ONLINE ESTIMATION OF THE BIOMASS ACTIVITY DURING ANIMAL-CELL CULTIVATIONS

A software sensor was developed to determine the volumetric biomass ac tivity of animal cell cultivations on-line. It was based on the on-lin e estimation of the ATP-production rate from the oxygen uptake and the lactic-acid production rate. The sensor was verified for a batch cult ure of Vero cells, and a batch and a continuous culture of hybridoma c ells. For the hybridoma cells, the sensor showed a good correlation wi th the biomass concentration. However, this was not the case for the V ero cells. As soon as glutamine was exhausted, the biomass activity st abilized, whereas the amount of biomass almost doubled. Because the se nsor developed responds to nutrient limitations much faster than becom es visible through cell density measurements, and because the volumetr ic biomass activity can be related to the volumetric consumption rates and production rates of important metabolites, it shows excellent pos sibilities for control purposes. (C) 1996 John Wiley & Sons, Inc.