A multi-chamber microfluidic device utilizing 3-D constructs of cell-embedded hydrogel was developed and used to test the effect of anti-cancer drugs and their metabolites. A microscale cell culture analog (CCA) device is a physical realization of a physiologically-based pharmacokinetic (PBPK) model, where chambers representing key organs are fabricated on a silicon chip and interconnected by microchannels for medium recirculation which emulates blood flow. We tested Tegafur, an oral prodrug of 5-FU which is a chemotherapeutic agent for colon cancer, using the CCA device with the HepG2/C3A cells and HCT-116 cells embedded in Matrigel constructs cultured in the liver and the tumor compartment, respectively. Tegafur is non-toxic to cells and is converted to 5-FU in the liver by cytochrome P450 enzyme system, which then exerts a toxic effect on cells. The results show that the CCA device was able to capture the metabolism in the liver compartment and consequent damages to the tumor cells, which was not observed in a traditional, static 96-well plate assay. This CCA device mimics dynamic multiple organ interactions and enables the study of pharmacokinetic/pharmacodynamic properties of a drug or a toxin in vitro in a more physiologically realistic microenvironment.

Jong Hwan Sung received his Bachelor’s degree in 2000 and Master’s degree in 2003 from department of chemical engineering, Seoul National University in Seoul , Korea . He is currently a fifth year graduate student in Chemical and Biomolecular Engineering working with Professor Michael Shuler. His research focuses on developing a microfluidic device for probing the pharmacokinetic and pharmacodynamic effect of chemotherapeutic agent.