Abstract

Coherent detection through two opposing objectives (4Pi configuration) improves the precision of three-dimensional (3D) single-molecule localization substantially along the axial direction, but suffers from instrument complexity and maintenance difficulty. To address these issues, we have realized 4Pi fluorescence detection by sandwiching the sample between the objective and a mirror, and create interference of direct incidence and mirror-reflected signal at the camera with a spatial light modulator. Multifocal imaging using this single-objective mirror interference scheme offers improvement in the axial localization similar to the traditional 4Pi method. We have also devised several PSF engineering schemes to enable 3D localization with a single emitter image, offering better axial precision than normal single-objective localization methods such as astigmatic imaging.

© 2013 OSA

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2012 (4)

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

G. Grover, K. DeLuca, S. Quirin, J. DeLuca, and R. Piestun, “Super-resolution photon-efficient imaging by nanometric double-helix point spread function localization of emitters (SPINDLE),” Opt. Express20(24), 26681–26695 (2012).
[CrossRef] [PubMed]

M. J. Paszek, C. C. DuFort, M. G. Rubashkin, M. W. Davidson, K. S. Thorn, J. T. Liphardt, and V. M. Weaver, “Scanning angle interference microscopy reveals cell dynamics at the nanoscale,” Nat. Methods9(8), 825–827 (2012).
[CrossRef] [PubMed]

S. Li, C. F. Kuang, X. Hao, Z. Gu, and X. T. Liu, “Generation of a 3D isotropic hollow focal spot for single-objective stimulated emission depletion microscopy,” J Optics-Uk 14 (2012).

2011 (4)

2010 (8)

M. A. Thompson, J. M. Casolari, M. Badieirostami, P. O. Brown, and W. E. Moerner, “Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.107(42), 17864–17871 (2010).
[CrossRef] [PubMed]

M. F. Juette and J. Bewersdorf, “Three-dimensional tracking of single fluorescent particles with submillisecond temporal resolution,” Nano Lett.10(11), 4657–4663 (2010).
[CrossRef] [PubMed]

M. Badieirostami, M. D. Lew, M. A. Thompson, and W. E. Moerner, “Three-dimensional localization precision of the double-helix point spread function versus astigmatism and biplane,” Appl. Phys. Lett.97(16), 161103 (2010).
[CrossRef] [PubMed]

G. Grover, S. R. Pavani, and R. Piestun, “Performance limits on three-dimensional particle localization in photon-limited microscopy,” Opt. Lett.35(19), 3306–3308 (2010).
[CrossRef] [PubMed]

E. Mudry, E. Le Moal, P. Ferrand, P. C. Chaumet, and A. Sentenac, “Isotropic diffraction-limited focusing using a single objective lens,” Phys. Rev. Lett.105(20), 203903 (2010).
[CrossRef] [PubMed]

K. I. Mortensen, L. S. Churchman, J. A. Spudich, and H. Flyvbjerg, “Optimized localization analysis for single-molecule tracking and super-resolution microscopy,” Nat. Methods7(5), 377–381 (2010).
[CrossRef] [PubMed]

C. S. Smith, N. Joseph, B. Rieger, and K. A. Lidke, “Fast, single-molecule localization that achieves theoretically minimum uncertainty,” Nat. Methods7(5), 373–375 (2010).
[CrossRef] [PubMed]

P. Kner, L. Winoto, D. A. Agard, and J. W. Sedat, “Closed loop adaptive optics for microscopy without a wavefront sensor,” Proc. SPIE7570(757006), 757006 (2010).

2009 (6)

M. Pitzek, R. Steiger, G. Thalhammer, S. Bernet, and M. Ritsch-Marte, “Optical mirror trap with a large field of view,” Opt. Express17(22), 19414–19423 (2009).
[CrossRef] [PubMed]

M. J. Mlodzianoski, M. F. Juette, G. L. Beane, and J. Bewersdorf, “Experimental characterization of 3D localization techniques for particle-tracking and super-resolution microscopy,” Opt. Express17(10), 8264–8277 (2009).
[CrossRef] [PubMed]

G. Shtengel, J. A. Galbraith, C. G. Galbraith, J. Lippincott-Schwartz, J. M. Gillette, S. Manley, R. Sougrat, C. M. Waterman, P. Kanchanawong, M. W. Davidson, R. D. Fetter, and H. F. Hess, “Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure,” Proc. Natl. Acad. Sci. U.S.A.106(9), 3125–3130 (2009).
[CrossRef] [PubMed]

S. Ram, P. Prabhat, E. S. Ward, and R. J. Ober, “Improved single particle localization accuracy with dual objective multifocal plane microscopy,” Opt. Express17(8), 6881–6898 (2009).
[CrossRef] [PubMed]

S. R. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.106(9), 2995–2999 (2009).
[CrossRef] [PubMed]

S. R. Pavani, J. G. DeLuca, and R. Piestun, “Polarization sensitive, three-dimensional, single-molecule imaging of cells with a double-helix system,” Opt. Express17(22), 19644–19655 (2009).
[CrossRef] [PubMed]

2008 (4)

B. Huang, W. Wang, M. Bates, and X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science319(5864), 810–813 (2008).
[CrossRef] [PubMed]

S. R. Pavani and R. Piestun, “Three dimensional tracking of fluorescent microparticles using a photon-limited double-helix response system,” Opt. Express16(26), 22048–22057 (2008).
[CrossRef] [PubMed]

S. Ram, P. Prabhat, J. Chao, E. S. Ward, and R. J. Ober, “High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells,” Biophys. J.95(12), 6025–6043 (2008).
[CrossRef] [PubMed]

