Glucose uptake rate as a tool to estimate hybridoma growth in a packed bed bioreactor

Abstract

The immobilisation of cells in a perfusion cul- ture allows to obtain a high cell concentration and an ef- ficient removal of the catabolites without cell loss. A disadvantage of this system is that the cell density cannot be directly monitored. The cellular metabolism is just followed by online measurements of pH and dissolved oxygen (DO) and off-line determinations of residual me- tabolites. In this article, we report a high cell density achieved by the cultivation of a hybridoma in a bubble- column bioreactor filled with hollow glass cylinders. The parameters monitored during the cultivation were pH, temperature, DO, glucose, lactate and monoclonal anti- body. The glucose uptake rate was used to estimate the cell concentration along the time. The maximum cell concen- tration calculated for the considered cultivation time was 2.7 · 10 7 cell AE ml )1 . The glucose concentration in the media decreased stepwise twice, causing a decrease on the specific growth rate, while maintaining high antibody productivity levels. Maximum monoclonal antibody pro- ductivity was 503 lg AE l )1 AE day )1 and specific productivi- ty, considering calculated cell density, was 0.019 ng AE cell )1 AE day )1 .