Abstract

Electrically tunable lenses exhibit strong potential for fast motion-free axial scanning in a variety of microscopes. However, they also lead to a degradation of the achievable resolution because of aberrations and misalignment between illumination and detection optics that are induced by the scan itself. Additionally, the typically nonlinear relation between actuation voltage and axial displacement leads to over- or under-sampled frame acquisition in most microscopic techniques because of their static depth-of-field. To overcome these limitations, we present an Adaptive-Lens-High-and-Low-frequency (AL-HiLo) microscope that enables volumetric measurements employing an electrically tunable lens. By using speckle-patterned illumination, we ensure stability against aberrations of the electrically tunable lens. Its depth-of-field can be adjusted a-posteriori and hence enables to create flexible scans, which compensates for irregular axial measurement positions. The adaptive HiLo microscope provides an axial scanning range of 1 mm with an axial resolution of about 4 μm and sub-micron lateral resolution over the full scanning range. Proof of concept measurements at home-built specimens as well as zebrafish embryos with reporter gene-driven fluorescence in the thyroid gland are shown.

© 2016 Optical Society of America

Full Article  |  PDF Article
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References

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    [Crossref]

2015 (3)

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

M. A. Lauterbach, E. Ronzitti, J. R. Sternberg, C. Wyart, and V. Emiliani, “Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy,” PloS one 10, e0143681 (2015).
[Crossref] [PubMed]

T. Hinsdale, B. H. Malik, C. Olsovsky, J. A. Jo, and K. C. Maitland, “Volumetric structured illumination microscopy enabled by a tunable-focus lens,” Opt. Lett. 40, 4943–4946 (2015).
[Crossref] [PubMed]

2014 (2)

2013 (1)

2012 (2)

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17, 21105–21107 (2012).
[Crossref]

2011 (1)

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt. 16, 016014 (2011).
[Crossref] [PubMed]

2010 (1)

J. Mertz and J. Kim, “Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection,” J. Biomed. Opt. 15, 16027 (2010).
[Crossref]

2009 (1)

2008 (2)

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett. 33, 1819–1821 (2008).
[Crossref] [PubMed]

S. J. Kirkpatrick, D. D. Duncan, and E. M. Wells-Gray, “Detrimental effects of speckle-pixel size matching in laser speckle contrast imaging,” Opt. Lett 33, 2886–2888 (2008).
[Crossref] [PubMed]

2007 (1)

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

2006 (1)

S. A. Khan and N. A. Riza, “Demonstration of a no-moving-parts axial scanning confocal microscope using liquid crystal optics,” Opt. Commun. 265, 461–467 (2006).
[Crossref]

2005 (1)

2004 (2)

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

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nature Biotech. 22, 1567–1572 (2004).
[Crossref]

1998 (1)

P. J. Verveer, Q. S. Hanley., P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” Journal of Microscopy 189, 192–198 (1998).
[Crossref]

1997 (1)

1988 (1)

M. Minsky, “Memoir on inventing the confocal scanning microscope,” Scanning 10, 128–138 (1988).
[Crossref]

1986 (1)

M. Imai, “Statistical properties of optical fiber speckles,” Bulletin of the Faculty of Engineering, Hokkaido University 130, 89–104 (1986).

1975 (1)

J. W. Goodman, “Dependence of image speckle contrast on surface roughness,” Opt. Commun. 14, 324–327 (1975).
[Crossref]

1974 (1)

C. Cremer and T. Cremer, “Considerations on a laser-scanning-microscope with high resolution and depth of field,” Microscopica Acta 81, 31–44 (1974).

1969 (1)

P. A. Stokseth, “Properties of a Defocused Optical System*,” Journal of the Optical Society of America 59, 1314 (1969).
[Crossref]

Amos, B.

B. Amos, G. McConnell, and T. Wilson, Comprehensive Biophysics (Elsevier, 2012).

Antonica, F.

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

Becker, K.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Boilot, V.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Burger, T.