C. von Middendorff, A. Egner, C. Geisler, S. W. Hell, and A. Schönle, “Isotropic 3D Nanoscopy based on single emitter switching,” Opt. Express16(25), 20774–20788 (2008).
[CrossRef] [PubMed]

2007 (5)

T. M. Watanabe, T. Sato, K. Gonda, and H. Higuchi, “Three-dimensional nanometry of vesicle transport in living cells using dual-focus imaging optics,” Biochem. Biophys. Res. Commun.359(1), 1–7 (2007).
[CrossRef] [PubMed]

E. Toprak, H. Balci, B. H. Blehm, and P. R. Selvin, “Three-dimensional particle tracking via bifocal imaging,” Nano Lett.7(7), 2043–2045 (2007).
[CrossRef] [PubMed]

L. Holtzer, T. Meckel, and T. Schmidt, “Nanometric three-dimensional tracking of individual quantum dots in cells,” Appl. Phys. Lett.90(5), 053902 (2007).
[CrossRef]

R. Di Leonardo, F. Ianni, and G. Ruocco, “Computer generation of optimal holograms for optical trap arrays,” Opt. Express15(4), 1913–1922 (2007).
[CrossRef] [PubMed]

R. W. Deming, “Phase retrieval from intensity-only data by relative entropy minimization,” J. Opt. Soc. Am. A24(11), 3666–3679 (2007).
[CrossRef] [PubMed]

2006 (1)

L. Moiseev, M. S. Unlü, A. K. Swan, B. B. Goldberg, and C. R. Cantor, “DNA conformation on surfaces measured by fluorescence self-interference,” Proc. Natl. Acad. Sci. U.S.A.103(8), 2623–2628 (2006).
[CrossRef] [PubMed]

2005 (1)

A. Egner and S. W. Hell, “Fluorescence microscopy with super-resolved optical sections,” Trends Cell Biol.15(4), 207–215 (2005).
[CrossRef] [PubMed]

2004 (3)

L. Moiseev, C. R. Cantor, M. I. Aksun, M. Dogan, B. B. Goldberg, A. K. Swan, and M. S. Unlu, “Spectral self-interference fluorescence microscopy,” J. Appl. Phys.96(9), 5311–5315 (2004).
[CrossRef]

B. M. Hanser, M. G. Gustafsson, D. A. Agard, and J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc.216(1), 32–48 (2004).
[CrossRef] [PubMed]

R. J. Ober, S. Ram, and E. S. Ward, “Localization accuracy in single-molecule microscopy,” Biophys. J.86(2), 1185–1200 (2004).
[CrossRef] [PubMed]

2003 (1)

2000 (1)

G. J. Schütz, V. Ph. Pastushenko, H. J. Gruber, H.-G. Knaus, B. Pragl, and H. Schindler, “3D Imaging of Individual Ion Channels in Live Cells at 40nm Resolution,” Single Molecules1(1), 25–31 (2000).
[CrossRef]

1999 (1)

M. G. Gustafsson, D. A. Agard, and J. W. Sedat, “I5M: 3D widefield light microscopy with better than 100 nm axial resolution,” J. Microsc.195(1), 10–16 (1999).
[CrossRef] [PubMed]

1994 (1)

H. P. Kao and A. S. Verkman, “Tracking of single fluorescent particles in three dimensions: use of cylindrical optics to encode particle position,” Biophys. J.67(3), 1291–1300 (1994).
[CrossRef] [PubMed]

1991 (1)

Agard, D. A.

P. Kner, L. Winoto, D. A. Agard, and J. W. Sedat, “Closed loop adaptive optics for microscopy without a wavefront sensor,” Proc. SPIE7570(757006), 757006 (2010).

B. M. Hanser, M. G. Gustafsson, D. A. Agard, and J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc.216(1), 32–48 (2004).
[CrossRef] [PubMed]

M. G. Gustafsson, D. A. Agard, and J. W. Sedat, “I5M: 3D widefield light microscopy with better than 100 nm axial resolution,” J. Microsc.195(1), 10–16 (1999).
[CrossRef] [PubMed]

Aksun, M. I.

L. Moiseev, C. R. Cantor, M. I. Aksun, M. Dogan, B. B. Goldberg, A. K. Swan, and M. S. Unlu, “Spectral self-interference fluorescence microscopy,” J. Appl. Phys.96(9), 5311–5315 (2004).
[CrossRef]

Aquino, D.

D. Aquino, A. Schönle, C. Geisler, C. V. Middendorff, C. A. Wurm, Y. Okamura, T. Lang, S. W. Hell, and A. Egner, “Two-color nanoscopy of three-dimensional volumes by 4Pi detection of stochastically switched fluorophores,” Nat. Methods8(4), 353–359 (2011).
[CrossRef] [PubMed]

Badieirostami, M.

M. D. Lew, S. F. Lee, M. Badieirostami, and W. E. Moerner, “Corkscrew point spread function for far-field three-dimensional nanoscale localization of pointlike objects,” Opt. Lett.36(2), 202–204 (2011).
[CrossRef] [PubMed]

M. A. Thompson, J. M. Casolari, M. Badieirostami, P. O. Brown, and W. E. Moerner, “Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.107(42), 17864–17871 (2010).
[CrossRef] [PubMed]

M. Badieirostami, M. D. Lew, M. A. Thompson, and W. E. Moerner, “Three-dimensional localization precision of the double-helix point spread function versus astigmatism and biplane,” Appl. Phys. Lett.97(16), 161103 (2010).
[CrossRef] [PubMed]

Balci, H.

