Review of the development of light sheet fluorescence microscopy

Zhang Zijian; Xu Xin; Wang Jixiang; Ye Hong; Zhang Xin; Shi Guohua

doi:10.12086/oee.2023.220045

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Zhang Z J, Xu X, Wang J X, et al. Review of the development of light sheet fluorescence microscopy[J]. Opto-Electron Eng, 2023, 50(5): 220045. doi: 10.12086/oee.2023.220045

Citation:

Zhang Z J, Xu X, Wang J X, et al. Review of the development of light sheet fluorescence microscopy[J]. Opto-Electron Eng, 2023, 50(5): 220045. doi: 10.12086/oee.2023.220045

Review of the development of light sheet fluorescence microscopy

1.
Department of Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
2.
Jiangsu Key Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, China

Fund Project: Strategic Priority Research Program of the Chinese Academy of Sciences Fund (XDB32030205), and Scientific Instrument Developing Project of the Chinese Academy of Sciences Fund(YJKYYQ20210029)

More Information

^*Corresponding author: ghshi_lab@sibet.ac.cn

Received Date 11 April 2022

Revised Date 23 September 2022

Accepted Date 13 October 2022

Available Online 01 June 2023

Published Date 09 June 2023

Abstract

Abstract

In a traditional epi-illumination fluorescence microscope, the detection path is coaxial with the illumination path, which induces the non-focal plane fluorescence and deteriorates the imaging quality. Light sheet fluorescence microscopy (LSFM), differing from the traditional fluorescence microscopes, adopts an orthogonal configuration of detection and illumination paths. A thin sheet is formed from the excitation beam, which only excites a single layer of the sample. This methodology prevents the excited fluorescence from the non-focal plane during imaging. Besides, the utilization of the laminar illumination light can significantly reduce the exposure time of the fluorescence imaging. As a result, the effects of photobleaching and phototoxicity are decreased. In this review, we first introduce the basic light path structure compositions of a LSFM system as well as the optimization and innovation based on these structures. Next, we discuss enormous processing methods developed for samples both in vitro and in vivo. Benefiting from all these innovations, LSFM outstands in performing the 3D imaging of the fluorescence-labeled biological samples and can function steadily for a long recording time. Finally, we propose potential researching directions in the future, and discuss the technical limitations of current LSFM. This review aims to provide researchers in the relevant scientific research fields with a comprehensive understanding and inspiring reference of LSFM techniques.
- light sheet fluorescence microscopy /
- sectioning ability /
- optical structures /
- sample processing

