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

这个ICORP项目扩大了市场的了解，并进行了广泛的客户发现 用于神经植入物的声学植入物保护系统。 原始摘要：此SBIR快速通道完成、测试和商业化声学植入物保护 (AIP)系统，该系统使用精密声场的应用穿透神经植入物，以防止 电极阻抗升高并改善植入物寿命。此提交是为了回应：特别通知 兴趣（NOSI）：NOT-MH-21-125将BRAIN Initiative技术转化为市场。 待解决的问题：慢性神经植入物具有阐明神经功能特征的巨大潜力， 治疗神经系统疾病，并使下一代基于脑机接口的 神经修复术穿透性微电极阵列提供了对神经信号的直接访问， 时空分辨率然而，它们的临床前和临床可行性受限于它们较差的寿命， 由于免疫反应或异物反应（FBR）导致的功能性变异。FBR会导致 在几周的时间内穿透阵列的电极部位附近的神经胶质瘢痕形成和神经细胞损失， 这是由于电隔离和空间距离引起的信号记录损失的主要原因 方面的影响. FBR开始于电极插入，此时血脑屏障的损伤激活星形胶质细胞 和小胶质细胞。尽管已经开发了“软”电极材料、更薄的柄和浮动阵列， 最大限度地减少大脑和植入物之间的不匹配，这些都没有证明足够的记录寿命 和联邦调查局的豁免权外源化学手段已被用于直接抑制FBR， 已经在不同程度上产生了积极的结果，但是有效性的限制、高成本和/或不期望的 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愈合作用 在脑疾病和损伤模型中，通过促进神经营养因子。AMI成功 在一项R21研究中利用这一原理，评价低强度脉冲超声（LIPUS）缓解 小胶质细胞反应和改善神经接口的寿命。产品：此快速通道提供AIP 用于临床前使用的系统，其具有可重复使用的（可释放的）环形换能器，该环形换能器输送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/系统适配。目标2 -确认超声参数 用于安全刺激皮质组织的AIP瓣环，与R21的Alpha设计相当。 第一阶段到第二阶段去不去。便携式，可重复使用的AIP原型产生了可衡量的改善神经 在临床前微电极研究中，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，并证明额外的神经- LIPUS在临床前研究中的保护作用（神经胶质细胞活化、E-I平衡）。

This ICORPs project expands market understanding and conducts extensive customer discovery for the Acoustic Implant Protection system for use with Neural Implants. Original Abstract: 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.