E. Toprak, H. Balci, B. H. Blehm, and P. R. Selvin, “Three-dimensional particle tracking via bifocal imaging,” Nano Lett.7(7), 2043–2045 (2007).
[CrossRef] [PubMed]

Bates, M.

B. Huang, W. Wang, M. Bates, and X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science319(5864), 810–813 (2008).
[CrossRef] [PubMed]

Beane, G. L.

Bernet, S.

Bewersdorf, J.

M. F. Juette and J. Bewersdorf, “Three-dimensional tracking of single fluorescent particles with submillisecond temporal resolution,” Nano Lett.10(11), 4657–4663 (2010).
[CrossRef] [PubMed]

M. J. Mlodzianoski, M. F. Juette, G. L. Beane, and J. Bewersdorf, “Experimental characterization of 3D localization techniques for particle-tracking and super-resolution microscopy,” Opt. Express17(10), 8264–8277 (2009).
[CrossRef] [PubMed]

Biteen, J. S.

S. R. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.106(9), 2995–2999 (2009).
[CrossRef] [PubMed]

Blehm, B. H.

E. Toprak, H. Balci, B. H. Blehm, and P. R. Selvin, “Three-dimensional particle tracking via bifocal imaging,” Nano Lett.7(7), 2043–2045 (2007).
[CrossRef] [PubMed]

Brown, P. O.

M. A. Thompson, J. M. Casolari, M. Badieirostami, P. O. Brown, and W. E. Moerner, “Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.107(42), 17864–17871 (2010).
[CrossRef] [PubMed]

Cantor, C. R.

L. Moiseev, M. S. Unlü, A. K. Swan, B. B. Goldberg, and C. R. Cantor, “DNA conformation on surfaces measured by fluorescence self-interference,” Proc. Natl. Acad. Sci. U.S.A.103(8), 2623–2628 (2006).
[CrossRef] [PubMed]

L. Moiseev, C. R. Cantor, M. I. Aksun, M. Dogan, B. B. Goldberg, A. K. Swan, and M. S. Unlu, “Spectral self-interference fluorescence microscopy,” J. Appl. Phys.96(9), 5311–5315 (2004).
[CrossRef]

Casolari, J. M.

M. A. Thompson, J. M. Casolari, M. Badieirostami, P. O. Brown, and W. E. Moerner, “Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.107(42), 17864–17871 (2010).
[CrossRef] [PubMed]

Chao, J.

S. Ram, P. Prabhat, J. Chao, E. S. Ward, and R. J. Ober, “High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells,” Biophys. J.95(12), 6025–6043 (2008).
[CrossRef] [PubMed]

Chaumet, P. C.

E. Le Moal, E. Mudry, P. C. Chaumet, P. Ferrand, and A. Sentenac, “Isotropic single-objective microscopy: theory and experiment,” J. Opt. Soc. Am. A28(8), 1586–1594 (2011).
[CrossRef] [PubMed]

E. Mudry, E. Le Moal, P. Ferrand, P. C. Chaumet, and A. Sentenac, “Isotropic diffraction-limited focusing using a single objective lens,” Phys. Rev. Lett.105(20), 203903 (2010).
[CrossRef] [PubMed]

Churchman, L. S.

K. I. Mortensen, L. S. Churchman, J. A. Spudich, and H. Flyvbjerg, “Optimized localization analysis for single-molecule tracking and super-resolution microscopy,” Nat. Methods7(5), 377–381 (2010).
[CrossRef] [PubMed]

Davidson, M. W.

M. J. Paszek, C. C. DuFort, M. G. Rubashkin, M. W. Davidson, K. S. Thorn, J. T. Liphardt, and V. M. Weaver, “Scanning angle interference microscopy reveals cell dynamics at the nanoscale,” Nat. Methods9(8), 825–827 (2012).
[CrossRef] [PubMed]

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D. Aquino, A. Schönle, C. Geisler, C. V. Middendorff, C. A. Wurm, Y. Okamura, T. Lang, S. W. Hell, and A. Egner, “Two-color nanoscopy of three-dimensional volumes by 4Pi detection of stochastically switched fluorophores,” Nat. Methods8(4), 353–359 (2011).
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S. Li, C. F. Kuang, X. Hao, Z. Gu, and X. T. Liu, “Generation of a 3D isotropic hollow focal spot for single-objective stimulated emission depletion microscopy,” J Optics-Uk 14 (2012).

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S. R. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.106(9), 2995–2999 (2009).
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L. Holtzer, T. Meckel, and T. Schmidt, “Nanometric three-dimensional tracking of individual quantum dots in cells,” Appl. Phys. Lett.90(5), 053902 (2007).
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Moerner, W. E.

M. D. Lew, S. F. Lee, M. Badieirostami, and W. E. Moerner, “Corkscrew point spread function for far-field three-dimensional nanoscale localization of pointlike objects,” Opt. Lett.36(2), 202–204 (2011).
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S. R. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.106(9), 2995–2999 (2009).
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L. Moiseev, M. S. Unlü, A. K. Swan, B. B. Goldberg, and C. R. Cantor, “DNA conformation on surfaces measured by fluorescence self-interference,” Proc. Natl. Acad. Sci. U.S.A.103(8), 2623–2628 (2006).
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L. Moiseev, C. R. Cantor, M. I. Aksun, M. Dogan, B. B. Goldberg, A. K. Swan, and M. S. Unlu, “Spectral self-interference fluorescence microscopy,” J. Appl. Phys.96(9), 5311–5315 (2004).
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K. I. Mortensen, L. S. Churchman, J. A. Spudich, and H. Flyvbjerg, “Optimized localization analysis for single-molecule tracking and super-resolution microscopy,” Nat. Methods7(5), 377–381 (2010).
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E. Le Moal, E. Mudry, P. C. Chaumet, P. Ferrand, and A. Sentenac, “Isotropic single-objective microscopy: theory and experiment,” J. Opt. Soc. Am. A28(8), 1586–1594 (2011).
[CrossRef] [PubMed]

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Ober, R. J.

