Pure and Applied Chemistry

Abstract: Using an in vitro platform technology that combines microfabricated devices with cell culture, we seek to understand the response of the human body to pharmaceuticals and combinations of pharmaceuticals. Computer models of the human body guide the design of in vitro systems we call micro cell culture analogs (μCCAs) or “body-on-a-chip” devices. A μCCA device is a physical representation of a physiologically based pharmacokinetic (PBPK) model and contains mammalian cells cultured in interconnected microchambers to represent key organs linked through a circulatory system. μCCAs can provide inexpensive means for realistic, accurate, and rapid-throughput toxicological studies that do not require experimenting with animals and reveal toxic effects that can result from interactions between organs. As the natural length scale in biological systems is on the order of 10–100 μm, operating on the microscale allows us to mimic physiological relationships more accurately. We summarize proof-of-concept experiments using mixtures of drugs to treat multidrug-resistant (MDR) cancer and colon cancer. We discuss the extension of the μCCA concept to systems that connect barrier tissues with systemic circulation. Examples with models of the gastro-intestinal (GI) tract are provided.