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20:
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built the first non microscopy-based cytophotometer. He did this by combining
Crosland-Taylor's breakthrough with the fluorescent dyes originally developed for microscopy and a laser-based fluorescent detection system — the flow cytometer as we know it today. Fulwyler, at Los Alamos as well, combines
356:
in 1968. Kamentsky’s device was commercialized by Bio/Physics
Systems Inc. as the Cytograph in 1970. These devices were able to count cells, like the earlier Coulter counter. But more importantly, they were also capable of measuring cellular characteristics. However, these early cytophotometers where
328:
The first attempts to automate cell counting were made around World War II. Gucker et al. builds a device to detect bacteria in aerosols. Lagercrantz builds an automated cell counter based on microscopy and identifies the difficulties in aligning cells to be individually counted using microscopy, as
305:
to quantify cellular nucleic acids and their relation to cell growth and function. Caspersson’s early apparatus now seems hopelessly primitive. But, even this primitive apparatus got results, and attracted the attention of other researchers. Many of the advances in analytical cytology from the 1940s
165:. The fluid stream is broken up into droplets by a mechanical vibration. The droplets are then electrically charged according to the characteristics of the cell contained within the droplet. Depending on their charge, the droplets are finally deflected by an electric field into different containers.
868:
147:. To detect specific molecules when optically characterized, cells are in most cases stained with the same type of fluorochromes that are used by image cytometers. Flow cytometers generally provide less data than image cytometers, but have a significantly higher throughput.
264:
in Jena constructed the first ultraviolet microscope. The intent of the microscope was to obtain higher optical resolution by using illumination with a shorter wavelength than visual light. However, they experienced difficulties with
117:, in the mid-1990s, the automation level of image cytometers has steadily increased. This has led to the commercial availability of automated image cytometers, ranging from simple cell counters to sophisticated
238:. However, the hemocytometer is still being used to count cells in cell culture laboratories. Successively the manual task of counting, using a microscope, is taken over by small automated image cytometers.
139:
has since the mid-1950s been the dominating cytometric device. Flow cytometers operate by aligning single cells using flow techniques. The cells are characterized optically or by the use of an
333:
circumnavigates these difficulties by inventing the principle of using electrical impedance to count and size microscopic particles suspended in a fluid. This principle is today known as the
1111:
Steinkamp, J. A.; Fulwyler, M. J.; Coulter, J. R.; Hiebert, R. D.; Horney, J. L.; Mullancy, P. F. (1973). "A new multiparameter separator for microscopic particles and biological cells".
77:. In a similar fashion, cytometry is also used in cell biology research and in medical diagnostics to characterize cells in a wide range of applications associated with diseases such as
293:
By the early 1930s various firms manufactured ultraviolet fluorescent microscopes. The stage was set for cytometry to now go beyond the now established hemocytometer. At this time,
611:
402:, a term which quickly became popular. At that point pulse cytophotometry had evolved into the modern form of flow cytometry, pioneered by Van Dilla ten years earlier.
161:
Cell sorters are flow cytometers capable of sorting cells according to their characteristics. The sorting is achieved by using technology similar to what is used in
269:
when observing biological material. Fortunately, Köhler saw the potential of fluorescence. A filtering technique for fluorescence excitation light was developed by
234:
Until the 1950s the hemocytometer was the standard method to count blood cells. In blood cell counting applications the hemocytometer has now been replaced by
371:
In 1953 Crosland-Taylor published an unsuccessful attempt to count red blood cells using microscopy in which he solved the problem of aligning cells by using
906:, Wolfgang Dittrich & Wolfgang Göhde, "Flow-through Chamber for Photometers to Measure and Count Particles in a Dispersion Medium"
1224:
973:
Van Dilla, M. A.; Trujillo, T. T.; Mullaney, P. F.; Coulter, J. R. (1969). "Cell microfluorometry: A method for rapid fluorescence measurement".
