Abstract

The signal and idler beams from a picosecond, synchronously pumped optical parametric oscillator (OPO) provide the two colors necessary for coherent anti-Stokes Raman scattering (CARS) microscopy. The OPO provides a continuously tunable frequency difference between the two beams over a broad range of Raman shifts (1003700cm1) by varying the temperature of a single nonlinear crystal. The near-infrared output (9001300nm) allows for deep penetration into thick samples and reduced nonlinear photodamage. Applications of this light source to in vivo cell and ex vivo tissue imaging are demonstrated.

© 2006 Optical Society of America

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  1. Special issue: Optical Imaging, Nat. Biotechnol. 21(11), (2003).
  2. J.-X. Cheng and S. Xie, J. Phys. Chem. B 108, 827 (2004).
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  4. E. O. Potma, D. J. Jones, J. X. Cheng, X. S. Xie, and J. Ye, Opt. Lett. 27, 1168 (2002).
    [CrossRef]
  5. C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 102, 16807 (2005).
    [CrossRef] [PubMed]
  6. T. W. Kee and M. T. Cicerone, Opt. Lett. 29, 2101 (2004).
    [CrossRef]
  7. S. Emanueli and A. Arie, Appl. Opt. 42, 6661 (2003).
    [CrossRef] [PubMed]
  8. G. D. Boyd and D. A. Kleinman, J. Appl. Phys. 39, 3597 (1970).
    [CrossRef]
  9. S. A. Akhmanov and K. N. Drabovich, IEEE J. Quantum Electron. QE-4, 598 (1968).
    [CrossRef]
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    [CrossRef]
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  12. A. Hopt and E. Neher, Biophys. J. 80, 2029 (2001).
    [CrossRef] [PubMed]

2005 (1)

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 102, 16807 (2005).
[CrossRef] [PubMed]

2004 (2)

T. W. Kee and M. T. Cicerone, Opt. Lett. 29, 2101 (2004).
[CrossRef]

J.-X. Cheng and S. Xie, J. Phys. Chem. B 108, 827 (2004).
[CrossRef]

2003 (2)

Special issue: Optical Imaging, Nat. Biotechnol. 21(11), (2003).

S. Emanueli and A. Arie, Appl. Opt. 42, 6661 (2003).
[CrossRef] [PubMed]

2002 (1)

2001 (3)

J.-X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, J. Phys. Chem. B 105, 1277 (2001).
[CrossRef]

J.-X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 100, 9826 (2001).
[CrossRef]

A. Hopt and E. Neher, Biophys. J. 80, 2029 (2001).
[CrossRef] [PubMed]

2000 (1)

1970 (1)

G. D. Boyd and D. A. Kleinman, J. Appl. Phys. 39, 3597 (1970).
[CrossRef]

1968 (1)

S. A. Akhmanov and K. N. Drabovich, IEEE J. Quantum Electron. QE-4, 598 (1968).
[CrossRef]

Akhmanov, S. A.

S. A. Akhmanov and K. N. Drabovich, IEEE J. Quantum Electron. QE-4, 598 (1968).
[CrossRef]

Araki, T.

Arie, A.

Book, L. D.

J.-X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, J. Phys. Chem. B 105, 1277 (2001).
[CrossRef]

Boyd, G. D.

G. D. Boyd and D. A. Kleinman, J. Appl. Phys. 39, 3597 (1970).
[CrossRef]

Cheng, J. X.

Cheng, J.-X.

J.-X. Cheng and S. Xie, J. Phys. Chem. B 108, 827 (2004).
[CrossRef]

J.-X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, J. Phys. Chem. B 105, 1277 (2001).
[CrossRef]

J.-X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 100, 9826 (2001).
[CrossRef]

Cicerone, M. T.

T. W. Kee and M. T. Cicerone, Opt. Lett. 29, 2101 (2004).
[CrossRef]

Cote, D.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 102, 16807 (2005).
[CrossRef] [PubMed]

Drabovich, K. N.

S. A. Akhmanov and K. N. Drabovich, IEEE J. Quantum Electron. QE-4, 598 (1968).
[CrossRef]

Emanueli, S.

Evans, C. L.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 102, 16807 (2005).
[CrossRef] [PubMed]

Hashimoto, M.

Hopt, A.

A. Hopt and E. Neher, Biophys. J. 80, 2029 (2001).
[CrossRef] [PubMed]

Jones, D. J.

Kawata, S.

Kee, T. W.

T. W. Kee and M. T. Cicerone, Opt. Lett. 29, 2101 (2004).
[CrossRef]

Kleinman, D. A.

