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Clinical Chemistry 48: 1819-1827, 2002;
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(Clinical Chemistry. 2002;48:1819-1827.)
© 2002 American Association for Clinical Chemistry, Inc.

Oak Ridge Conference

The History and Future of the Fluorescence Activated Cell Sorter and Flow Cytometry: A View from Stanford

Leonard A. Herzenberg1a, David Parks1, Bita Sahaf1, Omar Perez2, Mario Roederer3 and Leonore A. Herzenberg1

1 Stanford University, Department of Genetics, Stanford, CA 94305.

2 The Baxter Laboratory, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305.

3 Vaccine Research Center, NIH, Bethesda, MD 20892.

aAuthor for correspondence. E-mail lenherz{at}darwin.stanford.edu.


Abstract

The Fluorescence Activated Cell Sorter (FACS) was invented in the late 1960s by Bonner, Sweet, Hulett, Herzenberg, and others to do flow cytometry and cell sorting of viable cells. Becton Dickinson Immunocytometry Systems introduced the commercial machines in the early 1970s, using the Stanford patent and expertise supplied by the Herzenberg Laboratory and a Becton Dickinson engineering group under Bernie Shoor. Over the years, we have increased the number of measured FACS dimensions (parameters) and the speed of sorting to where we now simultaneously measure 12 fluorescent colors plus 2 scatter parameters. In this history, I illustrate the great utility of this state-of-the-art instrument, which allows us to simultaneously stain, analyze, and then sort cells from small samples of human blood cells from AIDS patients, infants, stem cell transplant patients, and others. I also illustrate analysis and sorting of multiple subpopulations of lymphocytes by use of 8–12 colors. In addition, I review single cell sorting used to clone and analyze hybridomas and discuss other applications of FACS developed over the past 30 years, as well as give our ideas on the future of FACS. These ideas are currently being implemented in new programs using the internet for data storage and analysis as well as developing new fluorochromes, e.g., green fluorescent protein and tandem dyes, with applications in such areas as apoptosis, gene expression, cytokine expression, cell biochemistry, redox regulation, and AIDS. Finally, I describe new FACS methods for measuring activated kinases and phosphatases and redox active enzymes in individual cells simultaneously with cell surface phenotyping. Thus, key functions can be studied in various subsets of cells without the need for prior sorting.




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