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References

[1]	Stephens D J, Allan V J. Light microscopy techniques for live cell imaging[J]. Science, 2003, 300(5616): 82−86. doi: 10.1126/science.1082160 CrossRef Google Scholar
[2]	Truong T V, Supatto W, Koos D S, et al. Deep and fast live imaging with two-photon scanned light-sheet microscopy[J]. Nat Methods, 2011, 8(9): 757−760. doi: 10.1038/nmeth.1652 CrossRef Google Scholar
[3]	Siedentopf H, Zsigmondy R. Uber sichtbarmachung und größenbestimmung ultramikoskopischer teilchen, mit besonderer anwendung auf goldrubingläser[J]. Ann Phys, 1902, 315(1): 1−39. doi: 10.1002/andp.19023150102 CrossRef Google Scholar
[4]	Voie A H, Burns D H, Spelman F A. Orthogonal-plane fluorescence optical sectioning: three-dimensional imaging of macroscopic biological specimens[J]. J Microsc, 1993, 170(3): 229−236. doi: 10.1111/j.1365-2818.1993.tb03346.x CrossRef Google Scholar
[5]	Stelzer E H K, Strobl F, Chang B J, et al. Light sheet fluorescence microscopy[J]. Nat Rev Methods Primers, 2021, 1(1): 73. doi: 10.1038/s43586-021-00069-4 CrossRef Google Scholar
[6]	Huisken J, Swoger J, Del Bene F, et al. Optical sectioning deep inside live embryos by selective plane illumination microscopy[J]. Science, 2004, 305(5686): 1007−1009. doi: 10.1126/science.1100035 CrossRef Google Scholar
[7]	Keller P J, Schmidt A D, Wittbrodt J, et al. Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy[J]. Science, 2008, 322(5904): 1065−1069. doi: 10.1126/science.1162493 CrossRef Google Scholar
[8]	Vettenburg T, Dalgarno H I C, Nylk J, et al. Light-sheet microscopy using an Airy beam[J]. Nat Methods, 2014, 11(5): 541−544. doi: 10.1038/nmeth.2922 CrossRef Google Scholar
[9]	Planchon T A, Gao L, Milkie D E, et al. Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination[J]. Nat Methods, 2011, 8(5): 417−423. doi: 10.1038/nmeth.1586 CrossRef Google Scholar
[10]	Chen B C, Legant W R, Wang K, et al. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution[J]. Science, 2014, 346(6208): 1257998. doi: 10.1126/science.1257998 CrossRef Google Scholar
[11]	Holekamp T F, Turaga D, Holy T E. Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy[J]. Neuron, 2008, 57(5): 661−672. doi: 10.1016/j.neuron.2008.01.011 CrossRef Google Scholar
[12]	Gao L, Shao L, Chen B C, et al. 3D live fluorescence imaging of cellular dynamics using Bessel beam plane illumination microscopy[J]. Nat Protoc, 2014, 9(5): 1083−1101. doi: 10.1038/nprot.2014.087 CrossRef Google Scholar
[13]	Chang B J, Kittisopikul M, Dean K M, et al. Universal light-sheet generation with field synthesis[J]. Nat Methods, 2019, 16(3): 235−238. doi: 10.1038/s41592-019-0327-9 CrossRef Google Scholar
[14]	Fiolka R, Stemmer A, Belyaev Y. Virtual slit scanning microscopy[J]. Histochem Cell Biol, 2007, 128(6): 499−505. doi: 10.1007/s00418-007-0342-2 CrossRef Google Scholar
[15]	Hosny N A, Seyforth J A, Spickermann G, et al. Planar Airy beam light-sheet for two-photon microscopy[J]. Biomed Opt Express, 2020, 11(7): 3927−3935. doi: 10.1364/BOE.395547 CrossRef Google Scholar
[16]	Huisken J, Stainier D Y R. Even fluorescence excitation by multidirectional selective plane illumination microscopy (mSPIM)[J]. Opt Lett, 2007, 32(17): 2608−2610. doi: 10.1364/OL.32.002608 CrossRef Google Scholar
[17]	Krzic U, Gunther S, Saunders T E, et al. Multiview light-sheet microscope for rapid in toto imaging[J]. Nat Methods, 2012, 9(7): 730−733. doi: 10.1038/nmeth.2064 CrossRef Google Scholar
[18]	Tomer R, Khairy K, Amat F, et al. Quantitative high-speed imaging of entire developing embryos with simultaneous multiview light-sheet microscopy[J]. Nat Methods, 2012, 9(7): 755−763. doi: 10.1038/nmeth.2062 CrossRef Google Scholar
[19]	Fu Q Y, Martin B L, Matus D Q, et al. Imaging multicellular specimens with real-time optimized tiling light-sheet selective plane illumination microscopy[J]. Nat Commun, 2016, 7(1): 11088. doi: 10.1038/ncomms11088 CrossRef Google Scholar
[20]	Gao L. Extend the field of view of selective plan illumination microscopy by tiling the excitation light sheet[J]. Opt Express, 2015, 23(5): 6102−6111. doi: 10.1364/OE.23.006102 CrossRef Google Scholar
