Heat flux and the calorimetric-respirometric ratio as measures of catabolic flux in mammalian cells

It is advocated that cellular heat flow rate (Phi = dQ/dt, where Q is heat) be expressed as an intensive quantity specific to cell size (X) and termed heat flux (J(Phi/X)). It has been the practice to cite such data on a 'per cell' basis, but it would be preferable to use biomass (cellular volume or mass). This quantity is shown to be a measure of metabolic activity and, more accurately, catabolic rate coupled to the demand for ATP in anabolic processes and work in the cell. Recent developments in flow microcalorimetry and dielectric spectroscopy reveal that heat flux can be measured on-line, with the potential of industrial use as a control variable in the growth of hybridoma and genetically engineered cells. This is because the enthalpy change of growth can be regarded as a unique kind of stoichiometric coefficient directly related to the mass coefficients in the growth reaction. This can be verified by an enthalpy balance comparing data for material fluxes of catabolites with the value for heat flux. Information revealed by the stoichiometric growth equation can be used to improve medium design. The ratio of heat flux to oxygen consumption (flux) is known as the calorimetric-respirometric (CR) ratio. It detects anaerobic processes when the value is more negative than -450 (+/-5%) kJ mol(-1) O-2. These processes are found in cells growing under fully aerobic conditions, because glycolysis provides biosynthetic precursors with lactate as the by-product. It is suggested that the CR ratio would be a powerful on-line control variable for the growth of animal cells in bioreactors. (C) 1997 Elsevier Science B.V.