A nanoscale calorimeter design based on temperature induced changes in a surface plasmon based photonics effect has the potential to decrease the mass of experimental compounds consumed and to increase the throughput of experiments investigating drug development. This calorimeter is based on a demonstrated surface plasmon biosensor in which index of refraction changes as small as 10−5 % caused by biochemical reactions on the sensor surface are detected. To achieve this sensitivity require that the device’s temperature be held constant to within ± 0.001 K. In the biosensor the temperature was held constant to measure the concentration changes. For the calorimeter the concentration is held constant and temperature changes are monitored. In the calorimeter design the nanohole array sensor will be used as a sensitive thermometer that will be used to determine the enthalpy of binding, equilibrium binding constant and entropy changes of biochemical reactions. The numerical analysis described in this work demonstrates that nanoscale calorimetry is possible. The simulations demonstrate that two designs can produce temperature rises of 5.5 and 40 C, respectively well above the (10−3) C resolution of the sensors. These results were obtained using less than three orders of magnitude less reactants than is currently being used in calorimetry studies which is a significant advance of this technology.

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