GROWTH AND PRODUCTION MODELING IN HYBRIDOMA CONTINUOUS CULTURES

Several experimental data on continuous cultures of hybridoma cells sh ow that monoclonal antibody productivity is a decreasing function of d ilution rate. It has been suggested that this unusual behavior may be due to the arrest of a fraction of cycling cells at a critical point o f Phase G1. Although this hypothesis has been recently investigated by using population balance models, mathematical analysis has been perfo rmed without accounting for the dynamics of the arrested cells properl y. In this article, a more general and accurate approach is presented and new specific assumptions are introduced to characterize the arrest and the later progress through the cycle. Two different models (stoch astic and deterministic) and two different critical points for the arr est (at the beginning and at the end of G1) are considered. The cell c ycle parameters are estimated so that data predicted by the model fit those reported in the literature. In particular, the fraction of arres ted cells, the cell arrest probability, and the mean cell generation t ime are computed as functions of the dilution rate. Results so far obt ained predict that there is an optimal value of dilution rate for maxi mizing specific production rate of monoclonal antibody. (C) 1993 John Wiley & Sons, Inc.