Abstract

We propose a scheme for achieving widefield coherent anti-Stokes Raman scattering (CARS) microscopy images with sub-diffraction-limited resolution. This approach adds structured illumination to the widefield CARS configuration [Applied Physics Letters 84, 816 (2004)]. By capturing a number of images at different phases of the standing wave pattern, an image with up to three times the resolution of the original can be constructed. We develop a theoretical treatment of this system and perform numerical simulations for a typical CARS system, which indicate that resolutions around 120 nm are obtainable with the present scheme. As an imaging system, this method combines the advantages of sub-diffraction-limited resolution, endogenous contrast generation, and a wide field of view.

© 2010 OSA

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  1. 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]
  2. H. Mizuno, P. Dedecker, R. Ando, T. Fukano, J. Hofkens, and A. Miyawaki, “Higher resolution in localization microscopy by slower switching of a photochromic protein,” Photochem. Photobiol. Sci. 9(2), 239–248 (2010).
    [CrossRef] [PubMed]
  3. 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]
  4. 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]
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    [CrossRef] [PubMed]
  6. R. Heintzmann, “Saturated patterned excitation microscopy with two-dimensional excitation patterns,” Micron 34(6-7), 283–291 (2003).
    [CrossRef] [PubMed]
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    [CrossRef]
  9. D. Wildanger, R. Medda, L. Kastrup, and S. W. Hell, “A compact STED microscope providing 3D nanoscale resolution,” J. Microsc. 236(1), 35–43 (2009).
    [CrossRef] [PubMed]
  10. A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
    [CrossRef]
  11. C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
    [CrossRef] [PubMed]
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    [CrossRef]
  13. E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
    [CrossRef]
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    [CrossRef]
  15. W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
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    [CrossRef] [PubMed]
  19. B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
    [CrossRef]
  20. T. Wilson, M. A. A. Neil, and R. Juskaitis, “Optically sectioned images in wide-field fluorescence microscopy,” Proc. SPIE 3261, 4–6 (1998).
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2010

H. Mizuno, P. Dedecker, R. Ando, T. Fukano, J. Hofkens, and A. Miyawaki, “Higher resolution in localization microscopy by slower switching of a photochromic protein,” Photochem. Photobiol. Sci. 9(2), 239–248 (2010).
[CrossRef] [PubMed]

W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
[CrossRef]

2009

W. P. Beeker, P. Gross, C. J. Lee, C. Cleff, H. L. Offerhaus, C. Fallnich, J. L. Herek, and K.-J. Boller, “A route to sub-diffraction-limited CARS Microscopy,” Opt. Express 17(25), 22632–22638 (2009).
[CrossRef]

E. Rittweger, K. Y. Han, S. E. Irvine, C. Eggeling, and S. W. Hell, “STED microscopy reveals crystal colour centres with nanometric resolution,” Nat. Photonics 3(3), 144–147 (2009).
[CrossRef]

D. Wildanger, R. Medda, L. Kastrup, and S. W. Hell, “A compact STED microscope providing 3D nanoscale resolution,” J. Microsc. 236(1), 35–43 (2009).
[CrossRef] [PubMed]

2008

2007

B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
[CrossRef]

2006

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]

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]

2005

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

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]

2004

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

C. Heinrich, S. Bernet, and M. Ritsch-Marte, “Wide-field coherent anti-Stokes Raman scattering microscopy,” Appl. Phys. Lett. 84(5), 816–818 (2004).
[CrossRef]

2003

R. Heintzmann, “Saturated patterned excitation microscopy with two-dimensional excitation patterns,” Micron 34(6-7), 283–291 (2003).
[CrossRef] [PubMed]

2002

M. Müller and J. M. Schins, “Imaging the thermodynamic state of lipid membranes with multiplex CARS microscopy,” J. Phys. Chem. B 106(14), 3715–3723 (2002).
[CrossRef]

2000

M. G. L. 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]

1999

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[CrossRef]

1998

T. Wilson, M. A. A. Neil, and R. Juskaitis, “Optically sectioned images in wide-field fluorescence microscopy,” Proc. SPIE 3261, 4–6 (1998).
[CrossRef]

1994

Ando, R.