S. Ram, P. Prabhat, E. S. Ward, and R. J. Ober, “Improved single particle localization accuracy with dual objective multifocal plane microscopy,” Opt. Express17(8), 6881–6898 (2009).
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S. Ram, P. Prabhat, J. Chao, E. S. Ward, and R. J. Ober, “High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells,” Biophys. J.95(12), 6025–6043 (2008).
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R. J. Ober, S. Ram, and E. S. Ward, “Localization accuracy in single-molecule microscopy,” Biophys. J.86(2), 1185–1200 (2004).
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D. Aquino, A. Schönle, C. Geisler, C. V. Middendorff, C. A. Wurm, Y. Okamura, T. Lang, S. W. Hell, and A. Egner, “Two-color nanoscopy of three-dimensional volumes by 4Pi detection of stochastically switched fluorophores,” Nat. Methods8(4), 353–359 (2011).
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M. J. Paszek, C. C. DuFort, M. G. Rubashkin, M. W. Davidson, K. S. Thorn, J. T. Liphardt, and V. M. Weaver, “Scanning angle interference microscopy reveals cell dynamics at the nanoscale,” Nat. Methods9(8), 825–827 (2012).
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S. Quirin, S. R. Pavani, and R. Piestun, “Optimal 3D single-molecule localization for superresolution microscopy with aberrations and engineered point spread functions,” Proc. Natl. Acad. Sci. U.S.A.109(3), 675–679 (2012).
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S. R. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.106(9), 2995–2999 (2009).
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S. R. Pavani and R. Piestun, “Three dimensional tracking of fluorescent microparticles using a photon-limited double-helix response system,” Opt. Express16(26), 22048–22057 (2008).
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S. Quirin, S. R. Pavani, and R. Piestun, “Optimal 3D single-molecule localization for superresolution microscopy with aberrations and engineered point spread functions,” Proc. Natl. Acad. Sci. U.S.A.109(3), 675–679 (2012).
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G. Grover, S. R. Pavani, and R. Piestun, “Performance limits on three-dimensional particle localization in photon-limited microscopy,” Opt. Lett.35(19), 3306–3308 (2010).
[CrossRef] [PubMed]

S. R. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.106(9), 2995–2999 (2009).
[CrossRef] [PubMed]

S. R. Pavani, J. G. DeLuca, and R. Piestun, “Polarization sensitive, three-dimensional, single-molecule imaging of cells with a double-helix system,” Opt. Express17(22), 19644–19655 (2009).
[CrossRef] [PubMed]

S. R. Pavani and R. Piestun, “Three dimensional tracking of fluorescent microparticles using a photon-limited double-helix response system,” Opt. Express16(26), 22048–22057 (2008).
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S. Ram, P. Prabhat, E. S. Ward, and R. J. Ober, “Improved single particle localization accuracy with dual objective multifocal plane microscopy,” Opt. Express17(8), 6881–6898 (2009).
[CrossRef] [PubMed]

S. Ram, P. Prabhat, J. Chao, E. S. Ward, and R. J. Ober, “High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells,” Biophys. J.95(12), 6025–6043 (2008).
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G. J. Schütz, V. Ph. Pastushenko, H. J. Gruber, H.-G. Knaus, B. Pragl, and H. Schindler, “3D Imaging of Individual Ion Channels in Live Cells at 40nm Resolution,” Single Molecules1(1), 25–31 (2000).
[CrossRef]

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Ram, S.

S. Ram, P. Prabhat, E. S. Ward, and R. J. Ober, “Improved single particle localization accuracy with dual objective multifocal plane microscopy,” Opt. Express17(8), 6881–6898 (2009).
[CrossRef] [PubMed]

S. Ram, P. Prabhat, J. Chao, E. S. Ward, and R. J. Ober, “High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells,” Biophys. J.95(12), 6025–6043 (2008).
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R. J. Ober, S. Ram, and E. S. Ward, “Localization accuracy in single-molecule microscopy,” Biophys. J.86(2), 1185–1200 (2004).
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Rieger, B.

C. S. Smith, N. Joseph, B. Rieger, and K. A. Lidke, “Fast, single-molecule localization that achieves theoretically minimum uncertainty,” Nat. Methods7(5), 373–375 (2010).
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Rubashkin, M. G.

M. J. Paszek, C. C. DuFort, M. G. Rubashkin, M. W. Davidson, K. S. Thorn, J. T. Liphardt, and V. M. Weaver, “Scanning angle interference microscopy reveals cell dynamics at the nanoscale,” Nat. Methods9(8), 825–827 (2012).
[CrossRef] [PubMed]

Ruocco, G.

Sato, T.

T. M. Watanabe, T. Sato, K. Gonda, and H. Higuchi, “Three-dimensional nanometry of vesicle transport in living cells using dual-focus imaging optics,” Biochem. Biophys. Res. Commun.359(1), 1–7 (2007).
[CrossRef] [PubMed]

Schindler, H.

