Abstract

Single-molecule switching (SMS) microscopy is a super-resolution method capable of producing images with resolutions far exceeding that of the classical diffraction limit. However, like all optical microscopes, SMS microscopes are sensitive to, and often limited by, specimen-induced aberrations. Adaptive optics (AO) has proven beneficial in a range of microscopes to overcome the limitations caused by aberrations. We report here on new AO methods for SMS microscopy that enable the feedback correction of specimen-induced aberrations. The benefits are demonstrated through two-dimensional and three-dimensional STORM imaging. We expect that this advance will broaden the scope of SMS microscopy by enabling deep-cell and tissue-level imaging.

© 2015 Optical Society of America

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2014 (2)

2013 (4)

S. Liu, E. B. Kromann, W. D. Krueger, J. Bewersdorf, K. A. Lidke, “Three dimensional single molecule localization using a phase retrieved pupil function,” Opt. Express 21, 29462–29487 (2013).
[Crossref]

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[Crossref]

R. P. J. Nieuwenhuizen, K. A. Lidke, M. Bates, D. L. Puig, D. Grunwald, S. Stallinga, B. Rieger, “Measuring image resolution in optical nanoscopy,” Nat. Methods 10, 557–562 (2013).
[Crossref]

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
[Crossref]

2012 (5)

2011 (4)

F. Huang, S. L. Schwartz, J. M. Byars, K. A. Lidke, “Simultaneous multiple-emitter fitting for single molecule super-resolution imaging,” Biomed. Opt. Express 2, 1377–1393 (2011).
[Crossref]

J. Engelhardt, J. Keller, P. Hoyer, M. Reuss, T. Staudt, S. W. Hell, “Molecular orientation affects localization accuracy in superresolution far-field fluorescence microscopy,” Nano Lett. 11, 209–213 (2011).
[Crossref]

D. Débarre, T. Vieille, E. Beaurepaire, “Simple characterisation of a deformable mirror inside a high numerical aperture microscope using phase diversity,” J. Microsc. 244, 136–143 (2011).
[Crossref]

A. Thayil, M. J. Booth, “Self calibration of sensorless adaptive optical microscopes,” J. Eur. Opt. Soc. 6, 11045 (2011).
[Crossref]

2010 (2)

C. S. Smith, N. Joseph, B. Rieger, K. A. Lidke, “Fast, single-molecule localization that achieves theoretically minimum uncertainty,” Nat. Methods 7, 373–375 (2010).
[Crossref]

T. Dertinger, R. Colyer, R. Vogel, J. Enderlein, S. Weiss, “Achieving increased resolution and more pixels with Superresolution Optical Fluctuation Imaging (SOFI),” Opt. Express 18, 18875–18885 (2010).
[Crossref]

2009 (2)

2008 (1)

B. Huang, W. Wang, M. Bates, X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science 319, 810–813 (2008).
[Crossref]

2007 (2)

L. Holtzer, T. Meckel, T. Schmidt, “Nanometric three-dimensional tracking of individual quantum dots in cells,” Appl. Phys. Lett. 90, 053902 (2007).
[Crossref]

B. Zhang, J. Zerubia, J.-C. Olivo-Marin, “Gaussian approximations of fluorescence microscope point-spread function models,” Appl. Opt. 46, 1819–1829 (2007).
[Crossref]

2006 (3)

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

M. J. Rust, M. Bates, X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy,” Nat. Methods 3, 793–796 (2006).
[Crossref]

S. T. Hess, T. P. K. Girirajan, M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91, 4258–4272 (2006).
[Crossref]

2004 (1)

B. M. Hanser, M. G. L. Gustafsson, D. A. Agard, J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc. 216, 32–48 (2004).
[Crossref]

2003 (1)

2002 (2)

M. J. Booth, M. A. A. Neil, R. Juškaitis, T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
[Crossref]

R. E. Thompson, D. R. Larson, W. W. Webb, “Precise nanometer localization analysis for individual fluorescent probes,” Biophys. J. 82, 2775–2783 (2002).
[Crossref]

1998 (1)

M. Booth, M. Neil, T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192, 90–98 (1998).
[Crossref]

1994 (1)

H. P. Kao, A. S. Verkman, “Tracking of single fluorescent particles in three dimensions: use of cylindrical optics to encode particle position,” Biophys. J. 67, 1291–1300 (1994).
[Crossref]

1982 (1)

1976 (1)

1873 (1)

E. Abbe, “Beiträge zur Theorie des Mikroskops und der mikroskopischen Wahrnehmung,” Archiv fuer Mikroskopische Anatomie und Entwicklungsmechanik 9, 413–418 (1873).
[Crossref]

Abbe, E.

