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. 2009 May 22;136(12):1963–1975. doi: 10.1242/dev.022426

Table 1.

Overview of fluorescence light-sheet techniques in comparison with epifluorescence, confocal and two-photon microscopy

Technique Unique features Advantages Disadvantages Ideal application References
Fluorescence microscopy
Epifluorescence microscopy Uniform illumination of the sample Easy to use, low cost No optical sectioning Screening, thin sections
Confocal microscopy Point illumination (laser focus) and point detection (pinhole) Optical sectioning, improved resolution (√2) Slow scanning, low penetration Medium-thick sections, surface of embryos Pawley, 2006
Two-photon microscopy True 3D imaging, infrared laser Low scattering, excellent penetration, reduced bleaching Slow scanning, low resolution, high cost, high power beam Deep penetration in scattering tissue Helmchen and Denk, 2005
Fluorescence light-sheet microscopy
Orthogonal-plane fluorescence optical sectioning (OPFOS) Single-sided light-sheet illumination Optical sectioning Shadows, stripes Fluorescently stained samples Voie et al., 1993
High-resolution orthogonal-plane fluorescence optical sectioning (HROPFOS) Like OPFOS, light-sheet translated Thin light-sheet of constant thickness Slow, shadows, stripes Like OPFOS Buytaert and Dirckx, 2007
3D light scanning macrography Extended depth of field Large samples Only surface Surface scanning of flies Huber et al., 2001
Thin light-sheet microscope (TLSM) Light-sheet illuminates tank of medium from the side Improved contrast in aqueous suspensions Low resolution Aquatic microbes Fuchs et al., 2002
Selective plane illumination microscopy (SPIM) Single-sided light-sheet illumination, sample rotation about vertical axis Fast acquisition, low photo-bleaching, good penetration, MVR Shadows, stripes Extended time-lapse imaging of millimetre-sized embryos, high speed movies Huisken et al., 2004
Objective coupled planar illumination (OCPI) microscopy Single-sided light-sheet illumination, attached to detection lens Fast stack acquisition, no sample movement, conventional sample Shadows, stripes Conventionally prepared samples, fast 3D imaging Holekamp et al., 2008
Ultramicroscopy Dual-sided light-sheet illumination, upright detection path Sealed chamber with clearing solution No index-matched optics, stripes Large fixed and cleared specimens Dodt et al., 2007
Digital scanned laser light-sheet fluorescence microscopy (DSLM) Like SPIM, light-sheet generated by beam scanning Like SPIM, uniform, adjustable light-sheet Like SPIM Like SPIM Keller et al., 2008
Multidirectional SPIM (mSPIM) Like SPIM, pivoting light-sheet, two alternating illumination arms Like SPIM, reduced stripes, reduced shading Space constraints Like SPIM, especially scattering and absorbing tissue Huisken and Stainier, 2007
Highly inclined and laminated optical sheet (HILO) microscopy Single lens for oblique light-sheet illumination and detection Single lens Very narrow FOV Single cell microscopy close to the coverslip Tokunaga et al., 2008
Oblique plane microscopy (OPM) Like HILO, matching, tilted image plane Like HILO, extended FOV Extensive optics Like HILO Dunsby, 2008