Nano-DSC: nano-Differential Scanning Calorimetry

Power compensation nano-DSC (Fig. 1A) is a high-resolution method for measuring thermal stability and/or unfolding of (bio)macromolecules in solution. The reference cell (filled with the solvent) and the measuring cell (filled with the sample solution) (Fig. 1B) are simultaneously heated/cooled in the range -10°C to 130°C with a slow heating rate (down to 0.001°C/min). The occurrence of a phase transition/unfolding/reaction in the sample determines a peak in the thermogram (Fig. 1C), allowing the direct and simultaneous measure of peak temperature, Tm, heat capacity change, ΔCp, and the enthalpy change, ΔH. Since nano-DSC works with solutions it allows to study the changes in secondary structure, the thermal stability and the enthalpy change when unfolding of (bio)macromolecules occurs. The design of the cells, the wide temperature range, a safety mechanism that stops the scanning when sample freezing is detected, the built-in pressure regulator up to 6 bars are all characteristics that make unique on the market. The nano-DSC unique capability to work under 0°C is very useful to study the cold denaturation of proteins. Regarding the cell, the combination of shape (capillary cells with spiral shape), volume (330 μL) and material (Pt, which allows cleaning with strong acid and bases) has many advantages including avoiding protein aggregation (Fig. 1D) that can overlap to the protein unfolding signal.