(447g) Body-on-a-Chip Systems for Drug Development

The current drug development process is costly (> 1 billion dollars) and requires considerable effort (ca. 12 to 15 yrs). Development of a human-based in vitro system has the potential to reduce or possibly eliminate dependency on animal testing and to make improved predictions of human response to drugs. We construct human surrogates using a combination of cell cultures and microfabrication to produce "Body-On-a-Chip" systems or multiorgan microphysiological systems. These devices are designed to be physical replicas of a physiologically based pharmacokinetic (PBPK) model where cell cultures or tissue engineered constructs are used to replace the differential equations for each organ compartment in the PBPK. A microfluidic system is used where each compartment is interconnected as they might be in a PBPK model. By using cell cultures in place of equations, interactions of the drug and it metabolites with each tissue and communication between each tissue can be replicated. Our systems are designed to operate as “pumpless” and for commercial development (Hesperos, Inc.) we use a serum free medium. Functional response of the system can be measured as chemical, biological, electrical or mechanical changes in the pseudo organs. Such "chips" should be relatively low cost to construct and have the potential for broad application in drug development or potentially to evaluate the toxicity of chemicals. I will discuss some of the issues in the design, construction and use of such devices and compare predictions from these systems to animal and clinical data.