Abstract

We present a correlation-differential confocal microscopy (CDCM), a novel method that can simultaneously improve the three-dimensional spatial resolution and axial focusing accuracy of confocal microscopy (CM). CDCM divides the CM imaging light path into two paths, where the detectors are before and after the focus with an equal axial offset in opposite directions. Then, the light intensity signals received from the two paths are processed by the correlation product and differential subtraction to improve the CM spatial resolution and axial focusing accuracy, respectively. Theoretical analyses and preliminary experiments indicate that, for the excitation wavelength of λ = 405 nm, numerical aperture of NA = 0.95, and the normalized axial offset of uM = 5.21, the CDCM resolution is improved by more than 20% and more than 30% in the lateral and axial directions, respectively, compared with that of the CM. Also, the axial focusing resolution important for the imaging of sample surface profiles is improved to 1 nm.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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2017 (2)

Y. Israel, R. Tenne, D. Oron, and Y. Silberberg, “Quantum correlation enhanced super-resolution localization microscopy enabled by a fibre bundle camera,” Nat. Commun. 8, 14786 (2017).
[Crossref] [PubMed]

H. Shen, L. J. Tauzin, R. Baiyasi, W. Wang, N. Moringo, B. Shuang, and C. F. Landes, “Single Particle Tracking: From Theory to Biophysical Applications,” Chem. Rev. 117(11), 7331–7376 (2017).
[Crossref] [PubMed]

2016 (1)

C. Zhang, C. Min, L. Du, and X.-C. Yuan, “Perfect optical vortex enhanced surface plasmon excitation for plasmonic structured illumination microscopy imaging,” Appl. Phys. Lett. 108(20), 201601 (2016).
[Crossref]

2015 (3)

M. Saxena, G. Eluru, and S. S. Gorthi, “Structured illumination microscopy,” Adv. Opt. Photonics 7(2), 241–275 (2015).
[Crossref]

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
[Crossref]

Y. Ma, C. Kuang, W. Gong, L. Xue, Y. Zheng, Y. Wang, K. Si, and X. Liu, “Improvements of axial resolution in confocal microscopy with fan-shaped apertures,” Appl. Opt. 54(6), 1354–1362 (2015).
[Crossref] [PubMed]

2014 (3)

D. Wang, D. Meza, Y. Wang, L. Gao, and J. T. C. Liu, “Sheet-scanned dual-axis confocal microscopy using Richardson-Lucy deconvolution,” Opt. Lett. 39(18), 5431–5434 (2014).
[Crossref] [PubMed]

S. Pechprasarn, B. Zhang, D. Albutt, J. Zhang, and M. Somekh, “Ultrastable embedded surface plasmon confocal interferometry,” Light Sci. Appl. 3(7), e187 (2014).
[Crossref]

W. Lu, M. Chang, P. C. Chen, and W. M. Luo, “Iterative deconvolution technique for measurements of diffraction-limited images on optical microscopes,” J. Mod. Opt. 61(sup1), S2–S9 (2014).
[Crossref] [PubMed]

2013 (2)

Y. Tan, W. Wang, C. Xu, and S. Zhang, “Laser confocal feedback tomography and nano-step height measurement,” Sci. Rep. 3(43), 2971 (2013).
[Crossref] [PubMed]

J. M. Cui, F. W. Sun, X. D. Chen, Z. J. Gong, and G. C. Guo, “Quantum statistical imaging of particles without restriction of the diffraction limit,” Phys. Rev. Lett. 110(15), 153901 (2013).
[Crossref] [PubMed]

2012 (2)

W. Zhao, C. Liu, and L. Qiu, “Laser divided-aperture differential confocal sensing technology with improved axial resolution,” Opt. Express 20(23), 25979–25989 (2012).
[Crossref] [PubMed]

O. Schwartz and D. Oron, “Improved resolution in fluorescence microscopy using quantum correlations,” Phys. Rev. A 85(3), 145–150 (2012).
[Crossref]

2011 (1)

W. Zhao, Q. Jiang, L. Qiu, and D. Liu, “Dual-axes differential confocal microscopy with high axial resolution and long working distance,” Opt. Commun. 284(1), 15–19 (2011).
[Crossref]

