A CELLULAR AUTOMATON MODEL FOR THE GROWTH OF ANCHORAGE-DEPENDENT MAMMALIAN-CELLS USED IN VACCINE PRODUCTION

In the production of human vaccines, the kinetics of anchorage-dependent cell growth on microcarriers is complicated by their spatial environment. As the cells begin to cover the surface area available for growth, the growth rate gradually decreases until the entire surface is covered, and growth ceases. This contact inhibition of cell growth makes it difficult to accurately determine key kinetic parameters such as the specific growth rate of a culture. In this paper, a simple, but useful cellular automaton model is proposed which is capable of decoupling the effect of contact inhibited cell growth from the overall kinetics of the culture. The automaton model is a good qualitative representation of cellular growth on microcarrier cultures. Moreover, quantitative comparison with experimental data is very good. The model is capable of fitting growth curves initiated al different inoculation levels by taking into account the initial cell attachment distribution for microcarrier cultures. Information generated by the automaton on the dynamic nature of the specific growth rate of a culture has been coupled to a kinetic model describing the dynamics of key nutrients and metabolites in both the batch and perfusion modes of bioreactor operation, and these results are compared to experimental data.