Application of on-line OUR measurements to detect actions points to improve baculovirus-insect cell cultures in bioreactors.

The continuous monitoring of a process based on the culture of Sf9 insect cells and infection by a baculovirus as a vector to obtain recombinant VP2 protein is studied. On-line OUR determination is based on the direct oxygen measurement in the cell culture vessel and the application of the dynamic method. This approximation allows a proper description of cell growth, with precise identification of the balanced cell growth end and the most important action times in the process, as virus infection time and final cell harvesting. A detailed study of the OUR profiles allows on-line monitoring of the effects of infection and expression protein process, a tool enabling the automatisation of the protein production process in a baculovirus-insect cell system. These parameters have been defined as time of action (TOAs), and include the most relevant actions to take in these type of processes: time of infection (TOI), time of feeding (TOF) and time of harvesting (TOH).