Abstract

We developed a compact plane illumination plugin (PIP) device which enabled plane illumination and light sheet fluorescence imaging on a conventional inverted microscope. The PIP device allowed the integration of microscope with tunable laser sheet profile, fast image acquisition, and 3-D scanning. The device is both compact, measuring approximately 15 by 5 by 5 cm, and cost-effective, since we employed consumer electronics and an inexpensive device molding method. We demonstrated that PIP provided significant contrast and resolution enhancement to conventional microscopy through imaging different multi-cellular fluorescent structures, including 3-D branched cells in vitro and live zebrafish embryos. Imaging with the integration of PIP greatly reduced out-of-focus contamination and generated sharper contrast in acquired 2-D plane images when compared with the stand-alone inverted microscope. As a result, the dynamic fluid domain of the beating zebrafish heart was clearly segmented and the functional monitoring of the heart was achieved. Furthermore, the enhanced axial resolution established by thin plane illumination of PIP enabled the 3-D reconstruction of the branched cellular structures, which leads to the improvement on the functionality of the wide field microscopy.

© 2015 Optical Society of America

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2014 (2)

B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
[Crossref] [PubMed]

C. Chardès, P. Mélénec, V. Bertrand, and P.-F. Lenne, “Setting up a simple light sheet microscope for in toto imaging of C. elegans development,” J. Vis. Exp. 87, 51342 (2014).
[PubMed]

2013 (6)

P. G. Pitrone, J. Schindelin, L. Stuyvenberg, S. Preibisch, M. Weber, K. W. Eliceiri, J. Huisken, and P. Tomancak, “OpenSPIM: an open-access light-sheet microscopy platform,” Nat. Methods 10(7), 598–599 (2013).
[Crossref] [PubMed]

Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
[Crossref] [PubMed]

J. Lee, M. E. Moghadam, E. Kung, H. Cao, T. Beebe, Y. Miller, B. L. Roman, C.-L. Lien, N. C. Chi, A. L. Marsden, and T. K. Hsiai, “Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis,” PLoS One 8(8), e72924 (2013).
[Crossref] [PubMed]

T. Panier, S. A. Romano, R. Olive, T. Pietri, G. Sumbre, R. Candelier, and G. Debrégeas, “Fast functional imaging of multiple brain regions in intact zebrafish larvae using Selective Plane Illumination Microscopy,” Front. Neural Circuits 7, 65 (2013).
[Crossref] [PubMed]

M. B. Ahrens, M. B. Orger, D. N. Robson, J. M. Li, and P. J. Keller, “Whole-brain functional imaging at cellular resolution using light-sheet microscopy,” Nat. Methods 10(5), 413–420 (2013).
[Crossref] [PubMed]

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
[Crossref] [PubMed]

2012 (3)

T.-Y. Chang, C. Pardo-Martin, A. Allalou, C. Wählby, and M. F. Yanik, “Fully automated cellular-resolution vertebrate screening platform with parallel animal processing,” Lab Chip 12(4), 711–716 (2012).
[Crossref] [PubMed]

A. Kaufmann, M. Mickoleit, M. Weber, and J. Huisken, “Multilayer mounting enables long-term imaging of zebrafish development in a light sheet microscope,” Development 139(17), 3242–3247 (2012).
[Crossref] [PubMed]

J. M. Taylor, J. M. Girkin, and G. D. Love, “High-resolution 3D optical microscopy inside the beating zebrafish heart using prospective optical gating,” Biomed. Opt. Express 3(12), 3043–3053 (2012).
[Crossref] [PubMed]

2011 (6)

R.-A. Lorbeer, M. Heidrich, C. Lorbeer, D. F. Ramírez Ojeda, G. Bicker, H. Meyer, and A. Heisterkamp, “Highly efficient 3D fluorescence microscopy with a scanning laser optical tomograph,” Opt. Express 19(6), 5419–5430 (2011).
[Crossref] [PubMed]

J. Swoger, M. Muzzopappa, H. López-Schier, and J. Sharpe, “4D retrospective lineage tracing using SPIM for zebrafish organogenesis studies,” J. Biophotonics 4(1-2), 122–134 (2011).
[Crossref] [PubMed]

M. Weber and J. Huisken, “Light sheet microscopy for real-time developmental biology,” Curr. Opin. Genet. Dev. 21(5), 566–572 (2011).
[Crossref] [PubMed]

T. A. Planchon, L. Gao, D. E. Milkie, M. W. Davidson, J. A. Galbraith, C. G. Galbraith, and E. Betzig, “Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination,” Nat. Methods 8(5), 417–423 (2011).
[Crossref] [PubMed]

Y. Wu, A. Ghitani, R. Christensen, A. Santella, Z. Du, G. Rondeau, Z. Bao, D. Colón-Ramos, and H. Shroff, “Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17708–17713 (2011).
[Crossref] [PubMed]