[21]	Wang D Y, Jin Y X, Feng R L, et al. Tiling light sheet selective plane illumination microscopy using discontinuous light sheets[J]. Opt Express, 2019, 27(23): 34472−34483. doi: 10.1364/OE.27.034472 CrossRef Google Scholar
[22]	Zong W J, Zhao J, Chen X Y, et al. Large-field high-resolution two-photon digital scanned light-sheet microscopy[J]. Cell Res, 2015, 25(2): 254−257. doi: 10.1038/cr.2014.124 CrossRef Google Scholar
[23]	Dean K M, Roudot P, Welf E S, et al. Deconvolution-free subcellular imaging with axially swept light sheet microscopy[J]. Biophys J, 2015, 108(12): 2807−2815. doi: 10.1016/j.bpj.2015.05.013 CrossRef Google Scholar
[24]	Bouchard M B, Voleti V, Mendes C S, et al. Swept confocally-aligned planar excitation (SCAPE) microscopy for high-speed volumetric imaging of behaving organisms[J]. Nat Photonics, 2015, 9(2): 113−119. doi: 10.1038/nphoton.2014.323 CrossRef Google Scholar
[25]	Strnad P, Gunther S, Reichmann J, et al. Inverted light-sheet microscope for imaging mouse pre-implantation development[J]. Nat Methods, 2016, 13(2): 139−142. doi: 10.1038/nmeth.3690 CrossRef Google Scholar
[26]	Greer C J, Holy T E. Fast objective coupled planar illumination microscopy[J]. Nat Commun, 2019, 10(1): 4483. doi: 10.1038/s41467-019-12340-0 CrossRef Google Scholar
[27]	Fan J T, Suo J L, Wu J M, et al. Video-rate imaging of biological dynamics at centimetre scale and micrometre resolution[J]. Nat Photonics, 2019, 13(11): 809−816. doi: 10.1038/s41566-019-0474-7 CrossRef Google Scholar
[28]	Tsien R Y. The green fluorescent protein[J]. Annu Rev Biochem, 1998, 67: 509−544. doi: 10.1146/annurev.biochem.67.1.509 CrossRef Google Scholar
[29]	Keppler A, Gendreizig S, Gronemeyer T, et al. A general method for the covalent labeling of fusion proteins with small molecules in vivo[J]. Nat Biotechnol, 2003, 21(1): 86−89. doi: 10.1038/nbt765 CrossRef Google Scholar
[30]	Los G V, Encell L P, McDougall M G, et al. HaloTag: a novel protein labeling technology for cell imaging and protein analysis[J]. ACS Chem Biol, 2008, 3(6): 373−382. doi: 10.1021/cb800025k CrossRef Google Scholar
[31]	Shaner N C, Steinbach P A, Tsien R Y. A guide to choosing fluorescent proteins[J]. Nat Methods, 2005, 2(12): 905−909. doi: 10.1038/nmeth819 CrossRef Google Scholar
[32]	Matz M V, Fradkov A F, Labas Y A, et al. Fluorescent proteins from nonbioluminescent Anthozoa species[J]. Nat Biotechnol, 1999, 17(10): 969−973. doi: 10.1038/13657 CrossRef Google Scholar
[33]	Ai H W, Baird M A, Shen Y, et al. Engineering and characterizing monomeric fluorescent proteins for live-cell imaging applications[J]. Nat Protoc, 2014, 9(4): 910−928. doi: 10.1038/nprot.2014.054 CrossRef Google Scholar
[34]	Chen T W, Wardill T J, Sun Y, et al. Ultrasensitive fluorescent proteins for imaging neuronal activity[J]. Nature, 2013, 499(7458): 295−300. doi: 10.1038/nature12354 CrossRef Google Scholar
[35]	Kim S Y, Cho J H, Murray E, et al. Stochastic electrotransport selectively enhances the transport of highly electromobile molecules[J]. Proc Natl Acad Sci USA, 2015, 112(46): E6274−E6283. doi: 10.1073/pnas.1510133112 CrossRef Google Scholar
[36]	Costantini I, Cicchi R, Silvestri L, et al. In-vivo and ex-vivo optical clearing methods for biological tissues: review[J]. Biomed Opt Express, 2019, 10(10): 5251−5267. doi: 10.1364/BOE.10.005251 CrossRef Google Scholar
[37]	Richardson D S, Lichtman J W. Clarifying tissue clearing[J]. Cell, 2015, 162(2): 246−257. doi: 10.1016/j.cell.2015.06.067 CrossRef Google Scholar
[38]	Chakraborty T, Driscoll M K, Jeffery E, et al. Light-sheet microscopy of cleared tissues with isotropic, subcellular resolution[J]. Nat Methods, 2019, 16(11): 1109−1113. doi: 10.1038/s41592-019-0615-4 CrossRef Google Scholar
[39]	Glaser A K, Reder N P, Chen Y, et al. Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues[J]. Nat Commun, 2019, 10(1): 2781. doi: 10.1038/s41467-019-10534-0 CrossRef Google Scholar
[40]	Dodt H U, Leischner U, Schierloh A, et al. Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain[J]. Nat Methods, 2007, 4(4): 331−336. doi: 10.1038/nmeth1036 CrossRef Google Scholar
[41]	Hama H, Kurokawa H, Kawano H, et al. Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain[J]. Nat Neurosci, 2011, 14(11): 1481−1488. doi: 10.1038/nn.2928 CrossRef Google Scholar
