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

该SBIR快速通道完成、测试声学植入保护(AIP)系统并将其商业化，该系统 应用精密声场穿透神经植入物以防止电极阻抗 提高和提高种植体寿命。本意见书是回应：特别利益通告：非- MH-21-125将大脑首创技术翻译到市场。 有待解决的问题：慢性神经植入物在阐明神经功能特征方面具有巨大潜力， 治疗神经疾病，并使下一代基于脑机接口的 神经假体。穿透性微电极阵列提供对高密度神经信号的直接访问 时间空间分辨率。然而，它们的临床前和临床生存能力受到它们较差的寿命和 由于免疫反应或异物反应(FBR)而导致的功能变化。FBR可能会导致 在几周的时间里，穿透阵列电极位置附近的胶质瘢痕和神经细胞丢失， 它们是通过电隔离和空间距离造成信号记录损失的主要原因 效果。FBR始于电极插入，此时血脑屏障受损激活星形胶质细胞 和小胶质细胞。尽管“软”电极材料、更薄的刀柄和浮动阵列已经被开发出来 尽量减少大脑和植入物之间的不匹配，这些都没有表现出足够的记录寿命 以及对联邦调查局的豁免权。外源化学手段被用来直接抑制快堆，以及 在不同程度上产生了积极的结果，但有效性的局限性、高昂的成本和/或不受欢迎 副作用仍然存在。需要一种简单的方法来缓解临床前和临床使用的FBR。 解决方案：亚阈值治疗性超声波最近被证明具有保护和愈合作用 在脑部疾病和损伤模型中，通过促进神经营养因子。AMI成功 在评估低强度脉冲超声(LIPUS)的R21研究中利用这一原理来缓解 小胶质细胞的反应和提高神经接口的寿命。产品：此快速通道提供AIP 临床前使用的具有可重复使用(可释放的)环形换能器的系统，该换能器输送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--临床前研究的电子学/系统适应性。目标2-确认超声参数 用于安全刺激皮质组织的AIP环，可与R21的Alpha设计相媲美。 第一阶段到第二阶段-不通过。可移植、可重复使用的AIP原型在神经方面取得了可衡量的改善 临床前微电极研究中信号寿命超过6周。来自潜在终端用户的积极反馈。 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，并显示额外的神经- LIPUS在临床前研究中的保护作用(胶质细胞激活，E-I平衡)。

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.