Differential Scanning Calorimetry (μ-DSC) Services

MicroCal Differential Scanning Calorimetry (μ-DSC) is a highly sensitive technique applied to study thermally induced transitions, such as phase changes and folding/unfolding of proteins. It is considered the gold standard for thermal stability analysis of biomolecules in protein engineering and in biopharmaceutical formulation development. Various advantages of μ-DSC include a high reproducibility, few restrictions concerning formulations / solvents and no need for markers or tryptophan in the analyte. It provides a direct and label-free measurement of biomolecular stability in solution.

During the heating of a biomolecule or mixture, several thermal events may occur simultaneously or sequentially, indicating the unfolding or melting temperatures of different domains of the same molecule. The µ-DSC thermograms register the respective midpoints (Tm) by measuring the heat capacity change as a function of temperature. The enthalpies can be derived from this plot. When considering a protein’s folding/unfolding process, the higher the temperature at which this event takes place, the more thermodynamically stable the molecule.

Conformational changes are easily accessible by μ-DSC thermograms. The variation in heat capacity as a protein unfolds is primarily due to the changes in hydration of side chains – buried in the protein when in its native state – that become exposed to the solvent when unfolded. Proteins with high temperature midpoints are less likely to denaturation at lower temperatures, therefore, Tm is a good indicator of protein thermostability.

In addition to stability, binding and drug delivery systems integrate μ-DSC wide range of applications. Upon binding of ligands and drug uptake, intra and intermolecular interaction changes, as well as the dynamic of the components, and can be investigated by monitoring the phase transition temperatures and enthalpies from the thermograms.