Abstract

Light sheet microscopy is a relatively new form of fluorescence microscopy that has been receiving a lot of attention recently. The strong points of the technique, such as high signal to noise ratio and its reduced photodamage of fluorescently labelled samples, come from its unique feature to illuminate only a thin plane in the sample that coincides with the focal plane of the detection lens. Typically this requires two closely positioned perpendicular objective lenses, one for detection and one for illumination. Apart from the fact that this special configuration of objective lenses is incompatible with standard microscope bodies, it is particularly problematic for high-resolution lenses which typically have a short working distance. To address these issues we developed sample holders with an integrated micromirror to perform single lens light sheet microscopy, also known as single objective single plane illumination microscopy (SoSPIM). The first design is based on a wet-etched silicon substrate, the second on a microfabricated polished polymer plug. We achieved an on-chip light sheet thickness of 2.3 μm (FWHM) at 638 nm with the polymer micromirror and of 1.7 μm (FWHM) at 638 nm with the silicon micromirror, comparable to reported light sheet thicknesses obtained on dedicated light sheet microscopes. A marked contrast improvement was obtained with both sample holders as compared to classic epi-fluorescence microscopy. In order to evaluate whether this technology could be made available on a larger scale, in a next step we evaluated the optical quality of inexpensive replicas from both types of master molds. We found that replicas from the polished polymer based mold have an optical quality close to that of the master component, while replicas from the silicon based mold were of slightly lower but still acceptable quality. The suitability of the replicated polymer based sample holder for single-lens light sheet microscopy was finally demonstrated by imaging breast cancer spheroids.

© 2017 Optical Society of America

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References

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    [Crossref] [PubMed]

2016 (1)

Z. Lavagnino, G. Sancataldo, M. d’Amora, P. Follert, D. De Pietri Tonelli, A. Diaspro, and F. Cella Zanacchi, “4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM),” Sci. Rep. 6, 23923 (2016).
[Crossref] [PubMed]

2015 (4)

M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms,” Nat. Photonics 9(2), 113–119 (2015).
[Crossref] [PubMed]

R. Galland, G. Grenci, A. Aravind, V. Viasnoff, V. Studer, and J. B. Sibarita, “3D high- and super-resolution imaging using single-objective SPIM,” Nat. Methods 12(7), 641–644 (2015).
[Crossref] [PubMed]

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

V. Trivedi, T. V. Truong, A. Trinh, D. B. Holland, M. Liebling, and S. E. Fraser, “Dynamic structure and protein expression of the live embryonic heart captured by 2-photon light sheet microscopy and retrospective registration,” Biomed. Opt. Express 6(6), 2056–2066 (2015).
[Crossref] [PubMed]

2014 (5)

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]

M. Jemielita, M. J. Taormina, A. R. Burns, J. S. Hampton, A. S. Rolig, K. Guillemin, and R. Parthasarathy, “Spatial and Temporal Features of the Growth of a Bacterial Species Colonizing the Zebrafish Gut,” MBio 5(6), 01751 (2014).
[Crossref] [PubMed]

M. Mickoleit, B. Schmid, M. Weber, F. O. Fahrbach, S. Hombach, S. Reischauer, and J. Huisken, “High-resolution reconstruction of the beating zebrafish heart,” Nat. Methods 11(9), 919–922 (2014).
[Crossref] [PubMed]

E. G. Reynaud, J. Peychl, J. Huisken, and P. Tomancak, “Guide to light-sheet microscopy for adventurous biologists,” Nat. Methods 12(1), 30–34 (2014).
[Crossref] [PubMed]

N. Vladimirov, Y. Mu, T. Kawashima, D. V. Bennett, C. T. Yang, L. L. Looger, P. J. Keller, J. Freeman, and M. B. Ahrens, “Light-sheet functional imaging in fictively behaving zebrafish,” Nat. Methods 11(9), 883–884 (2014).
[Crossref] [PubMed]

2013 (4)

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

F. Cella Zanacchi, Z. Lavagnino, M. Faretta, L. Furia, and A. Diaspro, “Light-Sheet Confined Super-Resolution Using Two-Photon Photoactivation,” PLoS One 8(7), e67667 (2013).
[Crossref] [PubMed]

J. C. Gebhardt, D. M. Suter, R. Roy, Z. W. Zhao, A. R. Chapman, S. Basu, T. Maniatis, and X. S. Xie, “Single-molecule imaging of transcription factor binding to DNA in live mammalian cells,” Nat. Methods 10(5), 421–426 (2013).
[Crossref] [PubMed]

F. O. Fahrbach, V. Gurchenkov, K. Alessandri, P. Nassoy, and A. Rohrbach, “Light-sheet microscopy in thick media using scanned Bessel beams and two-photon fluorescence excitation,” Opt. Express 21(11), 13824–13839 (2013).
[Crossref] [PubMed]

2012 (1)

U. Krzic, S. Gunther, T. E. Saunders, S. J. Streichan, and L. Hufnagel, “Multiview light-sheet microscope for rapid in toto imaging,” Nat. Methods 9(7), 730–733 (2012).
[Crossref] [PubMed]

