QUANTITATIVE ASSESSMENT OF CELL-DENSITY EFFECT ON THE METABOLISM AND ANTIBODY-PRODUCTION RATE OF HYBRIDOMA CELLS AT HIGH CELL-DENSITY

Newly proposed kinetic models for the metabolism and antibody producti on of hybridoma cells (Zeng (1995a) Biotechnol. Bioeng. 46, 314-324; Z eng (1995b) Biotechnol. Bioeng, in press; Zeng and Deckwer (1995) Biot echnol. Bioeng. 47, 334-346) are used to examine the significance of p ossible cell density effect(s) on two hybridoma cultures grown in perf usion bioreactors. By introducing the term 'specific concentration of nutrients' the models satisfactorily describe the consumption rates of glucose and glutamine and the formation rates of lactate, ammonium an d monoclonal antibody over a viable cell density range of 10(6)-10(7) ml(-1), having about 8-15% deviations from experimental results. A den sity effect can be generally assumed for these cultures. However, the effect is only significant for the rates of glucose consumption and la ctate formation of one cell line under the experimental conditions. Th e observed variations of metabolism and antibody production rate at di fferent cell densities can be attributed to the varying availability o f nutrients. Among others, the relative concentration of glucose and g lutamine may be decisive for the uptake of glucose and glutamine and f or the production of lactate, ammonia and antibody under certain condi tions. Furthermore, the specific formation rate of antibody in these c ultures is found to be strongly affected by the perfusion rate, indica ting that antibody production is limited by component(s) of the medium not yet identified. The implication of these results for the optimiza tion of animal cell culture is discussed.