The application of heat flux measurements to improve the growth of mammalian cells in culture

There is a paucity of on-line biosensors to monitor the changes in the proc esses that occur in cultures of animal cells growing in a bioreactor. It wo uld be preferable for such a probe to measure a metabolic variable. Since t here is a sound theoretical basis for supposing that hear flux is a reflect ion of the overall metabolic flux, it was decided to explore the possibilit ies of marrying heat conduction calorimetry that measures heat flow rate wi th a dielectric spectrometer that estimates the viable biomass. The ratio o f the two signals gives scalar heat flux. Previous work had shown that this variable could be used to validate the growth reaction of the cells in ter ms of the Mayer enthalpy balance method. It was revealed by the description of this reaction that the ratio of glucose to glutamine in the culture med ium was incorrect. The finding stimulated the formulation of a revised medi um that improved the specific growth rate of CHO320 cells producing recombi nant interferon-gamma (IFN-gamma), as well as allowed a considerably greate r yield of the target protein. In addition, the glucose and lactate fluxes decreased, indicating that there was less demand for biosynthetic precursor s from glucose. (C) 2000 Elsevier Science B.V. All rights reserved.