E. Abbe, “Beiträge zur Theorie des Mikroskops und der mikroskopischen Wahrnehmung,” Archiv fuer Mikroskopische Anatomie und Entwicklungsmechanik 9, 413–418 (1873).
[Crossref]

Agard, D. A.

B. M. Hanser, M. G. L. Gustafsson, D. A. Agard, J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc. 216, 32–48 (2004).
[Crossref]

Andilla, J.

Baird, M. A.

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
[Crossref]

Bates, M.

R. P. J. Nieuwenhuizen, K. A. Lidke, M. Bates, D. L. Puig, D. Grunwald, S. Stallinga, B. Rieger, “Measuring image resolution in optical nanoscopy,” Nat. Methods 10, 557–562 (2013).
[Crossref]

B. Huang, W. Wang, M. Bates, X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science 319, 810–813 (2008).
[Crossref]

M. J. Rust, M. Bates, X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy,” Nat. Methods 3, 793–796 (2006).
[Crossref]

Beane, G. L.

Beaurepaire, E.

D. Débarre, T. Vieille, E. Beaurepaire, “Simple characterisation of a deformable mirror inside a high numerical aperture microscope using phase diversity,” J. Microsc. 244, 136–143 (2011).
[Crossref]

Beheiry, M. E.

Betzig, E.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

Bewersdorf, J.

Bonifacino, J. S.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

Booth, M.

M. Booth, M. Neil, T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192, 90–98 (1998).
[Crossref]

Booth, M. J.

M. J. Booth, “Adaptive optical microscopy: the ongoing quest for a perfect image,” Light Sci. Appl. 3, e165 (2014).
[Crossref]

T. J. Gould, D. Burke, J. Bewersdorf, M. J. Booth, “Adaptive optics enables 3D STED microscopy in aberrating specimens,” Opt. Express 20, 20998–21009 (2012).
[Crossref]

A. Thayil, M. J. Booth, “Self calibration of sensorless adaptive optical microscopes,” J. Eur. Opt. Soc. 6, 11045 (2011).
[Crossref]

B. Wang, M. J. Booth, “Optimum deformable mirror modes for sensorless adaptive optics,” Opt. Commun. 282, 4467–4474 (2009).
[Crossref]

M. J. Booth, M. A. A. Neil, R. Juškaitis, T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
[Crossref]

Burke, D.

Byars, J. M.

Ciepielewski, D.

Colyer, R.

Dahan, M.

Darzacq, X.

Davidson, M. W.

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
[Crossref]

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

Débarre, D.

D. Débarre, T. Vieille, E. Beaurepaire, “Simple characterisation of a deformable mirror inside a high numerical aperture microscope using phase diversity,” J. Microsc. 244, 136–143 (2011).
[Crossref]

Dertinger, T.

Duim, W. C.

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
[Crossref]

Enderlein, J.

Engelhardt, J.

J. Engelhardt, J. Keller, P. Hoyer, M. Reuss, T. Staudt, S. W. Hell, “Molecular orientation affects localization accuracy in superresolution far-field fluorescence microscopy,” Nano Lett. 11, 209–213 (2011).
[Crossref]

Girirajan, T. P. K.

S. T. Hess, T. P. K. Girirajan, M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91, 4258–4272 (2006).
[Crossref]

Gönczy, P.

N. Olivier, D. Keller, P. Gönczy, S. Manley, “Resolution doubling in 3D-STORM imaging through improved buffers,” PLoS One 8, e69004 (2013).
[Crossref]

Gould, T. J.

Grunwald, D.

R. P. J. Nieuwenhuizen, K. A. Lidke, M. Bates, D. L. Puig, D. Grunwald, S. Stallinga, B. Rieger, “Measuring image resolution in optical nanoscopy,” Nat. Methods 10, 557–562 (2013).
[Crossref]

Gustafsson, M. G. L.

B. M. Hanser, M. G. L. Gustafsson, D. A. Agard, J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc. 216, 32–48 (2004).
[Crossref]

Hanser, B. M.

B. M. Hanser, M. G. L. Gustafsson, D. A. Agard, J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc. 216, 32–48 (2004).
[Crossref]

Hartwich, T. M. P.

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
[Crossref]

Hell, S. W.