J. Draheim, F. Schneider, T. Burger, R. Kamberger, and U. Wallrabe, in 2010 International Conference on Optical MEMS and Nanophotonics (OPT MEMS), (2010), pp. 15–16.

Campbell, R. E.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nature Biotech. 22, 1567–1572 (2004).
[Crossref]

Chu, K. K.

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt. 16, 016014 (2011).
[Crossref] [PubMed]

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett. 33, 1819–1821 (2008).
[Crossref] [PubMed]

Clark, J.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Clarkson, E.

Costagliola, S.

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

Cremer, C.

C. Cremer and T. Cremer, “Considerations on a laser-scanning-microscope with high resolution and depth of field,” Microscopica Acta 81, 31–44 (1974).

Cremer, T.

C. Cremer and T. Cremer, “Considerations on a laser-scanning-microscope with high resolution and depth of field,” Microscopica Acta 81, 31–44 (1974).

Czarske, J. W.

Deininger, K.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Del Bene, F.

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

Deussing, J. M.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Diaspro, A.

Dodt, H.-U.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Draheim, J.

J. Draheim, F. Schneider, T. Burger, R. Kamberger, and U. Wallrabe, in 2010 International Conference on Optical MEMS and Nanophotonics (OPT MEMS), (2010), pp. 15–16.

Draviam, V. M.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Duncan, D. D.

S. J. Kirkpatrick, D. D. Duncan, and E. M. Wells-Gray, “Detrimental effects of speckle-pixel size matching in laser speckle contrast imaging,” Opt. Lett 33, 2886–2888 (2008).
[Crossref] [PubMed]

Duocastella, M.

Eder, M.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Emiliani, V.

M. A. Lauterbach, E. Ronzitti, J. R. Sternberg, C. Wyart, and V. Emiliani, “Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy,” PloS one 10, e0143681 (2015).
[Crossref] [PubMed]

Fahrbach, F. O.

Finkeldey, M.

Fischer, A.

Ford, T. N.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17, 21105–21107 (2012).
[Crossref]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt. 16, 016014 (2011).
[Crossref] [PubMed]

Funahashi, A.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Gerhardt, N. C.

Giepmans, B. N. G.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nature Biotech. 22, 1567–1572 (2004).
[Crossref]

Goodman, J.

J. Goodman, Introduction to Fourier Optics (McGraw-Hill, 1996).

Goodman, J. W.

J. W. Goodman, “Dependence of image speckle contrast on surface roughness,” Opt. Commun. 14, 324–327 (1975).
[Crossref]

J. W. Goodman, Speckle Phenomena in Optics: Theory and Applications (Roberts and Company Publishers, 2007).

Hanley., Q. S.

P. J. Verveer, Q. S. Hanley., P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” Journal of Microscopy 189, 192–198 (1998).
[Crossref]

Helmchen, F.

Hinsdale, T.

Hiraiwa, T.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Hiroi, N.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Hofmann, M. R.

Huisken, J.

F. O. Fahrbach, F. F. Voigt, B. Schmid, F. Helmchen, and J. Huisken, “Rapid 3D light-sheet microscopy with a tunable lens,” Opt. Express 21, 21010–26 (2013).
[Crossref] [PubMed]

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

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

Imai, M.

M. Imai, “Statistical properties of optical fiber speckles,” Bulletin of the Faculty of Engineering, Hokkaido University 130, 89–104 (1986).

Jährling, N.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Janssens, V.

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

Jo, J. A.

Jovin, T. M.

P. J. Verveer, Q. S. Hanley., P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” Journal of Microscopy 189, 192–198 (1998).
[Crossref]

Juskaitis, R.

Kamberger, R.

J. Draheim, F. Schneider, T. Burger, R. Kamberger, and U. Wallrabe, in 2010 International Conference on Optical MEMS and Nanophotonics (OPT MEMS), (2010), pp. 15–16.

Kang, D.

Khan, S. A.

S. A. Khan and N. A. Riza, “Demonstration of a no-moving-parts axial scanning confocal microscope using liquid crystal optics,” Opt. Commun. 265, 461–467 (2006).
[Crossref]

Kim, J.

