Use of on-line gas analysis to monitor recombinant mammalian cell cultures.

The development of a system capable of accurately measuring the oxygen uptake and carbon dioxide production rates during mammalian cell cultures is described. A detailed study of the specifications of the various components used in the system for the measurement of gas flow rates and composition, coupled with the validation of the system independent of the bioreactor was carried out. The aim of this study was to identify and eliminate where possible the errors controlling the accuracy of determination of gaseous metabolic rates. This study showed the importance of controlling the temperature of gaseous oxygen entering the system. With such temperature control, it was possible to obtain data with an accuracy of +/- 5% at the 95% confidence level. Another source of error, the use of bi-carbonate buffer, was studied. A mathematical model was used to compensate for the affect of such buffers on the determination of carbon dioxide production rates. The use of the system for the continuous determination of gaseous metabolism during the growth and production phase for recombinant CHO cell cultures is described.