2010 (2)

C. B. Müller and J. Enderlein, “Image scanning microscopy,” Phys. Rev. Lett. 104(19), 198101 (2010).
[Crossref] [PubMed]

B. Huang, H. Babcock, and X. Zhuang, “Breaking the Diffraction Barrier: Super-Resolution Imaging of Cells,” Cell 143(7), 1047–1058 (2010).
[Crossref] [PubMed]

2009 (2)

2008 (2)

2007 (3)

M. Bates, B. Huang, G. T. Dempsey, and X. Zhuang, “Multicolor Super-Resolution Imaging with Photo-Switchable Fluorescent Probes,” Science 317(5845), 1749–1753 (2007).
[Crossref] [PubMed]

S. W. Hell, “Far-Field Optical Nanoscopy,” Science 316(5828), 1153–1158 (2007).
[Crossref] [PubMed]

G. Scarcelli and S. H. Yun, “Confocal Brillouin microscopy for three-dimensional mechanical imaging,” Nat. Photonics 2(1), 39–43 (2007).
[Crossref] [PubMed]

2006 (4)

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

M. J. Rust, M. Bates, and X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3(10), 793–795 (2006).
[Crossref] [PubMed]

P. J. Dwyer, C. A. DiMarzio, J. M. Zavislan, W. J. Fox, and M. Rajadhyaksha, “Confocal reflectance theta line scanning microscope for imaging human skin in vivo,” Opt. Lett. 31(7), 942–944 (2006).
[Crossref] [PubMed]

W. Zhao, L. Qiu, and Z. Feng, “Effect of fabrication errors on superresolution property of a pupil filter,” Opt. Express 14(16), 7024–7036 (2006).
[Crossref] [PubMed]

2005 (1)

M. G. L. Gustafsson, “Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution,” Proc. Natl. Acad. Sci. U.S.A. 102(37), 13081–13086 (2005).
[Crossref] [PubMed]

2003 (4)

2000 (1)

M. G. Gustafsson, “Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy,” J. Microsc. 198(Pt 2), 82–87 (2000).
[Crossref] [PubMed]

1996 (1)

1995 (1)

P. E. Hänninen, S. W. Hell, J. Salo, E. Soini, and C. Cremer, “Two-photon excitation 4Pi confocal microscope: Enhanced axial resolution microscope for biological research,” Appl. Phys. Lett. 66(13), 1698–1700 (1995).
[Crossref]

1994 (4)

S. Hell, S. Lindek, C. Cremer, and E. H. K. Stelzer, “Measurement of the 4Pi-confocal point spread function proves 75 nm axial resolution,” Appl. Phys. Lett. 64(11), 1335–1337 (1994).
[Crossref]

S. W. Hell and J. Wichmann, “Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy,” Opt. Lett. 19(11), 780–782 (1994).
[Crossref] [PubMed]

E. H. K. Stelzer and S. Lindek, “Fundamental reduction of the observation volume in far-field light microscopy by detection orthogonal to the illumination axis: confocal theta microscopy,” Opt. Commun. 111(5–6), 536–547 (1994).
[Crossref]

M. Gu, T. Tannous, and C. J. R. Sheppard, “Improved axial resolution in confocal fluorescence microscopy using annular pupils,” Opt. Commun. 110(5–6), 533–539 (1994).
[Crossref]

1992 (1)

1991 (1)

A. E. Dixon, S. Damaskinos, and M. R. Atkinson, “A scanning confocal microscope for transmission and reflecting imaging,” Nature 351(6327), 551–553 (1991).
[Crossref]

1990 (1)

G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
[Crossref] [PubMed]

1988 (1)

C. J. R. Sheppard, “Super-resolution in confocal imaging,” Optik (Stuttg.) 80(2), 53–54 (1988).

1987 (1)

J. G. White and W. B. Amos, “Confocal microscopy comes of age,” Nature 328(6126), 183–184 (1987).
[Crossref]

1983 (1)

Albutt, D.

