Origin of term ‘confluency’ in cell culture

Question

Since as long as I have been doing cell culture, the word confluency has been used to describe the percentage growth of cells or area covered by them. However, no dictionary that I have found uses this word. I was wondering if anyone could reliably state where the meaning comes from or how the association began, and truly what it means. I don't believe I can post this on another Stack Exchange because the word doesn't have even a resembling meaning in the dictionary. Cell culture is such an integral part of cell biology, medical research and biological manufacturing. And this term is an integral part of cell culture. I was surprised to be unable to reliably verify its meaning.

Answer 1

Besides the etymologic explanation that @aandreev gave, in cell culture this term is commonly used to describe the density of adherent cells and it is used as a measure of their proliferation. It is usually combined with an estimated (or counted) percentage, so 10% confluency means that 10% of the surface the dish or flask used is covered with cells, 100% means that it is entirely covered. The cells grow twodimensional on the surface of the flask in this case. The picture below (from here) illustrates different levels of confluency:

The level of confluency is important as the cells change their growth with changing densities. Low density cells (10-20%) usually grow slower than 50% confluent cells. If the plate is complete grown by cells, they tend to grow much slower again. This influences their genetic program, behaviour in experiments and transfections.

As @Roland pointed out it is important to say that confluency is not a hard measure, but rather an estimate of the cell density. Different people will get different estimations, but the trend should be the same.

Answer 2

con- (com-) is prefix that usually means "togetherness", joining. Root fluency/fluent comes from latin fluere, to flow.

Source: Google's definitions for con- and fluency (information scraped from OUP).

Answer 3

The word confluency is a variant of the word confluence, although this variant only appears with any frequency in the context of cell culture [1]. The word confluence itself appeared in the fifteenth century and is derived from the Late Latin confluentia meaning “a flowing together” [2]. In English it was initially used for the flowing together of two or more streams, but acquired a large variety of more figurative meanings [3].

The word confluence (but rarely confluency) occurs in various biological contexts in the first half of the twentieth century [4], but the first example I can find in relation to monolayer cell culture is in 1961 [5], although the term confluent appears in the 1950s [6]. The form confluency seems to have appeared at about the same time as confluence [7]. Since the 1960s both forms have been used by different authors, currently with comparable frequency [8]. Some authors employ either one or the other exclusively, others use confluency when indicating a percentage designation and confluence to indicate the absolute concept — or vice versa [9].

The reason that confluency is not defined in general dictionaries (or even in the Oxford Dictionary of Biology [10]) can only be surmized. None of the online dictionaries I have consulted [11] give the cell culture usage as an example of confluence, suggesting that its use is less frequent than in other technical contexts, where the meaning is similar. With this usage of confluence not being thought to merit separate mention (irrespective of the importance or otherwise of cell culture) then the need to define an alternative form would not have arisen.

It should be added that there is there is a Wikipedia entry for confluency [12] but, despite its title, this uses the term confluence in its definition:

“In cell culture biology, confluence refers to the percentage of the surface of a culture dish that is covered by adherent cells. For example, 50 percent confluence means roughly half of the surface is covered, while 100 percent confluence means the surface is completely covered by the cells, and no more room is left for the cells to grow as a monolayer.”

  Notes

[1] The hits reported by a Google Book ngram for the word confluency between 1800 and 1954 were analysed individually, as journal results from ngrams often have erroneous dates. There was one example (1829) of its occurrence before 1900, and 13 before 1950, about half in relation to vaccines or biological phenomena.

[2] The etymology of confluence given in the online etymological dictionary is: early 15c., “a flowing together, especially of two or more streams,” from Late Latin confluentia, from Latin confluentem (nominative confluens), present participle of confluere “to flow together," from assimilated form of com “with, together” (see con-) + fluere “to flow” (see fluent). I would emphasize that the word confluence is not a compound formed in English by adding a prefix to the word fluency, but derives from the compound word, confluentia, already evolved in Late Latin (i.e. by the sixth century).

[3] The Oxford English Dictionary quotes an early instance of the extension of the meaning of the word confluence (1606) as “In this confluence of so many prosperous successes”. A variety of examples, appearing to come from the fields of politics, philosophy and mathematics, can be found in the Cambridge Dictionary online for its second definition of confluence, “a situation in which two things join or come together”.

[4] This can be seen by going to the websites of some of the older biological journals (e.g. Journal of the National Cancer Institute or the Journal of Experimental Medicine) and searching for the word confluence.

[5] 1961 Yearbook of the Carnegie Institute of Washington (p.66).

[6] For example W.R.Earle (of Earle’s saline) uses it in a paper on the growth of fibroblasts in 1951, and T.T.Puck (of Puck’s saline) uses it in a 1958 article in Experientia. The earlier use of confluent (also of 15th century origin) in relation to monolayer culture suggests that the word confluency, rather being a corruption of confluence, may have been formed from the adjective — perhaps in ignorance that a noun form already existed.

[7] Königsberg et al. (1960) J. Biochem. Biophys. Cytol. 8 333–343.

[8] There seems to have been division at the outset. In the US, Harry Eagle and Renato Dulbecco used the term confluency, whereas Howard Green and George Todaro used confluence. What one might refer to as the Glasgow school always used confluence: John Paul) at the Beatson Institute and his student Ian Freshney, both authors of influential books on cell culture. The more recent frequency of use may be judged from a Google ngram for “cell confluence v. cell confluency”.

[9] Searching for confluence in the Journal of Cell Science and examining recent issues brings up results for both confluence and confluency. This recent paper uses confluence exclusively both as an absolute concept and as a percentage, whereas this recent paper, for example, uses confluency exclusively in both absolute and numerical senses. Another paper refers to confluency, but to 70% confluence, but exactly the opposite is found in this paper which refers to confluence, but 70–80% confluency. Some papers — e.g. this alternate at random. The editors of the journal obviously do not care.

[10] The Oxford Dictionary of Biology has nothing between the entries for cone and confocal.

[11] Collins, Chambers, Cambridge, Lexico or Merriam-Webster.

[12] Wikipedia entry for confluency.