J. Engelhardt, J. Keller, P. Hoyer, M. Reuss, T. Staudt, S. W. Hell, “Molecular orientation affects localization accuracy in superresolution far-field fluorescence microscopy,” Nano Lett. 11, 209–213 (2011).
[Crossref]

Hess, H. F.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

Hess, S. T.

T. J. Gould, S. T. Hess, J. Bewersdorf, “Optical nanoscopy: from acquisition to analysis,” Annu. Rev. Biomed. Eng. 14, 231–254 (2012). PMID: 22559319.
[Crossref]

S. T. Hess, T. P. K. Girirajan, M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91, 4258–4272 (2006).
[Crossref]

Holtzer, L.

L. Holtzer, T. Meckel, T. Schmidt, “Nanometric three-dimensional tracking of individual quantum dots in cells,” Appl. Phys. Lett. 90, 053902 (2007).
[Crossref]

Hoyer, P.

J. Engelhardt, J. Keller, P. Hoyer, M. Reuss, T. Staudt, S. W. Hell, “Molecular orientation affects localization accuracy in superresolution far-field fluorescence microscopy,” Nano Lett. 11, 209–213 (2011).
[Crossref]

Huang, B.

R. McGorty, J. Schnitzbauer, W. Zhang, B. Huang, “Correction of depth-dependent aberrations in 3D single-molecule localization and super-resolution microscopy,” Opt. Lett. 39, 275–278 (2014).
[Crossref]

B. Huang, W. Wang, M. Bates, X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science 319, 810–813 (2008).
[Crossref]

Huang, F.

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
[Crossref]

F. Huang, S. L. Schwartz, J. M. Byars, K. A. Lidke, “Simultaneous multiple-emitter fitting for single molecule super-resolution imaging,” Biomed. Opt. Express 2, 1377–1393 (2011).
[Crossref]

Izeddin, I.

Joseph, N.

C. S. Smith, N. Joseph, B. Rieger, K. A. Lidke, “Fast, single-molecule localization that achieves theoretically minimum uncertainty,” Nat. Methods 7, 373–375 (2010).
[Crossref]

Juette, M. F.

Juškaitis, R.

M. J. Booth, M. A. A. Neil, R. Juškaitis, T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
[Crossref]

Kao, H. P.

H. P. Kao, A. S. Verkman, “Tracking of single fluorescent particles in three dimensions: use of cylindrical optics to encode particle position,” Biophys. J. 67, 1291–1300 (1994).
[Crossref]

Keller, D.

N. Olivier, D. Keller, P. Gönczy, S. Manley, “Resolution doubling in 3D-STORM imaging through improved buffers,” PLoS One 8, e69004 (2013).
[Crossref]

Keller, J.

J. Engelhardt, J. Keller, P. Hoyer, M. Reuss, T. Staudt, S. W. Hell, “Molecular orientation affects localization accuracy in superresolution far-field fluorescence microscopy,” Nano Lett. 11, 209–213 (2011).
[Crossref]

Kromann, E. B.

Krueger, W. D.

Larson, D. R.

R. E. Thompson, D. R. Larson, W. W. Webb, “Precise nanometer localization analysis for individual fluorescent probes,” Biophys. J. 82, 2775–2783 (2002).
[Crossref]

Lidke, K. A.

S. Liu, E. B. Kromann, W. D. Krueger, J. Bewersdorf, K. A. Lidke, “Three dimensional single molecule localization using a phase retrieved pupil function,” Opt. Express 21, 29462–29487 (2013).
[Crossref]

R. P. J. Nieuwenhuizen, K. A. Lidke, M. Bates, D. L. Puig, D. Grunwald, S. Stallinga, B. Rieger, “Measuring image resolution in optical nanoscopy,” Nat. Methods 10, 557–562 (2013).
[Crossref]

F. Huang, S. L. Schwartz, J. M. Byars, K. A. Lidke, “Simultaneous multiple-emitter fitting for single molecule super-resolution imaging,” Biomed. Opt. Express 2, 1377–1393 (2011).
[Crossref]

C. S. Smith, N. Joseph, B. Rieger, K. A. Lidke, “Fast, single-molecule localization that achieves theoretically minimum uncertainty,” Nat. Methods 7, 373–375 (2010).
[Crossref]

Lin, Y.

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
[Crossref]

Lindwasser, O. W.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

Lippincott-Schwartz, J.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

Liu, S.

Long, J. J.