F. Cella Zanacchi, Z. Lavagnino, M. Perrone Donnorso, A. Del Bue, L. Furia, M. Faretta, and A. Diaspro, “Live-cell 3D super-resolution imaging in thick biological samples,” Nat. Methods 8(12), 1047–1049 (2011).
[Crossref] [PubMed]

2010 (3)

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7(8), 603–614 (2010).
[Crossref] [PubMed]

P. J. Keller, A. D. Schmidt, A. Santella, K. Khairy, Z. Bao, J. Wittbrodt, and E. H. Stelzer, “Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy,” Nat. Methods 7(8), 637–642 (2010).
[Crossref] [PubMed]

A. M. Petzold, V. M. Bedell, N. J. Boczek, J. J. Essner, D. Balciunas, K. J. Clark, and S. C. Ekker, “SCORE imaging: specimen in a corrected optical rotational enclosure,” Zebrafish 7(2), 149–154 (2010).
[Crossref] [PubMed]

2009 (2)

J. Huisken and D. Y. Stainier, “Selective plane illumination microscopy techniques in developmental biology,” Development 136(12), 1963–1975 (2009).
[Crossref] [PubMed]

S. P. Herbert, J. Huisken, T. N. Kim, M. E. Feldman, B. T. Houseman, R. A. Wang, K. M. Shokat, and D. Y. Stainier, “Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation,” Science 326(5950), 294–298 (2009).
[Crossref] [PubMed]

2008 (4)

P. J. Keller, A. D. Schmidt, J. Wittbrodt, and E. H. Stelzer, “Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy,” Science 322(5904), 1065–1069 (2008).
[Crossref] [PubMed]

T. F. Holekamp, D. Turaga, and T. E. Holy, “Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy,” Neuron 57(5), 661–672 (2008).
[Crossref] [PubMed]

J. G. Ritter, R. Veith, J.-P. Siebrasse, and U. Kubitscheck, “High-contrast single-particle tracking by selective focal plane illumination microscopy,” Opt. Express 16(10), 7142–7152 (2008).
[Crossref] [PubMed]

D. Turaga and T. E. Holy, “Miniaturization and defocus correction for objective-coupled planar illumination microscopy,” Opt. Lett. 33(20), 2302–2304 (2008).
[Crossref] [PubMed]

2007 (7)

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

R. Arnaout, T. Ferrer, J. Huisken, K. Spitzer, D. Y. Stainier, M. Tristani-Firouzi, and N. C. Chi, “Zebrafish model for human long QT syndrome,” Proc. Natl. Acad. Sci. U.S.A. 104(27), 11316–11321 (2007).
[Crossref] [PubMed]

T. Y. Choi, J. H. Kim, D. H. Ko, C. H. Kim, J. S. Hwang, S. Ahn, S. Y. Kim, C. D. Kim, J. H. Lee, and T. J. Yoon, “Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds,” Pigment Cell Res. 20(2), 120–127 (2007).
[Crossref] [PubMed]

C. J. Engelbrecht, K. Greger, E. G. Reynaud, U. Kržic, J. Colombelli, and E. H. Stelzer, “Three-dimensional laser microsurgery in light-sheet based microscopy (SPIM),” Opt. Express 15(10), 6420–6430 (2007).
[Crossref] [PubMed]

J. Swoger, P. Verveer, K. Greger, J. Huisken, and E. H. Stelzer, “Multi-view image fusion improves resolution in three-dimensional microscopy,” Opt. Express 15(13), 8029–8042 (2007).
[Crossref] [PubMed]

T. Breuninger, K. Greger, and E. H. Stelzer, “Lateral modulation boosts image quality in single plane illumination fluorescence microscopy,” Opt. Lett. 32(13), 1938–1940 (2007).
[Crossref] [PubMed]

J. Huisken and D. Y. Stainier, “Even fluorescence excitation by multidirectional selective plane illumination microscopy (mSPIM),” Opt. Lett. 32(17), 2608–2610 (2007).
[Crossref] [PubMed]

2006 (1)

2004 (1)

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
[Crossref] [PubMed]

1989 (1)

1983 (1)

1968 (1)

G. Boyd and D. Kleinman, “Parametric interaction of focused Gaussian light beams,” J. Appl. Phys. 39(8), 3597–3639 (1968).
[Crossref]

Aanstad, P.

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
[Crossref] [PubMed]

Ahn, S.

T. Y. Choi, J. H. Kim, D. H. Ko, C. H. Kim, J. S. Hwang, S. Ahn, S. Y. Kim, C. D. Kim, J. H. Lee, and T. J. Yoon, “Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds,” Pigment Cell Res. 20(2), 120–127 (2007).
[Crossref] [PubMed]

Ahrens, M. B.

M. B. Ahrens, M. B. Orger, D. N. Robson, J. M. Li, and P. J. Keller, “Whole-brain functional imaging at cellular resolution using light-sheet microscopy,” Nat. Methods 10(5), 413–420 (2013).
[Crossref] [PubMed]

Allalou, A.

