Structured Model of VERO Cells Metabolism in a Fixed-Bed Bioreactor

Abstract

In this work, a structured mathematical model of the VERvet Origin (VERO) cell metabolism in a fixed-bed bioreactor is developed. Mass balance equations for the extra- and intracellular species are written considering the main pathways of the animal cell metabolism. From the model equations, an undetermined set of equations relating the consumption or production velocities of the extracellular species and the velocities of the metabolic reactions can be developed. The monitoring of a reference cell culture enables to transform this undetermined set of equations in a determined one. The resolution of this determined set of equations enables to analyze and characterize the cell metabolism. From the model and the cell metabolism characterization, a monitoring tool is developed to simulate the time evolution of the species concentrations when the time evolution of the cell concentration is known. This simulation tool is used to simulate five experimental cell cultures. The comparison of the experimentally determined and computed time evolutions of the species concentrations enables to validate the developed monitoring tool. The validated monitoring tool can be used to optimize the operating conditions of the culture, as the medium feeding rate, the range of the species concentrations.