S. Pechprasarn, B. Zhang, D. Albutt, J. Zhang, and M. Somekh, “Ultrastable embedded surface plasmon confocal interferometry,” Light Sci. Appl. 3(7), e187 (2014).
[Crossref]

Amos, W. B.

J. G. White and W. B. Amos, “Confocal microscopy comes of age,” Nature 328(6126), 183–184 (1987).
[Crossref]

Arndt-Jovin, D. J.

G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
[Crossref] [PubMed]

Atkinson, M. R.

A. E. Dixon, S. Damaskinos, and M. R. Atkinson, “A scanning confocal microscope for transmission and reflecting imaging,” Nature 351(6327), 551–553 (1991).
[Crossref]

Babcock, H.

B. Huang, H. Babcock, and X. Zhuang, “Breaking the Diffraction Barrier: Super-Resolution Imaging of Cells,” Cell 143(7), 1047–1058 (2010).
[Crossref] [PubMed]

Baiyasi, R.

H. Shen, L. J. Tauzin, R. Baiyasi, W. Wang, N. Moringo, B. Shuang, and C. F. Landes, “Single Particle Tracking: From Theory to Biophysical Applications,” Chem. Rev. 117(11), 7331–7376 (2017).
[Crossref] [PubMed]

Bates, M.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
[Crossref]

M. Bates, B. Huang, G. T. Dempsey, and X. Zhuang, “Multicolor Super-Resolution Imaging with Photo-Switchable Fluorescent Probes,” Science 317(5845), 1749–1753 (2007).
[Crossref] [PubMed]

M. J. Rust, M. Bates, and X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3(10), 793–795 (2006).
[Crossref] [PubMed]

Betzig, E.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Bewersdorf, J.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
[Crossref]

Bonifacino, J. S.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Booth, M. J.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
[Crossref]

Castello, M.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
[Crossref]

Chang, M.

W. Lu, M. Chang, P. C. Chen, and W. M. Luo, “Iterative deconvolution technique for measurements of diffraction-limited images on optical microscopes,” J. Mod. Opt. 61(sup1), S2–S9 (2014).
[Crossref] [PubMed]

Chen, P. C.

W. Lu, M. Chang, P. C. Chen, and W. M. Luo, “Iterative deconvolution technique for measurements of diffraction-limited images on optical microscopes,” J. Mod. Opt. 61(sup1), S2–S9 (2014).
[Crossref] [PubMed]

Chen, X. D.

J. M. Cui, F. W. Sun, X. D. Chen, Z. J. Gong, and G. C. Guo, “Quantum statistical imaging of particles without restriction of the diffraction limit,” Phys. Rev. Lett. 110(15), 153901 (2013).
[Crossref] [PubMed]

Chiang, H. Y.

Cognet, L.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
[Crossref]

Contag, C. H.

Cordes, T.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
[Crossref]

Cremer, C.

S. Lindek, C. Cremer, and E. H. K. Stelzer, “Confocal theta fluorescence microscopy with annular apertures,” Appl. Opt. 35(1), 126–130 (1996).
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S. Hell, S. Lindek, C. Cremer, and E. H. K. Stelzer, “Measurement of the 4Pi-confocal point spread function proves 75 nm axial resolution,” Appl. Phys. Lett. 64(11), 1335–1337 (1994).
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J. M. Cui, F. W. Sun, X. D. Chen, Z. J. Gong, and G. C. Guo, “Quantum statistical imaging of particles without restriction of the diffraction limit,” Phys. Rev. Lett. 110(15), 153901 (2013).
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E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
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S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
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M. Bates, B. Huang, G. T. Dempsey, and X. Zhuang, “Multicolor Super-Resolution Imaging with Photo-Switchable Fluorescent Probes,” Science 317(5845), 1749–1753 (2007).
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S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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A. E. Dixon, S. Damaskinos, and M. R. Atkinson, “A scanning confocal microscope for transmission and reflecting imaging,” Nature 351(6327), 551–553 (1991).
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R. Dorn, S. Quabis, and G. Leuchs, “Sharper focus for a radially polarized light beam,” Phys. Rev. Lett. 91(23), 233901 (2003).
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C. Zhang, C. Min, L. Du, and X.-C. Yuan, “Perfect optical vortex enhanced surface plasmon excitation for plasmonic structured illumination microscopy imaging,” Appl. Phys. Lett. 108(20), 201601 (2016).
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S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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M. Saxena, G. Eluru, and S. S. Gorthi, “Structured illumination microscopy,” Adv. Opt. Photonics 7(2), 241–275 (2015).
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C. B. Müller and J. Enderlein, “Image scanning microscopy,” Phys. Rev. Lett. 104(19), 198101 (2010).
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S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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Gao, L.

