Microfabricated Models of the Human Body: Devices to Test New Drug Treatments

The current drug development process is inefficient, costly, and in preclinical studies dependent on animal models. Animal models predict human response accurately less than 10% of the time. Microfabicated systems (also known as "Body-on-a-Chip" or “microphysiological systems”) using human cells to make a preclinical HUMAN model to replace animals offers an alternative to increase success in determining which drugs will succeed in human clinical trials. Such increases would greatly decrease the cost of drug development and lead to more useful drugs. These human models are constructed using a combination of cell cultures and microfabrication and are based on a mathematical models known as physiologically based pharmacokinetic (PBPK) models. Here we replace the differential equations with living tissue or cell constructs. Since the constructs are connected in a physiologically relevant manner, they can emulate the exchange of metabolites and signal compounds between organs in response to exposure to drugs or environmental chemicals. By using a “pumpless” system, integrated measurements of functional responses (electrical and mechanical), and a microscale, self-contained system we can achieve a relatively low cost device. Devices with as many as 13 organ compartments have been demonstrated to be functional. I will discuss the microfabrication strategy for making such systems and provide examples of their use in drug testing.

Biography Dr. Michael L. Shuler is the Eckert Professor of Engineering in the Meing Department of Biomedical Engineering and in the School of Chemical and Biomolecular Engineering at Cornell University. Shuler has degrees in chemical engineering (BS, Notre Dame, 1969 and Ph.D., Minnesota, 1973) and has been at Cornell University since 1974. Shuler’s research includes development of “Body-on-a-Chip” for testing pharmaceuticals for toxicity and efficacy, creation of production systems for useful compounds, such as paclitaxel from plant cell cultures, and construction of whole cell models relating genome to physiology. Shuler is CEO and President of Hesperos, a company founded to implement the “Body-on-a-Chip” system. Shuler has been elected to the National Academy of Engineering and the American Academy of Arts and Science and is a fellow of numerous professional societies.