T.-Y. Chang, C. Pardo-Martin, A. Allalou, C. Wählby, and M. F. Yanik, “Fully automated cellular-resolution vertebrate screening platform with parallel animal processing,” Lab Chip 12(4), 711–716 (2012).
[Crossref] [PubMed]

Andersen, D. R.

Arnaout, R.

R. Arnaout, T. Ferrer, J. Huisken, K. Spitzer, D. Y. Stainier, M. Tristani-Firouzi, and N. C. Chi, “Zebrafish model for human long QT syndrome,” Proc. Natl. Acad. Sci. U.S.A. 104(27), 11316–11321 (2007).
[Crossref] [PubMed]

Balciunas, D.

A. M. Petzold, V. M. Bedell, N. J. Boczek, J. J. Essner, D. Balciunas, K. J. Clark, and S. C. Ekker, “SCORE imaging: specimen in a corrected optical rotational enclosure,” Zebrafish 7(2), 149–154 (2010).
[Crossref] [PubMed]

Bao, Z.

Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
[Crossref] [PubMed]

Y. Wu, A. Ghitani, R. Christensen, A. Santella, Z. Du, G. Rondeau, Z. Bao, D. Colón-Ramos, and H. Shroff, “Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17708–17713 (2011).
[Crossref] [PubMed]

P. J. Keller, A. D. Schmidt, A. Santella, K. Khairy, Z. Bao, J. Wittbrodt, and E. H. Stelzer, “Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy,” Nat. Methods 7(8), 637–642 (2010).
[Crossref] [PubMed]

Bedell, V. M.

A. M. Petzold, V. M. Bedell, N. J. Boczek, J. J. Essner, D. Balciunas, K. J. Clark, and S. C. Ekker, “SCORE imaging: specimen in a corrected optical rotational enclosure,” Zebrafish 7(2), 149–154 (2010).
[Crossref] [PubMed]

Beebe, T.

J. Lee, M. E. Moghadam, E. Kung, H. Cao, T. Beebe, Y. Miller, B. L. Roman, C.-L. Lien, N. C. Chi, A. L. Marsden, and T. K. Hsiai, “Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis,” PLoS One 8(8), e72924 (2013).
[Crossref] [PubMed]

Bembenek, J. N.

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Boczek, N. J.

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B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
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T. Panier, S. A. Romano, R. Olive, T. Pietri, G. Sumbre, R. Candelier, and G. Debrégeas, “Fast functional imaging of multiple brain regions in intact zebrafish larvae using Selective Plane Illumination Microscopy,” Front. Neural Circuits 7, 65 (2013).
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J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
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F. Cella Zanacchi, Z. Lavagnino, M. Perrone Donnorso, A. Del Bue, L. Furia, M. Faretta, and A. Diaspro, “Live-cell 3D super-resolution imaging in thick biological samples,” Nat. Methods 8(12), 1047–1049 (2011).
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A. M. Petzold, V. M. Bedell, N. J. Boczek, J. J. Essner, D. Balciunas, K. J. Clark, and S. C. Ekker, “SCORE imaging: specimen in a corrected optical rotational enclosure,” Zebrafish 7(2), 149–154 (2010).
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English, B. P.

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A. M. Petzold, V. M. Bedell, N. J. Boczek, J. J. Essner, D. Balciunas, K. J. Clark, and S. C. Ekker, “SCORE imaging: specimen in a corrected optical rotational enclosure,” Zebrafish 7(2), 149–154 (2010).
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F. Cella Zanacchi, Z. Lavagnino, M. Perrone Donnorso, A. Del Bue, L. Furia, M. Faretta, and A. Diaspro, “Live-cell 3D super-resolution imaging in thick biological samples,” Nat. Methods 8(12), 1047–1049 (2011).
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S. P. Herbert, J. Huisken, T. N. Kim, M. E. Feldman, B. T. Houseman, R. A. Wang, K. M. Shokat, and D. Y. Stainier, “Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation,” Science 326(5950), 294–298 (2009).
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R. Arnaout, T. Ferrer, J. Huisken, K. Spitzer, D. Y. Stainier, M. Tristani-Firouzi, and N. C. Chi, “Zebrafish model for human long QT syndrome,” Proc. Natl. Acad. Sci. U.S.A. 104(27), 11316–11321 (2007).
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Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
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B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
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F. Cella Zanacchi, Z. Lavagnino, M. Perrone Donnorso, A. Del Bue, L. Furia, M. Faretta, and A. Diaspro, “Live-cell 3D super-resolution imaging in thick biological samples,” Nat. Methods 8(12), 1047–1049 (2011).
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T. A. Planchon, L. Gao, D. E. Milkie, M. W. Davidson, J. A. Galbraith, C. G. Galbraith, and E. Betzig, “Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination,” Nat. Methods 8(5), 417–423 (2011).
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T. A. Planchon, L. Gao, D. E. Milkie, M. W. Davidson, J. A. Galbraith, C. G. Galbraith, and E. Betzig, “Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination,” Nat. Methods 8(5), 417–423 (2011).
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Y. Wu, A. Ghitani, R. Christensen, A. Santella, Z. Du, G. Rondeau, Z. Bao, D. Colón-Ramos, and H. Shroff, “Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17708–17713 (2011).
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Greger, K.

