Project Summary In cardiovascular disease diagnosis, treatment, and monitoring, a plethora of deformable biointerface devices are utilized. These devices are adept at gauging physiological metrics, administering bioelectrical modulation, or dispensing therapeutics. Notwithstanding the advent of preclinical biotechnologies like optogenetics and cell-based biological pacing, non-genetic electronic pacing persists as the predominant therapeutic approach for cardiac rhythm anomalies. Recently, semiconductors have been identified as promising instruments for non-genetic cardiovascular investigations. Our team is focusing on designing minimally invasive photostimulation tools specifically tailored for cardiac pacing applications. We recently published several photoelectrochemical methods for optically modulating cardiac activity in cultured cells and adult rodent models ex vivo. Using these methods, we can achieve light-activated modulation of cardiac tissue with a light intensity comparable to that used in optogenetics. In this current work, Tian, Hibino, Jia and Aziz will work together to expand and strengthen our newest photostimulation system, porosity-based silicon heterojunctions, for multi-site, leadless, nongenetic, and optoelectronic modulation of cardiac tissues. Specifically, our team aims to design, fabricate, and evaluate a range of porosity-based heterojunctions tailored for optical modulation of cardiac tissues. We will synthesize silicon membranes with non- porous/nanoporous heterojunctions and three-dimensional surface topographies. To enhance the stability of these heterojunctions and modulate their longevity under physiological conditions, we will employ atomic layer deposition to passivate the silicon interfaces. We plan to modify the surface with metal or metal-oxide catalysts to bolster signal transduction. To support the silicon heterojunctions, we will integrate soft matrices, including polymers and hydrogels, enhancing both biocompatibility and signal transduction at biointerfaces. Concurrently, we will produce biocompatible, stretchable optical fibers tailored for in vivo photostimulation. Our team is also developing a catheter-analogous minimally invasive photostimulation tool. For multi-site optical pacing, we will engineer and assess the requisite software, mechanical, electrical, and optical subsystems. We will validate the performance metrics of our random access photostimulation tools, including accuracy, scanning velocity, and power delivery, followed by ex vivo photostimulation trials. In vivo biocompatibility assessments will be conducted in a rat model, while we will gauge heart pacing efficacy in acute and chronic scenarios using single-chamber, dual-chamber, and multi-site stimulations in a pig model. We will test our hypothesis that deformable and biocompatible heterojunction devices can be used for multi-site cardiac resynchronization therapy. The new designs for semiconductor-based biointerfaces will allow for minimally-invasive, wireless, nongenetic, multiscale, and random access photostimulation.

Project Narrative We propose a class of porosity-based silicon heterojunctions for minimally invasive, multi-site, leadless, non- genetic, and optoelectronic modulation of the heart. These studies will accelerate progress in understanding and treating abnormalities in the electrical conduction systems of the heart in vivo.