The development and characterization of a high resolution bio-reaction calorimeter for weakly exothermic cultures

A unique bench-scale heat flux calorimeter is described, which is capable of detecting the low heat signal of an animal cell culture (a maximum of 200 mW/1 is produced with a batch culture of SF9 insect cells). After the technical modifications that enhanced the sensitivity of a commercial heat flux reaction calorimeter, RC1 from Mettler-Toledo AG. Switzerland, the behavior of this system is analyzed here under biological operation conditions. Not only the heat flows provoked by the bioprocess parameters largely determine the final calorimetric resolution, but they are also more important than the culture heat signal (heat of reaction). Structural modifications aiming at the limitation of the non-biological heat flows are described such as insulating and thermostatic housings, and glass reactors with a different geometry. The current resolution of the RC1 is from+/-4 to 12 mW/1 compared to the former +/-50 mW/1 [Biotechnol. Bioeng. 57 (1998) 610], under usual animal cell culture conditions. This resolution is similar to that of microcalorimeters [Biotechnol. Bioeng. 58 (1998) 464; Thermochim. Acta 309 (1998) 63; Thermochim. Acta 332 (1999) 211; J. Biochem. Biophys. Methods 32 (1996) 191] with the advantage of an in situ measurement technique and a well-controlled culture (from the biological point of view). The monitoring sensitivity and control capacity of this instrument shows a clear potentiality for metabolic studies of low heat effect cell cultures and as a metabolic probe for industrial scale bioreactors's control. (C) 2002 Elsevier Science B.V. All rights reserved.