On-line estimation of the biomass activity during animal-cell cultivations

A software sensor was developed to determine the volumetric biomass activity of animal cell cultivations on-line. It was based on the on-line estimation of the ATP-production rate from the oxygen uptake and the lactic-acid production rate. The sensor was verified for a batch culture of Vero cells, and a batch and a continuous culture of hybridoma cells. For the hybridoma cells, the sensor showed a good correlation with the biomass concentration. However, this was not the case for the Vero cells. As soon as glutamine was exhausted, the biomass activity stabilized, whereas the amount of biomass almost doubled. Because the sensor developed responds to nutrient limitations much faster than becomes visible through cell density measurements, and because the volumetric biomass activity can be related to the volumetric consumption rates and production rates of important metabolites, it shows excellent possibilities for control purposes.