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B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
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B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
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Heisterkamp, A.

Herbert, S. P.

S. P. Herbert, J. Huisken, T. N. Kim, M. E. Feldman, B. T. Houseman, R. A. Wang, K. M. Shokat, and D. Y. Stainier, “Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation,” Science 326(5950), 294–298 (2009).
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J. Lee, M. E. Moghadam, E. Kung, H. Cao, T. Beebe, Y. Miller, B. L. Roman, C.-L. Lien, N. C. Chi, A. L. Marsden, and T. K. Hsiai, “Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis,” PLoS One 8(8), e72924 (2013).
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P. G. Pitrone, J. Schindelin, L. Stuyvenberg, S. Preibisch, M. Weber, K. W. Eliceiri, J. Huisken, and P. Tomancak, “OpenSPIM: an open-access light-sheet microscopy platform,” Nat. Methods 10(7), 598–599 (2013).
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A. Kaufmann, M. Mickoleit, M. Weber, and J. Huisken, “Multilayer mounting enables long-term imaging of zebrafish development in a light sheet microscope,” Development 139(17), 3242–3247 (2012).
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T. Y. Choi, J. H. Kim, D. H. Ko, C. H. Kim, J. S. Hwang, S. Ahn, S. Y. Kim, C. D. Kim, J. H. Lee, and T. J. Yoon, “Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds,” Pigment Cell Res. 20(2), 120–127 (2007).
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B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
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Kaufmann, A.

A. Kaufmann, M. Mickoleit, M. Weber, and J. Huisken, “Multilayer mounting enables long-term imaging of zebrafish development in a light sheet microscope,” Development 139(17), 3242–3247 (2012).
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Khairy, K.

P. J. Keller, A. D. Schmidt, A. Santella, K. Khairy, Z. Bao, J. Wittbrodt, and E. H. Stelzer, “Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy,” Nat. Methods 7(8), 637–642 (2010).
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B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
[Crossref] [PubMed]

Sharpe, J.

J. Swoger, M. Muzzopappa, H. López-Schier, and J. Sharpe, “4D retrospective lineage tracing using SPIM for zebrafish organogenesis studies,” J. Biophotonics 4(1-2), 122–134 (2011).
[Crossref] [PubMed]

Shokat, K. M.

S. P. Herbert, J. Huisken, T. N. Kim, M. E. Feldman, B. T. Houseman, R. A. Wang, K. M. Shokat, and D. Y. Stainier, “Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation,” Science 326(5950), 294–298 (2009).
[Crossref] [PubMed]

Shroff, H.

Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
[Crossref] [PubMed]

Y. Wu, A. Ghitani, R. Christensen, A. Santella, Z. Du, G. Rondeau, Z. Bao, D. Colón-Ramos, and H. Shroff, “Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17708–17713 (2011).
[Crossref] [PubMed]

Siebrasse, J.-P.

Spitzer, K.

R. Arnaout, T. Ferrer, J. Huisken, K. Spitzer, D. Y. Stainier, M. Tristani-Firouzi, and N. C. Chi, “Zebrafish model for human long QT syndrome,” Proc. Natl. Acad. Sci. U.S.A. 104(27), 11316–11321 (2007).
[Crossref] [PubMed]

Stainier, D. Y.

J. Huisken and D. Y. Stainier, “Selective plane illumination microscopy techniques in developmental biology,” Development 136(12), 1963–1975 (2009).
[Crossref] [PubMed]

S. P. Herbert, J. Huisken, T. N. Kim, M. E. Feldman, B. T. Houseman, R. A. Wang, K. M. Shokat, and D. Y. Stainier, “Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation,” Science 326(5950), 294–298 (2009).
[Crossref] [PubMed]

R. Arnaout, T. Ferrer, J. Huisken, K. Spitzer, D. Y. Stainier, M. Tristani-Firouzi, and N. C. Chi, “Zebrafish model for human long QT syndrome,” Proc. Natl. Acad. Sci. U.S.A. 104(27), 11316–11321 (2007).
[Crossref] [PubMed]

J. Huisken and D. Y. Stainier, “Even fluorescence excitation by multidirectional selective plane illumination microscopy (mSPIM),” Opt. Lett. 32(17), 2608–2610 (2007).
[Crossref] [PubMed]

Stelzer, E. H.

