic factors. AMI successfully leveraged this principle in an R21 study evaluating low-intensity pulsed ultrasound (LIPUS) to mitigate the microglia response and improve longevity of neural interfaces. Product: This Fast-track delivers an AIP system for preclinical use with a reusable (releasable) annular transducer that delivers LIPUS to produce a neuro-protective environment around implanted microelectrodes. Phase I: Aim 1 – Electronics/System Adaptation for Preclinical Study. Aim 2 – Confirm ultrasound parameters for AIP annulus that safely stimulate cortical tissues comparable to Alpha design from R21. Phase I to Phase II Go-no-go. Portable, reusable AIP prototype produces measurable improvement in neural signal longevity over 6 weeks in preclinical microelectrode study. Positive feedback from potential end users. Aim 3– Integrate End User Design Feedback and Conduct Verification and Validation. Aim 4 – Optimize stimulation intervals for neural interface performance (SNR, unit detection) and demonstrate additional neuro- protective effects (glial cell activation, E-I balance) of LIPUS in preclinical studies.

该 SBIR 快速通道最终确定、测试了声学植入保护 (AIP) 系统并将其商业化，该系统 利用精密声场穿透神经植入物来防止电极阻抗 提高并延长种植体寿命 此提交是为了回应：特别兴趣通知 (NOSI)：NOT-。 MH-21-125 将 BRAIN Initiative 技术转化为市场。 待解决的问题：慢性神经植入物在阐明神经功能特征方面具有巨大潜力， 治疗神经系统疾病，并实现下一代基于脑机接口的 神经假体可以直接获取神经信号。 然而，它们的临床前和临床可行性因其寿命较短而受到限制。 免疫反应或异物反应 (FBR) 可能会导致功能变异。 几周内穿透阵列电极部位附近的神经胶质疤痕和神经细胞损失， 这是通过电气隔离和空间距离记录信号的主要原因 FBR 从电极插入开始，此时血脑屏障受损会激活星形胶质细胞。 尽管“软”电极材料、更细的柄和浮动阵列已经被开发出来。 最大限度地减少大脑和植入物之间的不匹配，但这些都没有证明足够的记录寿命 和对FBR的免疫已被用来直接抑制FBR，并且 已在不同程度上产生了积极的结果，但效果有限、成本高和/或不受欢迎 副作用仍然存在，需要一种简单的方法来减轻临床前和临床使用的 FBR。 解决方案：亚阈值治疗超声最近被证明具有保护和治疗作用 在脑疾病和损伤模型中，通过促进神经营养因子成功。 在一项评估低强度脉冲超声 (LIPUS) 的 R21 研究中利用了这一原理，以减轻 小胶质细胞反应并提高神经接口的寿命 产品：该快速通道提供 AIP。 用于临床前使用的系统，配有可重复使用（可释放）的环形传感器，可输送 LIPUS 以产生 植入微电极周围的神经保护环境。 第一阶段：目标 1 – 临床前研究的电子/系统适应目标 2 – 确认超声参数。 用于 AIP 环，可安全地刺激皮质组织，与 R21 的 Alpha 设计相当。 第一阶段到第二阶段 Go-no-go 便携式、可重复使用的 AIP 原型在神经方面产生了可测量的改善。 临床前微电极研究中的信号寿命超过 6 周，来自潜在最终用户的积极反馈。 目标 3 – 整合最终用户设计反馈并进行验证和确认 目标 4 – 优化。 神经接口性能（SNR、单位检测）的刺激间隔，并展示额外的神经 LIPUS 在临床前研究中的保护作用（胶质细胞激活、E-I 平衡）。