G. J. Schütz, V. Ph. Pastushenko, H. J. Gruber, H.-G. Knaus, B. Pragl, and H. Schindler, “3D Imaging of Individual Ion Channels in Live Cells at 40nm Resolution,” Single Molecules1(1), 25–31 (2000).
[CrossRef]

Schmidt, T.

L. Holtzer, T. Meckel, and T. Schmidt, “Nanometric three-dimensional tracking of individual quantum dots in cells,” Appl. Phys. Lett.90(5), 053902 (2007).
[CrossRef]

Schönle, A.

D. Aquino, A. Schönle, C. Geisler, C. V. Middendorff, C. A. Wurm, Y. Okamura, T. Lang, S. W. Hell, and A. Egner, “Two-color nanoscopy of three-dimensional volumes by 4Pi detection of stochastically switched fluorophores,” Nat. Methods8(4), 353–359 (2011).
[CrossRef] [PubMed]

C. von Middendorff, A. Egner, C. Geisler, S. W. Hell, and A. Schönle, “Isotropic 3D Nanoscopy based on single emitter switching,” Opt. Express16(25), 20774–20788 (2008).
[CrossRef] [PubMed]

Schütz, G. J.

G. J. Schütz, V. Ph. Pastushenko, H. J. Gruber, H.-G. Knaus, B. Pragl, and H. Schindler, “3D Imaging of Individual Ion Channels in Live Cells at 40nm Resolution,” Single Molecules1(1), 25–31 (2000).
[CrossRef]

Sedat, J. W.

P. Kner, L. Winoto, D. A. Agard, and J. W. Sedat, “Closed loop adaptive optics for microscopy without a wavefront sensor,” Proc. SPIE7570(757006), 757006 (2010).

B. M. Hanser, M. G. Gustafsson, D. A. Agard, and J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc.216(1), 32–48 (2004).
[CrossRef] [PubMed]

M. G. Gustafsson, D. A. Agard, and J. W. Sedat, “I5M: 3D widefield light microscopy with better than 100 nm axial resolution,” J. Microsc.195(1), 10–16 (1999).
[CrossRef] [PubMed]

Selvin, P. R.

E. Toprak, H. Balci, B. H. Blehm, and P. R. Selvin, “Three-dimensional particle tracking via bifocal imaging,” Nano Lett.7(7), 2043–2045 (2007).
[CrossRef] [PubMed]

Sentenac, A.

E. Le Moal, E. Mudry, P. C. Chaumet, P. Ferrand, and A. Sentenac, “Isotropic single-objective microscopy: theory and experiment,” J. Opt. Soc. Am. A28(8), 1586–1594 (2011).
[CrossRef] [PubMed]

E. Mudry, E. Le Moal, P. Ferrand, P. C. Chaumet, and A. Sentenac, “Isotropic diffraction-limited focusing using a single objective lens,” Phys. Rev. Lett.105(20), 203903 (2010).
[CrossRef] [PubMed]

Shtengel, G.

G. Shtengel, J. A. Galbraith, C. G. Galbraith, J. Lippincott-Schwartz, J. M. Gillette, S. Manley, R. Sougrat, C. M. Waterman, P. Kanchanawong, M. W. Davidson, R. D. Fetter, and H. F. Hess, “Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure,” Proc. Natl. Acad. Sci. U.S.A.106(9), 3125–3130 (2009).
[CrossRef] [PubMed]

Smith, C. S.

C. S. Smith, N. Joseph, B. Rieger, and K. A. Lidke, “Fast, single-molecule localization that achieves theoretically minimum uncertainty,” Nat. Methods7(5), 373–375 (2010).
[CrossRef] [PubMed]

Sougrat, R.

G. Shtengel, J. A. Galbraith, C. G. Galbraith, J. Lippincott-Schwartz, J. M. Gillette, S. Manley, R. Sougrat, C. M. Waterman, P. Kanchanawong, M. W. Davidson, R. D. Fetter, and H. F. Hess, “Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure,” Proc. Natl. Acad. Sci. U.S.A.106(9), 3125–3130 (2009).
[CrossRef] [PubMed]

Speidel, M.

Spudich, J. A.

K. I. Mortensen, L. S. Churchman, J. A. Spudich, and H. Flyvbjerg, “Optimized localization analysis for single-molecule tracking and super-resolution microscopy,” Nat. Methods7(5), 377–381 (2010).
[CrossRef] [PubMed]

Steiger, R.

Swan, A. K.

L. Moiseev, M. S. Unlü, A. K. Swan, B. B. Goldberg, and C. R. Cantor, “DNA conformation on surfaces measured by fluorescence self-interference,” Proc. Natl. Acad. Sci. U.S.A.103(8), 2623–2628 (2006).
[CrossRef] [PubMed]

L. Moiseev, C. R. Cantor, M. I. Aksun, M. Dogan, B. B. Goldberg, A. K. Swan, and M. S. Unlu, “Spectral self-interference fluorescence microscopy,” J. Appl. Phys.96(9), 5311–5315 (2004).
[CrossRef]

Thalhammer, G.

Thompson, M. A.

M. Badieirostami, M. D. Lew, M. A. Thompson, and W. E. Moerner, “Three-dimensional localization precision of the double-helix point spread function versus astigmatism and biplane,” Appl. Phys. Lett.97(16), 161103 (2010).
[CrossRef] [PubMed]

M. A. Thompson, J. M. Casolari, M. Badieirostami, P. O. Brown, and W. E. Moerner, “Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.107(42), 17864–17871 (2010).
[CrossRef] [PubMed]

S. R. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.106(9), 2995–2999 (2009).
[CrossRef] [PubMed]

Thorn, K. S.