G. D. Boyd and D. A. Kleinman, J. Appl. Phys. 39, 3597 (1970).
[CrossRef]

Lin, C. P.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 102, 16807 (2005).
[CrossRef] [PubMed]

Neher, E.

A. Hopt and E. Neher, Biophys. J. 80, 2029 (2001).
[CrossRef] [PubMed]

Pautot, S.

J.-X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 100, 9826 (2001).
[CrossRef]

Potma, E. O.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 102, 16807 (2005).
[CrossRef] [PubMed]

E. O. Potma, D. J. Jones, J. X. Cheng, X. S. Xie, and J. Ye, Opt. Lett. 27, 1168 (2002).
[CrossRef]

Puoris'haag, M.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 102, 16807 (2005).
[CrossRef] [PubMed]

Volkmer, A.

J.-X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, J. Phys. Chem. B 105, 1277 (2001).
[CrossRef]

Weitz, D. A.

J.-X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 100, 9826 (2001).
[CrossRef]

Xie, S.

J.-X. Cheng and S. Xie, J. Phys. Chem. B 108, 827 (2004).
[CrossRef]

Xie, X. S.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 102, 16807 (2005).
[CrossRef] [PubMed]

E. O. Potma, D. J. Jones, J. X. Cheng, X. S. Xie, and J. Ye, Opt. Lett. 27, 1168 (2002).
[CrossRef]

J.-X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 100, 9826 (2001).
[CrossRef]

J.-X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, J. Phys. Chem. B 105, 1277 (2001).
[CrossRef]

Ye, J.

Appl. Opt. (1)

Biophys. J. (1)

A. Hopt and E. Neher, Biophys. J. 80, 2029 (2001).
[CrossRef] [PubMed]

IEEE J. Quantum Electron. (1)

S. A. Akhmanov and K. N. Drabovich, IEEE J. Quantum Electron. QE-4, 598 (1968).
[CrossRef]

J. Appl. Phys. (1)

G. D. Boyd and D. A. Kleinman, J. Appl. Phys. 39, 3597 (1970).
[CrossRef]

J. Phys. Chem. B (2)

J.-X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, J. Phys. Chem. B 105, 1277 (2001).
[CrossRef]

J.-X. Cheng and S. Xie, J. Phys. Chem. B 108, 827 (2004).
[CrossRef]

Opt. Lett. (3)

Proc. Natl. Acad. Sci. U.S.A. (2)

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 102, 16807 (2005).
[CrossRef] [PubMed]

J.-X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, Proc. Natl. Acad. Sci. U.S.A. 100, 9826 (2001).
[CrossRef]

Other (1)

Special issue: Optical Imaging, Nat. Biotechnol. 21(11), (2003).

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Figures (4)

Fig. 1
Fig. 1

OPO resonator and external layout used for CARS microscopy. The OPO is singly resonant within the idler beam wavelength range. CM1, CM2, OPO cavity concave ( r = 100 mm ) mirrors with high reflection ( R > 99 % ) in the idler beam wavelength range. CM2 has 70 % 80 % transmission at the signal beam wavelengths. M1, high-reflecting mirror; M2, 10% output coupler for the idler beam; F1, F2, long-pass filters, > 850 nm ; L1, L2, L3, lenses with focal lengths of 50, 150, and 1000 mm , respectively; DM, dichroic mirror; WP, wedged plates for delay control.

Fig. 2
Fig. 2

A, Experimental (filled circles) wavelength tuning curve and accessible Raman frequencies as a function of the crystal temperature. The solid curves are result of the calculations. B, OPO output power versus pump power at the crystal facet. C and D show the typical signal pulse spectrum and autocorrelation trace at the OPO cavity detuning of minus 36 μ m , respectively.

Fig. 3
Fig. 3

CARS images at different Raman shifts. A, 1.5 μ m diameter polystyrene beads imaged at the C C stretching vibrational frequency, 1600 cm 1 . B, NIH 3T3-L1 cell cultured with deuterium-labeled oleic acid imaged at the CD 2 symmetric stretching vibration, 2100 cm 1 . Image size, 47 μ m × 47 μ m . C, NIH 3T3-L1 cell imaged at the CH 2 symmetric stretching vibration, 2850 cm 1 . Image size, 78 μ m × 78 μ m . D, 5 μ m size POPS multilamellar vesicle imaged at the OH stretch, 3375 cm 1 .

Fig. 4
Fig. 4

Forward CARS images of mouse ear tissue at the aliphatic CH 2 stretching frequency, 2850 cm 1 , at two different depths of z = 75 μ m and z = 130 μ m , taken with two different sources. A, B, the OPO. C, D, the two picosecond-Ti:sapphire-lasers-based system.

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