ELSEVIER Available online at www.sciencedirect.com SCIENCE DIRECT& Clinica Chimica Acta 369 (2006) 119-124 CA www.elsevier.com/locate/clinchim Review A selected history and future of immunoassay development and applications in clinical chemistry Alan H.B. Wu * Department of Laboratory Medicine, University of California, San Francisco, Clinical Chemistry Laboratory, San Francisco General Hospital, San Francisco, CA 94110, United States Received 27 January 2006; accepted 27 February 2006 Available online 27 March 2006 Abstract Background: The first immunoassay was described by Berson and Yalow in 1959. Their work resulted in their receipt of the Nobel Prize in Medicine in 1977. Since this introduction, immunoassays have evolved considerably. Methods: There have been several milestones that have led to the proliferation of modern immunoassays. The development of monoclonal antibodies from mouse hydridoma cells by Millstein and Kohler (Nobel Prize in 1984) enabled the production of high quantities of antibodies with well characterized epitope specificity. The first homogenous immunoassay (no separation step required) was the Enzyme Multiplied Immunoassay Technique (EMIT), which enabled adaptation of this assay onto automated chemistry platforms. EMIT was also one of the first immunoassay that made use of non-isotopic labels. Other non-isotopic labels became available such as chemiluminescence to improve the analytical sensitivity of immunoassays. The advantages of high-sensitivity immunoassays have created expanded diagnostic roles for some existing assays such as thyroid stimulating hormone for hyperthyroidism, C-reactive protein for cardiovascular risk assessment, and other applications. The development of instrumentation capable of automated heterogeneous immunoassays (separation step to improve sensitivity) has enabled movement of this technology from the "special chemistry" sections of a clinical laboratory into the "core" laboratory with other high-volume testing. Conclusion: Today, immunoassays play a prominent role in the analysis of many clinical laboratory analytes such as proteins, hormones, drugs, and nucleic acids. The future involves development of assays with higher sensitivities which will enable the discovery of new biomarkers for disease diagnosis, and technology that will enable simultaneous multimarker analysis of tests whose needs are naturally grouped together (e.g., cytokines and allergens). C 2006 Elsevier B.V. All rights reserved. Keywords: Radioimmunoassay; Sandwich; Competitive; Non-isotopic; Homogenous Contents 1. The origin of competitive immunoassays. 119 2. The impact of monoclonal antibody production on development of sandwich immunoassays . 120 3. The development of homogeneous immunoassays . 121 4. Evolution of non-isotopic labels and the impact on functional sensitivity 121 5. Future immunoassay platforms and new paradigm for testing 121 References 123 To celebrate the 50th anniversary of CCA, a number of invited review papers have been brought together, dealing with important research fields where CCA publications have contributed to the scientific exploration. * Fax: +1 415 206 3045. E-mail address: wualan@labmed2.ucsf.edu. 1. The origin of competitive immunoassays The immunoassay area in clinical chemistry began with the development of the first immunoassay for insulin by Solomon Berson and Rosalyn S. Yalow in 1959 [1]. This work was 0009-8981/$ - see front matter @ 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2006.02.045
120 A.H.B. Wu / Clinica Chimica Acta 369 (2006) 119-124 performed while both were