H. Mizuno, P. Dedecker, R. Ando, T. Fukano, J. Hofkens, and A. Miyawaki, “Higher resolution in localization microscopy by slower switching of a photochromic protein,” Photochem. Photobiol. Sci. 9(2), 239–248 (2010).
[CrossRef] [PubMed]

Bates, M.

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]

Beeker, W. P.

W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
[CrossRef]

W. P. Beeker, P. Gross, C. J. Lee, C. Cleff, H. L. Offerhaus, C. Fallnich, J. L. Herek, and K.-J. Boller, “A route to sub-diffraction-limited CARS Microscopy,” Opt. Express 17(25), 22632–22638 (2009).
[CrossRef]

Bernet, S.

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]

Boller, K. J.

W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
[CrossRef]

Boller, K.-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, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Ciardi, C.

Cleff, C.

W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
[CrossRef]

W. P. Beeker, P. Gross, C. J. Lee, C. Cleff, H. L. Offerhaus, C. Fallnich, J. L. Herek, and K.-J. Boller, “A route to sub-diffraction-limited CARS Microscopy,” Opt. Express 17(25), 22632–22638 (2009).
[CrossRef]

Côté, D.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

Davidson, M. 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).
[CrossRef] [PubMed]

Dedecker, P.

H. Mizuno, P. Dedecker, R. Ando, T. Fukano, J. Hofkens, and A. Miyawaki, “Higher resolution in localization microscopy by slower switching of a photochromic protein,” Photochem. Photobiol. Sci. 9(2), 239–248 (2010).
[CrossRef] [PubMed]

Eggeling, C.

E. Rittweger, K. Y. Han, S. E. Irvine, C. Eggeling, and S. W. Hell, “STED microscopy reveals crystal colour centres with nanometric resolution,” Nat. Photonics 3(3), 144–147 (2009).
[CrossRef]

Evans, C. L.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

Fallnich, C.

W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
[CrossRef]

W. P. Beeker, P. Gross, C. J. Lee, C. Cleff, H. L. Offerhaus, C. Fallnich, J. L. Herek, and K.-J. Boller, “A route to sub-diffraction-limited CARS Microscopy,” Opt. Express 17(25), 22632–22638 (2009).
[CrossRef]

Fukano, T.

H. Mizuno, P. Dedecker, R. Ando, T. Fukano, J. Hofkens, and A. Miyawaki, “Higher resolution in localization microscopy by slower switching of a photochromic protein,” Photochem. Photobiol. Sci. 9(2), 239–248 (2010).
[CrossRef] [PubMed]

Gross, P.

W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
[CrossRef]

W. P. Beeker, P. Gross, C. J. Lee, C. Cleff, H. L. Offerhaus, C. Fallnich, J. L. Herek, and K.-J. Boller, “A route to sub-diffraction-limited CARS Microscopy,” Opt. Express 17(25), 22632–22638 (2009).
[CrossRef]

Gustafsson, M. G. L.

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]

M. G. L. 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]

Han, K. Y.

E. Rittweger, K. Y. Han, S. E. Irvine, C. Eggeling, and S. W. Hell, “STED microscopy reveals crystal colour centres with nanometric resolution,” Nat. Photonics 3(3), 144–147 (2009).
[CrossRef]

Heckenberg, N.

B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
[CrossRef]

Heinrich, C.

Heintzmann, R.

R. Heintzmann, “Saturated patterned excitation microscopy with two-dimensional excitation patterns,” Micron 34(6-7), 283–291 (2003).
[CrossRef] [PubMed]

Hell, S. W.

D. Wildanger, R. Medda, L. Kastrup, and S. W. Hell, “A compact STED microscope providing 3D nanoscale resolution,” J. Microsc. 236(1), 35–43 (2009).
[CrossRef] [PubMed]

E. Rittweger, K. Y. Han, S. E. Irvine, C. Eggeling, and S. W. Hell, “STED microscopy reveals crystal colour centres with nanometric resolution,” Nat. Photonics 3(3), 144–147 (2009).
[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]

Herek, J. L.

W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
[CrossRef]

W. P. Beeker, P. Gross, C. J. Lee, C. Cleff, H. L. Offerhaus, C. Fallnich, J. L. Herek, and K.-J. Boller, “A route to sub-diffraction-limited CARS Microscopy,” Opt. Express 17(25), 22632–22638 (2009).
[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, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Hinsberg, W. D.

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

Hofer, A.

Hofkens, J.

