A calorimetrically based sequential flow injection method with enzyme catalyzed reactions is proposed and demonstrated. In contrast to multi-detection devices with immobilized enzymes miniaturized flow-through reaction calorimeters are used as sensing device with independent substrate and toggled enzyme solution flows. From the sequence of the heat power signals information about composition of the substrate is obtainable. A reasonable application of the method requires miniaturized calorimeters. Different constructions of flow-through reaction calorimeters based on silicon chips with integrated thermopiles as heat power transducers have been analyzed with respect to their sensitivities and mixing behavior. As an application the analysis of saccharides containing mixtures is discussed.