Historical Overview
von Bertalanffy & Bickis - 1956
The metachromatic fluorescence of AO was used to identify and quantitate RNA in tissues and that that normal and malignant cells could be discriminated.
Cytometry Analytic Techniques M.R. Mendelsohn - 1958
Pioneered photometry by the two-wavelength method with the appropriate mathematical manipulation of the transmittances.
Marylou Ingram - 1960's
Identified that radiation caused increase number of binucleated lymphocytes in peripheral blood - she used a scanner to detect these rare cells (1/10000).
Preston - 1964
Cytoanalyzer was designed to identify Ingram's rare cells using a Vidicon based system - digitized images of lymphocytes were produced stained with eosin-methylene azure dye combinations.
Early flow systems
Hallermann et al, Kosenow - 1964
AO staining of leukocytes - was able to use fluorescence (in a flow based system) to select leukocytes from red cells despite a low ratio (1/1000) because they took up lots of AO - also claimed to be able to discriminate between monocytes and PMN
Lou Kamentsky - IBM -1963
LA Kamentsky & CN Liu, Computer-automated design of multifont print recognition logic, IBM J. Research & Development 7, 1963
U.V. Scanning Measurements - 1963
Ultraviolet Absorption in Epidermoid Cancer Cells L.A. Kamentsky, H Derman and M. R. Melamed, Science 142, 1963
Kamentsky System - 1963
LA Kamentsky, MR Melamed & H. Derman, Spectrophotometer: New instrument for ultrarapid cell analysis, Science 150, 1965
1964 Kamentsky Sorter
Diagram of the aparatus
1964 Kamentsky Sorter
Spectrophotometric Cell Sorter; Louis A. Kamentsky
1 and Myron R. Melamed
2
1. IBM Watson Laboratory, Columbia University, New York
2. Memorial Sloan Kettering Cancer Center, New York
Science 9 June 1967: Vol. 156. no. 3780, pp. 1364 – 1365 ,DOI: 10.1126/science.156.3780.1364
1966 Kamentsky RCS: Four Sensors, Sorting, Auto Sampling and Computer Data Reduction
Two analytic instruments were built and one was delivered to LA Herzenberg at Stanford University 1967
Los Alamos Volume Sorter -1965
Mack Fulwyler worked in Marvin van Dilla's lab at Los Alamos.
He developed the sorter in 1965. He initially used electronic cell volume at Los Alamos National Labs.
This instrument separated cells based on electronic cell volume (same principle as the Coulter counter) and used electrostatic deflection to sort. The cells sorted were RBC because they observed a bimodal distribution of cell volume when counting cells.
The sorting principle was based on that developed for the inkjet printer by Richard Sweet at Stanford in 1965.
The mysterious red cell problem solved
So it was determined that RBC traveling through the orifice were identified as "different" only because of the rotation of the cells (which was essentially random)
After determining that the bimodal distribution was artifactual, this group were able to sort neutrophils and lymphocytes from blood.
Los Alamos Flow Microfluorometer
Marvin Van Dilla Working with Harry Crissman
at Los Alamos doing DNA analysis
Phywe AG of Gottingen - 1969
Produced
the first commercial flow cytometer built around a Zeiss fluorescent microscope.
ICP 11 (1969) Distributed by Phywe, Göttingen The first commercial flow cytometer
PDP 11 computer |
|
Wolfgang Göhde |
Lou Kamentsky - Biophysics Systems -1970
Bio/Physics Systems - 1970 commercial cytometer - the "Cytograph" He-Ne laser
system at 633 nm for scatter (and extinction) - supposedly the first commercial
instrument incorporating a laser. It could separate live and dead cells by
uptake of Trypan blue. A fluorescence version called the "Cytofluorograph"
followed using an air cooled argon laser at 488 nm excitation
Ortho Diagnostics (Johnson and Johnson) purchased Biophysics in 1976 and in 1977 the System 50 Cytofluorograph was developed - this was a droplet sorter, with a flat sided flow cell, forward and orthogonal scatter, extinction, 2 fluorescence parameters, multibeam excitation, computer analysis option. J&J exit business twice, mid 1980s and mid 1990s.
Herzenberg - Stanford - 1969
Len Herzenberg - Sorter based on fluorescence (arc lamp) built after working with one of Kamentsky's RCS systems where they built an instrument they called the Fluorescence Activated Cell Sorter (FACS)
Herzenberg -1972 - Argon laser flow sorter - placed an argon laser onto their sorter and successfully did high speed sorting - Coined the term Fluorescence Activated Cell Sorting (FACS) This instrument could detect weak fluorescence with rhodamine and fluorescein tagged antibodies. A commercial version was distributed by B-D in 1974 and could collect forward scatter and fluorescence above 530 nm.
Particle Technology Inc. - COULTER
-1971
· Fulwyler began consulting for Coulter in the late 1960's. Spinning out LASL FCM and Particle manufacturing technologies.
· In 1971, Mack Fulwyler resigned from LASL and established PTI as a Coulter subsidiary company
· 1976 PTI dissolved, technology transferred to Florida
Epics II 1975
Designed by Mack Fulwyler and Jim Corell
Delivered to NCI/NIH |
|
TPS 1974 - 1979
Designed by Bob Auer |
Hemalog D - 1974
Technicon - First commercial differential flow cytometer with light scatter
and absorption at different wavelengths. Chromogenic enzyme substrates were used to identify neutrophils and eosinophils by peroxidase and monocytes by esterase, basophils were identified by the presence of glycosaminoglycans using Alcian Blue.
The excitation for all measurements was a tungsten-halogen lamp.
Photo from Shapiro "Practical Flow Cytometry", 3rd. Ed.Wiley-Liss, 1994
Howard M. Shapiro - 1973-76
Shapiro and the Block instruments designed a series of multibeam flow cytometers that did differentials and multiple fluorescence excitation and emission
LLNL High Speed Sorter - 1978
Marv Van Dilla and Phil Dean sorting chromosomes at LLNL around 1978, on the first fluorescence-based sorter developed there. The sorter shown was later modified to become the first dual-beam, fully computer-controlled, multi-parameter sorter. Father of the MoFlo.
Invention of Monoclonal Antibody by Kohler and Milstein - 1975
 |
1984 Nobel price for medicine: Niels K. Jerne, Georges J.F. Köhler,
César Milstein "for theories concerning the
specificity in development and control of
the immune system and the discovery of the
principle for production of monoclonal
antibodies.
The referee reports were positive but cautious. The editors of Nature did not consider it of sufficient general interest to publish it as an article, and the original text had to be severely pruned to fit the length of a letter."Milstein commenting on his original paper in 1999 |
 |
Interesting factoid
· Len Herzenberg was doing a sabbatical in Cesar Milstein's laboratory in 1975 when Milstein had developed the Monoclonal Antibody.
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· It was Herzenberg that Milstein credited with coming up with a name for the cell than made the antibody - hybridoma!
· The term hybridoma was proposed by Len Herzenberg during a sabbatical in my laboratory in 1976/1977. At a high-table conversation at a Cambridge College, Len was told by one of the dons that hybridoma was garbled Greek. By then however, the term was becoming popular among us, and we decided to stick to it." The hybridoma revolution: an offshoot of basic research Cesar Milstein, Bioessays, 21:966-973,1999.
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Coulter Electronics
