SBIR Phase I: Microfluidic Environment Control for Hepatocyte Bioreactor Optimization

This Small Business Innovation Research (SBIR) Phase I project will investigate the application of a novel microfluidic system for tissue culture control and optimization. Primary cells (those derived from living organisms) represent an exciting opportunity to replicate physiologic behaviors in vitro. However, due to the stringent microenvironment demands for maintaining these cells in bioreactors, there is no suitable method to reliably and systematically culture primary cells. The objective of this research is to determine if the advantages of the microfluidic culture platform (increased cell density, continuous nutrient flow, more physiologic mass transport, reduced cell/reagent consumption, higher throughput capability) will result in a superior platform for primary cell culture experimentation. In this research, isolated hepatocytes will be used as the primary cell source. Known biochemical activities (e.g. glucose consumption and albumin synthesis) will be measured in the microfluidic format and compared to traditional plastic dish culture. It is expected that the improved culture conditions in the microfluidic format will lead to higher cell viability, longer culture times, and improved liver-specific functions. Furthermore, due to the low cost and multiplexed nature of the platform, the response of cultured cells to various mass transport and soluble factor conditions can be readily optimized. The broader impacts of this research can be broken down into four categories: basic scientific understanding, industrial drug screening, tissue engineering, and personalized clinical usage. From an academic standpoint, the proposed primary cell culture platform may offer a unique method to study cell biology. It is becoming more and more evident that cell behavior is not determined solely by genetic factors, and that the culture environment is a dominating source of cell signaling. A low cost, high throughput experimental platform will allow researchers to systematically investigate extracellular signaling events on primary cell behavior. From an industry standpoint, current drug development is limited by the ability to rapidly and accurately predict clinical behaviors of drugs. A screening platform that provides a more physiologically relevant cell culture model will improve the effectiveness of selecting lead compounds. As tissue engineering continues to advance, it will become necessary to have a tissue bioreactor that can adequately promote desired functionalities. The initial work presented here will further the understanding of how microfluidic technology can be applied to this field. Finally, a future version of the proposed technology can be used for clinical applications that require the culture of a patient's tissue for diagnostic purposes.