M. J. Paszek, C. C. DuFort, M. G. Rubashkin, M. W. Davidson, K. S. Thorn, J. T. Liphardt, and V. M. Weaver, “Scanning angle interference microscopy reveals cell dynamics at the nanoscale,” Nat. Methods9(8), 825–827 (2012).
[CrossRef] [PubMed]

Toprak, E.

E. Toprak, H. Balci, B. H. Blehm, and P. R. Selvin, “Three-dimensional particle tracking via bifocal imaging,” Nano Lett.7(7), 2043–2045 (2007).
[CrossRef] [PubMed]

Twieg, R. J.

S. R. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.106(9), 2995–2999 (2009).
[CrossRef] [PubMed]

Unlu, M. S.

L. Moiseev, C. R. Cantor, M. I. Aksun, M. Dogan, B. B. Goldberg, A. K. Swan, and M. S. Unlu, “Spectral self-interference fluorescence microscopy,” J. Appl. Phys.96(9), 5311–5315 (2004).
[CrossRef]

Unlü, M. S.

L. Moiseev, M. S. Unlü, A. K. Swan, B. B. Goldberg, and C. R. Cantor, “DNA conformation on surfaces measured by fluorescence self-interference,” Proc. Natl. Acad. Sci. U.S.A.103(8), 2623–2628 (2006).
[CrossRef] [PubMed]

Verkman, A. S.

H. P. Kao and A. S. Verkman, “Tracking of single fluorescent particles in three dimensions: use of cylindrical optics to encode particle position,” Biophys. J.67(3), 1291–1300 (1994).
[CrossRef] [PubMed]

von Middendorff, C.

Wang, W.

B. Huang, W. Wang, M. Bates, and X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science319(5864), 810–813 (2008).
[CrossRef] [PubMed]

Ward, E. S.

S. Ram, P. Prabhat, E. S. Ward, and R. J. Ober, “Improved single particle localization accuracy with dual objective multifocal plane microscopy,” Opt. Express17(8), 6881–6898 (2009).
[CrossRef] [PubMed]

S. Ram, P. Prabhat, J. Chao, E. S. Ward, and R. J. Ober, “High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells,” Biophys. J.95(12), 6025–6043 (2008).
[CrossRef] [PubMed]

R. J. Ober, S. Ram, and E. S. Ward, “Localization accuracy in single-molecule microscopy,” Biophys. J.86(2), 1185–1200 (2004).
[CrossRef] [PubMed]

Watanabe, T. M.

T. M. Watanabe, T. Sato, K. Gonda, and H. Higuchi, “Three-dimensional nanometry of vesicle transport in living cells using dual-focus imaging optics,” Biochem. Biophys. Res. Commun.359(1), 1–7 (2007).
[CrossRef] [PubMed]

Waterman, C. M.

G. Shtengel, J. A. Galbraith, C. G. Galbraith, J. Lippincott-Schwartz, J. M. Gillette, S. Manley, R. Sougrat, C. M. Waterman, P. Kanchanawong, M. W. Davidson, R. D. Fetter, and H. F. Hess, “Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure,” Proc. Natl. Acad. Sci. U.S.A.106(9), 3125–3130 (2009).
[CrossRef] [PubMed]

Weaver, V. M.

M. J. Paszek, C. C. DuFort, M. G. Rubashkin, M. W. Davidson, K. S. Thorn, J. T. Liphardt, and V. M. Weaver, “Scanning angle interference microscopy reveals cell dynamics at the nanoscale,” Nat. Methods9(8), 825–827 (2012).
[CrossRef] [PubMed]

Winoto, L.

P. Kner, L. Winoto, D. A. Agard, and J. W. Sedat, “Closed loop adaptive optics for microscopy without a wavefront sensor,” Proc. SPIE7570(757006), 757006 (2010).

Wurm, C. A.

D. Aquino, A. Schönle, C. Geisler, C. V. Middendorff, C. A. Wurm, Y. Okamura, T. Lang, S. W. Hell, and A. Egner, “Two-color nanoscopy of three-dimensional volumes by 4Pi detection of stochastically switched fluorophores,” Nat. Methods8(4), 353–359 (2011).
[CrossRef] [PubMed]

Zhuang, X.

B. Huang, W. Wang, M. Bates, and X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science319(5864), 810–813 (2008).
[CrossRef] [PubMed]

Appl. Opt. (1)

Appl. Phys. Lett. (2)

L. Holtzer, T. Meckel, and T. Schmidt, “Nanometric three-dimensional tracking of individual quantum dots in cells,” Appl. Phys. Lett.90(5), 053902 (2007).
[CrossRef]

M. Badieirostami, M. D. Lew, M. A. Thompson, and W. E. Moerner, “Three-dimensional localization precision of the double-helix point spread function versus astigmatism and biplane,” Appl. Phys. Lett.97(16), 161103 (2010).
[CrossRef] [PubMed]

Biochem. Biophys. Res. Commun. (1)

T. M. Watanabe, T. Sato, K. Gonda, and H. Higuchi, “Three-dimensional nanometry of vesicle transport in living cells using dual-focus imaging optics,” Biochem. Biophys. Res. Commun.359(1), 1–7 (2007).
[CrossRef] [PubMed]

Biomed. Opt. Express (1)

Biophys. J. (3)

H. P. Kao and A. S. Verkman, “Tracking of single fluorescent particles in three dimensions: use of cylindrical optics to encode particle position,” Biophys. J.67(3), 1291–1300 (1994).
[CrossRef] [PubMed]

S. Ram, P. Prabhat, J. Chao, E. S. Ward, and R. J. Ober, “High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells,” Biophys. J.95(12), 6025–6043 (2008).
[CrossRef] [PubMed]

R. J. Ober, S. Ram, and E. S. Ward, “Localization accuracy in single-molecule microscopy,” Biophys. J.86(2), 1185–1200 (2004).
[CrossRef] [PubMed]

Generation of a 3D isotropic hollow focal spot for single-objective stimulated emission depletion microscopy (1)

S. Li, C. F. Kuang, X. Hao, Z. Gu, and X. T. Liu, “Generation of a 3D isotropic hollow focal spot for single-objective stimulated emission depletion microscopy,” J Optics-Uk 14 (2012).

