The goal of this proposal is to complete development of a Microfluidic Liver Array (MLA) platform for improved and lower cost in vitro toxicity screening targeting the human liver. This funding will directly lead to the commercialization of a product with widespread application in the biopharmaceutical and chemical safety industry as an in vitro alternative to animal testing. The MLA uses state-of-the-art microfabrication technology to create high density arrays of "micro- liver" tissue populated with primary human hepatocytes. Our unique microfluidic design mimics the liver micro-vasculature, providing a continuous perfusion environment and 3D cellular architecture proven to enhance liver specific functions. The MLA is designed to conform to standard SBS (Society for Biomolecular Sciences) standards, allowing operation by existing screening instrumentation and assays. Moreover, our proprietary manufacturing process and reduction in cell/reagent usage will significantly reduce the overall cost of in vitro hepatocyte toxicity screening. In order to commercialize this technology, it is necessary to more fully validate the long term biologic functions of human hepatocytes cultured in the MLA, and compare with the best current in vitro and in vivo data. To facilitate this task, CellASIC has partnered with CellzDirect/Invitrogen Corporation, the global leader in hepatocyte related screening and research. This partnership will ensure that the MLA is rigorously tested against industry relevant benchmarks to maximize the commercial utility of the novel technology. The objective of this 2.5-year SBIR Fast Track grant proposal are: 1. Evaluate the long-term maintenance of human liver-specific xenobiotic metabolizing functions and pathways in the MLA compared with existing methods 2. Improve the MLA platform to suit commercial screening applications PUBLIC HEALTH RELEVANCE: There is a high demand both from regulatory agencies and pharmaceutical/chemical development companies for improved in vitro toxicity screening technologies that are predictive of human exposure risks while reducing the reliance on animal testing. CellASIC's Microfluidic Liver Array platform uses state-of-the-art microfluidics technology to recreate the liver tissue microenvironment in a high throughput array, resulting in more accurate chemical toxicity assessment at significantly reduced cost.