SEARCH FOR CELL-PROLIFERATION MARKERS SUITABLE FOR CELL COUNT IN CONTINUOUS IMMOBILIZED CELL BIOREACTORS

The control of hybridoma cell cultures in bioreactors requires the use of convenient indicators to monitor the proliferation of the biomass. In order to select appropriate indications, we followed the variation s of several compounds including tumoral markers, polyamines, sialic a cids, purine and pyrimidine bases, enzymes and metabolites such as glu cose, lactate and amino acids, and the variations of cell density duri ng batch culture. Significant correlations were found between the numb er of viable cells and alkaline phosphatase, beta-glucuronidase, gluco se and lactate measured in the culture medium of hybridoma strains. Th e correlation calculated from alkaline phosphatase and beta-glucuronid ase concentrations in culture medium underestimated cell number. The c orrelation established with glucose and lactate gave the best indicati on of cell proliferation in continuous culture with an immobilized cel l bioreactor. Finally, the exact quantification of the biomass in thes e culture conditions, can be obtained using the mean of glucose and la ctate correlations.