An integrated silicon thermophile as biosensor for the thermal monitoring of glucose, urea and penicillin.

A new kind of calorimetric biosensor for the measurement of the heat (molar enthalpy change) of enzymatic reactions is presented. The device operates according to the Seebeck effect, the same principle on which thermocouples are based. The thermopile used in this work consists of an array of p-type silicon/aluminium strips integrated on a thin silicon membrane (5 microns). Its sensitivity is about 1 V output voltage per watt of heating power, corresponding to a temperature resolution in the order of 10(-5) K and a heating power resolution of some tenths of a mu W in the flow system used. Furthermore, this performance is obtained without any control of external temperature because of the high common-mode thermal noise rejection ratio of the thermopile. The universal technique of calorimetry combined with the specificity of biochemical reactions makes this biosensor very versatile, with a broad range of possible applications. Glucose oxidase together with catalase for the determination of glucose, urease and penicillinase for the monitoring of urea and penicillin G, respectively, were immobilized directly onto the back side of the thermopile. The sensor was operated in conjunction with flow injection analysis which, in addition to its traditional advantages, allows preconditioning of the samples. Thus, artefacts due to mixing effects were suppressed and interference caused by differences in ionic strength between sample and carrier was strongly decreased. Detection limits between 1 and 2 mM were reported in the flow injection conditions described.