Monolithic Silicon Devices for Multisite, Multiscale and Translational Photostimulation

Electrode-based electrical stimulation is foundational for numerous clinical bioelectronic devices, including deep brain stimulators and cardiac pacemakers. However, achieving multisite or random access stimulation, vital for high-fidelity and efficient biological regulation, remains challenging even in high-density electrode arrays due to spatial access constraints. While optogenetics offers high-spatiotemporal multisite stimulation capabilities, its clinical adoption presents hurdles. In this work, we introduce a multisite photostimulation technique for cardiac systems via a non-genetic platform utilizing semiconductor-based biomodulation interfaces. We investigate the precision, accuracy, and resolution of the photostimulation by analyzing spatiotemporal photoelectrochemical currents in four leadless silicon-based monolithic photoelectrochemical devices. Our study validates the multisite stimulation capacity of these systems through optical overdrive pacing applied to cultured cardiomyocytes targeting multiple regions and length scales, isolated rat hearts in a Langendorff setup, and in vivo rat heart ischemia models. To demonstrate cardiac control under clinical conditions, we also perform the first optical pacing of a pig heart in vivo. To further solidify the clinical potentials, we fabricated minimally invasive device delivery and fiberoptics platform and successfully performed pig heart stimulation without opening the chest. Our findings underscore the potential of this leadless, lightweight photostimulation platform, possibly revolutionizing cardiac pacemaking in treatments like cardiac resynchronization therapy where lead-placement complications often arise.