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

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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.