EAGER: Real-Time: Free-Floating Wireless Implantable Optical Stimulators for Untethered Optogenetics

EAGER：实时：用于不受限制的光遗传学的自由浮动无线植入式光学刺激器

• 批准号: 1923187
• 负责人: Wen Li
• 金额: $ 8万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2020-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1923187&HistoricalAwards=false
• 关键词: EAGER; Real; Time; Free; Floating

Optogenetics, the use of light-gated ion channels or pumps to excite or inhibit the transient activity of genetically targeted neurons by pulses of light, has proved its enormous potential for understanding neuronal circuit mechanisms underlying brain functions and behavior, and ultimately, for providing therapeutics to treat numerous neurological and psychiatric disorders. Despite the rapid development of optogenetics tools over the past decade, tethered optical devices pose significant limitations in experimental animals and even more so in potential clinical applications. This proposed research will address fundamental challenges in tethered optogenetics systems, by developing a distributed, wireless (untethered and battery-less), implantable optical stimulator architecture that is more power efficient, significantly safer, and more practical for translation to clinical applications. The successful completion of the project will yield a new neural interface tool to significantly expand the utility of the rapidly growing field of optogenetics, which has become the frontier in brain science research, gene therapy, and new drug discovery for a variety of neural diseases. In addition, the project will train graduate students in multidisciplinary research and broaden K-12 education in Science, Technology, Engineering, and Mathematics (STEM) through integrated outreach activities, including the NSF sponsored Research Experiences for Teachers (RET) Program at Michigan State University.The proposed wireless optogenetics stimulator will integrate a mm-sized, Parylene-coated system-on-a-chip (SoC) with an embedded receiver coil, surface-mount storage capacitors, and microscale light-emitting diodes (microLEDs) to selectively stimulate the target neural tissue. Researchers will tackle inefficiencies in wireless power delivery to the neural tissue using: 1) a four-coil telemetry link including an implantable high quality factor resonator to enhance wireless power coupling efficiency; 2) a built-in mirror to reflect backside illumination of microLED for improving light throughput; and 3) a switched-capacitor stimulation (SCS) structure of the SoC to directly charge an array of storage capacitors from the inductive link and periodically discharge them into a microLED without loading the inductive link. A single wireless stimulator enables localized optical stimulation of targeted neurons with high spatiotemporal resolution, while a cluster of such implants enables easy access to large-scale neuronal circuits with minimal invasiveness and movement restriction. The proposed device also enables a significantly safer and more practical solution for potential translation of optogenetics into behaving animal research and clinical applications. Removing the chronic physical trauma of tethering can effectively minimize tissue damage and enable efficient and stable chronic wireless optical stimulation. Moreover, the distributed, epidural implantation strategy permits selective stimulation of any desired area in the cortex. This new paradigm will offer neuroscience community an unprecedented level of flexibility with unlimited experiment duration in an enriched, untethered environment, without requiring small animal subjects to carry bulky batteries around.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

光遗传学，利用光门控离子通道或泵通过光脉冲激发或抑制基因靶向神经元的瞬时活动，已证明其在理解大脑功能和行为背后的神经元回路机制以及最终提供治疗方面具有巨大的潜力治疗多种神经和精神疾病。尽管光遗传学工具在过去十年中发展迅速，但系留光学设备对实验动物造成了很大的限制，在潜在的临床应用中更是如此。这项拟议的研究将通过开发一种分布式、无线（无线且无电池）、植入式光刺激器架构来解决系留光遗传学系统的基本挑战，该架构更节能、更安全、更实用，可转化为临床应用。该项目的成功完成将产生一种新的神经接口工具，以显着扩展快速发展的光遗传学领域的实用性，该领域已成为脑科学研究、基因治疗和各种神经疾病新药发现的前沿。此外，该项目还将通过综合外展活动，包括 NSF 赞助的密歇根州立大学教师研究体验 (RET) 项目，培训跨学科研究的研究生，并扩大科学、技术、工程和数学 (STEM) 方面的 K-12 教育大学提出的无线光遗传学刺激器将集成毫米级、聚对二甲苯涂层的片上系统 (SoC) 和嵌入式接收器线圈、表面贴装存储电容器和微型发光二极管（microLED）选择性刺激目标神经组织。研究人员将使用以下方法解决向神经组织无线供电效率低下的问题：1）四线圈遥测链路，包括可植入的高品质因数谐振器，以提高无线功率耦合效率； 2) 内置镜子反射 microLED 的背面照明，以提高光通量； 3) SoC 的开关电容器激励 (SCS) 结构，可直接从感应链路对存储电容器阵列充电，并定期将其放电至 microLED，而不加载感应链路。单个无线刺激器能够以高时空分辨率对目标神经元进行局部光学刺激，而一组此类植入物可以以最小的侵入性和运动限制轻松访问大规模神经元回路。所提出的设备还为光遗传学潜在转化为行为动物研究和临床应用提供了一种更安全、更实用的解决方案。消除束缚带来的慢性物理创伤，可以有效减少组织损伤，实现高效、稳定的慢性无线光刺激。此外，分布式硬膜外植入策略允许选择性刺激皮质中的任何所需区域。这种新范式将为神经科学界提供前所未有的灵活性，在丰富、不受束缚的环境中进行无限的实验持续时间，而不需要小动物受试者携带笨重的电池。该奖项反映了 NSF 的法定使命，并通过使用评估来认为值得支持基金会的智力价值和更广泛的影响审查标准。