Modeling carbon dioxide transport in PDMS-based microfluidic cell culture devices

Abstract

Maintaining a proper pH level is crucial for successful cell culturing. Mammalian cells are commonly cultured in incubators, where the cell culture medium is saturated with a mixture of air and 5% carbon dioxide (CO2). Therefore, to keep cell culture medium pH in an acceptable level outside these incubators, a suitable CO2 concentration must be dissolved in the medium. However, it can be very difficult to control and measure precisely local concentration levels. Furthermore, possible undesired concentration gradients generated during long-term cell culturing are almost impossible to detect. Therefore, we have developed a computational model to estimate CO2 transport in silicone-based microfluidic devices. An extensive set of experiments was used to validate the finite element model. The model parameters were obtained using suitable measurement set-ups and the model was validated using a fully functional cell cultivation device. The predictions obtained by the simulations show very good responses to experiments. It is shown in this paper how the model helps to understand the dynamics of CO2 transport in silicone-based cell culturing devices possessing different geometries, thus providing cost-effective means for studying different device designs under a variety of experimental conditions without the need of actual testing. Finally, based on the results from the computational model, an alternative strategy for feeding CO2 is proposed to accelerate the system performance such that a faster and more uniform CO2 concentration response is achieved in the area of interest.