On-line determination of animal cell concentration

A new approach for the indirect determination of cell concentration in the case of nonconstant metabolic rates has been developed. The specific glucos e-uptake rate was shown to be nonconstant in batch cultures of free suspend ed and immobilized CHO SSF3 cells. Time-independent models correlating the specific rate to the limiting substrate concentration were established, thu s providing a continuous determination of the specific rate through on-line measurement of the limiting substrate. The method could be applied to dete rmine online cell concentration in both free suspended and immobilized cell cultures. Results were verified off-line by crystal violet nuclei counting . The predicted cell concentration was in very good agreement with the off- line reference during the whole exponential-growth phase, until the specifi c glucose-uptake rate tended to zero. (C) 2001 John Wiley & Sons, Inc.