Life-threatening cardiovascular diseases including heart failure and heart rhythm disorders (arrhythmias) have significant impact on the quality of life, morbidity, and mortality. Ventricular arrhythmias alone are responsible for 300,000 sudden cardiac deaths in the United States per year. The development of effective therapeutic and diagnostic approaches requires detailed understanding of the complex underlying pathophysiology of heart failure and arrhythmias. However, this is limited by available experimental cardiovascular electrophysiology technologies. This multidisciplinary project will develop the next generation of wireless multifunctional optoelectronic array tools for cardiac monitoring and modulation. Such a technology is critical for developmental, structural, and functional cardiac studies. It will lead to new insights in cardiovascular disease pathogenesis and facilitate the development of therapeutic/diagnostic options for various types of arrhythmias and heart failure. This multidisciplinary project will be integrated with educational/outreach activities, including adopting the results of this project into various courses being taught at the George Washington University, hands-on research training for undergraduate students from different disciplinary programs, and directly engaging underrepresented K-12 students. Results from this project will also be used in The George Washington University Pre-College Summer Immersion Program to boost underrepresented high school students' interests in biomedical engineering.
Current cardiac electrophysiology research is often based on acute in vitro and ex vivo experiments using cardiomyocytes or explanted hearts. Chronic in vivo cardiovascular studies on awake, freely behaving animals will offer some of the greatest areas of opportunity for understanding the complex pathogenesis of cardiovascular diseases. The goal of the project is to develop wireless, implantable optogenetic modulation and electrical sensing arrays to enable significant new opportunities for basic and translational cardiovascular studies with freely behaving animal subjects. This project includes three research objectives: (1) Develop cellular scale flexible transparent microelectrode arrays with superior electrochemical, optical, and mechanical properties for high-resolution electrophysiology. Efficient biocompatible encapsulation strategies will be explored for studying chronic disease models using the microelectrode arrays. (2) Design wireless, subdermally implantable, multifunctional, multisite microsystems consisting of transparent microelectrode arrays and microscale inorganic light-emitting diodes for simultaneous crosstalk-free electrophysiological recording and optogenetic modulation. (3) Validate the microsystems by studying the roles of specific cardiomyocytes and multisite pacing strategies in ventricular arrhythmias termination and in heart failure in freely moving mouse models. The wireless features of the devices will minimize adverse effects (e.g. motion artifacts, severe tissue damages, etc.) of conventional tethered, wired techniques associated with fiber optic cables and electrical wires. The proposed work will build upon the principal investigators' expertise in innovative materials, bioelectronic device fabrications, circuit designs, and cardiovascular physiology. The multifunctional implantable array tools will offer cardiovascular research community currently unavailable technological platforms for chronic research into the basic operating principles of cardiovascular physiology on freely moving animals and allow future development of therapeutic/diagnostic approaches in clinical medicine. The project will reveal the key parameters in designing high performance cellular scale transparent microelectrode arrays, provide versatile approaches for constructing minimally invasive wireless multifunctional bioelectronic interfaces, and demonstrate important new insights in cardiovascular physiology research.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.