2010 (3)

J. G. Ritter, R. Veith, A. Veenendaal, J. P. Siebrasse, and U. Kubitscheck, “Light sheet microscopy for single molecule tracking in living tissue,” PLoS One 5(7), e11639 (2010).
[Crossref] [PubMed]

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

E. Bosman, G. Van Steenberge, I. Milenkov, K. Panajotov, H. Thienpont, J. Bauwelinck, and P. Van Daele, “Fully Flexible Optoelectronic Foil,” Selected Topics in Quantum Electronics, IEEE Journal of 16(5), 1355–1362 (2010).
[Crossref]

2009 (1)

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

2008 (1)

Ahrens, M. B.

N. Vladimirov, Y. Mu, T. Kawashima, D. V. Bennett, C. T. Yang, L. L. Looger, P. J. Keller, J. Freeman, and M. B. Ahrens, “Light-sheet functional imaging in fictively behaving zebrafish,” Nat. Methods 11(9), 883–884 (2014).
[Crossref] [PubMed]

Alessandri, K.

Angles-Cano, E.

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Aravind, A.

R. Galland, G. Grenci, A. Aravind, V. Viasnoff, V. Studer, and J. B. Sibarita, “3D high- and super-resolution imaging using single-objective SPIM,” Nat. Methods 12(7), 641–644 (2015).
[Crossref] [PubMed]

Barton-Owen, T.

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

Basu, S.

J. C. Gebhardt, D. M. Suter, R. Roy, Z. W. Zhao, A. R. Chapman, S. Basu, T. Maniatis, and X. S. Xie, “Single-molecule imaging of transcription factor binding to DNA in live mammalian cells,” Nat. Methods 10(5), 421–426 (2013).
[Crossref] [PubMed]

Bauwelinck, J.

E. Bosman, G. Van Steenberge, I. Milenkov, K. Panajotov, H. Thienpont, J. Bauwelinck, and P. Van Daele, “Fully Flexible Optoelectronic Foil,” Selected Topics in Quantum Electronics, IEEE Journal of 16(5), 1355–1362 (2010).
[Crossref]

Bembenek, J. N.

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]

Bennett, D. V.

N. Vladimirov, Y. Mu, T. Kawashima, D. V. Bennett, C. T. Yang, L. L. Looger, P. J. Keller, J. Freeman, and M. B. Ahrens, “Light-sheet functional imaging in fictively behaving zebrafish,” Nat. Methods 11(9), 883–884 (2014).
[Crossref] [PubMed]

Betzig, E.

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]

Böhme, R.

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]

Bosman, E.

E. Bosman, G. Van Steenberge, I. Milenkov, K. Panajotov, H. Thienpont, J. Bauwelinck, and P. Van Daele, “Fully Flexible Optoelectronic Foil,” Selected Topics in Quantum Electronics, IEEE Journal of 16(5), 1355–1362 (2010).
[Crossref]

Bouchard, M. B.

M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms,” Nat. Photonics 9(2), 113–119 (2015).
[Crossref] [PubMed]

Bouquet, W.

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Bracke, M.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Braeckmans, K.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Bruno, R. M.

M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms,” Nat. Photonics 9(2), 113–119 (2015).
[Crossref] [PubMed]

Burns, A. R.

M. Jemielita, M. J. Taormina, A. R. Burns, J. S. Hampton, A. S. Rolig, K. Guillemin, and R. Parthasarathy, “Spatial and Temporal Features of the Growth of a Bacterial Species Colonizing the Zebrafish Gut,” MBio 5(6), 01751 (2014).
[Crossref] [PubMed]

Buyens, K.

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Cella Zanacchi, F.

Z. Lavagnino, G. Sancataldo, M. d’Amora, P. Follert, D. De Pietri Tonelli, A. Diaspro, and F. Cella Zanacchi, “4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM),” Sci. Rep. 6, 23923 (2016).
[Crossref] [PubMed]

F. Cella Zanacchi, Z. Lavagnino, M. Faretta, L. Furia, and A. Diaspro, “Light-Sheet Confined Super-Resolution Using Two-Photon Photoactivation,” PLoS One 8(7), e67667 (2013).
[Crossref] [PubMed]

Chapman, A. R.

J. C. Gebhardt, D. M. Suter, R. Roy, Z. W. Zhao, A. R. Chapman, S. Basu, T. Maniatis, and X. S. Xie, “Single-molecule imaging of transcription factor binding to DNA in live mammalian cells,” Nat. Methods 10(5), 421–426 (2013).
[Crossref] [PubMed]

Chen, B.-C.

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]

Chmelík, R.

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

Cižmár, T.

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

d’Amora, M.

Z. Lavagnino, G. Sancataldo, M. d’Amora, P. Follert, D. De Pietri Tonelli, A. Diaspro, and F. Cella Zanacchi, “4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM),” Sci. Rep. 6, 23923 (2016).
[Crossref] [PubMed]

Davidson, M. W.