J. Appl. Phys. (1)

L. Moiseev, C. R. Cantor, M. I. Aksun, M. Dogan, B. B. Goldberg, A. K. Swan, and M. S. Unlu, “Spectral self-interference fluorescence microscopy,” J. Appl. Phys.96(9), 5311–5315 (2004).
[CrossRef]

J. Microsc. (2)

M. G. Gustafsson, D. A. Agard, and J. W. Sedat, “I5M: 3D widefield light microscopy with better than 100 nm axial resolution,” J. Microsc.195(1), 10–16 (1999).
[CrossRef] [PubMed]

B. M. Hanser, M. G. Gustafsson, D. A. Agard, and J. W. Sedat, “Phase-retrieved pupil functions in wide-field fluorescence microscopy,” J. Microsc.216(1), 32–48 (2004).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A (2)

Nano Lett. (2)

E. Toprak, H. Balci, B. H. Blehm, and P. R. Selvin, “Three-dimensional particle tracking via bifocal imaging,” Nano Lett.7(7), 2043–2045 (2007).
[CrossRef] [PubMed]

M. F. Juette and J. Bewersdorf, “Three-dimensional tracking of single fluorescent particles with submillisecond temporal resolution,” Nano Lett.10(11), 4657–4663 (2010).
[CrossRef] [PubMed]

Nat. Methods (4)

M. J. Paszek, C. C. DuFort, M. G. Rubashkin, M. W. Davidson, K. S. Thorn, J. T. Liphardt, and V. M. Weaver, “Scanning angle interference microscopy reveals cell dynamics at the nanoscale,” Nat. Methods9(8), 825–827 (2012).
[CrossRef] [PubMed]

D. Aquino, A. Schönle, C. Geisler, C. V. Middendorff, C. A. Wurm, Y. Okamura, T. Lang, S. W. Hell, and A. Egner, “Two-color nanoscopy of three-dimensional volumes by 4Pi detection of stochastically switched fluorophores,” Nat. Methods8(4), 353–359 (2011).
[CrossRef] [PubMed]

K. I. Mortensen, L. S. Churchman, J. A. Spudich, and H. Flyvbjerg, “Optimized localization analysis for single-molecule tracking and super-resolution microscopy,” Nat. Methods7(5), 377–381 (2010).
[CrossRef] [PubMed]

C. S. Smith, N. Joseph, B. Rieger, and K. A. Lidke, “Fast, single-molecule localization that achieves theoretically minimum uncertainty,” Nat. Methods7(5), 373–375 (2010).
[CrossRef] [PubMed]

Opt. Express (8)

R. Di Leonardo, F. Ianni, and G. Ruocco, “Computer generation of optimal holograms for optical trap arrays,” Opt. Express15(4), 1913–1922 (2007).
[CrossRef] [PubMed]

C. von Middendorff, A. Egner, C. Geisler, S. W. Hell, and A. Schönle, “Isotropic 3D Nanoscopy based on single emitter switching,” Opt. Express16(25), 20774–20788 (2008).
[CrossRef] [PubMed]

M. J. Mlodzianoski, M. F. Juette, G. L. Beane, and J. Bewersdorf, “Experimental characterization of 3D localization techniques for particle-tracking and super-resolution microscopy,” Opt. Express17(10), 8264–8277 (2009).
[CrossRef] [PubMed]

M. Pitzek, R. Steiger, G. Thalhammer, S. Bernet, and M. Ritsch-Marte, “Optical mirror trap with a large field of view,” Opt. Express17(22), 19414–19423 (2009).
[CrossRef] [PubMed]

S. Ram, P. Prabhat, E. S. Ward, and R. J. Ober, “Improved single particle localization accuracy with dual objective multifocal plane microscopy,” Opt. Express17(8), 6881–6898 (2009).
[CrossRef] [PubMed]

S. R. Pavani, J. G. DeLuca, and R. Piestun, “Polarization sensitive, three-dimensional, single-molecule imaging of cells with a double-helix system,” Opt. Express17(22), 19644–19655 (2009).
[CrossRef] [PubMed]

S. R. Pavani and R. Piestun, “Three dimensional tracking of fluorescent microparticles using a photon-limited double-helix response system,” Opt. Express16(26), 22048–22057 (2008).
[CrossRef] [PubMed]

G. Grover, K. DeLuca, S. Quirin, J. DeLuca, and R. Piestun, “Super-resolution photon-efficient imaging by nanometric double-helix point spread function localization of emitters (SPINDLE),” Opt. Express20(24), 26681–26695 (2012).
[CrossRef] [PubMed]

Opt. Lett. (3)

Phys. Rev. Lett. (1)

E. Mudry, E. Le Moal, P. Ferrand, P. C. Chaumet, and A. Sentenac, “Isotropic diffraction-limited focusing using a single objective lens,” Phys. Rev. Lett.105(20), 203903 (2010).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (5)