Gong, W.

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J. M. Cui, F. W. Sun, X. D. Chen, Z. J. Gong, and G. C. Guo, “Quantum statistical imaging of particles without restriction of the diffraction limit,” Phys. Rev. Lett. 110(15), 153901 (2013).
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M. Saxena, G. Eluru, and S. S. Gorthi, “Structured illumination microscopy,” Adv. Opt. Photonics 7(2), 241–275 (2015).
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G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
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M. Gu, T. Tannous, and C. J. R. Sheppard, “Improved axial resolution in confocal fluorescence microscopy using annular pupils,” Opt. Commun. 110(5–6), 533–539 (1994).
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J. M. Cui, F. W. Sun, X. D. Chen, Z. J. Gong, and G. C. Guo, “Quantum statistical imaging of particles without restriction of the diffraction limit,” Phys. Rev. Lett. 110(15), 153901 (2013).
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Hamilton, D. K.

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P. E. Hänninen, S. W. Hell, J. Salo, E. Soini, and C. Cremer, “Two-photon excitation 4Pi confocal microscope: Enhanced axial resolution microscope for biological research,” Appl. Phys. Lett. 66(13), 1698–1700 (1995).
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Hardy, J.

Heintzmann, R.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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S. Hell, S. Lindek, C. Cremer, and E. H. K. Stelzer, “Measurement of the 4Pi-confocal point spread function proves 75 nm axial resolution,” Appl. Phys. Lett. 64(11), 1335–1337 (1994).
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S. Hell and E. H. K. Stelzer, “Properties of a 4Pi confocal fluorescence microscope,” J. Opt. Soc. Am. A 9(12), 2159–2166 (1992).
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S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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P. E. Hänninen, S. W. Hell, J. Salo, E. Soini, and C. Cremer, “Two-photon excitation 4Pi confocal microscope: Enhanced axial resolution microscope for biological research,” Appl. Phys. Lett. 66(13), 1698–1700 (1995).
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S. W. Hell and J. Wichmann, “Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy,” Opt. Lett. 19(11), 780–782 (1994).
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S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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Hess, H. F.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
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S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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Huang, B.

B. Huang, H. Babcock, and X. Zhuang, “Breaking the Diffraction Barrier: Super-Resolution Imaging of Cells,” Cell 143(7), 1047–1058 (2010).
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M. Bates, B. Huang, G. T. Dempsey, and X. Zhuang, “Multicolor Super-Resolution Imaging with Photo-Switchable Fluorescent Probes,” Science 317(5845), 1749–1753 (2007).
[Crossref] [PubMed]

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Y. Israel, R. Tenne, D. Oron, and Y. Silberberg, “Quantum correlation enhanced super-resolution localization microscopy enabled by a fibre bundle camera,” Nat. Commun. 8, 14786 (2017).
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Jakobs, S.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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W. Zhao, Q. Jiang, L. Qiu, and D. Liu, “Dual-axes differential confocal microscopy with high axial resolution and long working distance,” Opt. Commun. 284(1), 15–19 (2011).
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Jovin, T. M.

G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
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Kang, D.

Kino, G. S.

Klenerman, D.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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Landes, C. F.

H. Shen, L. J. Tauzin, R. Baiyasi, W. Wang, N. Moringo, B. Shuang, and C. F. Landes, “Single Particle Tracking: From Theory to Biophysical Applications,” Chem. Rev. 117(11), 7331–7376 (2017).
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Lee, C. H.

Leuchs, G.

