STTR Phase I: Standardized and reproducible culture and activation of endothelial cells in microfluidic devices for drug screening applications

The broader impact/commercial potential of this Small Business Technology Transfer Program (STTR) Phase I project is to develop a microfluidic assay for applications related to drug discovery/screening, personalized medicine, drug toxicity assessment, evaluation of patient clinical status, and predicting patient-specific responses to certain therapies. The proposed platforms allow drug testing under specific physiological conditions to investigate how certain drugs or drug combinations might affect specific cells. Currently available platforms are extremely complex and rely on costly, labor-intensive, time-consuming, and low-throughput fabrication methods, hampering the translation potential of such systems into a commercial setting. Moreover, standardization and analytic validation of such platforms are needed for reproducible and reliable sample testing, facilitating the process of regulatory approval. This project will significantly help standardize and validate a high-throughput platform for deployment at scale. This project will help reduce operational costs for preclinical drug discovery/screening studies and lower the drug failure rate, as patient-specific testing will be possible. This Small Business Technology Transfer Program (STTR) Phase I project proposes to develop a standardized and validated microfluidic platform integrated with human endothelial cells for drug discovery/screening purposes. Since the traditional in vivo and in vitro techniques that are employed in the preclinical stage of drug development are extremely costly, labor intensive, time-consuming, and can still lead to high failure rates, there is an urgent need for physiologically relevant in vitro assays for preclinical assessment of new drug candidates, particularly in the cardiovascular disease and blood disorders spaces. Microfluidic platforms allow for precise control of gas and flow conditions at a size scale equivalent to that of human microvasculature and offer physiologically relevant vascularized environments for in vitro testing. To ensure accuracy, reliability, and robustness of the assay, research objectives include a comprehensive and systematic approach to standardize the culture and activation of endothelial cells under physiologic flow conditions. Furthermore, standardized both short-term and long-term activation of endothelial cells via disease specific activators (e.g., heme, TNF-α, etc.) will be established to better mimic in vivo conditions. 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.