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 processes that occur in cultures of animal cells growing in a bioreactor. It would be preferable for such a probe to measure a metabolic variable. Since there is a sound theoretical basis for supposing that heat flux is a reflection of the overall metabolic flux, it was decided to explore the possibilities of marrying heat conduction calorimetry that measures heat flow rate with a dielectric spectrometer that estimates the viable biomass. The ratio of 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 terms 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 medium was incorrect. The finding stimulated the formulation of a revised medium that improved the specific growth rate of CHO320 cells producing recombinant interferon-γ (IFN-γ), as well as allowed a considerably greater yield of the target protein. In addition, the glucose and lactate fluxes decreased, indicating that there was less demand for biosynthetic precursors from glucose.