[42]	Ertürk A, Becker K, Jährling N, et al. Three-dimensional imaging of solvent-cleared organs using 3DISCO[J]. Nat Protoc, 2012, 7(11): 1983−1995. doi: 10.1038/nprot.2012.119 CrossRef Google Scholar
[43]	Chung K, Wallace J, Kim S Y, et al. Structural and molecular interrogation of intact biological systems[J]. Nature, 2013, 497(7449): 332−337. doi: 10.1038/nature12107 CrossRef Google Scholar
[44]	Park Y G, Sohn C H, Chen R, et al. Protection of tissue physicochemical properties using polyfunctional crosslinkers[J]. Nat Biotechnol, 2019, 37(1): 73−83. doi: 10.1038/nbt.4281 CrossRef Google Scholar
[45]	Pan C C, Cai R Y, Quacquarelli F P, et al. Shrinkage-mediated imaging of entire organs and organisms using uDISCO[J]. Nat Methods, 2016, 13(10): 859−867. doi: 10.1038/nmeth.3964 CrossRef Google Scholar
[46]	Chen F, Tillberg P W, Boyden E S. Expansion microscopy[J]. Science, 2015, 347(6221): 543−548. doi: 10.1126/science.1260088 CrossRef Google Scholar
[47]	Chen F, Wassie A T, Cote A J, et al. Nanoscale imaging of RNA with expansion microscopy[J]. Nat Methods, 2016, 13(8): 679−684. doi: 10.1038/nmeth.3899 CrossRef Google Scholar
[48]	Alon S, Goodwin D R, Sinha A, et al. Expansion sequencing: spatially precise in situ transcriptomics in intact biological systems[J]. Science, 2021, 371(6528): eaax2656. doi: 10.1126/science.aax2656 CrossRef Google Scholar
[49]	Kaufmann A, Mickoleit M, Weber M, et al. Multilayer mounting enables long-term imaging of zebrafish development in a light sheet microscope[J]. Development, 2012, 139(17): 3242−3247. doi: 10.1242/dev.082586 CrossRef Google Scholar
[50]	De Medeiros G, Balázs B, Hufnagel L. Light-sheet imaging of mammalian development[J]. Semin Cell Dev Biol, 2016, 55: 148−155. doi: 10.1016/j.semcdb.2015.11.001 CrossRef Google Scholar
[51]	Ichikawa T, Nakazato K, Keller P J, et al. Live imaging of whole mouse embryos during gastrulation: migration analyses of epiblast and mesodermal cells[J]. PLoS One, 2013, 8(7): e64506. doi: 10.1371/journal.pone.0064506 CrossRef Google Scholar
[52]	Udan R S, Piazza V G, Hsu C W, et al. Quantitative imaging of cell dynamics in mouse embryos using light-sheet microscopy[J]. Development, 2014, 141(22): 4406−4414. doi: 10.1242/dev.111021 CrossRef Google Scholar
[53]	McDole K, Guignard L, Amat F, et al. In toto imaging and reconstruction of post-implantation mouse development at the single-cell level[J]. Cell, 2018, 175(3): 859−876.e33. doi: 10.1016/j.cell.2018.09.031 CrossRef Google Scholar
[54]	Hillman E M C, Voleti V, Li W Z, et al. Light-sheet microscopy in neuroscience[J]. Annu Rev Neurosci, 2019, 42: 295−313. doi: 10.1146/annurev-neuro-070918-050357 CrossRef Google Scholar
[55]	Wan Y N, McDole K, Keller P J. Light-sheet microscopy and its potential for understanding developmental processes[J]. Annu Rev Cell Dev Biol, 2019, 35: 655−681. doi: 10.1146/annurev-cellbio-100818-125311 CrossRef Google Scholar
[56]	Poola P K, Afzal M I, Yoo Y, et al. Light sheet microscopy for histopathology applications[J]. Biomed Eng Lett, 2019, 9(3): 279−291. doi: 10.1007/s13534-019-00122-y CrossRef Google Scholar
[57]	Chang B J, Meza V D P, Stelzer E H K. csiLSFM combines light-sheet fluorescence microscopy and coherent structured illumination for a lateral resolution below 100 nm[J]. Proc Natl Acad Sci USA, 2017, 114(19): 4869−4874. doi: 10.1073/pnas.1609278114 CrossRef Google Scholar
[58]	Betzig E, Patterson G H, Sougrat R, et al. Imaging intracellular fluorescent proteins at nanometer resolution[J]. Science, 2006, 313(5793): 1642−1645. doi: 10.1126/science.1127344 CrossRef Google Scholar
[59]	Hell S W, Wichmann J. Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy[J]. Opt Lett, 1994, 19(11): 780−782. doi: 10.1364/OL.19.000780 CrossRef Google Scholar
[60]	Nelsen E, Hobson C M, Kern M E, et al. Combined atomic force microscope and volumetric light sheet system for correlative force and fluorescence mechanobiology studies[J]. Sci Rep, 2020, 10(1): 8133. doi: 10.1038/s41598-020-65205-8 CrossRef Google Scholar
[61]	Royer L A, Lemon W C, Chhetri R K, et al. A practical guide to adaptive light-sheet microscopy[J]. Nat Protoc, 2018, 13(11): 2462−2500. doi: 10.1038/s41596-018-0043-4 CrossRef Google Scholar