J. Mertz and J. Kim, “Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection,” J. Biomed. Opt. 15, 16027 (2010).
[Crossref]

Kirkpatrick, S. J.

S. J. Kirkpatrick, D. D. Duncan, and E. M. Wells-Gray, “Detrimental effects of speckle-pixel size matching in laser speckle contrast imaging,” Opt. Lett 33, 2886–2888 (2008).
[Crossref] [PubMed]

Koukourakis, N.

Lauterbach, M. A.

M. A. Lauterbach, E. Ronzitti, J. R. Sternberg, C. Wyart, and V. Emiliani, “Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy,” PloS one 10, e0143681 (2015).
[Crossref] [PubMed]

Leischner, U.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Leithold, C.

Lim, D.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17, 21105–21107 (2012).
[Crossref]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt. 16, 016014 (2011).
[Crossref] [PubMed]

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett. 33, 1819–1821 (2008).
[Crossref] [PubMed]

Maitland, K. C.

Malik, B. H.

Maquet, E.

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

Mauch, C. P.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

McConnell, G.

B. Amos, G. McConnell, and T. Wilson, Comprehensive Biophysics (Elsevier, 2012).

Mertz, J.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17, 21105–21107 (2012).
[Crossref]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt. 16, 016014 (2011).
[Crossref] [PubMed]

J. Mertz and J. Kim, “Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection,” J. Biomed. Opt. 15, 16027 (2010).
[Crossref]

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett. 33, 1819–1821 (2008).
[Crossref] [PubMed]

C. Ventalon and J. Mertz, “Quasi-confocal fluorescence sectioning with dynamic speckle illumination,” Opt. Lett. 30, 3350 (2005).
[Crossref]

J. Mertz, Introduction to Optical Microscopy (Roberts, 2010).

Milster, T. D.

Minsky, M.

M. Minsky, “Memoir on inventing the confocal scanning microscope,” Scanning 10, 128–138 (1988).
[Crossref]

Nakai, Y.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Neil, M. A. A.

Nonaka, S.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Oku, H.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Olsovsky, C.

Opitz, R.

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

Ozeki, M.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Palmer, A. E.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nature Biotech. 22, 1567–1572 (2004).
[Crossref]

Pottier, G.

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

Riza, N. A.

S. A. Khan and N. A. Riza, “Demonstration of a no-moving-parts axial scanning confocal microscope using liquid crystal optics,” Opt. Commun. 265, 461–467 (2006).
[Crossref]

Ronzitti, E.

M. A. Lauterbach, E. Ronzitti, J. R. Sternberg, C. Wyart, and V. Emiliani, “Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy,” PloS one 10, e0143681 (2015).
[Crossref] [PubMed]

Schierloh, A.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Schmid, B.

Schneider, F.

J. Draheim, F. Schneider, T. Burger, R. Kamberger, and U. Wallrabe, in 2010 International Conference on Optical MEMS and Nanophotonics (OPT MEMS), (2010), pp. 15–16.

Shaner, N. C.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nature Biotech. 22, 1567–1572 (2004).
[Crossref]

Shrestha, R.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Steinbach, P. A.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nature Biotech. 22, 1567–1572 (2004).
[Crossref]

Stelzer, E. H. K.

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

Sternberg, J. R.

M. A. Lauterbach, E. Ronzitti, J. R. Sternberg, C. Wyart, and V. Emiliani, “Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy,” PloS one 10, e0143681 (2015).
[Crossref] [PubMed]

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P. A. Stokseth, “Properties of a Defocused Optical System*,” Journal of the Optical Society of America 59, 1314 (1969).
[Crossref]

Stürmer, M.

Swoger, J.

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

Tamura, N.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Taniguchi, A.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Tanimoto, R.

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Trubiroha, A.

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

Tsien, R. Y.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nature Biotech. 22, 1567–1572 (2004).
[Crossref]

Van Vliet, L. J.

P. J. Verveer, Q. S. Hanley., P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” Journal of Microscopy 189, 192–198 (1998).
[Crossref]

Ventalon, C.

