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A nanocalorimetric suspended membrane sensor for pL volumes of aqueous media was fabricated by bulk silicon micromachining using anisotropic wet etching and photo and electron beam lithographic techniques. A high-temperature sensitivity of 125 μK and a rapid unfiltered time constant of 12 ms have been achieved by integrating a miniaturized reaction vessel of 0.7-nL volume on a 800-nm-thick and 300×300- μm2-large silicon nitride membrane, thermally insulated from the surrounding bulk silicon. The combination of a ten-junction gold and nickel thermoelectric sensor with an integrated ultralow noise preamplifier has enabled the resolution of 15-nW power in a single measurement, a result confirmed by electrical calibration. The combination of a high sensitivity and rapid response time is a consequence of miniaturization. The choice of gold and nickel as sensor material provided the maximum thermal sensitivity in the context of ease of fabrication and cost. The nanocalorimetric sensor has the potential for integration in an ultralow-volume high-density array format for the characterization of processes in which there is an exchange of heat.