A polymer-based MEMS differential scanning calorimeter

We present a flexible, polymer based MEMS differential scanning calorimetric (DSC) device combining integrated microfluidic channels, highly sensitive thermoelectric sensing, and real-time temperature monitoring for thermodynamic characterization of biomolecular samples with minimized sample consumption. The device uses an inexpensive, commercially available polymer substrate and a novel fabrication approach to create a microstructure consisting of a pair of microchannels (containing the sample and reference buffer, respectively), which are integrated with resistive temperature sensors (for in-situ measurement of sample temperature) and an antimony-bismuth (Sb-Bi) thermopile (for measurement of the temperature difference between the sample and reference channels). We demonstrate the utility of this MEMS DSC device by measuring the unfolding of lysozyme in a small volume (1 μL), and at practically relevant protein concentrations (approaching 1 mg/mL). Thermodynamic properties including the total enthalpy change per mole of protein (ΔH) and melting temperature (T_m) at different protein concentrations during this conformational transition are determined and found to agree with published data.