431:
223:
and others blood cell concentration could by the late 19th century be accurately measured using a blood cell counting chamber, the
348:
During the 1960s
Dittrich, Göhde and Kamentsky improves the design pioneered by Caspersson 30 years earlier. Dittrich and Göhde’s
297:, working at the Karolinska Institute in Stockholm, developed a series of progressively more sophisticated instruments called
98:
Image cytometry is the oldest form of cytometry. Image cytometers operate by statically imaging a large number of cells using
1214:
380:
277:. However, the "Lumineszenzmikroskop" he developed was only second on the market, after the one independently developed by
102:. Prior to analysis, cells are commonly stained to enhance contrast or to detect specific molecules by labeling these with
1219:
734:
Gucker, F. T.; O’Konski, C. T.; Pickard, H. B.; Pitts, J. N. (1947). "A photoelectronic counter for colloidal particles".
211:
The early history of cytometry is closely associated with the development of the blood cell counting. Through the work of
1045:
Robinson, J. P. (2009). "Cytometry – a
Definitive History of the Early Days". In Sack, U.; Tárnok, A.; Rothe, G. (eds.).
1204:
922:
Kamentsky, L. A.; Melamed, M. R.; Derman, H (1965). "Spectrophotometer: New instrument for ultrarapid cell analysis".
314:
235:
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Crosland-Taylor, P. J. (1953). "A device for counting small particles suspended in a fluid through a tube".
247:
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to facilitate continuous observation of cellular processes without heat building up inside the incubator.
118:
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A key characteristic of time-lapse cytometers is their use of non heat-generating light sources such as
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74:
866:, Coulter W. H., "Means for Counting Particles Suspended in a Fluid.", issued 1953-10-20
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Lagercrantz, C. (1948). "Photo-electric
Counting of Individual Microscopic Plant and Animal Cells".
633:
394:
In 1978, at the
Conference of the American Engineering Foundation in Pensacola, Florida, the name
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In 1973 Steinkamp and the team at Los Alamos follow up with a fluorescence-based cell sorter.
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Moldavan, A. (1934). "Photo-Electric
Technique for the Counting of Microscopical Cells".
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was built around a Zeiss fluorescent microscope and commercialized as the ICP 11 by
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who worked at C Reichert, Optische Werke AG in Vienna, which today is a part of
34:
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Fulwyler, M. J. (1965). "Electronic separation of biological cells by volume".
576:
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66:
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are the instruments which count the blood cells in the common blood test.
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177:. This allows a time-lapse cytometer to be placed inside a conventional
1047:
Cellular
Diagnostics. Basics, Methods and Clinical Applications of Flow
306:
and on-wards were made by people who made the pilgrimage to
Stockholm.
58:
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19:
790:
480:
78:
313:
188:
18:
82:
41:. Variables that can be measured by cytometric methods include
54:
337:
and was used in the automated blood cell counter released by
301:. These instruments combined a fluorescent microscope with a
135:
Due to the early difficulties of automating microscopy, the
353:
432:"International Society for Advancement of Cytometry"
57:content, and the existence or absence of specific
16:Measurement of number and characteristics of cells
651:Heimstädt O. (1911). "Das Fluoreszenzmikroskop".
561:"Some nineteenth-century pioneers of haematology"
674:. Cambridge University Press. pp. 183–187.
65:. Cytometry is used to characterize and count
8:
512:"The Evolution of Blood-Counting Techniques"
1181:by Purdue University Cytometry Laboratories
379:the cells. In the late 1960s, Van Dilla at
345:” was the first commercial flow cytometer.
106:. Traditionally, cells are viewed within a
1027:. Purdue University Cytometry Laboratories
454:
452:
329:Moldavan had proposed in 1934. Joseph and
702:
606:
604:
584:
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388:to create the first cell sorter in 1965.
49:, cell morphology (shape and structure),
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324:— The first commercial flow cytometer
7:
386:continuous inkjet printer technology
273:at Zeiss in 1910, based on work by
1025:"Cytometry Volume 10 – Los Alamos"
14:
672:Fluorescent microscopy, volume II
37:of number and characteristics of
1113:Review of Scientific Instruments
1225:Biological techniques and tools
612:"The History of Flow Cytometry"
638:Milestones in Light Microscopy
381:Los Alamos National Laboratory
113:Since the introduction of the
61:on the cell surface or in the
1:
995:10.1126/science.163.3872.1213
687:"The Evolution of Cytometers"
634:"The fluorescence microscope"
1082:10.1126/science.150.3698.910
944:10.1126/science.150.3696.630
842:10.1126/science.80.2069.188
384:the Coulter principle with
1241:
640:. Nature Publishing Group.
