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

光遗传学，使用光门控离子通道或泵通过光脉冲来激发或抑制遗传靶向神经元的瞬时活动，已证明其在理解脑功能和行为的神经元回路机制方面的巨大潜力，并最终提供治疗多种神经和精神疾病的疗法。尽管光遗传学工具在过去十年中发展迅速，但系留光学设备在实验动物中存在显着限制，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（无束缚和无电池）、可植入的光刺激器架构来解决束缚光遗传学系统的根本挑战，该架构更节能、更安全，并且更实用，可用于临床应用。该项目的成功完成将产生一种新的神经接口工具，以显着扩大光遗传学快速发展领域的实用性，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，该项目将通过综合推广活动，包括NSF赞助的密歇根州立大学教师研究经验（RET）计划，培训多学科研究的研究生，并拓宽K-12教育的科学，技术，工程和数学（STEM）。聚对二甲苯涂层片上系统（SoC），具有嵌入式接收器线圈、表面贴装存储电容器和微型发光二极管（microLED），可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传输无线功率的效率低下问题：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，用于反射microLED的背面照明，以提高光通量;以及3）开关电容器刺激（SCS）SoC的结构，以从电感链路直接对存储电容器阵列充电，并周期性地将它们放电到微LED中，而不加载微LED。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，而一组这样的植入物能够以最小的侵入性和运动限制轻松访问大规模神经元电路。所提出的设备还为光遗传学转化为行为动物研究和临床应用提供了更安全、更实用的解决方案。去除拴系的慢性物理创伤可以有效地最小化组织损伤，并实现高效且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期望区域。这一新的范例将为神经科学界提供前所未有的灵活性，在一个丰富的、不受束缚的环境中进行无限的实验，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，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

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.