Label-free in solution analysis techniques are used in the direct study of native molecules. They generate biologically relevant data that enable understanding of molecular interactions without using artificial probes or labels. This is a key advantage since labels can disturb the higher order structure that is crucial for binding, introduce artifacts into the data, and even inactivate or destabilize the molecule of interest.

Microcalorimetry is a powerful, well-established label-free, in-solution analysis technique. Microcalorimeters are used to detect the association and dissociation of molecular complexes by measuring changes in the heat released or absorbed. The resulting information-rich data provides insight into the biological processes and the mechanisms driving molecular interactions. Label-free technologies are attractive to researchers across a diverse range of applications, such as; biological research, biotherapeutic and small molecule drug discovery and development, immunogenicity studies, vaccine development and QC.

These biological processes are often studied using two calorimetric techniques: Isothermal Titration Calorimetry (ITC) and Differential Scanning Calorimetry (DSC).

Microcalorimetry requires no labeling and minimal assay development, is convenient, quick and suitable for turbid and colored solutions.

  • Isothermal Titration Calorimetry (ITC) can quantify binding affinity (KD), binding stoichiometry (n), enthalpy (ΔH), and entropy (ΔS) in a single experiment and enables the elucidation of binding mechanism and determination of enzyme kinetics. The data can be used to assess target activity, hit validation and lead optimization.
  • Differential Scanning Calorimetry (DSC) assesses thermal stability (Tm) and addresses issues such as whether the protein is properly folded, homogeneous and thermally stable. This vital information can be used to assess, for example, manufacturability and optimal formulation.