Sensitive to the yoctomole limit

One of the important concepts a chemistry teacher has to explain to students is the concept of the mole. He/she usually explains that a chemical mole is not the small burrowing animal known to biologists but, rather, stands for ∼6×1023 (Avogadro's number) species (e.g. molecules, ions or electrons). The mole is a number; elementary chemistry books sometimes call it `the chemist's dozen'.While we can count a dozen eggs one egg at a time, the magnitude of Avogadro's number normally rules out direct counting of objects. The number of moles present in a given quantity of any substance is instead obtained from indirect measurements—for example, from the mass of a substance that has a known elementary formula or, alternatively, from the volume of a gas or from charge measurements of ionic substances (using the Faraday constant).The magnitude of Avogadro's number has always created problems for individuals analysing substances that are present in a specimen at very low concentration. For example, 30 years ago the absolute sensitivity of peptide analysis was at the micromole level, and analysts were obliged to collect at least 6×1017 molecules of the same peptide in order to determine its sequence. In 1970, Burgus and colleagues[1xBurgus, R. et al. Nature. 1970; 226: 5243–5244Crossref | Scopus (282)See all References][1]used 500 tons of sheep brain in order to obtain enough peptide to characterize the structure of the TSH-releasing factor. Since then, a continuous improvement in detection methods has allowed chemical analysis to reach sensitivities at the nano-, pico- and femto-mole levels. A combination of capillary electrophoresis and laser-induced fluorescence has recently improved chemical analysis to the degree that it is now sensitive at the atto- and zepto-mole levels. Indeed, sensitivity at the yoctomole level has been demonstrated[2xDavies, M.J. and Hounsell, E.F. Biomed. Chromatogr. 1996; 10: 285–289Crossref | Scopus (26)See all References, 3xChen, D.Y. and Dovichi, N.J. J. Chromatogr B. 1994; 657: 265–272Crossref | Scopus (85)See all References]. The relationships between the number of molecules and various fractions of a mole are summarized in Table 1Table 1. As far as egg counting goes, it is better and simpler to say, `Please, give me four eggs', than to ask for `one third of a dozen eggs'. It should surely therefore be better to discuss sensitivity levels in term of hundreds of molecules than in terms of a `zeptomole sensitivity level'. A search using Medline retrieved 18 publications that used just such a phrase (Table 1Table 1). Moreover, it is obvious that the manipulation of a twentieth of a dozen inevitably leads to broken eggs and, therefore, researchers can only introduce the yoctomole limit if they are planning to expand their culinary skill towards the preparation of a sub-molecular omelette!Table 1Relationships between number of molecules and number of molesPrefixNumber of molesNumber of moleculesNumber of Medline entries(mole)16×1023N/Amilli1×10−36×102067micro1×10−66×1017114nano1×10−96×1014245pico1×10−126×1011619femto1×10−156×108243atto1×10−186×10588zepto1×10−2160018yocto1×10−24<14 View Table in HTML