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]

De Pietri Tonelli, D.

Z. Lavagnino, G. Sancataldo, M. d’Amora, P. Follert, D. De Pietri Tonelli, A. Diaspro, and F. Cella Zanacchi, “4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM),” Sci. Rep. 6, 23923 (2016).
[Crossref] [PubMed]

De Smedt, S. C.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

De Vos, F.

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Demeester, J.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Deschout, H.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Dholakia, K.

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

Diaspro, A.

Z. Lavagnino, G. Sancataldo, M. d’Amora, P. Follert, D. De Pietri Tonelli, A. Diaspro, and F. Cella Zanacchi, “4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM),” Sci. Rep. 6, 23923 (2016).
[Crossref] [PubMed]

F. Cella Zanacchi, Z. Lavagnino, M. Faretta, L. Furia, and A. Diaspro, “Light-Sheet Confined Super-Resolution Using Two-Photon Photoactivation,” PLoS One 8(7), e67667 (2013).
[Crossref] [PubMed]

Doeuvre, L.

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Dostál, Z.

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

English, B. P.

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]

Fahrbach, F. O.

M. Mickoleit, B. Schmid, M. Weber, F. O. Fahrbach, S. Hombach, S. Reischauer, and J. Huisken, “High-resolution reconstruction of the beating zebrafish heart,” Nat. Methods 11(9), 919–922 (2014).
[Crossref] [PubMed]

F. O. Fahrbach, V. Gurchenkov, K. Alessandri, P. Nassoy, and A. Rohrbach, “Light-sheet microscopy in thick media using scanned Bessel beams and two-photon fluorescence excitation,” Opt. Express 21(11), 13824–13839 (2013).
[Crossref] [PubMed]

Faretta, M.

F. Cella Zanacchi, Z. Lavagnino, M. Faretta, L. Furia, and A. Diaspro, “Light-Sheet Confined Super-Resolution Using Two-Photon Photoactivation,” PLoS One 8(7), e67667 (2013).
[Crossref] [PubMed]

Ferrier, D. E.

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

Follert, P.

Z. Lavagnino, G. Sancataldo, M. d’Amora, P. Follert, D. De Pietri Tonelli, A. Diaspro, and F. Cella Zanacchi, “4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM),” Sci. Rep. 6, 23923 (2016).
[Crossref] [PubMed]

Fraser, S. E.

Freeman, J.

N. Vladimirov, Y. Mu, T. Kawashima, D. V. Bennett, C. T. Yang, L. L. Looger, P. J. Keller, J. Freeman, and M. B. Ahrens, “Light-sheet functional imaging in fictively behaving zebrafish,” Nat. Methods 11(9), 883–884 (2014).
[Crossref] [PubMed]

Fritz-Laylin, L.

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]

Furia, L.

F. Cella Zanacchi, Z. Lavagnino, M. Faretta, L. Furia, and A. Diaspro, “Light-Sheet Confined Super-Resolution Using Two-Photon Photoactivation,” PLoS One 8(7), e67667 (2013).
[Crossref] [PubMed]

Galland, R.

R. Galland, G. Grenci, A. Aravind, V. Viasnoff, V. Studer, and J. B. Sibarita, “3D high- and super-resolution imaging using single-objective SPIM,” Nat. Methods 12(7), 641–644 (2015).
[Crossref] [PubMed]

Gebhardt, J. C.

J. C. Gebhardt, D. M. Suter, R. Roy, Z. W. Zhao, A. R. Chapman, S. Basu, T. Maniatis, and X. S. Xie, “Single-molecule imaging of transcription factor binding to DNA in live mammalian cells,” Nat. Methods 10(5), 421–426 (2013).
[Crossref] [PubMed]

Grenci, G.

R. Galland, G. Grenci, A. Aravind, V. Viasnoff, V. Studer, and J. B. Sibarita, “3D high- and super-resolution imaging using single-objective SPIM,” Nat. Methods 12(7), 641–644 (2015).
[Crossref] [PubMed]

Grill, S. W.

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]

Grueber, W. B.

M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms,” Nat. Photonics 9(2), 113–119 (2015).
[Crossref] [PubMed]

Guillemin, K.

M. Jemielita, M. J. Taormina, A. R. Burns, J. S. Hampton, A. S. Rolig, K. Guillemin, and R. Parthasarathy, “Spatial and Temporal Features of the Growth of a Bacterial Species Colonizing the Zebrafish Gut,” MBio 5(6), 01751 (2014).
[Crossref] [PubMed]

Gunther, S.

U. Krzic, S. Gunther, T. E. Saunders, S. J. Streichan, and L. Hufnagel, “Multiview light-sheet microscope for rapid in toto imaging,” Nat. Methods 9(7), 730–733 (2012).
[Crossref] [PubMed]

Gurchenkov, V.

Hammer, J. A.

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]

Hampton, J. S.