Verbeek, P. W.

P. J. Verveer, Q. S. Hanley., P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” Journal of Microscopy 189, 192–198 (1998).
[Crossref]

Verveer, P. J.

P. J. Verveer, Q. S. Hanley., P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” Journal of Microscopy 189, 192–198 (1998).
[Crossref]

Vicidomini, G.

Voigt, F. F.

Wallrabe, U.

Wells-Gray, E. M.

S. J. Kirkpatrick, D. D. Duncan, and E. M. Wells-Gray, “Detrimental effects of speckle-pixel size matching in laser speckle contrast imaging,” Opt. Lett 33, 2886–2888 (2008).
[Crossref] [PubMed]

Wilson, T.

Wittbrodt, J.

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

Wyart, C.

M. A. Lauterbach, E. Ronzitti, J. R. Sternberg, C. Wyart, and V. Emiliani, “Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy,” PloS one 10, e0143681 (2015).
[Crossref] [PubMed]

Zieglgänsberger, W.

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Bulletin of the Faculty of Engineering, Hokkaido University (1)

M. Imai, “Statistical properties of optical fiber speckles,” Bulletin of the Faculty of Engineering, Hokkaido University 130, 89–104 (1986).

Developmental biology (1)

R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Developmental biology 372, 203–216 (2012).
[Crossref] [PubMed]

J. Biomed. Opt. (3)

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt. 16, 016014 (2011).
[Crossref] [PubMed]

J. Mertz and J. Kim, “Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection,” J. Biomed. Opt. 15, 16027 (2010).
[Crossref]

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17, 21105–21107 (2012).
[Crossref]

Journal of Microscopy (1)

P. J. Verveer, Q. S. Hanley., P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” Journal of Microscopy 189, 192–198 (1998).
[Crossref]

Journal of the Optical Society of America (1)

P. A. Stokseth, “Properties of a Defocused Optical System*,” Journal of the Optical Society of America 59, 1314 (1969).
[Crossref]

Microscopica Acta (1)

C. Cremer and T. Cremer, “Considerations on a laser-scanning-microscope with high resolution and depth of field,” Microscopica Acta 81, 31–44 (1974).

Nature Biotech. (1)

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nature Biotech. 22, 1567–1572 (2004).
[Crossref]

Nature Methods (1)

H.-U. Dodt, U. Leischner, A. Schierloh, N. Jährling, C. P. Mauch, K. Deininger, J. M. Deussing, M. Eder, W. Zieglgänsberger, and K. Becker, “Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain,” Nature Methods 4, 331–336 (2007).
[Crossref] [PubMed]

Opt. Commun. (2)

S. A. Khan and N. A. Riza, “Demonstration of a no-moving-parts axial scanning confocal microscope using liquid crystal optics,” Opt. Commun. 265, 461–467 (2006).
[Crossref]

J. W. Goodman, “Dependence of image speckle contrast on surface roughness,” Opt. Commun. 14, 324–327 (1975).
[Crossref]

Opt. Express (4)

Opt. Lett (1)

S. J. Kirkpatrick, D. D. Duncan, and E. M. Wells-Gray, “Detrimental effects of speckle-pixel size matching in laser speckle contrast imaging,” Opt. Lett 33, 2886–2888 (2008).
[Crossref] [PubMed]

Opt. Lett. (4)

PloS one (1)

M. A. Lauterbach, E. Ronzitti, J. R. Sternberg, C. Wyart, and V. Emiliani, “Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy,” PloS one 10, e0143681 (2015).
[Crossref] [PubMed]

Rev. Sci. Instrum. (1)

Y. Nakai, M. Ozeki, T. Hiraiwa, R. Tanimoto, A. Funahashi, N. Hiroi, A. Taniguchi, S. Nonaka, V. Boilot, R. Shrestha, J. Clark, N. Tamura, V. M. Draviam, and H. Oku, “High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes,” Rev. Sci. Instrum. 86, 013707 (2015).
[Crossref] [PubMed]

Scanning (1)

