Analysis of oxygen transport in microfluidic bioreactors for cell culture and organ-on-chip applications

Abstract

In the recent decade, development of microfluidic bioreactors and organ-on-chip platforms for drug screening and disease modeling has been rising significantly. Prediction of oxygen level within the microfluidic bioreactors to create physiologically relevant oxygen tension for realistic cellular behavior is of critical importance. This article presented an analytical method to calculate oxygen tension in microchannel parallel plate bioreactors. Two-dimensional convection-diffusion equation was solved analytically with considering diffusion in two directions. Cellular oxygen consumption was assumed to follow Michaelis-Menten kinetics. Effects of oxygenator design, gas permeability of the microfluidic channels, as well as flow rate and cell density on the oxygen distribution within the bioreactor were examined. In addition, a mathematical model was developed to predict oxygen tension in a fluidic circuit containing two interconnected bioreactors with and without recirculation of the media for the culture of hepatocytes and cardiomyocytes. The oxygenators were used to maintain normoxia in the bioreactors independently. The model allowed for the prediction and independent modulation of oxygen tension in the two bioreactors through changing the length of the oxygenators. In overall, the obtained results provide critical insights required for the design and operation of microfluidic bioreactors with desired levels of oxygen tension.