M. Jemielita, M. J. Taormina, A. R. Burns, J. S. Hampton, A. S. Rolig, K. Guillemin, and R. Parthasarathy, “Spatial and Temporal Features of the Growth of a Bacterial Species Colonizing the Zebrafish Gut,” MBio 5(6), 01751 (2014).
[Crossref] [PubMed]

Hendrix, A.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Hillman, E. M. C.

M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms,” Nat. Photonics 9(2), 113–119 (2015).
[Crossref] [PubMed]

Holland, D. B.

Hombach, S.

M. Mickoleit, B. Schmid, M. Weber, F. O. Fahrbach, S. Hombach, S. Reischauer, and J. Huisken, “High-resolution reconstruction of the beating zebrafish heart,” Nat. Methods 11(9), 919–922 (2014).
[Crossref] [PubMed]

Hufnagel, L.

U. Krzic, S. Gunther, T. E. Saunders, S. J. Streichan, and L. Hufnagel, “Multiview light-sheet microscope for rapid in toto imaging,” Nat. Methods 9(7), 730–733 (2012).
[Crossref] [PubMed]

Huisken, J.

M. Mickoleit, B. Schmid, M. Weber, F. O. Fahrbach, S. Hombach, S. Reischauer, and J. Huisken, “High-resolution reconstruction of the beating zebrafish heart,” Nat. Methods 11(9), 919–922 (2014).
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E. G. Reynaud, J. Peychl, J. Huisken, and P. Tomancak, “Guide to light-sheet microscopy for adventurous biologists,” Nat. Methods 12(1), 30–34 (2014).
[Crossref] [PubMed]

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

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]

Jemielita, M.

M. Jemielita, M. J. Taormina, A. R. Burns, J. S. Hampton, A. S. Rolig, K. Guillemin, and R. Parthasarathy, “Spatial and Temporal Features of the Growth of a Bacterial Species Colonizing the Zebrafish Gut,” MBio 5(6), 01751 (2014).
[Crossref] [PubMed]

Jiguet, S.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Joye, P.

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Kawashima, T.

N. Vladimirov, Y. Mu, T. Kawashima, D. V. Bennett, C. T. Yang, L. L. Looger, P. J. Keller, J. Freeman, and M. B. Ahrens, “Light-sheet functional imaging in fictively behaving zebrafish,” Nat. Methods 11(9), 883–884 (2014).
[Crossref] [PubMed]

Keller, P. J.

N. Vladimirov, Y. Mu, T. Kawashima, D. V. Bennett, C. T. Yang, L. L. Looger, P. J. Keller, J. Freeman, and M. B. Ahrens, “Light-sheet functional imaging in fictively behaving zebrafish,” Nat. Methods 11(9), 883–884 (2014).
[Crossref] [PubMed]

Kiehart, D. P.

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]

Kollárová, V.

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

Krzic, U.

U. Krzic, S. Gunther, T. E. Saunders, S. J. Streichan, and L. Hufnagel, “Multiview light-sheet microscope for rapid in toto imaging,” Nat. Methods 9(7), 730–733 (2012).
[Crossref] [PubMed]

Kubitscheck, U.

J. G. Ritter, R. Veith, A. Veenendaal, J. P. Siebrasse, and U. Kubitscheck, “Light sheet microscopy for single molecule tracking in living tissue,” PLoS One 5(7), e11639 (2010).
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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]

Lacefield, C.

M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms,” Nat. Photonics 9(2), 113–119 (2015).
[Crossref] [PubMed]

Lavagnino, Z.

Z. Lavagnino, G. Sancataldo, M. d’Amora, P. Follert, D. De Pietri Tonelli, A. Diaspro, and F. Cella Zanacchi, “4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM),” Sci. Rep. 6, 23923 (2016).
[Crossref] [PubMed]

F. Cella Zanacchi, Z. Lavagnino, M. Faretta, L. Furia, and A. Diaspro, “Light-Sheet Confined Super-Resolution Using Two-Photon Photoactivation,” PLoS One 8(7), e67667 (2013).
[Crossref] [PubMed]

Legant, W. R.

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]

Liebling, M.

Lippincott-Schwartz, J.

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]

Liu, Z.

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]

Looger, L. L.

N. Vladimirov, Y. Mu, T. Kawashima, D. V. Bennett, C. T. Yang, L. L. Looger, P. J. Keller, J. Freeman, and M. B. Ahrens, “Light-sheet functional imaging in fictively behaving zebrafish,” Nat. Methods 11(9), 883–884 (2014).
[Crossref] [PubMed]

Maniatis, T.

J. C. Gebhardt, D. M. Suter, R. Roy, Z. W. Zhao, A. R. Chapman, S. Basu, T. Maniatis, and X. S. Xie, “Single-molecule imaging of transcription factor binding to DNA in live mammalian cells,” Nat. Methods 10(5), 421–426 (2013).
[Crossref] [PubMed]

Mann, R. S.

M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms,” Nat. Photonics 9(2), 113–119 (2015).
[Crossref] [PubMed]

Maoddi, P.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Mendes, C. S.