L. Moiseev, M. S. Unlü, A. K. Swan, B. B. Goldberg, and C. R. Cantor, “DNA conformation on surfaces measured by fluorescence self-interference,” Proc. Natl. Acad. Sci. U.S.A.103(8), 2623–2628 (2006).
[CrossRef] [PubMed]

G. Shtengel, J. A. Galbraith, C. G. Galbraith, J. Lippincott-Schwartz, J. M. Gillette, S. Manley, R. Sougrat, C. M. Waterman, P. Kanchanawong, M. W. Davidson, R. D. Fetter, and H. F. Hess, “Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure,” Proc. Natl. Acad. Sci. U.S.A.106(9), 3125–3130 (2009).
[CrossRef] [PubMed]

M. A. Thompson, J. M. Casolari, M. Badieirostami, P. O. Brown, and W. E. Moerner, “Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.107(42), 17864–17871 (2010).
[CrossRef] [PubMed]

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

S. R. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Proc. Natl. Acad. Sci. U.S.A.106(9), 2995–2999 (2009).
[CrossRef] [PubMed]

Proc. SPIE (1)

P. Kner, L. Winoto, D. A. Agard, and J. W. Sedat, “Closed loop adaptive optics for microscopy without a wavefront sensor,” Proc. SPIE7570(757006), 757006 (2010).

Science (1)

B. Huang, W. Wang, M. Bates, and X. Zhuang, “Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy,” Science319(5864), 810–813 (2008).
[CrossRef] [PubMed]

Single Molecules (1)

G. J. Schütz, V. Ph. Pastushenko, H. J. Gruber, H.-G. Knaus, B. Pragl, and H. Schindler, “3D Imaging of Individual Ion Channels in Live Cells at 40nm Resolution,” Single Molecules1(1), 25–31 (2000).
[CrossRef]

Trends Cell Biol. (1)

A. Egner and S. W. Hell, “Fluorescence microscopy with super-resolved optical sections,” Trends Cell Biol.15(4), 207–215 (2005).
[CrossRef] [PubMed]

Other (2)

J. Bewersdorf, A. Egner, and S. W. Hell, “4Pi Microscopy,” in Handbook of Biological Confocal Microscopy, J. Pawley, ed. (Springer, New York, 2006), pp. 561–570.

S. Zwick, T. Haist, Y. Miyamoto, L. He, M. Warber, A. Hermerschmidt, and W. Osten, “Holographic twin traps,” J Opt a-Pure Appl Op 11 (2009).

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Figures (4)

Fig. 1
Fig. 1

Schematic of 4Pi detection with a single-objective and the experimental setup. (a) A fluorophore and its reflection (red stars) are imaged by an infinity corrected microscope (blue), which generates an image and a mirror image of the fluorophore along the optical axis (gray ellipses). Phase modulation in the pupil plane with an SLM (green) can overlay the two images (red ellipse) at the camera plane (orange), creating a virtual focal plane (violet) at the fluorophore position. (b) The emission phase of a fluorophore in front of a mirror at the pupil plane are concentric rings of either 0 or π and is strongly dependent on the distance between fluorophore and mirror. Modulation of this phase with its exact opposite (middle) results in a plane wave (right), which is focused at the camera plane. (c) The experimental setup is based on a Nikon Ti-U microscope with a custom excitation path and a relayed emission path. The SLM is located at the Fourier plane of relay lens 1. The sample is sandwiched between the coverglass and a mirror.

Fig. 2
Fig. 2

Simulated and experimental PSFs of a conventional (a, e), single-objective interference (b, f) and dual-objective 4Pi (c) microscopes and their axial intensity profile (d, g). Experimental PSFs show an axial scan of a 100 nm fluorescent bead at 1.04 µm distance to a mirror. The simulations show the axial scan of a point source at the same position.

Fig. 3
Fig. 3

Simulations and experiments of the proposed four plane mirror interference setup and interference PSF engineering. The phase modulations at the pupil plane are shown on top. Below are simulated and measured lateral slices of the respective PSFs at five axial positions. (a) In this proposed setup the emission is split into four paths, each with a different focal plane modulation, and imaged separately. (b) The modulation is split into four quadrants with the quadrants in horizontal direction encoding a different virtual focal plane than the quadrants in vertical direction. (c) The modulation encodes for a virtual focal plane for each radial angle in a ramp with a span of one emission wavelength. (d) Three virtual focal planes are superimposed with a phase tilt so that the images are shifted laterally. The modulation is a random mix of the three tilted focal planes.

Fig. 4
Fig. 4

Simulated CRLBs (standard deviation) for (a) astigmatic, (b) conventional biplane, (c) four-phase dual-objective 4Pi, (d) four plane single-objective interference and (e, f, g) PSF engineered particle localization. The simulation for astigmatic imaging introduced a 340 nm offset between the x and y focal planes. The detection planes for conventional biplane imaging are simulated 380 nm apart. These separations were chosen for the most uniform z localization precision across the entire range. The simulation conditions for (d-g) are identical to those in Fig. 3a-d, except for that (g) used an image shift of 772 nm instead of 440 nm, which gives better CRLB. For the PSF engineered cases, we plotted the CRLB for 50% (dashed) and 100% (solid) photon recovery, representing a polarization dependent and a polarization independent SLM, respectively.

Equations (2)

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

PSF( x,y,z )= | FFT{ P( k x , k y )×exp[ 2πi k z ( k x , k y )z ] } | 2
CRL B θ ( z )= { x,y 1 PSF( x,y,z )+b [ PSF( x,y,z ) θ ] 2 } 1 2 , θ=x,y,z

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