364:
245:
204:
154:
128:
577:10.1017/s0025727300016124
528:10.1017/s0025727300029392
1049:. Karger. pp. 1–28.
236:electronic cell counters
110:to aid manual counting.
864:U.S. patent 2656508
670:Rost, F. W. D. (1995).
248:Fluorescence microscope
242:Fluorescence microscope
377:hydrodynamically focus
325:
217:Louis-Charles Malassez
197:
179:cell culture incubator
119:high-content screening
27:
1215:Laboratory techniques
614:. Beckman-Coulter Inc
559:Verso, M. L. (1971).
510:Verso, M. L. (1964).
317:
192:
175:light-emitting diodes
169:Time-lapse cytometers
22:
1220:Laboratory equipment
1155:"Partec Flow Museum"
704:10.1002/cyto.a.10111
396:pulse cytophotometry
350:pulse cytophotometer
310:Pulse cytophotometry
141:electrical impedance
75:complete blood count
1179:Cytometry Volume 10
1125:1973RScI...44.1301S
1074:1965Sci...150..910F
987:1969Sci...163.1213V
981:(3872): 1213–1214.
936:1965Sci...150..630K
834:1934Sci....80..188M
783:1948Natur.161...25L
748:10.1021/ja01202a053
685:Shapiro H. (2004).
473:1953Natur.171...37C
339:Coulter Electronics
295:Torbjörn Caspersson
1205:Clinical pathology
357:microscopy-based.
326:
283:Leica Microsystems
229:optical microscope
198:
143:method called the
100:optical microscopy
89:Cytometric devices
28:
1133:10.1063/1.1686375
828:(2069): 188–189.
742:(10): 2422–2431.
632:Rusk, N. (2009).
335:Coulter principle
303:spectrophotometer
213:Karl von Vierordt
145:Coulter principle
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434:. Archived from
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271:Heinrich Lehmann
267:autofluorescence
94:Image cytometers
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398:was changed to
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343:Coulter counter
331:Wallace Coulter
321:Coulter Counter
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299:cytophotometers
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279:Oskar Heimstädt
254:Moritz von Rohr
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163:inkjet printers
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367:Flow cytometry
365:Main article:
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361:Flow cytometry
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341:in 1954. The “
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436:the original
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373:sheath fluid
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151:Cell sorters
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73:such as the
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1195:Blood tests
354:Partec GmbH
275:Robert Wood
221:Karl BĂĽrker
71:blood tests
67:blood cells
35:measurement
1189:Categories
1161:2013-08-25
1031:2013-08-24
904:DE 1815352
889:2013-08-24
659:: 330–337.
618:2013-03-31
442:2013-03-31
418:References
262:Carl Zeiss
69:in common
51:cell cycle
47:cell count
24:Cytometers
565:Med. Hist
516:Med. Hist
252:In 1904,
227:, and an
121:systems.
63:cytoplasm
43:cell size
31:Cytometry
1011:13190489
960:34776930
850:17817054
799:18933853
756:20268300
713:14994215
546:14139094
489:13025472
406:See also
319:Model A
59:proteins
1141:4279087
1121:Bibcode
1090:5891056
1070:Bibcode
1062:Science
1003:5812751
983:Bibcode
975:Science
952:5837105
932:Bibcode
924:Science
830:Bibcode
822:Science
807:4132780
779:Bibcode
595:4929622
586:1034115
537:1033366
497:4273373
469:Bibcode
185:History
53:phase,
33:is the
1139:
1098:459342
1096:
1088:
1009:
1001:
958:
950:
910:
870:
848:
805:
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771:Nature
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721:836749
719:
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583:
544:
534:
495:
487:
461:Nature
79:cancer
1094:S2CID
1007:S2CID
956:S2CID
803:S2CID
717:S2CID
493:S2CID
39:cells
1137:PMID
1086:PMID
999:PMID
948:PMID
846:PMID
795:PMID
752:PMID
709:PMID
591:PMID
542:PMID
485:PMID
256:and
83:AIDS
81:and
1129:doi
1078:doi
1066:150
991:doi
979:163
940:doi
928:150
838:doi
787:doi
775:161
744:doi
699:doi
695:58A
581:PMC
573:doi
532:PMC
524:doi
477:doi
465:171
375:to
260:at
55:DNA
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