M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms,” Nat. Photonics 9(2), 113–119 (2015).
[Crossref] [PubMed]

Mernier, G.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Mickoleit, M.

M. Mickoleit, B. Schmid, M. Weber, F. O. Fahrbach, S. Hombach, S. Reischauer, and J. Huisken, “High-resolution reconstruction of the beating zebrafish heart,” Nat. Methods 11(9), 919–922 (2014).
[Crossref] [PubMed]

Milenkov, I.

E. Bosman, G. Van Steenberge, I. Milenkov, K. Panajotov, H. Thienpont, J. Bauwelinck, and P. Van Daele, “Fully Flexible Optoelectronic Foil,” Selected Topics in Quantum Electronics, IEEE Journal of 16(5), 1355–1362 (2010).
[Crossref]

Milkie, D. E.

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]

Mimori-Kiyosue, Y.

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]

Mitchell, D. M.

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]

Mu, Y.

N. Vladimirov, Y. Mu, T. Kawashima, D. V. Bennett, C. T. Yang, L. L. Looger, P. J. Keller, J. Freeman, and M. B. Ahrens, “Light-sheet functional imaging in fictively behaving zebrafish,” Nat. Methods 11(9), 883–884 (2014).
[Crossref] [PubMed]

Mullins, R. D.

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]

Nassoy, P.

Neyts, K.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Nylk, J.

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

Panajotov, K.

E. Bosman, G. Van Steenberge, I. Milenkov, K. Panajotov, H. Thienpont, J. Bauwelinck, and P. Van Daele, “Fully Flexible Optoelectronic Foil,” Selected Topics in Quantum Electronics, IEEE Journal of 16(5), 1355–1362 (2010).
[Crossref]

Parthasarathy, R.

M. Jemielita, M. J. Taormina, A. R. Burns, J. S. Hampton, A. S. Rolig, K. Guillemin, and R. Parthasarathy, “Spatial and Temporal Features of the Growth of a Bacterial Species Colonizing the Zebrafish Gut,” MBio 5(6), 01751 (2014).
[Crossref] [PubMed]

Peychl, J.

E. G. Reynaud, J. Peychl, J. Huisken, and P. Tomancak, “Guide to light-sheet microscopy for adventurous biologists,” Nat. Methods 12(1), 30–34 (2014).
[Crossref] [PubMed]

Plawinski, L.

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Plöschner, M.

M. Plöschner, V. Kollárová, Z. Dostál, J. Nylk, T. Barton-Owen, D. E. Ferrier, R. Chmelík, K. Dholakia, and T. Čižmár, “Multimode fibre: Light-sheet microscopy at the tip of a needle,” Sci. Rep. 5, 18050 (2015).
[Crossref] [PubMed]

Raemdonck, K.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Reischauer, S.

M. Mickoleit, B. Schmid, M. Weber, F. O. Fahrbach, S. Hombach, S. Reischauer, and J. Huisken, “High-resolution reconstruction of the beating zebrafish heart,” Nat. Methods 11(9), 919–922 (2014).
[Crossref] [PubMed]

Renaud, P.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Reymann, A.-C.

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]

Reynaud, E. G.

E. G. Reynaud, J. Peychl, J. Huisken, and P. Tomancak, “Guide to light-sheet microscopy for adventurous biologists,” Nat. Methods 12(1), 30–34 (2014).
[Crossref] [PubMed]

Ritter, A. 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]

Ritter, J. G.

J. G. Ritter, R. Veith, A. Veenendaal, J. P. Siebrasse, and U. Kubitscheck, “Light sheet microscopy for single molecule tracking in living tissue,” PLoS One 5(7), e11639 (2010).
[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]

Roding, M.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Rohrbach, A.

Rolig, A. S.

M. Jemielita, M. J. Taormina, A. R. Burns, J. S. Hampton, A. S. Rolig, K. Guillemin, and R. Parthasarathy, “Spatial and Temporal Features of the Growth of a Bacterial Species Colonizing the Zebrafish Gut,” MBio 5(6), 01751 (2014).
[Crossref] [PubMed]

Romero, D. P.

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]

Roy, R.

J. C. Gebhardt, D. M. Suter, R. Roy, Z. W. Zhao, A. R. Chapman, S. Basu, T. Maniatis, and X. S. Xie, “Single-molecule imaging of transcription factor binding to DNA in live mammalian cells,” Nat. Methods 10(5), 421–426 (2013).
[Crossref] [PubMed]

Rudemo, M.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Sancataldo, G.

Z. Lavagnino, G. Sancataldo, M. d’Amora, P. Follert, D. De Pietri Tonelli, A. Diaspro, and F. Cella Zanacchi, “4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM),” Sci. Rep. 6, 23923 (2016).
[Crossref] [PubMed]

Sanders, N. N.

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Saunders, T. E.

U. Krzic, S. Gunther, T. E. Saunders, S. J. Streichan, and L. Hufnagel, “Multiview light-sheet microscope for rapid in toto imaging,” Nat. Methods 9(7), 730–733 (2012).
[Crossref] [PubMed]

Schmid, B.