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
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N. Olivier, D. Keller, P. Gönczy, S. Manley, “Resolution doubling in 3D-STORM imaging through improved buffers,” PLoS One 8, e69004 (2013).
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S. T. Hess, T. P. K. Girirajan, M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91, 4258–4272 (2006).
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Mothes, W.

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
[Crossref]

Myers, J. R.

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
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M. Booth, M. Neil, T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192, 90–98 (1998).
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M. J. Booth, M. A. A. Neil, R. Juškaitis, T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
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R. P. J. Nieuwenhuizen, K. A. Lidke, M. Bates, D. L. Puig, D. Grunwald, S. Stallinga, B. Rieger, “Measuring image resolution in optical nanoscopy,” Nat. Methods 10, 557–562 (2013).
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Olenych, S.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

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N. Olivier, D. Keller, P. Gönczy, S. Manley, “Resolution doubling in 3D-STORM imaging through improved buffers,” PLoS One 8, e69004 (2013).
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Olivo-Marin, J.-C.

Patterson, G. H.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
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Pavani, S. R. P.

S. Quirin, S. R. P. Pavani, R. Piestun, “Optimal 3D single-molecule localization for superresolution microscopy with aberrations and engineered point spread functions,” Proc. Natl. Acad. Sci. USA 109, 675–679 (2012).

Piestun, R.

S. Quirin, S. R. P. Pavani, R. Piestun, “Optimal 3D single-molecule localization for superresolution microscopy with aberrations and engineered point spread functions,” Proc. Natl. Acad. Sci. USA 109, 675–679 (2012).

Poyneer, L. A.

Puig, D. L.

R. P. J. Nieuwenhuizen, K. A. Lidke, M. Bates, D. L. Puig, D. Grunwald, S. Stallinga, B. Rieger, “Measuring image resolution in optical nanoscopy,” Nat. Methods 10, 557–562 (2013).
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S. Quirin, S. R. P. Pavani, R. Piestun, “Optimal 3D single-molecule localization for superresolution microscopy with aberrations and engineered point spread functions,” Proc. Natl. Acad. Sci. USA 109, 675–679 (2012).

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F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
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M. J. Rust, M. Bates, X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy,” Nat. Methods 3, 793–796 (2006).
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L. Holtzer, T. Meckel, T. Schmidt, “Nanometric three-dimensional tracking of individual quantum dots in cells,” Appl. Phys. Lett. 90, 053902 (2007).
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Schwartz, S. L.

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B. M. Hanser, M. G. L. Gustafsson, D. A. Agard, J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc. 216, 32–48 (2004).
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C. S. Smith, N. Joseph, B. Rieger, K. A. Lidke, “Fast, single-molecule localization that achieves theoretically minimum uncertainty,” Nat. Methods 7, 373–375 (2010).
[Crossref]

Sougrat, R.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

Stallinga, S.

R. P. J. Nieuwenhuizen, K. A. Lidke, M. Bates, D. L. Puig, D. Grunwald, S. Stallinga, B. Rieger, “Measuring image resolution in optical nanoscopy,” Nat. Methods 10, 557–562 (2013).
[Crossref]

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J. Engelhardt, J. Keller, P. Hoyer, M. Reuss, T. Staudt, S. W. Hell, “Molecular orientation affects localization accuracy in superresolution far-field fluorescence microscopy,” Nano Lett. 11, 209–213 (2011).
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A. Thayil, M. J. Booth, “Self calibration of sensorless adaptive optical microscopes,” J. Eur. Opt. Soc. 6, 11045 (2011).
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R. E. Thompson, D. R. Larson, W. W. Webb, “Precise nanometer localization analysis for individual fluorescent probes,” Biophys. J. 82, 2775–2783 (2002).
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F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
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F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
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D. Débarre, T. Vieille, E. Beaurepaire, “Simple characterisation of a deformable mirror inside a high numerical aperture microscope using phase diversity,” J. Microsc. 244, 136–143 (2011).
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Wang, B.

B. Wang, M. J. Booth, “Optimum deformable mirror modes for sensorless adaptive optics,” Opt. Commun. 282, 4467–4474 (2009).
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Wang, W.

B. Huang, W. Wang, M. Bates, X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science 319, 810–813 (2008).
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R. E. Thompson, D. R. Larson, W. W. Webb, “Precise nanometer localization analysis for individual fluorescent probes,” Biophys. J. 82, 2775–2783 (2002).
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Weiss, S.

Wilhjelm, J. E.

Wilson, T.

M. J. Booth, M. A. A. Neil, R. Juškaitis, T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
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M. Booth, M. Neil, T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192, 90–98 (1998).
[Crossref]

Zerubia, J.

