Monitoring of mammalian cell growth and virus production process using on-line oxygen uptake rate measurement

Porcine epithelial cells were cultivated on microspheres with an average diameter of 35 μm in a stirred tank bioreactor for virus production. The oxygen uptake rate (OUR) was determined on-line by a dynamic method. This on-line measurement was used to estimate glucose consumption rate for perfusion rate adjustment. Using this on-line technique, the time points for virus infection and harvest were also determined. After virus infection, the OUR continued to increase until it reached a maximum. Subsequently, the OUR decreased rapidly as a result of a decrease of cell metabolic activities or cell lysis caused by virus production. The peak of OUR was correlated to the maximum virus titer. On-line OUR monitoring is easy to implement and is a powerful tool for monitoring the virus infection process.