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-onchip 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.

The Long and Winding Road to Cardiac Regeneration

“…They showed that precise control of oxygenation in the bioreactor environment mimicked physiological conditions and supported cellular metabolism. This study emphasized the significance of maintaining sufficient oxygen levels for promoting proper cellular function and tissue development [279].…”

Advancing Intelligent Organ‐on‐a‐Chip Systems with Comprehensive In Situ Bioanalysis

“…[ 102 ] A typical workflow of numerical simulation involves problem definition, modeling, discretization, boundary setting, numerical solution, and post‐processing. Numerical simulation techniques help eliminate the need to repeat experimental measurements (e.g., shear stress [ 103 ] and oxygen distribution [ 104 ] ) and allow the optimization of iOOC systems at a lower cost. [ 105 ] Further, these techniques can improve the understanding of the physical phenomena and tissue behaviors in the microenvironment of iOOC systems.…”

Design considerations of benchtop fluid flow bioreactors for bio-engineered tissue equivalents in vitro

“…For applications which require lower oxygen levels a commonly used method is to reduce the partial pressure of atmospheric oxygen with technology such as hypoxic chambers. Alternatively reductions in oxygen delivery to media, either actively through the control of flow rates or passively through oxygen-permeable membranes, can be another useful tool particularly if access to a gas supply is limited [ 138 , [141] , [142] , [143] , [144] ]. This leads to wide variability in the effectiveness of oxygenation systems and characterisation of oxygenation levels is important if results can be accurately replicated [131] .…”