Biological reaction calorimetry: Development of high sensitivity bio-calorimeters

A review of different types of biological reaction calorimetry systems currently used together with the operating principles is presented. The average resolution of these systems is approximately 20 to 1000 mW l(-1), sufficient for studies of a wide range of cell culture processes. Poorly exothermic and endothermic processes require the development of even higher resolution systems. To this end, the Mettler-Toledo RCl calorimeter has been extensively studied to determine the factors which limit the resolution. By changing both the hardware and software, the resolution has been increased to 2-5 mW l(-1) for non-aerated processes and to 10-15 mW l(-1) for aerated systems. The changes include a switchable electrical heater for the oil circulation thermostat, a new higher resolution AID board, PI controller and a thermostat reactor housing. The on-line measurement of the power input through agitation is proposed to be essential for low heat output biological processes, even under conditions where the rheological properties of the culture are not believed to be changing. The results show that it is possible to develop high-resolution systems capable of operating under standard laboratory bioreactor conditions; however, it is felt that the limits to the instrument resolution have been attained and that the calorimetric signal resolution is limited by the requirement of high agitation, nutrient feeds, gassing, pH control and other external effects which can only be overcome by heat-balancing methods. (C) 1998 Elsevier Science B.V.