Zhang, B.

Zhang, W.

Zhuang, X.

B. Huang, W. Wang, M. Bates, X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science 319, 810–813 (2008).
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M. J. Rust, M. Bates, X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy,” Nat. Methods 3, 793–796 (2006).
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T. J. Gould, S. T. Hess, J. Bewersdorf, “Optical nanoscopy: from acquisition to analysis,” Annu. Rev. Biomed. Eng. 14, 231–254 (2012). PMID: 22559319.
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Appl. Opt. (2)

Appl. Phys. Lett. (1)

L. Holtzer, T. Meckel, T. Schmidt, “Nanometric three-dimensional tracking of individual quantum dots in cells,” Appl. Phys. Lett. 90, 053902 (2007).
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Archiv fuer Mikroskopische Anatomie und Entwicklungsmechanik (1)

E. Abbe, “Beiträge zur Theorie des Mikroskops und der mikroskopischen Wahrnehmung,” Archiv fuer Mikroskopische Anatomie und Entwicklungsmechanik 9, 413–418 (1873).
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Biomed. Opt. Express (1)

Biophys. J. (3)

S. T. Hess, T. P. K. Girirajan, M. D. Mason, “Ultra-high resolution imaging by fluorescence photoactivation localization microscopy,” Biophys. J. 91, 4258–4272 (2006).
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H. P. Kao, A. S. Verkman, “Tracking of single fluorescent particles in three dimensions: use of cylindrical optics to encode particle position,” Biophys. J. 67, 1291–1300 (1994).
[Crossref]

R. E. Thompson, D. R. Larson, W. W. Webb, “Precise nanometer localization analysis for individual fluorescent probes,” Biophys. J. 82, 2775–2783 (2002).
[Crossref]

J. Eur. Opt. Soc. (1)

A. Thayil, M. J. Booth, “Self calibration of sensorless adaptive optical microscopes,” J. Eur. Opt. Soc. 6, 11045 (2011).
[Crossref]

J. Microsc. (3)

M. Booth, M. Neil, T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192, 90–98 (1998).
[Crossref]

D. Débarre, T. Vieille, E. Beaurepaire, “Simple characterisation of a deformable mirror inside a high numerical aperture microscope using phase diversity,” J. Microsc. 244, 136–143 (2011).
[Crossref]

B. M. Hanser, M. G. L. Gustafsson, D. A. Agard, J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc. 216, 32–48 (2004).
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J. Opt. Soc. Am. (2)

Light Sci. Appl. (1)

M. J. Booth, “Adaptive optical microscopy: the ongoing quest for a perfect image,” Light Sci. Appl. 3, e165 (2014).
[Crossref]

Nano Lett. (1)

J. Engelhardt, J. Keller, P. Hoyer, M. Reuss, T. Staudt, S. W. Hell, “Molecular orientation affects localization accuracy in superresolution far-field fluorescence microscopy,” Nano Lett. 11, 209–213 (2011).
[Crossref]

Nat. Methods (4)

M. J. Rust, M. Bates, X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy,” Nat. Methods 3, 793–796 (2006).
[Crossref]

C. S. Smith, N. Joseph, B. Rieger, K. A. Lidke, “Fast, single-molecule localization that achieves theoretically minimum uncertainty,” Nat. Methods 7, 373–375 (2010).
[Crossref]

F. Huang, T. M. P. Hartwich, F. E. Rivera-Molina, Y. Lin, W. C. Duim, J. J. Long, P. D. Uchil, J. R. Myers, M. A. Baird, W. Mothes, M. W. Davidson, D. Toomre, J. Bewersdorf, “Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms,” Nat. Methods 10, 653–658 (2013).
[Crossref]

R. P. J. Nieuwenhuizen, K. A. Lidke, M. Bates, D. L. Puig, D. Grunwald, S. Stallinga, B. Rieger, “Measuring image resolution in optical nanoscopy,” Nat. Methods 10, 557–562 (2013).
[Crossref]

Opt. Commun. (1)

B. Wang, M. J. Booth, “Optimum deformable mirror modes for sensorless adaptive optics,” Opt. Commun. 282, 4467–4474 (2009).
[Crossref]

Opt. Express (5)

Opt. Lett. (2)

PLoS One (1)

N. Olivier, D. Keller, P. Gönczy, S. Manley, “Resolution doubling in 3D-STORM imaging through improved buffers,” PLoS One 8, e69004 (2013).
[Crossref]

Proc. Natl. Acad. Sci. USA (2)

M. J. Booth, M. A. A. Neil, R. Juškaitis, T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
[Crossref]

S. Quirin, S. R. P. Pavani, R. Piestun, “Optimal 3D single-molecule localization for superresolution microscopy with aberrations and engineered point spread functions,” Proc. Natl. Acad. Sci. USA 109, 675–679 (2012).

