A MEMS differential scanning calorimeter for thermodynamic characterization of biomolecules

We present a MEMS-based differential scanning calorimetric (DSC) device combining highly sensitive thermoelectric sensing, on-chip self-calibration, and microfluidic regulation for thermodynamic characterization of biomolecular samples on a minimized scale. The device integrates well-defined microfluidic reaction chambers and utilizes a three-dimensional structure in which a layer of resistive microheaters and temperature sensors are precisely aligned to these chambers to provide uniform heating, in-situ temperature sensing, and convenient self-calibration. Notably, this device exploits the novel use of an antimony-bismuth (Sb-Bi) thermopile with high thermoelectric performance to significantly enhance device sensitivity and thus allow for DSC detection with minimized sample consumption. We demonstrate the utility of this MEMS DSC device by characterizing the unfolding of proteins in a minimized volume (1 μL), and at low protein concentrations approaching practically useful levels (1 mg/mL). Quantitative thermodynamic properties including the total enthalpy change (ΔH) and melting temperature (T
_m
) during this conformational transition are determined and found to agree with published data.