High-Throughput Organoid Screening Platform for Military Exposures

Military exposures to toxic agents, blast waves, chemical burns, impact, and penetrating injuries can have devastating consequences to overall human health. Neurological deficits in response to these exposures have contributed to a large population of affected service members. Efforts to identify sensitive biomarkers as brain health diagnostics are ongoing and current treatments for neurotoxins and TBI are insufficient for preventing long-term consequences for the warfighter. Improved, versatile, and translational platforms are needed to replicate extreme conditions, define cellular mechanisms contributing to poor brain health, and screen for adverse reactions during therapeutic development. The proposed work aims to advance critical research investigating neurodiagnostic and neurotherapeutic strategies through the development and characterization of a high-throughput brain organoid platform capable of replicating neurophysiological responses to military exposures. We propose to leverage our experience integrating organoids into automated microphysiological system to create a modular system that is organoid agnostic and can accommodate organoids representing different organs. Automated input and mixing in the system will permit introduction of agents (insults such as viruses, or therapeutic compounds of interest) to the organoids. Combined with automated control of environmental parameters (e.g. temperature and oxygen) the cross section between exposures and environment can be interrogated within the system in an automated manner. The proposed automated platform with its ability to culture organoids for months to years, will provide the ability to screen for both acute and chronic combinatorial effects. Phase I will establish proof-of-concept for the proposed system and Phase II will result in a prototype multiplexed organoid platform and demonstration of the platform against selected military relevant exposures.