R. Dorn, S. Quabis, and G. Leuchs, “Sharper focus for a radially polarized light beam,” Phys. Rev. Lett. 91(23), 233901 (2003).
[Crossref] [PubMed]

Lindek, S.

S. Lindek, C. Cremer, and E. H. K. Stelzer, “Confocal theta fluorescence microscopy with annular apertures,” Appl. Opt. 35(1), 126–130 (1996).
[Crossref] [PubMed]

E. H. K. Stelzer and S. Lindek, “Fundamental reduction of the observation volume in far-field light microscopy by detection orthogonal to the illumination axis: confocal theta microscopy,” Opt. Commun. 111(5–6), 536–547 (1994).
[Crossref]

S. Hell, S. Lindek, C. Cremer, and E. H. K. Stelzer, “Measurement of the 4Pi-confocal point spread function proves 75 nm axial resolution,” Appl. Phys. Lett. 64(11), 1335–1337 (1994).
[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, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
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Lippincott-Schwartz, J.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
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Liu, C.

Liu, D.

W. Zhao, Q. Jiang, L. Qiu, and D. Liu, “Dual-axes differential confocal microscopy with high axial resolution and long working distance,” Opt. Commun. 284(1), 15–19 (2011).
[Crossref]

Liu, J. T. C.

Liu, X.

Lounis, B.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
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W. Lu, M. Chang, P. C. Chen, and W. M. Luo, “Iterative deconvolution technique for measurements of diffraction-limited images on optical microscopes,” J. Mod. Opt. 61(sup1), S2–S9 (2014).
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Luo, W. M.

W. Lu, M. Chang, P. C. Chen, and W. M. Luo, “Iterative deconvolution technique for measurements of diffraction-limited images on optical microscopes,” J. Mod. Opt. 61(sup1), S2–S9 (2014).
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Ma, Y.

Mandella, M. J.

Meza, D.

Min, C.

C. Zhang, C. Min, L. Du, and X.-C. Yuan, “Perfect optical vortex enhanced surface plasmon excitation for plasmonic structured illumination microscopy imaging,” Appl. Phys. Lett. 108(20), 201601 (2016).
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Mong, H. Y.

Moringo, N.

H. Shen, L. J. Tauzin, R. Baiyasi, W. Wang, N. Moringo, B. Shuang, and C. F. Landes, “Single Particle Tracking: From Theory to Biophysical Applications,” Chem. Rev. 117(11), 7331–7376 (2017).
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Müller, C. B.

C. B. Müller and J. Enderlein, “Image scanning microscopy,” Phys. Rev. Lett. 104(19), 198101 (2010).
[Crossref] [PubMed]

Olenych, S.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Oron, D.

Y. Israel, R. Tenne, D. Oron, and Y. Silberberg, “Quantum correlation enhanced super-resolution localization microscopy enabled by a fibre bundle camera,” Nat. Commun. 8, 14786 (2017).
[Crossref] [PubMed]

O. Schwartz and D. Oron, “Improved resolution in fluorescence microscopy using quantum correlations,” Phys. Rev. A 85(3), 145–150 (2012).
[Crossref]

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G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
[Crossref] [PubMed]

Patterson, G. H.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Pechprasarn, S.

S. Pechprasarn, B. Zhang, D. Albutt, J. Zhang, and M. Somekh, “Ultrastable embedded surface plasmon confocal interferometry,” Light Sci. Appl. 3(7), e187 (2014).
[Crossref]

Piyawattanametha, W.

Puppels, G. J.

G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
[Crossref] [PubMed]

Qiu, L.

Quabis, S.

R. Dorn, S. Quabis, and G. Leuchs, “Sharper focus for a radially polarized light beam,” Phys. Rev. Lett. 91(23), 233901 (2003).
[Crossref] [PubMed]

Ra, H.

Rajadhyaksha, M.

Robert-Nicoud, M.

G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
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M. J. Rust, M. Bates, and X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3(10), 793–795 (2006).
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S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
[Crossref]

Salo, J.

