Monolithic Silicon for High Spatiotemporal In Vitro and In Vivo Optoelectronic Modulation

Leadless flexible bioelectronics that mimic the body’s natural bioelectrical signaling can offer innovative electrophysiology platforms and treatments for neurodegenerative and cardiac diseases.[1] Optically mediated genetic systems provide high spatiotemporal resolution and tunability, allowing for precise cellular and tissue stimulation. For clinical applications, recent non-genetic photodiode-based optoelectronic devices, which convert light into electrical currents, have shown efficiency in modulating cells and tissues at optical-power levels like those used in optogenetics.[2] Here, we reported nanoengineered monolithic silicon devices for high spatiotemporal and multiscale biological modulation in <i>in vitro</i> cultured rat cardiomyocytes, <i>ex vivo</i> rat heart tissues and <i>in vivo</i> ischemic rat heart models.[3] Through rational design of nanostructures, we screened various silicon-based diodes and achieved nanoporous single crystalline silicon capable of injecting highly-localized photocurrents – a property promising for random-access and multisite photostimulation, enabled by minority carrier depletion and diffusion restriction in nanopores. We demonstrate reliable multisite cardiac control using millisecond-duration light pulses in a live pig heart experiment under clinical open-thoracic conditions. Additionally, we showcase closed-thoracic pig heart stimulation with a custom endoscopic operation system, underscoring its translational potential. This procedure offers new solutions for temporary heartbeat regulation following open-heart surgeries, which are performed on over two million patients worldwide each year.<br/>Further efforts have focused on developing low-power, wearable, and long-term solutions for deep tissue modulation, which current optoelectronic devices cannot achieve.[4] Inspired by neurons, new materials and neuromorphic designs bridge the gap between optically accessible depths and deeper tissues. This approach reduces the required irradiance for optical tissue stimulation by two to three orders of magnitude and ensures stable functioning in fully implanted, long-term applications.<br/> <br/>[1] <b><u>P. J. Li</u></b>, S. Kim, B. Z. Tian, Nano-Bioelectronics: Beyond 25 years of Biomedical Innovation. <b><i>Device</i></b>, 2024, in press.<br/>[2] A. Prominski, J. Y. Shi, <b><u>P. J. Li</u></b>, J. P. Yue, Y. L. Lin, J. Park, B. Z. Tian, M. Y. Rotenberg. Porosity-based heterojunctions enable leadless optoelectronic modulation of tissues. <b><i>Nature Materials</i></b>, 2022, DOI: 10.1038/s41563-022-01249-7.<br/>[3] <b><u>P. J. Li</u></b>, J. Zhang, H. Hayashi, J. P. Yue, W. Li, C. W. Yang, C. X. Sun, J. Y. Shi, J. Huberman-Shlaes, N. Hibino, B. Z. Tian, Monolithic silicon for high-spatiotemporal translational photostimulation. <b><i>Nature</i></b>, 2024, DOI: 10.1038/s41586-024-07016-9.<br/>[4] C. W. Yang, Z. Cheng, <b><u>P. J. Li</u></b>*, B. Z. Tian*, Exploring present and future directions in nano-enhanced optoelectronic neuromodulation. Accounts of Chemical Research, 2024, DOI: 10.1021/acs.accounts.4c00086.