A microfabricated nanocalorimeter: design, characterization, and chemical calibration.

A microfabricated titration calorimeter having nanowatt sensitivity is presented. The device is achieved by modifying a commercial, suspended-membrane, thin-film thermopile infrared sensor. Chemical reactions are studied by placing a 50.0 nL droplet of one reagent directly on the sensor and injecting nanoliter droplets of a second reagent through a micropipette by means of a pressure-driven droplet injector with 1% reliability in volume delivery. External thermal noise is minimized by a two-layer thermal shielding system. Evaporation is prevented by positioning the micropipette through a tiny hole in a cover glass, sealed by a drop of oil. The device is calibrated using two acid-base reactions: H2SO4 + HEPES buffer, and NaOH + HCl. The measured power sensitivity is 2.90(4) V/W, giving a detection limit of 22 nW. The 1/e time constant for a single injection is 1.1 s. The day-to-day power sensitivity is reproducible to approximately 2%. A computational model of the sensor reproduces the power sensitivity within 10% and the time constant within 20%. For a 50 nL sample and 0.8-1.5 nL titrant injection volumes, the heat uncertainty of 44 nJ corresponds to a 3sigma detection limit of 132 nJ, or the binding energy associated with 2.9 pM of IgG-protein A complex.