M. Mickoleit, B. Schmid, M. Weber, F. O. Fahrbach, S. Hombach, S. Reischauer, and J. Huisken, “High-resolution reconstruction of the beating zebrafish heart,” Nat. Methods 11(9), 919–922 (2014).
[Crossref] [PubMed]

Seydoux, G.

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]

Shao, L.

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]

Sibarita, J. B.

R. Galland, G. Grenci, A. Aravind, V. Viasnoff, V. Studer, and J. B. Sibarita, “3D high- and super-resolution imaging using single-objective SPIM,” Nat. Methods 12(7), 641–644 (2015).
[Crossref] [PubMed]

Siebrasse, J. P.

J. G. Ritter, R. Veith, A. Veenendaal, J. P. Siebrasse, and U. Kubitscheck, “Light sheet microscopy for single molecule tracking in living tissue,” PLoS One 5(7), e11639 (2010).
[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]

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

U. Krzic, S. Gunther, T. E. Saunders, S. J. Streichan, and L. Hufnagel, “Multiview light-sheet microscope for rapid in toto imaging,” Nat. Methods 9(7), 730–733 (2012).
[Crossref] [PubMed]

Stremersch, S.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Strubbe, F.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Studer, V.

R. Galland, G. Grenci, A. Aravind, V. Viasnoff, V. Studer, and J. B. Sibarita, “3D high- and super-resolution imaging using single-objective SPIM,” Nat. Methods 12(7), 641–644 (2015).
[Crossref] [PubMed]

Suter, D. M.

J. C. Gebhardt, D. M. Suter, R. Roy, Z. W. Zhao, A. R. Chapman, S. Basu, T. Maniatis, and X. S. Xie, “Single-molecule imaging of transcription factor binding to DNA in live mammalian cells,” Nat. Methods 10(5), 421–426 (2013).
[Crossref] [PubMed]

Taormina, M. J.

M. Jemielita, M. J. Taormina, A. R. Burns, J. S. Hampton, A. S. Rolig, K. Guillemin, and R. Parthasarathy, “Spatial and Temporal Features of the Growth of a Bacterial Species Colonizing the Zebrafish Gut,” MBio 5(6), 01751 (2014).
[Crossref] [PubMed]

Thienpont, H.

E. Bosman, G. Van Steenberge, I. Milenkov, K. Panajotov, H. Thienpont, J. Bauwelinck, and P. Van Daele, “Fully Flexible Optoelectronic Foil,” Selected Topics in Quantum Electronics, IEEE Journal of 16(5), 1355–1362 (2010).
[Crossref]

Tomancak, P.

E. G. Reynaud, J. Peychl, J. Huisken, and P. Tomancak, “Guide to light-sheet microscopy for adventurous biologists,” Nat. Methods 12(1), 30–34 (2014).
[Crossref] [PubMed]

Trinh, A.

Trivedi, V.

Truong, T. V.

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]

Van Daele, P.

E. Bosman, G. Van Steenberge, I. Milenkov, K. Panajotov, H. Thienpont, J. Bauwelinck, and P. Van Daele, “Fully Flexible Optoelectronic Foil,” Selected Topics in Quantum Electronics, IEEE Journal of 16(5), 1355–1362 (2010).
[Crossref]

Van den Broecke, R.

H. Deschout, K. Raemdonck, S. Stremersch, P. Maoddi, G. Mernier, P. Renaud, S. Jiguet, A. Hendrix, M. Bracke, R. Van den Broecke, M. Roding, M. Rudemo, J. Demeester, S. C. De Smedt, F. Strubbe, K. Neyts, and K. Braeckmans, “On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids,” Nanoscale 6, 1741(2013).
[PubMed]

Van Steenberge, G.

E. Bosman, G. Van Steenberge, I. Milenkov, K. Panajotov, H. Thienpont, J. Bauwelinck, and P. Van Daele, “Fully Flexible Optoelectronic Foil,” Selected Topics in Quantum Electronics, IEEE Journal of 16(5), 1355–1362 (2010).
[Crossref]

Veenendaal, A.

J. G. Ritter, R. Veith, A. Veenendaal, J. P. Siebrasse, and U. Kubitscheck, “Light sheet microscopy for single molecule tracking in living tissue,” PLoS One 5(7), e11639 (2010).
[Crossref] [PubMed]

Veith, R.

J. G. Ritter, R. Veith, A. Veenendaal, J. P. Siebrasse, and U. Kubitscheck, “Light sheet microscopy for single molecule tracking in living tissue,” PLoS One 5(7), e11639 (2010).
[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]

Vervaet, C.

K. Braeckmans, K. Buyens, W. Bouquet, C. Vervaet, P. Joye, F. De Vos, L. Plawinski, L. Doeuvre, E. Angles-Cano, N. N. Sanders, J. Demeester, and S. C. De Smedt, “Sizing nanomatter in biological fluids by fluorescence single particle tracking,” Nano Lett. 10(11), 4435–4442 (2010).
[Crossref] [PubMed]

Viasnoff, V.