P. E. Hänninen, S. W. Hell, J. Salo, E. Soini, and C. Cremer, “Two-photon excitation 4Pi confocal microscope: Enhanced axial resolution microscope for biological research,” Appl. Phys. Lett. 66(13), 1698–1700 (1995).
[Crossref]

Saxena, M.

M. Saxena, G. Eluru, and S. S. Gorthi, “Structured illumination microscopy,” Adv. Opt. Photonics 7(2), 241–275 (2015).
[Crossref]

Scarcelli, G.

G. Scarcelli and S. H. Yun, “Confocal Brillouin microscopy for three-dimensional mechanical imaging,” Nat. Photonics 2(1), 39–43 (2007).
[Crossref] [PubMed]

Schwartz, O.

O. Schwartz and D. Oron, “Improved resolution in fluorescence microscopy using quantum correlations,” Phys. Rev. A 85(3), 145–150 (2012).
[Crossref]

Shen, H.

H. Shen, L. J. Tauzin, R. Baiyasi, W. Wang, N. Moringo, B. Shuang, and C. F. Landes, “Single Particle Tracking: From Theory to Biophysical Applications,” Chem. Rev. 117(11), 7331–7376 (2017).
[Crossref] [PubMed]

Sheppard, C. J.

Sheppard, C. J. R.

W. T. Tang, E. Y. Yew, and C. J. R. Sheppard, “Polarization conversion in confocal microscopy with radially polarized illumination,” Opt. Lett. 34(14), 2147–2149 (2009).
[Crossref] [PubMed]

M. Gu, T. Tannous, and C. J. R. Sheppard, “Improved axial resolution in confocal fluorescence microscopy using annular pupils,” Opt. Commun. 110(5–6), 533–539 (1994).
[Crossref]

C. J. R. Sheppard, “Super-resolution in confocal imaging,” Optik (Stuttg.) 80(2), 53–54 (1988).

Shtengel, G.

S. W. Hell, S. J. Sahl, M. Bates, X. Zhuang, R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel, H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa, L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling, D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello, A. Diaspro, and T. Cordes, “The 2015 super-resolution microscopy roadmap,” J. Phys. D Appl. Phys. 48(44), 443001 (2015).
[Crossref]

Shuang, B.

H. Shen, L. J. Tauzin, R. Baiyasi, W. Wang, N. Moringo, B. Shuang, and C. F. Landes, “Single Particle Tracking: From Theory to Biophysical Applications,” Chem. Rev. 117(11), 7331–7376 (2017).
[Crossref] [PubMed]

Si, K.

Silberberg, Y.

Y. Israel, R. Tenne, D. Oron, and Y. Silberberg, “Quantum correlation enhanced super-resolution localization microscopy enabled by a fibre bundle camera,” Nat. Commun. 8, 14786 (2017).
[Crossref] [PubMed]

Soini, E.

P. E. Hänninen, S. W. Hell, J. Salo, E. Soini, and C. Cremer, “Two-photon excitation 4Pi confocal microscope: Enhanced axial resolution microscope for biological research,” Appl. Phys. Lett. 66(13), 1698–1700 (1995).
[Crossref]

Solgaard, O.

Somekh, M.

S. Pechprasarn, B. Zhang, D. Albutt, J. Zhang, and M. Somekh, “Ultrastable embedded surface plasmon confocal interferometry,” Light Sci. Appl. 3(7), e187 (2014).
[Crossref]

Sougrat, R.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging Intracellular Fluorescent Proteins at Nanometer Resolution,” Science 313(5793), 1642–1645 (2006).
[Crossref] [PubMed]

Stelzer, E. H. K.

