Abstract

Circulatory System on a Chip -- From in vitro to in vivo, From Single Cell to Microphysiological Systems

Abraham Lee, William J. Link Professor and Chair, University of California-Irvine

The circulatory system is a critical physiological process of the human body that maintains homeostasis by balancing biological parameters by the delivery and removal of nutrients/waste and fighting off invading pathogens.  Through the advancement of microfluidics technologies, we have enabled the automation of biological fluids delivery through physiological vasculature networks that mimic the physiological circulation of the human body.  The critical bottleneck is to engineer the microenvironment for the formation of 3D tissues and organs and to also pump and perfuse the tissue vascular network for on-chip microcirculation.  On the other hand, microfluidics play an important role in the recent advances in liquid biopsy, an emerging technique that analyzes biological samples such as blood for the detection of biomolecules or cells that are indicative of disease or physiological state.  Specifically, liquid biopsy has become a promising technology to isolate and target rare cells such as circulating tumor cells (CTCs) in body fluids thanks to many of these microfluidic cell sorting techniques.  This advent of microfluidic liquid biopsy provides an in vitro snap shot into the patient’s physiological status via the in vivo circulation that enables one to monitor disease state and progression for diagnosis and prognosis. A key bottleneck is to identify the critical subpopulation of cells, often at single cell resolution among billions of cells in circulation. Along with the aforementioned in vitro on-chip perfused vascularized tissue platforms, these two technologies go hand-in-hand to connect in vitro screening to in vivo screening with great potential in the development of personalized medicine.  Ultimately this is the microfluidic maintenance of physiological equilibrium, or ‘microfluidic homeostasis.'