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Light sheet fluorescence microscopy (LSFM) is an imaging method that uses one or more illumination objectives to excite fluorophores in a specimen with a thin sheet of light. Emitted light from the sample is then visualized by a separate imaging objective that is perpendicular to the illuminating lightsheet. 

Image courtesy of Carl Zeiss AG

Light sheet microscopy (LSFM) has several advantages over confocal microscopy (LSCM):

• Excellent sample penetration- In conventional confocal microscopy, excitation illumination must pass from the objective through the sample to the plane of focus, then emitted light must return through the sample and into the objective via the same light path.  The compounded scattering of both excitatory and emitted light limits sensitivity and resolution in thick samples.  In LSFM, the excitation light sheet comes from dedicated illumination objectives and emitted light from the sample is detected by a separate imaging objective.  This reduces light scattering and improves imaging in thick specimens.
• High speed- In confocal microscopy, the excitation laser scans across the sample field and emitted light is captured by a photo-multiplier tube, constructing an image pixel by pixel.  In LSFM, The entire focal plane is illuminated at once, allowing an image to be collected using a high speed camera. 
• Minimal phototoxicity and photobleaching- Because excitatory light is passing through the entire depth of the sample in confocal microscopy, there can be significant bleaching of the sample and a high risk for phototoxicity in live specimens.  Because only a thin sheet of excitatory light is used in LSFM and because imaging with a camera is rapid, this method dramatically reduces photobleaching and phototoxicity.

These properties make LSFM ideal for many biological imaging applications, including:

• Fluorescence imaging of thick samples
• Long term imaging of live samples

For more information about LSFM, visit MicroscopyU.

Exact properties for each method are dependent on specific system configurations. General properties shown here are derived from published sources (Combs and Shroff, 2017).

*Instruments available in the CGI Core
**Instruments available in Light Microscopy Core.

The CGI Core offers two microscopes capable of performing LSFM, the Zeiss Lightsheet Z.1 and the Leica SP8 DLS. They use very different implementations to create a light sheet (see individual microscope pages).

The table below highlights operational differences between the two microscopes.

For more information or to discuss the best options for your imaging application, please contact us.

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A.L. Byrd et al. (2023). Dysregulated Polycomb Repressive Complex 2 contributes to chronic obstructive pulmonary disease by rewiring stem cell fate. Stem Cell Reports 18:289-304.

Z.R. Hettinger et al. (2022). Mechanotherapy reprograms aged muscle stromal cells to remodel the extracellular matrix during recovery from disuse. FUNCTION 3:zqac015.

Y. Wen, D.A. Englund, B.D. Peck, K.A. Murach, J.J. McCarthy, C.A. Peterson (2021). Myonuclear transcriptional dynamics in response to exercise following satellite cell depletion. iScience 24:102838.

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K.F. Titialii-Torres and A.C. Morris (2022). Embryonic hyperglycemia perturbs the development of specific retinal cell types, including photoreceptors.  J. Cell Sci. 135(1): jcs259187.

C.E. Coomer et al. (2020). Her9/Hes4 is required for retinal photoreceptor development, maintenance, and survival. Sci Rep 10:11316.

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