P. J. Keller, A. D. Schmidt, A. Santella, K. Khairy, Z. Bao, J. Wittbrodt, and E. H. Stelzer, “Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy,” Nat. Methods 7(8), 637–642 (2010).
[Crossref] [PubMed]

P. J. Keller, A. D. Schmidt, J. Wittbrodt, and E. H. Stelzer, “Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy,” Science 322(5904), 1065–1069 (2008).
[Crossref] [PubMed]

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

C. J. Engelbrecht, K. Greger, E. G. Reynaud, U. Kržic, J. Colombelli, and E. H. Stelzer, “Three-dimensional laser microsurgery in light-sheet based microscopy (SPIM),” Opt. Express 15(10), 6420–6430 (2007).
[Crossref] [PubMed]

J. Swoger, P. Verveer, K. Greger, J. Huisken, and E. H. Stelzer, “Multi-view image fusion improves resolution in three-dimensional microscopy,” Opt. Express 15(13), 8029–8042 (2007).
[Crossref] [PubMed]

T. Breuninger, K. Greger, and E. H. Stelzer, “Lateral modulation boosts image quality in single plane illumination fluorescence microscopy,” Opt. Lett. 32(13), 1938–1940 (2007).
[Crossref] [PubMed]

C. J. Engelbrecht and E. H. Stelzer, “Resolution enhancement in a light-sheet-based microscope (SPIM),” Opt. Lett. 31(10), 1477–1479 (2006).
[Crossref] [PubMed]

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
[Crossref] [PubMed]

Stuyvenberg, L.

P. G. Pitrone, J. Schindelin, L. Stuyvenberg, S. Preibisch, M. Weber, K. W. Eliceiri, J. Huisken, and P. Tomancak, “OpenSPIM: an open-access light-sheet microscopy platform,” Nat. Methods 10(7), 598–599 (2013).
[Crossref] [PubMed]

Sumbre, G.

T. Panier, S. A. Romano, R. Olive, T. Pietri, G. Sumbre, R. Candelier, and G. Debrégeas, “Fast functional imaging of multiple brain regions in intact zebrafish larvae using Selective Plane Illumination Microscopy,” Front. Neural Circuits 7, 65 (2013).
[Crossref] [PubMed]

Swoger, J.

J. Swoger, M. Muzzopappa, H. López-Schier, and J. Sharpe, “4D retrospective lineage tracing using SPIM for zebrafish organogenesis studies,” J. Biophotonics 4(1-2), 122–134 (2011).
[Crossref] [PubMed]

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

J. Swoger, P. Verveer, K. Greger, J. Huisken, and E. H. Stelzer, “Multi-view image fusion improves resolution in three-dimensional microscopy,” Opt. Express 15(13), 8029–8042 (2007).
[Crossref] [PubMed]

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
[Crossref] [PubMed]

Taylor, J. M.

Thierbach, K.

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
[Crossref] [PubMed]

Tomancak, P.

P. G. Pitrone, J. Schindelin, L. Stuyvenberg, S. Preibisch, M. Weber, K. W. Eliceiri, J. Huisken, and P. Tomancak, “OpenSPIM: an open-access light-sheet microscopy platform,” Nat. Methods 10(7), 598–599 (2013).
[Crossref] [PubMed]

Tristani-Firouzi, M.

R. Arnaout, T. Ferrer, J. Huisken, K. Spitzer, D. Y. Stainier, M. Tristani-Firouzi, and N. C. Chi, “Zebrafish model for human long QT syndrome,” Proc. Natl. Acad. Sci. U.S.A. 104(27), 11316–11321 (2007).
[Crossref] [PubMed]

Tulu, U. S.

B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
[Crossref] [PubMed]

Turaga, D.

D. Turaga and T. E. Holy, “Miniaturization and defocus correction for objective-coupled planar illumination microscopy,” Opt. Lett. 33(20), 2302–2304 (2008).
[Crossref] [PubMed]

T. F. Holekamp, D. Turaga, and T. E. Holy, “Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy,” Neuron 57(5), 661–672 (2008).
[Crossref] [PubMed]

Veith, R.

Verveer, P.

Verveer, P. J.

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

Wählby, C.

T.-Y. Chang, C. Pardo-Martin, A. Allalou, C. Wählby, and M. F. Yanik, “Fully automated cellular-resolution vertebrate screening platform with parallel animal processing,” Lab Chip 12(4), 711–716 (2012).
[Crossref] [PubMed]

Wang, J. T.

B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
[Crossref] [PubMed]

Wang, K.

B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
[Crossref] [PubMed]

Wang, R. A.

S. P. Herbert, J. Huisken, T. N. Kim, M. E. Feldman, B. T. Houseman, R. A. Wang, K. M. Shokat, and D. Y. Stainier, “Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation,” Science 326(5950), 294–298 (2009).
[Crossref] [PubMed]

Waterman, C. M.

Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
[Crossref] [PubMed]

Wawrzusin, P.

Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
[Crossref] [PubMed]

Weber, M.

