Time-lapse microscopy

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Time-lapse microscope
A time-lapse microscope. The transparent cell incubator is necessary to keep cells alive during observation.
Other names(Time-lapse) microcinematograph, (Time-lapse) video microscope, Time-lapse cinemicrograph
UsesObservation of slow microscopic processes
InventorJean Comandon and other contemporaries
Related itemsTime-lapse photography, Live-cell imaging

Time-lapse microscopy is time-lapse photography applied to microscopy. Microscope image sequences are recorded and then viewed at a greater speed to give an accelerated view of the microscopic process.

Before the introduction of the video tape recorder in the 1960s, time-lapse microscopy recordings were made on photographic film. During this period, time-lapse microscopy was referred to as microcinematography. With the increasing use of video recorders, the term time-lapse video microscopy was gradually adopted. Today, the term video is increasingly dropped, reflecting that a digital still camera is used to record the individual image frames, instead of a video recorder.


A time-lapse movie of dividing cancer cells, created by using a phase-contrast microscope.
Cell division over 42 hours. The time-lapse movie was created by using a phase microscope.
Jean Comandon, pioneer of microcinematography, recorded this time-lapse film in c. 1910, using an ultramicroscope. The film show living spiral shaped syphilis bacteria moving among red blood cells of frog. Notice the back-and-forth movement, characterizing the disease-causing form.

Time-lapse microscopy can be used to observe any microscopic object over time. However, its main use is within cell biology to observe artificially cultured cells. Depending on the cell culture, different microscopy techniques can be applied to enhance characteristics of the cells as most cells are transparent.[1]

To enhance observations further, cells have therefore traditionally been stained before observation. Unfortunately, the staining process kills the cells. The development of less destructive staining methods and methods to observe unstained cells has led to that cell biologists increasingly observe living cells. This is known as live-cell imaging. A few tools have been developed to identify and analyze single cells during live-cell imaging.[2][3][4]

Time-lapse microscopy is the method that extends live-cell imaging from a single observation in time to the observation of cellular dynamics over long periods of time.[5][6] Time-lapse microscopy is primarily used in research, but is clinically used in IVF clinics as studies has proven it to increase pregnancy rates, lower abortion rates and predict aneuploidy[7][8]

Modern approaches are further extending time-lapse microscopy observations beyond making movies of cellular dynamics. Traditionally, cells have been observed in a microscope and measured in a cytometer. Increasingly this boundary is blurred as cytometric techniques are being integrated with imaging techniques for monitoring and measuring dynamic activities of cells and subcellular structures.[5]


One of the microcinematographs used at the Marey Institute during the late 19th century

The Cheese Mites by Martin Duncan from 1903 is one of the earliest microcinematographic films.[9] However, the early development of scientific microcinematography took place in Paris. The first reported time-lapse microscope was assembled in the late 1890s at the Marey Institute, founded by the pioneer of chronophotography, Étienne-Jules Marey.[10][11][12] It was, however, Jean Comandon who made the first significant scientific contributions around 1910.[13][14]

Comandon was a trained microbiologist specializing in syphilis research. Inspired by Victor Henri's microcinematic work on Brownian motion,[15][16][17] he used the newly invented ultramicroscope to study the movements of the syphilis bacteria.[18] At the time, the ultramicroscope was the only microscope in which the thin spiral shaped bacteria was visible. Using an enormous cinema camera bolted to the fragile microscope, he demonstrated visually that the movement of the disease-causing bacteria is uniquely different from the non-disease-causing form. Comandon's films proved instrumental in teaching doctors how to distinguish the two forms.[19][20]

Comandon's extensive pioneering work inspired others to adopt microcinematography. Heniz Rosenberger builds a microcinematograph in the mid-1920s. In collerboration with Alexis Carrel, they used the device to further develop Carrel's cell culturing techniques.[21] Similar work was conducted by Warren Lewis.[22]

During World War II, Carl Zeiss AG released the first phase-contrast microscope on the market. With this new microscope, cellular details could for the first time be observed without using lethal stains.[1] By setting up some of the first time-lapse experiments with chicken fibroblasts and a phase-contrast microscope, Michael Abercrombie described the basis of our current understanding of cell migration in 1953.[23][24]

With the broad introduction of the digital camera at the beginning of this century, time-lapse microscopy has been made dramatically more accessible and is currently experiencing an unrepresented raise in scientific publications.[5]

See also[edit]