R. Galland, G. Grenci, A. Aravind, V. Viasnoff, V. Studer, and J. B. Sibarita, “3D high- and super-resolution imaging using single-objective SPIM,” Nat. Methods 12(7), 641–644 (2015).
[Crossref] [PubMed]

Vladimirov, N.

N. Vladimirov, Y. Mu, T. Kawashima, D. V. Bennett, C. T. Yang, L. L. Looger, P. J. Keller, J. Freeman, and M. B. Ahrens, “Light-sheet functional imaging in fictively behaving zebrafish,” Nat. Methods 11(9), 883–884 (2014).
[Crossref] [PubMed]

Voleti, V.

M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms,” Nat. Photonics 9(2), 113–119 (2015).
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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]

Weber, M.

M. Mickoleit, B. Schmid, M. Weber, F. O. Fahrbach, S. Hombach, S. Reischauer, and J. Huisken, “High-resolution reconstruction of the beating zebrafish heart,” Nat. Methods 11(9), 919–922 (2014).
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Wu, X. S.

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[Crossref] [PubMed]

J. C. Gebhardt, D. M. Suter, R. Roy, Z. W. Zhao, A. R. Chapman, S. Basu, T. Maniatis, and X. S. Xie, “Single-molecule imaging of transcription factor binding to DNA in live mammalian cells,” Nat. Methods 10(5), 421–426 (2013).
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Supplementary Material (10)

NameDescription
» Visualization 1: AVI (15631 KB)      Contrast epifluorescence C: 0 nM Cy5
» Visualization 2: AVI (15631 KB)      Contrast epifluorescence C: 500 nM Cy5
» Visualization 3: AVI (15631 KB)      Contrast epifluorescence C: 2000 nM Cy5
» Visualization 4: AVI (18444 KB)      Contrast LSM polymer sample holder C: 0 nM Cy5
» Visualization 5: AVI (14069 KB)      Contrast LSM polymer sample holder C: 500 nM Cy5
» Visualization 6: AVI (14069 KB)      Contrast LSM polymer sample holder C: 2000 nM Cy5
» Visualization 7: AVI (7349 KB)      Contrast LSM silicon sample holder C: 0 nM Cy5
» Visualization 8: AVI (7349 KB)      Contrast LSM silicon sample holder C: 500 nM Cy5
» Visualization 9: AVI (7349 KB)      Contrast LSM silicon sample holder C: 2000 nM Cy5
» Visualization 10: AVI (3656 KB)      Spheroids imaged with epi-fluorescence illumination

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Figures (11)

Fig. 1
Fig. 1

Master mold with tilted micromirrors fabricated in silicon. (A) Schematic top and side view showing the microcavity with tilted micromirror walls into which the sample can be placed. (B) Top view picture of a microfabricated silicon master mold. (C) SEM micrograph showing the tilted walls of the master mold in one of the corners of the microcavity.

Fig. 2
Fig. 2

Master mold with polished tilted micromirrors fabricated in polyimide. (A) Schematic top and side view of the polished polymer plug. (B) A simple master mold is created by gluing two of those polymer plugs, coated with aluminum (or gold), to a microscope slide. The sample can be placed in between the polymer plugs. (C) SEM micrograph of the polished polymer tilted mirror.

Fig. 3
Fig. 3

Single lens light-sheet microscopy is achieved by reflection of an elongated elliptical gaussian beam in a sample holder with integrated microfabricated tilted mirror (TM). After collimation (C), the laser beam passes through a variable beam expander consisting of three lenses (section S1), that allow to adjust the waist thickness and divergence of the light sheet in the channel. The light sheet focus in the sample holder is manipulated independently by the three telescopes (T.a, T.b and T.c) depicted in section S2. The laser beam is shaped into an elliptical Gaussian beam by a telescope in section S3 with a cylindrical back lens (CL). The fluorescent light emitted passes through a dichroic mirror (DM) and is imaged on the camera by a tube lens (TL).

Fig. 4
Fig. 4

Characterization of a beam reflected by the tilted micromirror in the silicon based mold (A) and the polymer based mold (B). The beam is imaged by filling the channel in both sample holders with a solution of 10 µM ATTO647. The red rectangles indicate the position where the excitation beam is reflected on the micromirrors (MM) while the white rectangle indicates the analyzed region (AR). The red arrows indicate the direction of the propagation of light. Scale Bar = 16 μm. (C) and (D) The FWHM of the beam was determined along its optical axis in the analyzed region. The beam profile is fitted with Eq. (1) (black line). The silicon based mold had a beam waist of 1.6 ± 0.3 µm (FWHM) and a DoF of 10.0 ± 1.0 µm. The polished polymer chip was found to have a beam waist of 2.4 ± 0.3 µm (FWHM) and a depth of focus (DoF) of 19 ± 0.3 µm.

