Like all forms of calorimetry, isothermal titration calorimetry (ITC) measures the flow of heat. ITC is commonly used in life science applications focusing on the binding or affinity of two different interacting molecules. This is important in developing new medical therapies because the interactions of potential drug compounds with target proteins or other biomolecules related to diseases or disorders can be studied.

Although a number of techniques can be used to measure binding, ITC provides particularly complete and rich data, making it especially useful in drug discovery and for optimizing drug candidates. Drug discovery represents the major source of demand and presents favorable opportunities for the technology’s growth. ITC can be applied to both small-molecule pharmaceuticals and protein therapeutics. There are basic-research applications for general chemistry and in academic and government labs that focus on the kinetics and thermodynamics of molecular interactions of enzymes and other biological molecules.

An important aspect of ITS is that it measures differences between the response of the sample cell and a reference cell of identical size and shape. The cells are simple chambers typically made from a superalloy designed to withstand both corrosion and high temperatures. While the reference cell contains only water or a standard solution, the sample cell also contains one of the two molecules of interest. The cells share a temperature bath with a thermocouple noting any differences in temperature between them. To increase responsiveness, relatively small volumes are used—generally less than 1 mL—which is ideal for rare or expensive samples. Once the cells are prepared, the titration system injects a solution containing the second molecule into the sample cell, either continuously or in controlled volumes at set times. When the molecules react, heat is either produced or absorbed, affecting the temperature of the sample cell. A heating system maintains the sample cell at the same temperature as the reference cell. During the experiment—usually on the order of hours—the instrument measures the power supplied to keep the temperature constant. Through mathematical integration and standard thermodynamic identities, these data can be converted into heat of reaction, enthalpy change, and other reaction-kinetics properties as functions of time or the relative molarity of the two compounds.

Few vendors compete in the ITC market. The two dominant players are MicroCal and Waters’s TA Instruments business. MicroCal was acquired by GE in 2008 (see IBO 9/30/08) but will be sold to Malvern Instruments (Spectris) later this year (see IBO 6/15/14). TA Instruments is the only other significant competitor in ITC. An upstart company, Chreston, has recently entered the market. Affinimeter is a Spanish company that produces software for ITC. The total market demand for ITC in 2013 was about $50–$60 million.

Isothermal Titration Calorimetry at a Glance:

Leading Suppliers

• MicroCal

• TA Instruments (Waters)

Largest Markets

• Pharmaceutical

• Biotech

• Academia

Instrument Cost

• $50K–$150K