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Review
. 2015 Apr;5(4):150019.
doi: 10.1098/rsob.150019.

From Animaculum to single molecules: 300 years of the light microscope

Adam J M Wollman  1 , Richard Nudd  1 , Erik G Hedlund  1 , Mark C Leake  2
Affiliations
Review

From Animaculum to single molecules: 300 years of the light microscope

Adam J M Wollman et al. Open Biol. 2015 Apr.

Abstract

Although not laying claim to being the inventor of the light microscope, Antonj van Leeuwenhoek (1632-1723) was arguably the first person to bring this new technological wonder of the age properly to the attention of natural scientists interested in the study of living things (people we might now term 'biologists'). He was a Dutch draper with no formal scientific training. From using magnifying glasses to observe threads in cloth, he went on to develop over 500 simple single lens microscopes (Baker & Leeuwenhoek 1739 Phil. Trans. 41, 503-519. (doi:10.1098/rstl.1739.0085)) which he used to observe many different biological samples. He communicated his finding to the Royal Society in a series of letters (Leeuwenhoek 1800 The select works of Antony Van Leeuwenhoek, containing his microscopical discoveries in many of the works of nature, vol. 1) including the one republished in this edition of Open Biology. Our review here begins with the work of van Leeuwenhoek before summarizing the key developments over the last ca 300 years, which has seen the light microscope evolve from a simple single lens device of van Leeuwenhoek's day into an instrument capable of observing the dynamics of single biological molecules inside living cells, and to tracking every cell nucleus in the development of whole embryos and plants.

Keywords: fluorescence; optical microscopy; superresolution.

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Figures

Figure 1.
Figure 1.
Optical microscope designs through the ages. (a) One design of a simple compound microscope used by Hooke while writing Micrographia. (b) An example of the single spherical lens mount system that van Leeuwenhoek used, approximately 5 cm in height. (c) A simple epi-fluorescence system. (d) A simple modern-day confocal microscope.
Figure 2.
Figure 2.
Mathematically generated PSF images from different light microscope designs. (a) The Airy pattern, a disc and one of the rings produced by a point source emitter imaged using a spherical lens. (b) Two such Airy discs separated by less than the Abbe limit for optical resolution. (c) The lateral xy stretching exhibited in astigmatic imaging systems when the height z of a point source emitter is above or below the focal plane, the degree of stretching a metric for z. (d) Expected pattern when a point source emitter is defocused. (e) Two-lobed PSF used in double-helix PSF techniques, where the rotation of the lobes about the central point is used to calculate z.
Figure 3.
Figure 3.
By chance, in the last days of finishing this review, the corresponding author was staying approximately 100 m from Leeuwenhoek's final resting place in the Oude Kerk, Delft, and captured these images.
See this image and copyright information in PMC

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References

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    1. Hooke R. 1665. Micrographia: or some physiological descriptions of minute bodies made by magnifying glasses, with observations and inquiries thereupon. Courier Corporation.
    1. Baker H, Leeuwenhoek M. 1739. An account of Mr. Leeuwenhoek's microscopes; by Mr. Henry Baker F. R. S. 1739. Phil. Trans. 41, 503–519 (doi:10.1098/rstl.1739.0085) - DOI
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