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Calorimetry is the science of measuring heat changes from chemical reactions or physical events.

Calorimetry relies on the fact that all chemical reactions involve a change in energy, usually accompanied by heat release (exothermic) or absorption (endothermic). Microcalorimetry is an ultrasensitive development of the technique that measures very small heat changes in small sample volumes, making it suitable for biomaterials.

Microcalorimetry is used to study reactions involving biomolecules, including interactions between molecules and conformational changes such as protein folding. Applications range from confirming intended binding targets in small molecule drug discovery to the development of stable biotherapeutics.

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

Isothermal Titration Calorimetry (ITC)

Isothermal Titration Calorimetry (ITC) is used to study the binding behavior of biomolecules. It is an essential tool for drug design and the study and regulation of protein interactions.

ITC directly measures the heat released or absorbed during a biomolecular binding event. This allows accurate determination of binding constants (KD), reaction stoichiometry (n), enthalpy (∆H), and entropy (ΔS).

ITC is used for:

  • Quantify binding affinity.
  • Candidate selection and optimization.
  • Measurement of thermodynamics and active concentration.
  • Characterization of mechanism of action.
  • Confirmation of intended binding targets in small molecule drug discovery.
  • Determination of binding specificity and stoichiometry.
  • Validation of IC50 and EC50 values during hit-to-lead.
  • Measurement of enzyme kinetics.

Differential Scanning Calorimetry (DSC)

Differential Scanning Calorimetry (DSC) is a technique for understanding the stability of proteins and other biomolecules. It has wide application in protein engineering, rational drug design and biopharmaceutical production, where developing stable proteins is a critical goal.

DSC is a key thermal analysis technique that measures heat changes that occur in the biomolecule during a controlled increase or decrease in temperature, making it possible to study materials in their native state.

DSC enables:

  • Characterization and selection of the most stable proteins/potential candidates in biotherapeutic development.
  • Ligand interaction studies.
  • Rapid optimization of purification and manufacturing conditions.
  • Easy, rapid determination of optimum conditions for liquid formulations.
  • Quick stability-indicating assay for target proteins for use in screening.

Related products

MicroCal range Microcalorimeters for characterizing the stability of proteins and other biomolecules ITC_set
Measurement
Microcalorimetry, Label-free analysis
Accuracy
1% (non-condensing)
Sample throughput
2per 8h day to 50per 24h day
Technology
Isothermal Titration Calorimetry, Differential Scanning Calorimetry
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Application protocols for MicroCal Auto-iTC200 Technical Note (English)

MicroCal Auto-iTC200 comes with a preloaded set of automation methods. This protocol describes the usage of the standard automation methods.


Keywords: English Technical Note MicroCal Auto-iTC200 Isothermal Titration Calorimetry Microcalorimetry Label-free analysis 

Applications of Isothermal Titration Calorimetry and differential scanning calorimetry in biopharmaceutical Application Note (English)

In this application note, ITC and DSC enabled characterization of protein-excipient binding as one of the many interactions possible in a complex protein solution formulation.


Keywords: English Application Note MicroCal range Differential Scanning Calorimetry Isothermal Titration Calorimetry Microcalorimetry Label-free analysis 

The use of ITC for obtaining enzyme kinetic constants Whitepaper (English)

Almost every significant life process is dependent on enzyme activity. Therefore the assay and pharmacological regulation of enzymes are key elements in clinical diagnosis and therapeutics. There are many enzymes of interest for which there a...


Keywords: English Whitepaper Proteins Bioformulation development MicroCal ITC range Isothermal Titration Calorimetry Microcalorimetry Label-free analysis 

Differential Scanning Calorimetry: Theory and practice Whitepaper (English)

Differential scanning calorimetry (DSC) is an analytical technique with a proven track record for biomolecular stability studies. The technique is based on forced thermal denaturation of the biomolecules. It is extensively used for compar...


Keywords: English Whitepaper Proteins Biological drug characterization and development Bioformulation development MicroCal DSC range Differential Scanning Calorimetry Microcalorimetry Label-free analysis 

Studying low-affinity fragments of ligands by ITC Whitepaper (English)

Dissecting a ligand into smaller fragments can provide a strategy for analyzing the role of key functional groups in a protein-ligand interaction. Conversely, low-affinity ligand fragments that are able to occupy a receptor-binding site s...


Keywords: English Whitepaper Proteins Bioformulation development MicroCal ITC range Isothermal Titration Calorimetry Microcalorimetry Label-free analysis 
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