H. Mizuno, P. Dedecker, R. Ando, T. Fukano, J. Hofkens, and A. Miyawaki, “Higher resolution in localization microscopy by slower switching of a photochromic protein,” Photochem. Photobiol. Sci. 9(2), 239–248 (2010).
[CrossRef] [PubMed]

Holtom, G. R.

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[CrossRef]

Irvine, S. E.

E. Rittweger, K. Y. Han, S. E. Irvine, C. Eggeling, and S. W. Hell, “STED microscopy reveals crystal colour centres with nanometric resolution,” Nat. Photonics 3(3), 144–147 (2009).
[CrossRef]

Jones, D.

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

Juskaitis, R.

T. Wilson, M. A. A. Neil, and R. Juskaitis, “Optically sectioned images in wide-field fluorescence microscopy,” Proc. SPIE 3261, 4–6 (1998).
[CrossRef]

Kastrup, L.

D. Wildanger, R. Medda, L. Kastrup, and S. W. Hell, “A compact STED microscope providing 3D nanoscale resolution,” J. Microsc. 236(1), 35–43 (2009).
[CrossRef] [PubMed]

Lai, K.

B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
[CrossRef]

Lee, C. J.

W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
[CrossRef]

W. P. Beeker, P. Gross, C. J. Lee, C. Cleff, H. L. Offerhaus, C. Fallnich, J. L. Herek, and K.-J. Boller, “A route to sub-diffraction-limited CARS Microscopy,” Opt. Express 17(25), 22632–22638 (2009).
[CrossRef]

Leone, S. R.

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

Lin, C. P.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

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).
[CrossRef] [PubMed]

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).
[CrossRef] [PubMed]

Littleton, B.

B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
[CrossRef]

Longstaff, D.

B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
[CrossRef]

Medda, R.

D. Wildanger, R. Medda, L. Kastrup, and S. W. Hell, “A compact STED microscope providing 3D nanoscale resolution,” J. Microsc. 236(1), 35–43 (2009).
[CrossRef] [PubMed]

Miyawaki, A.

H. Mizuno, P. Dedecker, R. Ando, T. Fukano, J. Hofkens, and A. Miyawaki, “Higher resolution in localization microscopy by slower switching of a photochromic protein,” Photochem. Photobiol. Sci. 9(2), 239–248 (2010).
[CrossRef] [PubMed]

Mizuno, H.

H. Mizuno, P. Dedecker, R. Ando, T. Fukano, J. Hofkens, and A. Miyawaki, “Higher resolution in localization microscopy by slower switching of a photochromic protein,” Photochem. Photobiol. Sci. 9(2), 239–248 (2010).
[CrossRef] [PubMed]

Müller, M.

M. Müller and J. M. Schins, “Imaging the thermodynamic state of lipid membranes with multiplex CARS microscopy,” J. Phys. Chem. B 106(14), 3715–3723 (2002).
[CrossRef]

Munroe, P.

B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
[CrossRef]

Muntean, L.

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

Neil, M. A. A.

T. Wilson, M. A. A. Neil, and R. Juskaitis, “Optically sectioned images in wide-field fluorescence microscopy,” Proc. SPIE 3261, 4–6 (1998).
[CrossRef]

Offerhaus, H. L.

W. P. Beeker, C. J. Lee, K. J. Boller, P. Gross, C. Cleff, C. Fallnich, H. L. Offerhaus, and J. L. Herek, “Spatially dependent Rabi oscillations: An approach to sub-diffraction-limited coherent anti-Stokes Raman-scattering microscopy,” Phys. Rev. A 81(1), 012507 (2010).
[CrossRef]

W. P. Beeker, P. Gross, C. J. Lee, C. Cleff, H. L. Offerhaus, C. Fallnich, J. L. Herek, and K.-J. Boller, “A route to sub-diffraction-limited CARS Microscopy,” Opt. Express 17(25), 22632–22638 (2009).
[CrossRef]

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]

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]

Potma, E. O.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

Preusser, J.

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

Puoris’haag, M.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

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Ritsch-Marte, M.