P. G. Pitrone, J. Schindelin, L. Stuyvenberg, S. Preibisch, M. Weber, K. W. Eliceiri, J. Huisken, and P. Tomancak, “OpenSPIM: an open-access light-sheet microscopy platform,” Nat. Methods 10(7), 598–599 (2013).
[Crossref] [PubMed]

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
[Crossref] [PubMed]

A. Kaufmann, M. Mickoleit, M. Weber, and J. Huisken, “Multilayer mounting enables long-term imaging of zebrafish development in a light sheet microscope,” Development 139(17), 3242–3247 (2012).
[Crossref] [PubMed]

M. Weber and J. Huisken, “Light sheet microscopy for real-time developmental biology,” Curr. Opin. Genet. Dev. 21(5), 566–572 (2011).
[Crossref] [PubMed]

Winter, P. W.

Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
[Crossref] [PubMed]

Wittbrodt, J.

P. J. Keller, A. D. Schmidt, A. Santella, K. Khairy, Z. Bao, J. Wittbrodt, and E. H. Stelzer, “Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy,” Nat. Methods 7(8), 637–642 (2010).
[Crossref] [PubMed]

P. J. Keller, A. D. Schmidt, J. Wittbrodt, and E. H. Stelzer, “Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy,” Science 322(5904), 1065–1069 (2008).
[Crossref] [PubMed]

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
[Crossref] [PubMed]

Wu, X. S.

B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
[Crossref] [PubMed]

Wu, Y.

Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
[Crossref] [PubMed]

Y. Wu, A. Ghitani, R. Christensen, A. Santella, Z. Du, G. Rondeau, Z. Bao, D. Colón-Ramos, and H. Shroff, “Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17708–17713 (2011).
[Crossref] [PubMed]

Yanik, M. F.

T.-Y. Chang, C. Pardo-Martin, A. Allalou, C. Wählby, and M. F. Yanik, “Fully automated cellular-resolution vertebrate screening platform with parallel animal processing,” Lab Chip 12(4), 711–716 (2012).
[Crossref] [PubMed]

Yoon, T. J.

T. Y. Choi, J. H. Kim, D. H. Ko, C. H. Kim, J. S. Hwang, S. Ahn, S. Y. Kim, C. D. Kim, J. H. Lee, and T. J. Yoon, “Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds,” Pigment Cell Res. 20(2), 120–127 (2007).
[Crossref] [PubMed]

York, A. G.

Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
[Crossref] [PubMed]

Appl. Opt. (1)

Biomed. Opt. Express (1)

Curr. Opin. Genet. Dev. (1)

M. Weber and J. Huisken, “Light sheet microscopy for real-time developmental biology,” Curr. Opin. Genet. Dev. 21(5), 566–572 (2011).
[Crossref] [PubMed]

Development (2)

J. Huisken and D. Y. Stainier, “Selective plane illumination microscopy techniques in developmental biology,” Development 136(12), 1963–1975 (2009).
[Crossref] [PubMed]

A. Kaufmann, M. Mickoleit, M. Weber, and J. Huisken, “Multilayer mounting enables long-term imaging of zebrafish development in a light sheet microscope,” Development 139(17), 3242–3247 (2012).
[Crossref] [PubMed]

Front. Neural Circuits (1)

T. Panier, S. A. Romano, R. Olive, T. Pietri, G. Sumbre, R. Candelier, and G. Debrégeas, “Fast functional imaging of multiple brain regions in intact zebrafish larvae using Selective Plane Illumination Microscopy,” Front. Neural Circuits 7, 65 (2013).
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J. Appl. Phys. (1)

G. Boyd and D. Kleinman, “Parametric interaction of focused Gaussian light beams,” J. Appl. Phys. 39(8), 3597–3639 (1968).
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J. Swoger, M. Muzzopappa, H. López-Schier, and J. Sharpe, “4D retrospective lineage tracing using SPIM for zebrafish organogenesis studies,” J. Biophotonics 4(1-2), 122–134 (2011).
[Crossref] [PubMed]

J. Opt. Soc. Am. A (1)

J. Vis. Exp. (1)

C. Chardès, P. Mélénec, V. Bertrand, and P.-F. Lenne, “Setting up a simple light sheet microscope for in toto imaging of C. elegans development,” J. Vis. Exp. 87, 51342 (2014).
[PubMed]

Lab Chip (1)

T.-Y. Chang, C. Pardo-Martin, A. Allalou, C. Wählby, and M. F. Yanik, “Fully automated cellular-resolution vertebrate screening platform with parallel animal processing,” Lab Chip 12(4), 711–716 (2012).
[Crossref] [PubMed]

Nat. Biotechnol. (1)

Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colón-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31(11), 1032–1038 (2013).
[Crossref] [PubMed]

Nat. Commun. (1)

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
[Crossref] [PubMed]

Nat. Methods (7)

