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

基本信息

批准号：
10552838
负责人：
Maureen L. Mulvihill
金额：
$ 50.02万
依托单位：
ACTUATED MEDICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-05 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10552838
关键词：
Acoustics Amputees Anti-Inflammatory Agents Astrocytes BRAIN initiative Blood - brain barrier anatomy Brain Cerebrum Chemicals Chondroitin ABC Lyase Chronic Cicatrix Clinical Detection Development Devices Dexamethasone Disease Effectiveness Electrodes Electronics Electrophysiology (science)Environment Enzymes Equilibrium Equipment Malfunction Exploratory/Developmental Grant Failure Feedback Foreign Bodies Future Goals Head Human Immune response Immunity Impairment Implant Implanted Electrodes Incidence Individual Inflammation Inflammatory Response Injury Laboratory Research Life Longevity Measurable Mechanics Medical Microelectrodes Microglia Modeling Monitor Morphology Neurodegenerative Disorders Neurons Neurophysiology - biologic function Noise Oligodendroglia Outcome Paraplegia Pathology Pathway interactions Performance Peripheral Nervous System Phase Physiologic pulse Population Pre-Clinical Model Prosthesis Rattus Research Research Personnel Resolution Risk Rodent Signal Transduction Site Small Business Innovation Research Grant System Technology Temperature Testing Therapeutic Time Tissues Transducers Translating Translations base brain computer interface brain machine interface cell motility clinical application commercialization cost design electric impedance glial activation healing human model implantation improved innovation interest miniaturize motor control nervous system disorder neural implant neuromechanism neuroprosthesis neurotransmission neurotrophic factor next generation portability pre-clinical pre-clinical research preclinical study prevent prototype relating to nervous system response side effect tool ultrasound verification and validation

项目摘要

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.

此SBIR快速轨道最终确定，测试和商业化了声学植入物保护（AIP）系统，该系统利用精确的声场在穿透神经植物中的应用来防止电极阻抗上升并改善植入物的寿命。此提交的响应是：特殊利益通知（NOSI）：不 - MH-21-125大脑启动技术转换为市场。要解决的问题：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界面神经假想。穿透微电极阵列可直接访问高较高的神经元信号暂时空间分辨率。但是，它们的临床前和临床生存能力受其寿命差的限制和由于免疫响应或异物反应（FBR）引起的功能变化。 FBR可能导致在几周内，胶质疤痕和神经细胞损失在穿透阵列的电极位点附近，这是通过电隔离和空间距离导致信号记录损失的主要原因效果。 FBR始于电极插入，当对血脑屏障的损害激活星形胶质细胞时和小胶质细胞。最大程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生活和对FBR的免疫力。外源化学方法已被用于直接抑制FBR，并且在不同程度上产生了积极的结果，但是有效性，高成本和/或不良的局限性副作用仍然存在。需要一种简单的方法来减轻FBR的临床前和临床用途。解决方案：最近已证明亚阈值热超声受到保护和愈合效果通过促进神经营养因素的脑疾病和损伤模型。 ami成功在评估低强度脉冲超声（Lipus）的R21研究中利用了这一原理小胶质细胞反应并改善神经界面的寿命。产品：此快速轨道提供AIP 临床前使用系统，可重复使用（可释放的）环形传感器，可提供Lipus产生脂肪植入微电极周围的神经保护环境。 I阶段：AIM 1 - 临床前研究的电子/系统适应。 AIM 2 - 确认超声参数对于安全刺激与R21α设计相当的皮质组织的AIP环。第一阶段到II期。便携式，可重复使用的AIP原型可产生中性的可测量改进临床前微电极研究中的6周信号寿命。潜在最终用户的积极反馈。目标3 - 整合最终用户设计反馈，并进行验证和验证。目标4 - 优化神经元界面性能（SNR，单位检测）的刺激界面，并展示了其他神经 - 临床前研究中脂肪的保护作用（神经胶质细胞激活，E-I平衡）。