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E. Rittweger, K. Y. Han, S. E. Irvine, C. Eggeling, and S. W. Hell, “STED microscopy reveals crystal colour centres with nanometric resolution,” Nat. Photonics 3(3), 144–147 (2009).
[CrossRef]

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B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
[CrossRef]

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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).
[CrossRef] [PubMed]

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B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
[CrossRef]

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E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

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M. Müller and J. M. Schins, “Imaging the thermodynamic state of lipid membranes with multiplex CARS microscopy,” J. Phys. Chem. B 106(14), 3715–3723 (2002).
[CrossRef]

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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).
[CrossRef] [PubMed]

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D. Wildanger, R. Medda, L. Kastrup, and S. W. Hell, “A compact STED microscope providing 3D nanoscale resolution,” J. Microsc. 236(1), 35–43 (2009).
[CrossRef] [PubMed]

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T. Wilson, M. A. A. Neil, and R. Juskaitis, “Optically sectioned images in wide-field fluorescence microscopy,” Proc. SPIE 3261, 4–6 (1998).
[CrossRef]

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C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[CrossRef]

Ye, J.

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
[CrossRef]

Zhuang, X.

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]

Zumbusch, A.

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[CrossRef]

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[CrossRef] [PubMed]

D. Wildanger, R. Medda, L. Kastrup, and S. W. Hell, “A compact STED microscope providing 3D nanoscale resolution,” J. Microsc. 236(1), 35–43 (2009).
[CrossRef] [PubMed]

J. Phys. Chem. B

M. Müller and J. M. Schins, “Imaging the thermodynamic state of lipid membranes with multiplex CARS microscopy,” J. Phys. Chem. B 106(14), 3715–3723 (2002).
[CrossRef]

E. O. Potma, X. S. Xie, L. Muntean, J. Preusser, D. Jones, J. Ye, S. R. Leone, W. D. Hinsberg, and W. Schade, “Chemical Imaging of Photoresists with Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 108(4), 1296–1301 (2004).
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R. Heintzmann, “Saturated patterned excitation microscopy with two-dimensional excitation patterns,” Micron 34(6-7), 283–291 (2003).
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B. Littleton, K. Lai, D. Longstaff, V. Sarafis, P. Munroe, N. Heckenberg, and H. Rubinsztein-Dunlop, “Coherent super-resolution microscopy via laterally structured illumination,” Micron 38(2), 150–157 (2007).
[CrossRef]

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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).
[CrossRef] [PubMed]

Nat. Photonics

E. Rittweger, K. Y. Han, S. E. Irvine, C. Eggeling, and S. W. Hell, “STED microscopy reveals crystal colour centres with nanometric resolution,” Nat. Photonics 3(3), 144–147 (2009).
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[CrossRef]

Proc. Natl. Acad. Sci. U.S.A.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

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Proc. SPIE

T. Wilson, M. A. A. Neil, and R. Juskaitis, “Optically sectioned images in wide-field fluorescence microscopy,” Proc. SPIE 3261, 4–6 (1998).
[CrossRef]

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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).
[CrossRef] [PubMed]

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Figures (5)

Fig. 1
Fig. 1

The CARS energy condition.

Fig. 2
Fig. 2

Schematic diagram of CARS excitation and signal beams impinging on a microscopy sample in the widefield phase-matching geometry. The Stokes beam ω S (red) is incident on the sample from above, through the microscope objective. A single pump beam ω p is split in two such that two coherent pump beams impinge on the sample from below, opposing each other to generate a standing wave. The standing wave phase can be varied with the piezo-driven mirror located in one arm of the pump beam ‘interferometer’. The anti-Stokes signal beam ω as is emitted anti-parallel to the Stokes beam and is imaged through the microscope objective onto a detector. Inset shows that | Δ k | is minimized.

Fig. 3
Fig. 3

Diagram of the microscope passband in spatial frequency (m) space, showing the increase in effective passband from using structured illumination. The microscope passband (purple) is determined by the NA of the objective lens and the wavevector of the imaged light. Structured illumination creates shift frequencies at ± ( k px ) / π with which additional frequency regions (green) are convolved and imaged. With the choice of NA = k px / k as the resulting effective passband is three times that of the microscope.

Fig. 4
Fig. 4

Simulation of the point spread function (PSF) of the proposed super-resolved CARS system (blue, solid line) compared to the same system with standard CARS imaging (magenta, dashed line). The proposed system has a resolution increase of three times over standard imaging. The superCARS PSF overlaps that obtained from the comparison case of a standard imaging system with three times the microscope passband (not seen in figure due to overlap).