T. A. Planchon, L. Gao, D. E. Milkie, M. W. Davidson, J. A. Galbraith, C. G. Galbraith, and E. Betzig, “Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination,” Nat. Methods 8(5), 417–423 (2011).
[Crossref] [PubMed]

P. J. Keller, A. D. Schmidt, A. Santella, K. Khairy, Z. Bao, J. Wittbrodt, and E. H. Stelzer, “Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy,” Nat. Methods 7(8), 637–642 (2010).
[Crossref] [PubMed]

M. B. Ahrens, M. B. Orger, D. N. Robson, J. M. Li, and P. J. Keller, “Whole-brain functional imaging at cellular resolution using light-sheet microscopy,” Nat. Methods 10(5), 413–420 (2013).
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F. Cella Zanacchi, Z. Lavagnino, M. Perrone Donnorso, A. Del Bue, L. Furia, M. Faretta, and A. Diaspro, “Live-cell 3D super-resolution imaging in thick biological samples,” Nat. Methods 8(12), 1047–1049 (2011).
[Crossref] [PubMed]

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7(8), 603–614 (2010).
[Crossref] [PubMed]

P. G. Pitrone, J. Schindelin, L. Stuyvenberg, S. Preibisch, M. Weber, K. W. Eliceiri, J. Huisken, and P. Tomancak, “OpenSPIM: an open-access light-sheet microscopy platform,” Nat. Methods 10(7), 598–599 (2013).
[Crossref] [PubMed]

Neuron (1)

T. F. Holekamp, D. Turaga, and T. E. Holy, “Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy,” Neuron 57(5), 661–672 (2008).
[Crossref] [PubMed]

Opt. Express (4)

Opt. Lett. (4)

Pigment Cell Res. (1)

T. Y. Choi, J. H. Kim, D. H. Ko, C. H. Kim, J. S. Hwang, S. Ahn, S. Y. Kim, C. D. Kim, J. H. Lee, and T. J. Yoon, “Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds,” Pigment Cell Res. 20(2), 120–127 (2007).
[Crossref] [PubMed]

PLoS One (1)

J. Lee, M. E. Moghadam, E. Kung, H. Cao, T. Beebe, Y. Miller, B. L. Roman, C.-L. Lien, N. C. Chi, A. L. Marsden, and T. K. Hsiai, “Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis,” PLoS One 8(8), e72924 (2013).
[Crossref] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (2)

Y. Wu, A. Ghitani, R. Christensen, A. Santella, Z. Du, G. Rondeau, Z. Bao, D. Colón-Ramos, and H. Shroff, “Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17708–17713 (2011).
[Crossref] [PubMed]

R. Arnaout, T. Ferrer, J. Huisken, K. Spitzer, D. Y. Stainier, M. Tristani-Firouzi, and N. C. Chi, “Zebrafish model for human long QT syndrome,” Proc. Natl. Acad. Sci. U.S.A. 104(27), 11316–11321 (2007).
[Crossref] [PubMed]

Science (4)

B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A. C. Reymann, R. Böhme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution,” Science 346(6208), 1257998 (2014).
[Crossref] [PubMed]

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
[Crossref] [PubMed]

P. J. Keller, A. D. Schmidt, J. Wittbrodt, and E. H. Stelzer, “Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy,” Science 322(5904), 1065–1069 (2008).
[Crossref] [PubMed]

S. P. Herbert, J. Huisken, T. N. Kim, M. E. Feldman, B. T. Houseman, R. A. Wang, K. M. Shokat, and D. Y. Stainier, “Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation,” Science 326(5950), 294–298 (2009).
[Crossref] [PubMed]

Zebrafish (1)

A. M. Petzold, V. M. Bedell, N. J. Boczek, J. J. Essner, D. Balciunas, K. J. Clark, and S. C. Ekker, “SCORE imaging: specimen in a corrected optical rotational enclosure,” Zebrafish 7(2), 149–154 (2010).
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Other (2)

B. K. Koo, Development and Optimization of High-Throughput Zebrafish Screening Platform (Massachusetts Institute of Technology, 2010).

A. Siegman, Lasers (University Science, Mill Valley, Calif., (1986) Chap 13, pp. 663–680.

Supplementary Material (4)

NameDescription
» Data File 1: CSV (1 KB)      part list with vendors, specifications and costs
» Data File 2: CSV (0 KB)      calculation result of the beam profile
» Visualization 1: PDF (301 KB)      the CAD drawings and the step-by-step assembling protocal
» Visualization 2: AVI (1144 KB)      the assembling animation of the device

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Figures (6)

