Over the last decades, biologists and bioengineers have attempted to engineer "living" cell masses that exhibit tissues and organ structure and function outside of the body. These "living" cell masses, named organoids, can serve as a low-cost, rapid, but precise drug-screening platform and, ultimately, replace animal models. Despite the promise, there remains a lack of tools to enable real-time, non-invasive monitoring of the organoids' biological activities. This project supports an integrated research and educational program with goals to (1) develop a three-dimensional flexible sensor deciphering electrophysiological actions of human heart-like organoids and use it to predict the effect of potential anti-viral drugs for COVID-19 on the human heart, and (2) develop a multidisciplinary educational framework associated with the biosensor for multiple levels of students, especially from traditionally underrepresented groups in science and engineering. The proposed research will make a positive and immediate impact on U.S. health and economy by providing a novel organoid-sensor platform useful to determine powerful therapeutics to the on-going COVID-19 and future, unforeseeable outbreak.
For the last decades, extensive efforts have been made to recapitulate the multicellular, anatomical, and functional hallmarks of organs, thereby offering comprehensive frameworks to model organ development, homeostasis, regeneration, and disease. These movements have quickly engineered a variety of organ-like multicellular clusters named organoids. However, there remains a lack of tools enabling label-free, real-time, and non-invasive monitoring of intra-organoid functions. This project aims to establish a set of materials, design layouts, and assembly methods to develop a three-dimensional flexible intra-organoid sensor instrumented with vertically ordered silicon nanoneedles. As a model system, this sensor will be tailored for label-free spatial mapping of electrocardiogram signals from the inside of cardiovascular organoids that are engineered by orchestrating spatially-organized co-differentiation of pluripotent stem cells to cardiac muscle cells and endothelial cells. The quantitative readout of the intra-organoid activities will facilitate improved understanding of the underlying anatomical-electrophysiological-mechanical relationships of cardiac function. Furthermore, this intra-organoid sensor platform will become a transformative organ-on-a-chip tool that will greatly assist efforts to determine the efficacy of newly developed drugs as well as the impact of unidentified toxins. Complementary experimental and computational methods will be established for analyzing time-series data associated with vascularized cardiac muscle functions. This collaborative research has been built upon a strong research tie of the Multiple-PIs in joint efforts over the past 2 years based on a long-standing relationship between Purdue University and the University of Illinois at Urbana-Champaign. Because the universities are within close geographic proximity in the Midwest, the investigators at Purdue University will be able to spend significant amounts of time in the clinical setting at the University of Illinois at Urbana-Champaign in order to not only obtain timely feedback from the clinical perspectives but also ensure the progress of the proposed tasks.
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.
