I-Corps: Translation Potential of an organ-on-chip (OoC) microfluidic platform for pharmaceutical and biotechnology preclinical testing

This I-Corps project is based on the development of a tool for drug discovery that models the function of the enteric (gut) nervous system and its connections to the brain to be used in a laboratory setting. Drug development for organs of the digestive system, involuntary systems, and neurodegenerative diseases suffer from high failure rates because current laboratory models do not adequately capture how organs function or how they respond to disease and treatment. This technology recreates the cellular environment of human organ systems on a miniaturized chip with integrated real-time optical sensing, simultaneous testing of multiple conditions, and options for mid-experiment tissue retrieval. Together, these capabilities offer pharmaceutical and biotechnology companies a human-relevant tool for preclinical drug screening that is faster, more informative, and more predictive than current alternatives. This technology has the potential to reduce drug development costs, improve success rates, and accelerate the delivery of new therapies that may improve patient outcomes. This I-Corps project utilizes experiential learning coupled with first-hand investigation of the industry ecosystem to assess the translation potential of a reconfigurable, scalable, innervated organ-on-chip microphysiological tool for drug discovery. This technology is based on the combination of three systems not available together in any existing commercial system. It includes an integrated optical fiber photometry sensing system that enables continuous, non-invasive, real-time measurement of barrier function, calcium dynamics, and metabolic state directly on-chip without destructive sampling. In addition, it includes a validated twelve-chip parallel architecture that supports pharmaceutical-scale screening throughput. Also, the tool is designed to be reconfigurable, and supports innervation of organ systems and provides a demountable assembly option enabling mid-experiment tissue retrieval for high-resolution molecular analysis when needed. The platform has been validated with human enteric neurons integrated with intestinal epithelium as well as across multiple organ systems. This technology may accelerate translation of foundational enteric neuroscience research into practical preclinical tools, improve the predictive fidelity of drug development pipelines for gastrointestinal and autonomic nervous system disorders, and may be applied to a broad range of disease modeling applications. 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.