Enzymelinked Immunosorbent Assay Elisa

Stratis Avrameas and Thérèse Ternynck, Department of Immunology, Institut Pasteur, Paris, France

Yalow and Berson's development in 1959 of the radioimmunoassay based on the use of a new tool, i.e. an antigen labeled with a radioactive tracer, introduced the ability to measure a substance with both accuracy and high specificity. Although radioimmunoassay is highly sensitive and versatile and it has been applied with success in various fields, its further extensive development has been hampered by the inherent drawbacks encountered with radioisotopes. In order to overcome these difficulties, several alternative procedures based on the use of other marker substances, such as free radicals, chemi-luminescent or fluorescent labels, bacteriophages and enzymes, were proposed. Among them, enzyme immunoassays, probably because of the high amplifying capacity of the enzyme marker and the relatively simple laboratory equipment they require, have been extensively developed during the past 15 years.

Enzyme immunoassays were first reported in 1971 by S. Avrameas and B. Guilbert in France, E. Engvall and P. Perlmann in Sweden, and B. van Weemen and H. Schuurs in Holland. They were employed for the quantitation of antigens and subsequently for the titration of antibodies. These enzyme immunoassays were based on principles similar to those of radioimmunoassays and, therefore, necessitated the use of an antigen or antibody immobilized on a solid phase, i.e. an immunoadsorbent, to separate the free antigen or antibody from the antigen-antibody immune complex. These heterogeneous or solid-phase enzyme immunoassays were termed, by Engvall and Perlmann, enzyme-linked immunosorbent assay or ELISA. In 1972 Rubinstein and collaborators introduced enzyme-multiplied immunotechnique (EMIT), a homogeneous enzyme immunoassay, in which the immunological reaction and the measurement of the enzyme were performed in the same liquid medium without an immunoadsorbent.

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