Abstract

Making Microphysiological Systems (MPS) Useful

Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University; President Hesperos, Inc.

We will discuss briefly some of the origins and history of multiorgan  MPS development as well as current applications of the technology. The differences between multiorgan (e.g., "body-on-a chip") and single organ models will be discussed. Examples of current uses will be described including the use of MPS data to gain FDA approval for clinical trials.  Current "Body-on-a-Chip" systems combine organized tissue/organ mimics with the techniques of microfabrication based on PBPK (Physiologically Based?Pharmacokinetic) models. These systems are "self-contained" and do not require external pumps, leading to "pumpless systems" which reduce system cost and improve?operational reliability. While the fluid (or blood?surrogate) in these systems can be sampled directly to allow measurement of?concentrations of drug,?metabolites or biomarkers, they can also be interrogated in situ to determine functional responses such as electrical response, force generation, or barrier?integrity . The blood?surrogate can be made to be as a serum-free, chemically defined medium facilitating interpretations of responses that are more mechanistic than with serum?containing media. We have constructed models of barrier tissues and have integrated them into a multiorgan system.  A key advantage of this "Body-on-a-Chip" approach is that we can predict both human efficacy and toxicity of a drug or drug combination in preclinical trails, A Hesperos system has been used as the sole source of efficacy data for an IND application by Sanofi for a drug currently in a Phase 2 clinical?trial?demonstrating that these systems are beginning to have direct commercial impact as well as helping companies evaluate drug leads.