page_title: Isothermal microcalorimetry
section_title: Microbiology
hierarchical_section_title: Isothermal microcalorimetry / Applications / Examples of applications / Biology and medicine / Microbiology
caption_attribution_description: English: Illustration of how IMC time of detection of the presence of bacteria depends on the initial number of bacteria present (CFU), the sensitivity of the instrument and the level of heat flow above baseline that is selected as indicating bacterial growth. CFU = colony forming unit. (adapted from Braissant et al 2010 with publisher permission).
context_page_description: Isothermal microcalorimetry 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 at a constant set temperature.
  IMC accomplishes this dynamic analysis by measuring and recording vs. elapsed time the net rate of heat flow to or from the specimen ampoule, and the cumulative amount of heat 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 in a few grams of material, or processes which generate minuscule amounts of heat.
  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.
context_section_description: Publications describing use of IMC in microbiology began in the 1980s (Jesperson 1982). While some IMC microbiology studies have been directed at viruses (Heng et al. 2005) and fungi (Antoci et al. 1997), most have been concerned with bacteria. A recent paper (Braissant et al. 2010) provides a general introduction to IMC metabolismic methods in microbiology and an overview of applications in medical and environmental microbiology. The paper also explains how heat flow vs. time data for bacteria in culture are an exact expression—as they occur over time—of the fluctuations in microorganism metabolic activity and replication rates in a given medium (Fig. 6).
  In general, bacteria are about 1/10 the size of mammalian cells and produce perhaps 1/10 as much metabolic heat-i.e. ca. 3x10⁻¹² W/cell. Thus, compared to mammalian cells (see above) ca. 10X as many bacteria—ca. 330,000—must be present to produce detectable heat flow—i.e. 1 μW. However, many bacteria replicate orders of magnitude more rapidly in culture than mammalian cells, often doubling their number in a matter of minutes (see Bacterial growth). As a result, a small initial number of bacteria in culture and initially undetectable by IMC rapidly produce a detectable number. For example, 100 bacteria doubling every 20 minutes will in less than 4 hours produce >330,000 bacteria and thus an IMC-detectable heat flow. Consequently, IMC can be used for easy, rapid detection of bacteria in the medical field. Examples include detection of bacteria in human blood platelet products (Trampuz et al. 2007) and urine (Bonkat et al. 2011) and rapid detection of tuberculosis (Braissant et al. 2010, Rodriguez et al. 2011). Fig. 7 shows an example of detection times of tuberculosis bacteria as a function of the initial amount of bacteria present in a closed IMC ampoule containing a culture medium.
  For microbes in growth media in closed ampoules, IMC heat flow data can also be used to closely estimate basic microbial growth parameters; i.e. maximum growth rate and duration time of the lag phase before maximum growth rate is achieved. This is an important special application of the basic analysis of these parameters explained previously (Overview: Data Obtained).
  Unfortunately, the IMC literature contains some  published papers in which the relation between heat flow data and microbial growth in closed ampoules has been misunderstood. However, in 2013 an extensive clarification was published, describing (a) details of the relation between IMC heat flow data and microbial growth, (b) selection of mathematical models which describe microbial growth and (c) determination of microbial growth parameters from IMC data using these models (Braissant et al. 2013).
caption: Illustration of how IMC time of detection of the presence of bacteria depends on the initial number of bacteria present (CFU), the sensitivity of the instrument and the level of heat flow above baseline that is selected as indicating bacterial growth. CFU = colony forming unit. (adapted from Braissant et al. 2010 with publisher permission). Fig.7
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