This research focuses on the development of a non-invasive/minimally invasive optogenetic technique. The study delves into how visible (VIS) and near-infrared (NIR) light interacts with ex vivo mouse head tissues, highlighting the advantages of the NIR-II biological window for deeper tissue penetration and reduced light absorption and scattering. Our computer simulations and experimental results demonstrated that over 12% of initial light irradiation passes through 1 mm tissue (skin and skull), reaching the brain cortex, potentially enabling minimally invasive neural activation. Moreover, this work reveals the nonlinear optical properties of genetically engineered truncated monomeric and dimeric bacterial phytochromes, demonstrating their photoconversion efficiency of up to 73% in the NIR-II range and potential for optogenetics. This discovery opens new avenues in advanced neurostimulation and biomedical research by enhancing tissue penetration and minimizing invasiveness.
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