MONOCLONAL-ANTIBODY PRODUCTIVITY AND THE METABOLIC PATTERN OF PERFUSION CULTURES UNDER VARYING OXYGEN-TENSIONS

The metabolic pattern and cell culture kinetics of high-cell-density p erfusion cultures were compared under two different oxygen transfer co nditions: oxygen limiting and not limiting. When oxygen was a limiting factor during perfusion culture, both specific glucose uptake and lac tate production rates increased, compared to non-oxygen-limited condit ion, by about 60% and 30%, respectively. The specific glutamine uptake rate under oxygen-limited conditions was almost 4.0 times higher than that under non-oxygen-limited conditions. The activity of lactate deh ydrogenase (LDH) released into the medium by the dead cells can be use d as an indicator for the metabolic and physiological conditions relat ed to oxygen limitation. There was a 3.2 times higher specific rate of LDH activity released by dead cells in oxygen-limited cultures than t hose in non-oxygen-limited cultures. The specific production rate of m onoclonal antibody was not significantly affected by the oxygen transf er conditions during the rapid cell growth period, but it rapidly incr eased toward the end of perfusion cultures. The higher perfusion rate may have limited further cell growth during high-cell-density perfusio n culture, because cell damage was caused by the hydrodynamic shear wi thin a hollow fiber microfiltration cartridge installed to withdraw th e spent medium and the waste metabolites. (C) 1993 John Wiley & Sons, Inc.