S. Lindek, C. Cremer, and E. H. K. Stelzer, “Confocal theta fluorescence microscopy with annular apertures,” Appl. Opt. 35(1), 126–130 (1996).
[Crossref] [PubMed]

E. H. K. Stelzer and S. Lindek, “Fundamental reduction of the observation volume in far-field light microscopy by detection orthogonal to the illumination axis: confocal theta microscopy,” Opt. Commun. 111(5–6), 536–547 (1994).
[Crossref]

S. Hell, S. Lindek, C. Cremer, and E. H. K. Stelzer, “Measurement of the 4Pi-confocal point spread function proves 75 nm axial resolution,” Appl. Phys. Lett. 64(11), 1335–1337 (1994).
[Crossref]

S. Hell and E. H. K. Stelzer, “Properties of a 4Pi confocal fluorescence microscope,” J. Opt. Soc. Am. A 9(12), 2159–2166 (1992).
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Figures (9)

Fig. 1
Fig. 1 Schematic of a CDCM measurement. (a) CDCM’s imaging path before the focus, (b) CDCM’s imaging path after the focus, (c) CM’s light path diagram, (d) 3D intensity response IC (v, u) of CM, (e) 3D intensity response IA (v, u, -uM) of CDCM’s imaging path before the focus, (f) 3D intensity response IB(v, u, + uM) of CDCM’s imaging path after the focus. Here, v is the normalized lateral coordinate, u is the normalized axial coordinate, uM is the normalized detector axial off-focus offset.
Fig. 2
Fig. 2 Intensity responses. (a) Intensity response ID(v, u, uM) obtained using the differential subtraction of intensity responses IA(v, u, -uM) and IB(v, u, + uM) (b) Intensity responses IA(v, u, -uM) and IB(v, u, + uM) (c) Intensity response IR(v, u, uM) obtained by a correlation product processing of intensity responses IA(v, u, -uM) and IB(v, u, + uM).
Fig. 3
Fig. 3 Comparison of the simulated CDCM and CM lateral edge intensity responses. (a) Lateral edge intensity responses of CDCM and CM. (b) Normalized lateral edge intensity responses of CDCM and CM.
Fig. 4
Fig. 4 Comparison of the simulated CDCM and CM axial intensity responses. (a) Axial intensity responses of CDCM and CM. (b) Normalized axial intensity responses of CDCM and CM.
Fig. 5
Fig. 5 Comparison of the simulated CDCM and CM axial focusing intensity responses. (a) Axial focusing intensity response of CDCM and CM. (b) Normalized axial focusing intensity response of CDCM and CM.
Fig. 6
Fig. 6 (a) Measured CDCM and CM lateral edge intensity responses. (b) CDCM and CM normalized lateral edge intensity responses IR(r, 0, M) and IC(r, 0).
Fig. 7
Fig. 7 (a) Measured CDCM and CM axial intensity responses. (b) CDCM and CM normalized axial intensity responses IR(0, z, M) and IC(0, z).
Fig. 8
Fig. 8 (a) Measured CDCM and CM axial focusing intensity responses. (b) Intensity responses of CDCM and CM to the axial feed of 1nm.
Fig. 9
Fig. 9 Profiles of the step samples measured by AFM, CDCM, and CM. (a)Profiles of the samples that have a height step of 100 nm, measured by AFM. (b) Profiles of the samples that have a height step of 100 nm, measured by CM. (c) Profile of the sample with 100-nm height step measured by a CDCM-correlation method.

Equations (9)

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I A (v,u,- u M )= | h i ( v,u ) | 2 [ | h c ( v,u,- u M ) | 2 D( v ) ]
I B (v,u,+ u M )= | h i ( v,u ) | 2 [ | h c ( v,u,+ u M ) | 2 D( v ) ]
I C (v,u, u M =0)= | h i ( v,u ) | 2 [ | h c ( v,u, u M =0 ) | 2 D( v ) ]
h i (v,u)= 0 a 0 J 0 ( vsinθ sin a 0 ) e iu sin 2 (θ/2)/ 2 sin 2 ( a 0 /2) sinθ cosθ dθ
h c (v,u, u M )= 0 a 0 J 0 ( vsinθ sin a 0 ) e i( u± u M ) sin 2 (θ/2)/ 2 sin 2 ( a 0 /2) sinθ cosθ dθ
D(v)=δ( u M ){ 1, v v D 0, else
I R ( v,u, u M )= I A ( v,u,- u M )× I B ( v,u,+ u M )
I D ( v,u, u M )= I A ( v,u,- u M ) I B ( v,u,+ u M )
h( r )={ 8, r>0 0, r<0

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