Segregated Model of Adherent Cell Culture in a Fixed-Bed Bioreactor

Abstract

In this work, a mathematical model of a fixed-bed bioreactor for the animal cell culture is developed to study the optimization and the scale-up of this bioreactor. Several cell populations are considered: the cells in suspension in the medium at the beginning of the process and the adhering cells to the fixed-bed. The model includes a capture rate kinetic of the cells in suspension by the fixed-bed and a spatial distribution of the nutrient and by-product concentrations in the fixed-bed. Therefore, the model reports the potential gradients of the cell concentrations in the fixed-bed. Some model parameters are experimentally identified and the model is validated using experimental data obtained with two pilot bioreactors. The model is used as a simulation tool to study the influence of the bioreactor design or the velocity field of the culture medium on the cell concentration gradients in the fixed-bed bioreactor and to optimize the operating conditions, the design, and the scale-up of this bioreactor.