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The problem faced and surmounted by immunologists in effecting the transition from research tool to routine clinical assay bears a remarkable similarity to that confronting the molecular biologist today; i.e., how can nucleic acid hybridization, a technique of obvious potential (Meinkoth and Wahl: <jats:italic>Anal Biochem<\/jats:italic> 138:267\u2010284, 1984; Syvanen: <jats:italic>Med Biol<\/jats:italic> 64:313\u2010324, 1986; Matthews and Kricka: <jats:italic>Anal Biochem<\/jats:italic> 169:l\u201025, 1988), be modified in order to fulfill all necessary parameters of a routine diagnostic assay? There are several such requirements, and the importance placed on each depends on the objectives of the assay: the technique must be sensitive, specific, and reproducible. Other advantages would be cost\u2010effectiveness, ease of manipulation, and amenability to automation. Ideally, the signal detection should be based on a non\u2010radioactive system, because of the instability of probes labelled with isotopes like <jats:sup>32<\/jats:sup>p, and the potential hazards involved in their handling and disposal.<\/jats:p><jats:p>The sandwich hybridization for the analysis of nucleic acid sequences was first used in 1977 (Dunn and Hassell: <jats:italic>Cell<\/jats:italic> 12:23\u201036, 1977), but its potential as a diagnostic assay was not realized until 1983, when it was applied to the detection of adenovirus DNA in nasopharyngeal aspirates from children with acute respiratory infection (Ranki et al: <jats:italic>Gene<\/jats:italic> 21:77\u201085, 1983). It has since been modified and used not only for the detection of microbial infection (Virtanen et al.: <jats:italic>Lancet<\/jats:italic> i:381\u2010383, 1983; Ranki et al.: <jats:italic>Cur Top Microbiol Immunol<\/jats:italic> 104:307\u2010318, 1983; Lehtomaki et al.: <jats:italic>J Clin Microbiol<\/jats:italic> 24:108\u2010111, 1986; Virtanen et al.: <jats:italic>J Clin Microbiol<\/jats:italic> 20:1083\u20101088, 1984; Palva and Ranki: <jats:italic>Clin Lab Med<\/jats:italic> 5475\u2010490, 1985; Polsky\u2010Cynkin et al.: <jats:italic>Clin Chem<\/jats:italic> 31:1438\u20101443, 1985; Parkkinen et al.: <jats:italic>J Med Virol<\/jats:italic> 20:279\u2010288, 1986; Palva: <jats:italic>FEMS Microbiol Lett<\/jats:italic> 28%\u201091, 1985; Palva et al: <jats:italic>FEMS Microbiol Lett<\/jats:italic>2333\u201089,1984; Zolg et al.: <jats:italic>Mol Biochem Parasitol<\/jats:italic> 22:145\u2010151, 1987; Palva: <jats:italic>J Clin Microbiol<\/jats:italic> 18:92\u2010100, 1983), but also for the analysis of nucleotide sequence variations (Langdale and Malcolm: Gene 36:201\u2010210, 1985). We will discuss the development of the sandwich technique and the advantages it conveys over the more conventional nucleic acid hybridization formats, together with new developments which will ensure that it earns a place alongside immunoassay in the diagnostic laboratory.<\/jats:p>","DOI":"10.1002\/jcla.1860030210","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T19:32:15Z","timestamp":1173123135000},"page":"122-135","source":"Crossref","is-referenced-by-count":32,"title":["Nucleic acid analysis by sandwich hybridization"],"prefix":"10.1002","volume":"3","author":[{"given":"Peter J.","family":"Nicholls","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan D. B.","family":"Malcolm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,8]]},"reference":[{"key":"e_1_2_1_2_2","volume-title":"Immunology. 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