M. Minsky, “Memoir on inventing the confocal scanning microscope,” Scanning 10, 128–138 (1988).
[Crossref]

Science (1)

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

Other (5)

J. W. Goodman, Speckle Phenomena in Optics: Theory and Applications (Roberts and Company Publishers, 2007).

J. Mertz, Introduction to Optical Microscopy (Roberts, 2010).

B. Amos, G. McConnell, and T. Wilson, Comprehensive Biophysics (Elsevier, 2012).

J. Goodman, Introduction to Fourier Optics (McGraw-Hill, 1996).

J. Draheim, F. Schneider, T. Burger, R. Kamberger, and U. Wallrabe, in 2010 International Conference on Optical MEMS and Nanophotonics (OPT MEMS), (2010), pp. 15–16.

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Figures (9)

Fig. 1
Fig. 1

Experimental setup. A laser beam is coupled into a multi mode fiber (MMF) that can be vibrated by alternating magnetic fields. After passing a beam splitter (BS), the light is focused into the sample by a combination of an adaptive (AL) and an objective lens (OL). The fluorescence light passes the same optical path backwards and is eventually detected by a camera.

Fig. 2
Fig. 2

a) Refractive power of the adaptive lens as a function of the applied voltage with hysteresis behaviour. b) resonance spectrum of a similar electrically tunable lens.

Fig. 3
Fig. 3

Axial scanning curve: Axial displacement as a function of the actuation voltage of the electrically tunable lens.

Fig. 4
Fig. 4

Images of a) fluorescent particles with varying voltage applied at the adaptive lens. The images of the fluorescent particles are a 491×400 pixels-sized subimage taken out of the middle of the original camera images. b) The resulting relative magnification normalized to the magnification with 0 V actuation voltage.

Fig. 5
Fig. 5

a) Experimentally and theoretically obtained axial resolution (FWHMs of the point spread function) for high- and low-frequency components of HiLo images. b) Axial resolution of overall HiLo microscopy as well as for confocal and widefield microscopy with identical objectives.

Fig. 6
Fig. 6

a) Optical sectioning curves of HiLo images for six selected actuation voltages. Adjusting the depth-of-fields (DOF) of the HiLo mechanism ensures that the full axial range is covered. Simultaneously the optical sections are as thin as possible.

Fig. 7
Fig. 7

a–c) Selected images with uniform illumination. d–f) Selected HiLo images for different axial planes. The axial scanning is conducted by tuning the adaptive lens.

Fig. 8
Fig. 8

Dotted lines: integrated intensity for selected beads (cf. Fig. 7) along axial direction in uniform illumination images. Solid lines: integrated intensity for HiLo images.

Fig. 9
Fig. 9

a) HiLo images and b) images with uniform illumination of reporter-gene driven mcherry fluorescence of transgenic zebrafish. The fluorescence is regulated by part of the promotor region of the thyreoglobulin gene, coding for a thyroid hormone precursor. The optical sectioning provided by the HiLo algorithm leads to the rejection of the out-of-focus contributions and thus increased contrast of the images compared to the uniformly illuminated images. Scalebar is 10 μm.

Equations (11)

Equations on this page are rendered with MathJax. Learn more.

I HiLo ( r ) = I Hi ( r ) + η I Lo ( r ) ,
I Hi ( r ) = H P { I u ( r ) } ,
I Lo ( r ) = L P { C S ( r ) I u ( r ) }
I δ ( r ) = I n ( r ) I u ( r )
C S ( r ) = σ δ ( r ) A I n ( r ) A ,
W ( κ ) = exp ( | κ 2 | 2 σ w 2 ) exp ( | κ 2 | σ w 2 )
FWHM x , y = 0.37 λ NA eff ( U ) 500 nm
FWHM Lo 0.54 κ S NA eff ( U )
FWHM Hi 0.68 κ c NA eff ( U )
FWHM HiLo , exp = FWHM measured 2 d bead 2
FWHM WideField = 0.88 λ n n 2 NA 2 , FWHM Confocal = 0.64 λ n n 2 NA 2 .

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