Overview

Overview

Light sheet fluorescence microscopy (LSFM), as a type of fluorescence microscope, can image fluorescence-labelled specific ribosomes, proteins, and cells, and observe their positions and functions in biological tissues. Different from traditional fluorescence microscopes, LSFM’s detection path and illumination path are arranged at orthogonal orientation. The excitation beam is a thin sheet, only a slice region of the sample is illuminated, thus reducing the fluorescence generation in the non-focal plane. Besides only a single plane is illuminated by the laser at a time, which significantly reduces the exposure time of the fluorescent molecules, thereby minimizing the effects of photobleaching and phototoxicity. Due to these properties, LSFM can perform 3D imaging of fluorescence-labeled biological samples for a long recording time. Nowadays, it has been widely used in many biological fields such as neuroscience, developmental biology, and histopathology.

In the first part, the LSFM with classical optical path configurations, such as SPIM, OCPI, and DSLM are described from the perspective of optical path construction. The work made by researchers to promote the resolution and imaging throughput based on those work are introduced. These methods include changing the beam structure, shortening the optical path distance, and increasing the imaging speed, many of which are still beneficial to us today. In the second part, fluorescent dyes and immunofluorescence staining techniques for biological samples used in LSFM are described, including tissue transparency and sample fixing of living animals. These sample processing methods have greatly promoted the development of fluorescence microscopes, and representative studies are listed.

Finally, the review summarizes both the advantages and disadvantages of LSFM as well as the potential development direction and limitations. The orthogonal optical path configuration limits the lateral size of the sample, and the imaging performance is poor for the opaque or high-scattering samples. LSFM has higher requirements for both the size and transparency of the sample. It is considered that the breakthrough of the LSFM in future breakthroughs mainly lies in two aspects: improving the imaging parameters and adapting to more biological applications. It should be done from a biological point of view, in conjunction with other technologies, to advance the development of LSFM. Finally, this review is expected to provide researchers with a more systematic knowledge of light-sheet fluorescence microscopy and some useful references.