Science (2)

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

B. Huang, W. Wang, M. Bates, X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science 319, 810–813 (2008).
[Crossref]

Other (1)

R. K. Tyson, Principles of Adaptive Optics (Academic, 1998).

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Figures (11)

Fig. 1.
Fig. 1.

Simplified schematic of our custom-built microscope. Illumination from a 405 and a 655 nm laser were combined and focused into a 1.4 NA objective lens to create wide-field illumination. The light emitted was separated from the excitation light by a dichroic filter and an emission filter before being relayed onto a 140-actuator DM and finally focused onto an EMCCD camera.

Fig. 2.
Fig. 2.

Principle of aberration measurement. For each aberration mode Zi, a number of images are acquired, each with different amplitude of the mode applied to the DM (red dots). The image metric S is plotted as a function of the total aberration amplitude a. The metric value is then calculated for each image and the peak of the metric curve is estimated via a Gaussian fit to the values (green dot). A coma aberration mode is used for illustration purposes.

Fig. 3.
Fig. 3.

(a) Maximum projection of a captured SMS data set, equivalent to a diffraction-limited image. (b) A reconstructed super-resolution SMS image, with an FRC resolution of 42 nm and localization precisions of σx=9nm and σy=9nm. The scale bar is 1 μm in both images.

Fig. 4.
Fig. 4.

Correction of specimen-induced aberrations. An SMS image was reconstructed [(a1) and (b1)] with the AO set to correct for instrumental aberrations only and [(a2) and (b2)] with modes Z4Z15 corrected using sensorless AO. Spherical aberration dominated the correction of the specimen-induced aberrations (insets). The insets show the specimen-only component of the applied correction. The scale bar is 1 μm and the units of phase are radians.

Fig. 5.
Fig. 5.

Zernike decompositions of the specimen-induced aberrations presented in Figs. 4(a2) and 4(b2). The correction is dominated in these cases by spherical aberration (mode 11), although there is also a significant specimen-dependent component that varies between specimens. The amplitude units correspond to the RMS phase in radians.

Fig. 6.
Fig. 6.

3D SMS image was reconstructed (a) with the AO set to correct for instrumental aberrations only and (b) with the AO set to correct for instrumental and specimen-induced aberrations. The inset shows the specimen-only component of the applied phase correction. The scale bar is 1 μm and the units of phase are radians.

Fig. 7.
Fig. 7.

3D SMS image was reconstructed (a) with the AO set to correct for instrumental aberrations only and (b) with the AO set to correct for instrumental and specimen-induced aberrations. The inset shows the specimen-only component of the applied correction. The scale bar is 1 μm and the units of phase are radians.

Fig. 8.
Fig. 8.

Zernike decompositions of the specimen-induced aberrations presented in Figs. 6 and 7. The aberrations contained significant nonspherical components, including [in (a)] trefoil (mode 9) and [in (b)] astigmatism (modes 5 and 6).

Fig. 9.
Fig. 9.

xz projections of the three locations marked in Fig. 6. The top row are the instrumental correction projections and the bottom row are the specimen-corrected projections. AO correction of specimen-induced aberrations resulted in denser and more localizations than without AO correction. The scale bar is 100 nm.

Fig. 10.
Fig. 10.

Localization precisions in x, y, and z versus the single-molecule photon detection threshold, expressed as effective photon count. The detection threshold was varied between 200 and 900 photons and the x, y, and z localization precisions were estimated at each threshold. Correction of the specimen aberrations resulted in better localizations along each spatial axis for all detection thresholds tested here.

Fig. 11.
Fig. 11.

Number of “good” fits versus the single-molecule photon detection threshold, expressed as effective photon count. A good fit was defined as having σx and σy less than 20 nm and σz less than 40 nm. Correction of the specimen-induced aberrations resulted in a significant increase in the number of good localizations at all detection thresholds tested here.

Tables (1)

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Table 1. Summary of Fitting Results for the 3D Microtubule Imaginga

Equations (2)

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

S=n,mμn,mI^n,m(n2+m2)/n,mI^n,m,
μn,m={1,n2+m2w0,n2+m2>w,

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