Fig. 1
Fig. 1

Schematic of the Plane Illumination Plugin (PIP) and its working principle. (a) The configuration of the PIP, which is based on fast 3D printing and several small optics. The key components include a laser diode module as light source, a cylindrical lens for light sheet generation, a micrometer drive for optical control, and a disposable cuvette as the sample holder. (b) Sample manipulation setup in PIP. A FEP tubing with sample mounted inside is connected to a micrometer via an L shape adapter. By tuning the micrometer, the sample together with the tubing can be vertically scanned through the light sheet, inside a water environment. (c) The working status of the PIP. The laser sheet propagates horizontally through the sample, generating a plane illumination on the fluorophores. The existing fluorescence detection system inside the microscope collects the sample signal and images it onto the camera. (d) The working principle of PIP with a Nikon Eclipse TE-2000 inverted microscope. A lens adapter is added on the objective lens to increase the working distance. Through mounting the PIP on the stage and inserting the sample, LSFM is enabled on a conventional wide-field microscope. (e), (f) show the photographs of the real PIP device with (e) the scene of PIP device working with a Nikon TE-2000 inverted microscope. (f) The image of PIP with ruler showing its dimensions.

Fig. 2
Fig. 2

Characterization of the tunable laser sheet of PIP. (a) Tuning the laser sheet thickness simply by adjusting the diaphragm. As the beam width decreases through reducing the aperture size of diaphragm from 1.8 mm (top) to 1 mm (bottom), the laser sheet becomes less focused and linearly thicker at the waist. The scale bars are 200 μm in i to ii, and 10 μm in inserts, respectively. (b) The corresponding change of the confocal region, which represents the available area for light sectioning. The double-headed arrow line shows the length of the confocal range (x direction), within which the light sheet can be considered uniform. The length of the confocal range is inversely proportional to the square of the light sheet thickness. The scare bars are 100 μm.

Fig. 3
Fig. 3

The comparison of resolving power measured before and after the PIP was mounted. (a) Visualization of the 400 nm point source by regular inverted microscope using a 10X/0.3 air objective. The subsets from the left to the right correspondingly show the x-y, x-z, y-z planes and the volumetric rendering. The axial extent is obviously larger than the lateral extents, due to the relatively low numerical aperture. (b) - (c), Visualization of the 400 nm point source by the same optical setting of the inverted microscope, but with PIP mounted. In (b), the aperture of the PIP are set to be 1 mm while in (c), this value is 1.8 mm. With PIP mounted, the axial extents become significantly smaller due to the sharp plane illumination. Scale bars in (a) to (c) are 5 microns. (d) - (e), normalized line intensity plots of the resolved point source images, along lateral and axial directions, respectively. 1/2 intensity levels are drawn in the cyan lines, to show the FWHMs that reflect the resolutions of the systems. 1/e2 intensity level is drawn in green line to indicate the actually resolved diameters of the nano-particle.

Fig. 4
Fig. 4

Contrast-enhanced light sheet imaging of beating embryonic zebrafish heart by PIP mounted microscope. (a) Light sheet sectioning inside a live embryonic zebrafish heart (4 d.p.f., Tg: (cmlc: gfp)). PIP enables the selective plane illumination on specific region of interest of the beating heart. (b) and (c) show the image comparison between regular inverted microscope and PIP mounted inverted microscope. The dynamic inner and outer boundaries of the beating heart can be clearly resolved when PIP is added. (d) shows the control heart images (same stage embryo) from a home-built, standard SPIM system with identical illumination and detection settings of PIP imaging. Scale bars in all images are 50 μm.

Fig. 5
Fig. 5

Quantifying the area dynamics of beating embryonic zebrafish heart. (a) Segmentation of the ventricle’s inner and outer boundary. In the wide-field fluorescent image, due to the out-of-focus blur, only the outer boundary of the ventricle can be identified (yellow line). In PIP and SPIM images, by significantly enhancing image contrast, the inner boundary as well as ventricle’s myocardium structure (red area) can be accurately segmented. Scale bars in all sub-graphs are 50 μm. (b) The calculated area variation of the complete ventricle area in 400 millisecond time. (c) The normalized area change of the inside fluid domain, which is only enabled in PIP and SPIM image results. (d) The corresponding area change of the segmented ventricle muscle during heart beating. (e) The strain rate of the beating embryonic zebrafish heart during a cardiac cycle. The strain under each time point was calculated based on the girth variation of the ventricle inner boundary.

Fig. 6
Fig. 6

Visualization of 3D-cultured cell branches using PIP-integrated conventional microscope. (a) Sequential image slices acquired by a conventional inverted microscope using 10X/0.3 air objective. Out-of-focus excitation caused drastic image deterioration. (b) Sequential image slices acquired at the same z depths using identical wide-field detection plus 10 μm optical sectioning of PIP. (c) - (d) The maximum intensity projections (MIPs) and the volume renderings obtained without and with PIP, respectively. y-z, x-z projections of the 3D reconstructed images were also shown. The incorporation of PIP achieved significant axial resolution enhancement and background noise reduction. The cells geometry and intracellular morphology were also exclusively revealed by clear volume rendering in PIP group (rightmost). Scale bars in all images are 100 μm.

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