A cellular automaton model for microcarrier cultures.

In order to achieve high cell densities anchoragedependent cells are commonly cultured on microcarriers, where spatial restrictions to cell growth complicates the determination of the growth kinetics. To design and operate large-scale bioreactors for microcarrier cultures, the effect of this spatial restriction to growth, referred to as contact inhibition, must be decoupled from the growth kinetics. In this article, a cellular automaton approach is recommended to model the growth of anchorage-dependent cells on microcarriers. The proposed model is simple to apply yet provides an accurate representation of contact-inhibited cell growth on microcarriers. The distribution of the number of neighboring cells per cell, microcarrier surface areas, and inoculation densities are taken into account with this model. When compared with experimental data for Vero and MRC-5 microcarrier cultures, the cellular automaton predictions were very good. Furthermore, the model can be used to generate contact-inhibition growth curves to decouple the effect of contact-inhibition from growth kinetics. With this information, the accurate determination of kinetic parameters, such as nutrient uptake rates, and the effects of other environmental factors, such as toxin levels, may be determined. (c) 1994 John Wiley & Sons, Inc.