Rules for the design of silicon chip based devices for liquid phase calorimetry are discussed. In contrast to the study of fast reactions the investigation of slow processes like the metabolic heat production requires sample volumes of at least a few micro-liters if a signal resolution in the mW l(-1) range is necessary. On the other hand, increasing sensitivity gradients inside the reaction chamber and external temperature perturbations restrict its enlargement. Therefore, a careful optimization of the device with respect to the sample volume is necessary if one likes to use the advantages of chip calorimeters. The presented study was performed by use of a new designed flow-through chip calorimeter. (c) 2006 Elsevier B.V. All rights reserved.