  1. ^ a b "The Phase Contrast Microscope". Nobel Media AB.
  2. ^ Stylianidou, Stella; Brennan, Connor; Nissen, Silas B.; Kuwada, Nathan J.; Wiggins, Paul A. (August 29, 2016). "SuperSegger: robust image segmentation, analysis and lineage tracking of bacterial cells" (PDF). Molecular Microbiology. 102 (4): 690–700. doi:10.1111/mmi.13486. PMID 27569113. S2CID 10684951.
  3. ^ Young, Jonathan W.; Locke, James C. W.; Altinok, Alphan; Rosenfeld, Nitzan; Bacarian, Tigran; Swain, Peter S.; Mjolsness, Eric; Elowitz, Michael B. (December 15, 2011). "Measuring single-cell gene expression dynamics in bacteria using fluorescence time-lapse microscopy". Nature Protocols. 7 (1): 80–88. doi:10.1038/nprot.2011.432. PMC 4161363. PMID 22179594.
  4. ^ Merouane, Amine; Rey-Villamizar, Nicolas; Lu, Yanbin; Liadi, Ivan; Romain, Gabrielle; Lu, Jennifer; Singh, Harjeet; Cooper, Laurence J. N.; Varadarajan, Navin; Roysam, Badrinath (2015-10-01). "Automated profiling of individual cell–cell interactions from high-throughput time-lapse imaging microscopy in nanowell grids (TIMING)". Bioinformatics. 31 (19): 3189–3197. doi:10.1093/bioinformatics/btv355. ISSN 1367-4803. PMC 4693004. PMID 26059718.
  5. ^ a b c Coutu, D. L.; Schroeder, T. (2013). "Probing cellular processes by long-term live imaging - historic problems and current solutions". Journal of Cell Science. 126 (Pt 17): 3805–15. doi:10.1242/jcs.118349. PMID 23943879.
  6. ^ Landecker, H. (2009). "Seeing things: From microcinematography to live cell imaging". Nature Methods. 6 (10): 707–709. doi:10.1038/nmeth1009-707. PMID 19953685. S2CID 6521488.
  7. ^ Meseguer, M.; Rubio, I.; Cruz, M.; Basile, N.; Marcos, J.; Requena, A. (2012). "Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: A retrospective cohort study". Fertility and Sterility. 98 (6): 1481–1489.e10. doi:10.1016/j.fertnstert.2012.08.016. PMID 22975113.
  8. ^ Campbell, A.; Fishel, S.; Bowman, N.; Duffy, S.; Sedler, M.; Hickman, C. F. L. (2013). "Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics". Reproductive BioMedicine Online. 26 (5): 477–485. doi:10.1016/j.rbmo.2013.02.006. PMID 23518033.
  9. ^ Rohrer, Finlo. "Cheese mites and other wonders". BBC News Magazine. Retrieved 2011-04-24.
  10. ^ Talbot, Frederick A. (1913). Practical cinematography and its applications. W. Heinemann. OL 7220960M.
  11. ^ "Le cinéma au service de la science". Institut national de l'audiovisuel. Retrieved 2013-01-09.
  12. ^ Landecker, Hannah (2006). "Microcinematography and the History of Science and Film". Isis. 97: 121–132. doi:10.1086/501105. S2CID 144554305.
  13. ^ "Jean Comandon (1877-1970)". Institut Pasteur. Archived from the original on 2014-12-05.
  14. ^ "MICROBES CAUGHT IN ACTION.; Moving Pictures of Them a Great Aid In Medical Research". The New York Times. October 31, 1909.
  15. ^ Bigg, Charlotte (2011). "Chapter 6: A visual history of Jean Perrin's Brownian motion curves" (PDF). In Daston, Lorraine; Lunbeck, Elizabeth (eds.). Histories of Scientific Observation. The University of Chicago Press.[permanent dead link]
  16. ^ Bigg, Charlotte (2008). "Evident atoms: visuality in Jean Perrin's Brownian motion research" (PDF). Studies in History and Philosophy of Science Part A. 39 (3): 312–322. doi:10.1016/j.shpsa.2008.06.003.[permanent dead link]
  17. ^ Henri, Victor (1908). "Étude cinématographique des mouvements browniens". Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences (146): 1024–1026.
  18. ^ Landecker, Hannah (2005). "Cellular Features: Microcinematography and Film Theory". Critical Inquiry. 31 (4): 903–937. doi:10.1086/444519. S2CID 162894152.
  19. ^ Bayly, H. W. (1910). "Demonstration by the Ultra-microscope of living Treponema pallidum and various Spirochaetes". Proceedings of the Royal Society of Medicine. 3 (Clin Sect): 3–6. doi:10.1177/003591571000300202. PMC 1961544. PMID 19974144.
  20. ^ Roux, P.; Münter, S.; Frischknecht, F.; Herbomel, P.; Shorte, S. L. (2004). "Focusing light on infection in four dimensions". Cellular Microbiology. 6 (4): 333–343. doi:10.1111/j.1462-5822.2004.00374.x. PMID 15009025. S2CID 12228598.
  21. ^ Rosenberger, Heinz (1929). "Micro-Cinematography in Medical Research". J Dent Res. 9 (3): 343–352. doi:10.1177/00220345290090030501. S2CID 71952151.
  22. ^ "Warren H. (Warren Harmon) Lewis papers, ca. 1913-1964". American Philosophical Society. Retrieved 2011-04-24.
  23. ^ Hoyos-Flight, Monica. "Milestone 2: Nature Milestones in Cytoskeleton". Nature Publishing Group.
  24. ^ Abercrombie, M.; Heaysman, J. E. (1953). "Observations on the social behaviour of cells in tissue culture. I. Speed of movement of chick heart fibroblasts in relation to their mutual contacts". Experimental Cell Research. 5 (1): 111–131. doi:10.1016/0014-4827(53)90098-6. PMID 13083622.

External links[edit]

Historic time-lapse microscopy films[edit]