Fig. 5
Fig. 5

One-dimensional simulation of the image intensity for a sample of randomly distributed 100 nm polystyrene ‘beads’. The distribution of beads is shown offset below the image intensity curves (black, solid line). The proposed superCARS system (blue, solid line) is seen to possess a significant resolution enhancement over standard CARS imaging (magenta, dashed line).

Equations (17)

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I ( x , y ) = | F [ c ( m , n ) F [ o ( x ' , y ' ) ] ] | 2 ,
o ( x , y ) = a χ ( 3 ) N ( x , y ) E p 2 ( x , y ) E S * ( x , y ) ,
O ( m , n ) F [ N ( x , y ) ] F [ E p 2 ( x , y ) ] F [ E S * ( x , y ) ] N ( m , n ) ( 2 δ ( m , n ) + e i ϕ δ ( m k px / π , n ) + e - i ϕ δ ( m + k px / π , n ) ) { 2 N ( m , n ) + e i ϕ N ( m k px / π , n ) + e - i ϕ N ( m + k px / π , n ) } ,
I ( x , y , ϕ ) | 2 F [ c ( m , n ) N ( m , n ) ] + exp ( i (-2k px x + ϕ ) ) F [ c ( m + k px / π , n ) N ( m , n ) ] + exp ( i (2k px x ϕ ) ) F [ c ( m k px / π , n ) N ( m , n ) ] | 2 .
I ( x , y , ϕ ) A + B cos ( 2 k px x ϕ ) + C sin ( 2 k px x ϕ ) + D cos ( 4 k px x 2 ϕ ) + E sin ( 4 k px x 2 ϕ ) ,
I super-resolved ( x , y ) = 1 4 A+ 1 2 B+D+ 3 4 D 2 + E 2
A ( x , y ) = 4 | F [ c ( m , n ) N ( m , n ) ] | 2 + | F [ c ( m + k px / π , n ) N ( m , n ) ] | 2 + | F [ c ( m k px / π , n ) N ( m , n ) ] | 2 ,
B ( x , y ) = 4 Re ( F [ c ( m , n ) N ( m , n ) ] F * [ c ( m + k px / π , n ) N ( m , n ) ] ) + 4 Re ( F [ c ( m , n ) N ( m , n ) ] F * [ c ( m k px / π , n ) N ( m , n ) ] ) ,
C ( x , y ) = 4 Im ( F [ c ( m , n ) N ( m , n ) ] F * [ c ( m k px / π , n ) N ( m , n ) ] ) 4 Im ( F [ c ( m , n ) N ( m , n ) ] F * [ c ( m + k px / π , n ) N ( m , n ) ] ) ,
D ( x , y ) = 2 Re ( F [ c ( m + k px / π , n ) N ( m , n ) ] F * [ c ( m k px / π , n ) N ( m , n ) ] ) ,
E ( x , y ) = 2 Im ( F [ c ( m + k px / π , n ) N ( m , n ) ] F * [ c ( m k px / π , n ) N ( m , n ) ] ) ,
A ( x , y ) = 1 n i n I ( x , y , ϕ i ) ,
B ( x , y ) = 2 n i n cos ( 2 k px x ϕ i ) I ( x , y , ϕ i ) ,
C ( x , y ) = 2 n i n sin ( 2 k px x ϕ i ) I ( x , y , ϕ i ) ,
D ( x , y ) = 2 n i n cos ( 4 k px x 2 ϕ i ) I ( x , y , ϕ i ) ,
E ( x , y ) = 2 n i n sin ( 4 k px x 2 ϕ i ) I ( x , y , ϕ i ) ,
I ideal ( x , y ) { | F [ c ( m , n ) N ( m , n ) ] | 2 + | F [ c ( m + k px / π , n ) N ( m , n ) ] | 2 + | F [ c ( m k px / π , n ) N ( m , n ) ] | 2 } + { 2 Re ( F [ c ( m , n ) N ( m , n ) ] F * [ c ( m + k px / π , n ) N ( m , n ) ] ) + 2 Re ( F [ c ( m , n ) N ( m , n ) ] F * [ c ( m k px / π , n ) N ( m , n ) ] ) } + { 2 Re ( F [ c ( m + k px / π , n ) N ( m , n ) ] F * [ c ( m k px / π , n ) N ( m , n ) ] ) } .

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