Fluidic Programmable Gravi-maze Array (FPGA) for Multi-organs Drug Testing

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Fluidic Programmable Gravi-maze Array (FPGA) for Multi-organs Drug Testing Abstract Organ on a chip systems with the interaction of multiple organs, using cells from experimental animal models, recapitulate in-vivo tissue-like realistic cellular behavior and provide information on quantitative, time-dependent phenomena when combined with a pharmacokinetic modeling approach. Improving the accuracy of preclinical drug screening using these organotypic interacting-organs will generate dramatic cost and time savings and can provide alternatives to animal testing. These, value-added, more complex non-human animal-derived microphysiological assays can build a bridge between existing in vivo animal toxicity data and human cell-based in vitro data to set the hope to de-risk human safety. These organotypic culture models can be established for preclinical drug development that facilitates current efforts to reduce, refine, and ultimately could replace animal models. However, there are several challenges to advance these in-vitro organ systems to preclinical drug toxicity studies, in the evaluation of organ function and improved prediction upon exposure to drugs and their metabolites. Moreover, currently, there is no passive, scalable and perfusable multiplexed multi-organs organotypic culture platform available to advance toxicological profiling. Therefore, Biopico Systems Inc proposes to develop a Fluidic Programmable Gravi-maze Array (FPGA) for multiple organs based drug screening. This allows multiple organs developed on inserts to interact in a specific direction in serial or parallel with one another using gravity-driven unidirectional recirculation in an array format. Such alternate animal profiling in the FPGA system enables early identification of off-target toxicities that would help in the redesign of a drug in predictive toxicology and safety testing. In Phase I, Biopico will develop the fluidic platform in 24-well format and validate the metabolic interaction between liver and heart that mimic physiological phenomena for accurate drug safety testing. The specific aims are as follows. Aim 1: optimize the design of FPGA Chip for recirculations through series-parallel transwell-Insert organs. Aim 2: develop vascularized organs in FPGA system for drug testing and measurement. Aim 3: characterize FPGA system to study the toxicological effects of interacting liver-heart organs. This platform allows the design of self-contained integrated vasculature and other shear stress-sensitive organ systems that are easy and cost-effective to construct and maintain compared to animals. Biopico envisions that FPGA will be adapted by the pharmacological industries and researchers as an animal alternative for testing drugs with the unknown metabolic property while gaining broader use to generate safer compounds.