Isothermal microcalorimetry

Isothermal microcalorimetry (IMC) is a laboratory method for real-time monitoring and dynamic analysis of chemical, physical and biological processes. Over a period of hours or days, IMC determines the onset, rate, extent and energetics of such processes for specimens in small ampoules (e.g. 3–20 ml) at a constant set temperature (c. 15 °C–150 °C). IMC accomplishes this dynamic analysis by measuring and recording vs. elapsed time the net rate of heat flow (μJ/s = μW) to or from the specimen ampoule, and the cumulative amount of heat (J) consumed or produced. IMC is a powerful and versatile analytical tool for four closely related reasons: All chemical and physical processes are either exothermic or endothermic—produce or consume heat. The rate of heat flow is proportional to the rate of the process taking place. IMC is sensitive enough to detect and follow either slow processes (reactions proceeding at a few % per year) in a few grams of material, or processes which generate minuscule amounts of heat (e.g. metabolism of a few thousand living cells). IMC instruments generally have a huge dynamic range—heat flows as low as ca. 1 μW and as high as ca. 50,000 μW can be measured by the same instrument. The IMC method of studying rates of processes is thus broadly applicable, provides real-time continuous data, and is sensitive. The measurement is simple to make, takes place unattended and is non-interfering (e.g. no fluorescent or radioactive markers are needed). However, there are two main caveats that must be heeded in use of IMC: Missed data: If externally prepared specimen ampoules are used, it takes ca. 40 minutes to slowly introduce an ampoule into the instrument without significant disturbance of the set temperature in the measurement module. Thus any processes taking place during this time are not monitored. Extraneous data: IMC records the aggregate net heat flow produced or consumed by all processes taking place within an ampoule.