Building an experimental model of the human body with non-physiological parameters
Abstract
New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform — commonly called a ‘human-on-a-chip (HOC)’ — requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo-like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale ([Formula: see text]) microfluidic model of the human body.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2017
- Source ID
- 10.1142/s2339547817500029
Entities
People
- Brendan M. Leung
- Christopher Moraes
- David R. Mertz
- Joseph M. Labuz
- Shuichi Takayama
Organizations
- Banting Research Foundation
- Dalhousie University
- Defense Threat Reduction Agency
- McGill University
- National Institutes of Health
- Natural Sciences and Engineering Research Council
- University of Michigan