Fig. 5
Fig. 5

Contrast comparison between light sheet illumination in the master component and epi-fluorescence illumination. Contrast was determined for fluorescent nanospheres suspended in solutions with increasing concentration of the red fluorescent dye Cy5. Measurements were performed in both molds and compared with normal epi-fluorescence imaging.

Fig. 6
Fig. 6

Characterization of a beam in disposable sample holders replicated from the silicon (A) and polymer (B) based master mold. The beam is imaged by filling the channel in both sample holders with a solution of 10 µM ATTO647. The red rectangles indicate the position where the excitation beam is reflected on the micromirrors (MM) while the white rectangle indicates the analyzed region (AR). The red arrows indicate the direction of propagation of the light. Scale Bar = 16 μm. (C, D) The FWHM of the beam was determined along its optical axis in the analyzed region indicated in figure A and B. The beam profile is fitted with the Eq. (1) (black line). The FWHM profile of the beam imaged using the replicated sample holder is compared to the profile obtained from the master components. The sample holder replicated from the silicon based master component was found to have a beam waist of 2.6 ± 0.3 µm (FWHM) and a depth of focus (DoF) of 12.0 ± 0.5 µm. The sample holder replicated from the polished polymer master component had a beam waist of 1.9 ± 0.3 µm (FWHM) and a DoF of 17.3 ± 1.1 µm. (E and F) Comparison between contrast measured in the replicated sample holders and in the master components of fluorescent nanospheres suspended in solutions with increasing concentration of Cy5.

Fig. 7
Fig. 7

Images of MCF-7 human breast cancer spheroids at different planes. Cells were imaged from bottom to top and the z-planes were 1 µm apart.

Fig. 8
Fig. 8

Fabrication procedure of the silicon based master mold. The process is divided in three parts, namely photolithography, etching and cleaning. A thermo-oxidized wafer (silicon dioxide layer: 1 µm thick) is spin coated with a primer and subsequently with a positive photoresist, both followed by a 3 minutes baking step at 110°C. Afterwards, the wafer is covered with a chrome mask, that defines the position of the tilted walls and the channel, and subsequently exposed to UV light for 200 seconds. The wafer is immersed for 90 s in an aqueous solution consisting of 1 part Developer 400K and 2 parts distilled water in order to remove the UV illuminated regions of the photoresist. In the subsequent etching step, the wafer is placed for 16 min into a buffered 7:1 HF solution that dissolves the unprotected regions of the silicon dioxide and exposes the underlying bare silicon. Next, the wafer is placed for 5 min in an ultrasonic bath filled with acetone to remove the photoresist layer. Then the wafer is put into a stirred KOH bath (KOH/Water/IPA 20/64/16) at 70°C that will selectively remove silicon in the <100> crystal direction, thus etching the channel with tilted walls at approximately 40 µm/hour. A careful monitoring of the etch rate by means of temperature and concentration of the etchant is of utmost importance since the etch rate can influence the wall roughness. Finally an RCA-1 clean was performed as follows. A solution of 5 parts water, 1 part 27% ammonium hydroxide and 1 part 30% hydrogen peroxide is heated at 70°C, then the wafer is soaked in the solution for 15 min, rinsed with water and put for 5 min into a 5% HCl solution.

Fig. 9
Fig. 9

Fabrication procedure of the polymer-based master mold. 1. A 500-μm-thick flexible PI wafer is clamped in a special PMMA device with a 45° trench. 2. The device is polished to provide a 45° polished end facet to the PI wafer. 3. The wafer is polished and thinned down at both sides to the desired thickness. This step also removes unwanted edge defects. 4. The wafer is cut into small parts of the desired length and width by a wafer dicer with a diamond coated blade. 5. The tilted end facets are then coated with a 120-nm-thin gold layer by vapor deposition, or with an aluminium layer applied by sputtering. 6. The polymer plug is now ready to be glued to a microscopy slide.

Fig. 10
Fig. 10

Schematic overview of the replication process. 1. The polymer or silicon based master components are covered with a UV-curable, transparent fluorinated molding material. 2. The molding material is polymerized by UV illumination. 3. The polymerized mold is easily peeled off from the master component. 4. The material is used as a stamp to fabricate the actual replicas. A drop of a UV-curable epoxy is thus dispersed on a glass slide and the molding stamp is peeled off. 6. The replicated micromirrors are coated with a 200 nm reflective layer of either gold (evaporation) or aluminum (sputtering).

Fig. 11
Fig. 11

Influence of metal coating on the beam profile (left) and on the contrast (right). Two polymer master molds were considered, one coated with aluminum through sputtering, the second coated with gold through evaporation. The beam profile was determined as described in the main text (section 4.1) and in Fig. 4. Contrast was determined for fluorescent nanospheres suspended in solutions with increasing concentration of the red fluorescent dye Cy5. Measurements were performed in both molds and compared with normal epi-fluorescence imaging. Neither the beam profile nor the contrast seem effected by the metal used for coating the micromirror.

Equations (1)

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W(x)= W 0 1+ ( 2x Do F eff ) 2

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