INTRODUCTION TO FLOW CYTOMETRY - Flow Cytometry in Drug Discovery and Development - page 2

by enumerating the number of CD4 þ T cells by flow cytometric analysis [26-30].
Currently, there are emerging areas with flow cytometric applications including the
enumeration of CD34 þ hematopoietic stem cells [29, 31, 32], detection of circulating
metastatic tumor cells [33-37], determination of antigen-specific T cells [38-40], and
identification of pathogens [41-45], to list a few. Combination of sorting with
molecular analysis represents an important use of the sorting aspects of flow
cytometers. There are over 100,000 flow cytometers in use and the employment of
this instrument in clinical diagnostics has increased dramatically, particularlywith the
increase in FDA-approved fluorochrome reagents for in vitro diagnostics (fluoro-
chrome-conjugated antibodies). However, in third-world countries, access to clinical
flow cytometers is not optimal [46, 47]. The use of flow cytometers and the impact of
this instrument on biomedical and clinical studies can be appreciated by looking at the
increase in publications in which the word “flow cytometry” appeared in the abstract
or title with time (Figure 1.1).
Improvements in instrumentation and computer-assisted analysis have made the
flow cytometer a critical instrument in biomedical research, clinical diagnostics, and
drug discovery. Herzenberg was honored for his work in flow cytometry by the
American Association for Clinical Chemistry with the Ullman Award in 2002 and
some of the history described in this chapter comes from his lecture and the
accompanying article [19]. The original description of the first flow cytometer was
provided in Scientific American [48]. This instrument consisted of one laser and two
light detectors, one for forward scatter to measure cell size and the other for
fluorescence. This meant that one was restricted to measuring a single marker. When
one of the authors of this article used that prototype instrument, the LASL, we were
measuring the DNA content of individual cells. This was one of the first uses of these
FIGURE 1.1 A bar graph showing the number of publications having “flow cytometry” in
their title/abstract since 1970 to present. There is almost a 150% increase since 1980-1989.