The Power of 40 Years Flow Cytometry

From the first fluorescence-based FCM instrument, ICP 11, to the newest FCM Technologies for dedicated applications

Abstract from 17th Annual Meeting of the German Society for Cytometry, 2007

The first fluorescence-based flow cytometry device (ICP 11) was developed in the year 1968 by researchers of the University of Münster in Germany (Patent No. DE1815352) and first commercialized in 1968/69 by Partec in Münster through Phywe in Göttingen, at a time in which absorption methods were still favored by other scientists over fluorescence methods (e.g. Kamentsky, Proceedings of the Conference „Cytology Automation" in Edinburgh, 1970).

The original name of the flow cytometry technology was pulse cytophotometry (German: Impulscytophotometrie). Only 10 years later, in 1978, at the Conference of the American Engineering Foundation in Pensacola, Florida, the name was changed to "flow cytometry", a term which quickly became popular.  However, this change in nomenclature causes literary searches using only that term, to retrieve information dated from 1978 on, while older references are usually not found. Fluorescence-based flow cytometry is used today as a standard method for automated rapid cell analysis, but was, in fact, a European invention used for cancer cell detection from the beginning.

Rapidly, the ICP 11 became very popular in a wide-spread field of various applications. By 1972, it was used for research in pathology, quantitative cytology, gynaecology, haematology, radiology, cancer research, pharmacology, biophysics and molecular biology, oncology, dermatology, cell and proliferation kinetics, and in the clinical field, e.g. for differentiation of normal and neoplastic cell populations, prescreening of vaginal and cervical smears, leukemia, and therapy control of skin tumors. Between 1969 and 1972, pulse cytophotometry by the ICP 11 was presented at 54 conferences and congresses in Europe, the US, Japan, and Brazil. In 1971, the instrument was awarded the Gold Medal at the internationally renowned Leipzig Trade Fair. It is interesting to note that by 1973, this instrument was already being used successfully for plant flow cytometry and, by 1974,  as a reference method for milk quality control by ETH Zurich, in Switzerland. These applications, surprisingly, were not continued in the FCM field for almost 20 years, until they were taken up again in the early 1990s. These serve as great examples of flow cytometric solutions introduced ahead of their time.

Subsequently introduced flow cytometry instruments were the Cytograph (1970) and the Cytofluorograph (1971) from Bio/Physics Systems Inc. (later: Ortho Diagnostics), the PAS 8000 (1973) from Partec, the first FACS instrument from Becton Dickinson (1974), the absorption and scatter-based Hemalog D (1974) from Technicon (later: Bayer Diagnostics), the ICP 22 (1975) from Partec/Phywe and the Epics from Coulter (1977/78). Using a sublicense from Phywe, Ortho introduced the ICP 22 A in 1977. The PAS-II from Partec followed in 1979. Despite the significant potential of flow cytometry, only a relatively small number of manufacturers entered the field, a majority of which exited relatively soon, including Ortho, Leitz, Skatron, BioRad, Heka, Bruker, and Showa Denko. The major FCM companies, therefore, remain B-D, Partec, and Beckman Coulter, while Guava (1998) and Dako (acquiring Cytomation in 2001) joined the field of flow cytometry instrumentation later on.

In general, flow cytometers have been traditionally designed with the intent to cover a wide range of research and clinical applications with just one instrument.  This made sense for large institutions with the need to perform a variety of applications and this made production highly efficient for the manufacturers. However, this functional versatility also added to the complexity and cost of the instrument, while not all application fields require the full configurations (number of optical parameters and fluorescence channels) of such devices. Consequently, in the year 2000, Partec introduced the portable CyFlow SL for dedicated applications in HIV monitoring, microbiology, and industry.  Due to the developments in modern component technology for laser modules, electronics, optoelectronics, and fluidics, FCM instruments can now be made significantly more compact and robust. The modularity and flexibility of this new generation of flow cytometers permits the configuration of specifically tailored system solutions, e.g. for quality control in the food industry and dairy products, as well as for increasingly important or new niche fields, including plant and animal breeding, quality control in the beverage industry (breweries, wineries, distilleries, fruit juice), the paper industry, etc.

A general tendency can be observed that, in the future, highly dedicated instrument types will be offered, which will address the exact requirements of specific applications. It can be expected that in many fields, the names of upcoming instruments may be defined by their targeted application. Terms like "wine analyser“ or "wood pitch analyser” may be more widely used than "flow cytometer“, as is already the case for “CD4 counter” and “ploidy analyzer”. Development of a wide range of highly dedicated instruments may become more important for the future of flow cytometry than further increasing the number of fluorescence parameters of high-end systems, beyond the current 14 (Partec CyFlow ML) or 18 colours (BD LSR-II).