History of Flow Cytometry

1930's Moldavan in Science described the counting of blood cells filing through a capillary tube using a photoelectric sensor.

1940's US Army constructed a device that detected bacteria in a stream of air, using a Ford headlight as a light source and a photomultiplier tube as a detector. 60% ~ 0.6 μm

1950's Caspersson measured nucleic acid and protein metabolism for normal and abnormal cell growth using a Cadmium spark as a UV light source. Coulter constructed a cell counter based on the fact that the electrical conductivity of cells is lower than that of saline. Saline conducts, cells impede.

1960's Kamentsky at IBM developed the Rapid Cell Spectrophotometer. It used an arc lamp source and measured nucleic acid content and cell size. A computer measured and analyzed the data. IBM loaned Herzenberg a prototype and he developed the first real FACS.

1970's Industry takes over technical development: BD, Beckman, Ortho etc.

Frequency distribution of DNA content Cells from a normal cervix Cells from a cervical carcinoma Premalignant cells from the epithelium Quantitative cytochemical studies on normal, malignant, premalignant and atypical cell populations from the human uterine cervix, Acta Cytologica 8, 1964 O. Caspersson 1964 Images from Dr. Louis Kamentsky

The Coulter Counter: Counts cells and measures their size based. Patent The first commercial version of the Coulter Counter

LA Kamentsky, MR Melamed & H. Derman, Spectrophotometer: New instrument for ultrarapid cell analysis, Science 150, 1965

Herzenberg Lab at Stanford, Early sorters and analyzers.

Flow cytometry has benefited from the technological development of:

• Monoclonal antibodies
• Fluorochromes
• DNA, RNA and Functional stains
• Computers and the miniaturization of Electronics
• Lasers