Calorimetric bioprocess monitoring by small modifications to a standard bench-scale bioreactor

Heat released during whole cell bioconversions provides information about the stoichiometry and kinetics of growth and product formation. It is considered as a potent control variable because it reflects immediately changes in metabolism. Furthermore, the sensitivity of calorimetric measurements is improving with increasing ratios of heat producing volume to heat exchanging surface and therefore with any scaling-up. However, the development and testing of calorimetry-based control strategies at the bench scale is difficult. Common microcalorimeters are unsuited due to their high price, the reactor volume (1-100mL) and the reactor design. Reaction calorimeters are even more expensive, less sensitive than microcalorimeters and often not adapted to bioprocesses. This paper describes a way-out by integrating calorimetric measurement principles into bench-scale standard bioreactors. The proposed solution benefits from all the measurement and control features of bench-scale bioreactors for, e.g. aeration, stirring, pH-control and substrate dosage. The additional calorimetric option can be easily constructed and integrated into an existing bioreactor at relatively low cost. The achieved sensitivity of 50 mW L(-1), stability of 0.2 mW L(-1)h(-1) and response time of a 1-2 min is in the same magnitude or even better than those of established reaction calorimeters. The calorimetrically monitored growth of the halophilic strain Halomonas elongata DMSZ 2581(T) demonstrates the applicability of the proposed solution for bioprocess analysis and control.