BME PhD Prospectus Presentation: Xinrui Gong

Title: "Non-genetic neuromodulation through photoacoustic and microwave energy transduction"

Advisory Committee: Ji-Xin Cheng, PhD - ECE (Research Advisor) Anna Devor, PhD – BME (Chair) Jerome Mertz, PhD – BME Michael Economo, PhD – BME

Abstract: Non-genetic neuromodulation provides an opportunity to control neuronal activity without permanent genetic modification, but existing approaches often face tradeoffs among spatial precision, tissue penetration, invasiveness, and mechanistic understanding. Photoacoustic (PA) stimulation and microwave (MW) modulation are particularly attractive non-genetic neuromodulation approaches with their potential to combine relatively large penetration depth with high spatial precision. However, most existing PA neuromodulation strategies rely on engineered optical absorbers or implanted optoacoustic transducers, while localized MW neuromodulation has largely relied on rigid metallic resonators that introduce substantial mechanical mismatch with soft neural tissue. In addition, the membrane-level neuronal responses to PA and MW stimulation remain incompletely understood. In this proposal, we aim to develop more tissue-compatible strategies for PA and MW neuromodulation and to directly characterize their effects on neuronal electrical activity. In Aim 1, we will establish the endogenous water as an intrinsic PA absorber using water-induced photoacoustic stimulation. Nanosecond infrared excitation near the water absorption band generates PA pressure without an exogenous absorber, and spatial separation between the dominant photothermal field and neuronal responses supports an acoustic contribution to stimulation. In Aim 2 we will develop a flexible microwave-powered injectable neuromodulation implant (flexMINI) based on conductive PEDOT:PSS to provide localized MW coupling with substantially improved mechanical compliance compared with rigid metallic resonators. Aim 3 will define the membrane-level neuronal responses to PA and MW stimulation using complementary voltage and calcium imaging. High-speed voltage imaging will determine whether these physical stimuli produce depolarization, hyperpolarization, altered action-potential firing, or subthreshold membrane responses that are not fully resolved by calcium measurements.