Particle enhanced immunoassays have been in use since the 1920s. In 1925 Jules Freund published an article demonstrating that, if soluble proteins were adsorbed onto the surfaces of small particles they would agglutinate when mixed with antisera raised against the protein.! Freund used tubercle bacteria for his particle and was then followed by several other workers.v' What were probably the first synthetic particles were reported in the 1920s by Loeb, who used collodion, a form of nitrocellulose.' Their use became more widespread following the work of Cannon and Marshall in the 1940s 6 who demonstrated the usefulness of coupling antigen to particles as a rapid means of evaluating the titre of antisera, particularly in the development of a test for anti-tuberculin sera. In 1943 Cavelti explored some of the characteristics of collodion particles that were important in enabling specific antibody mediated aggregations to occur. 7 From these earliest days workers became aware of one of the major problems of particle based assays, that of non-specific aggregation, a problem that still requires careful attention today.
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Newman et al. (1992) studied this question.
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