Abstract

Dual-cladding photonic crystal fibers (PCFs) with two zero-dispersion points are used to enhance the two-photon excited luminescence (TPL) response from fluorescent protein biomarkers and neuron activity reporters in dye-cell experiments and in in vivo work on transgenic mice and tadpoles. The soliton transmission of ultrashort pulses through a PCF suppresses dispersion-induced temporal pulse spreading, maintaining a high level of field intensity needed for efficient TPL excitation. The soliton self-frequency shift, stabilized against laser power fluctuations by a specific PCF dispersion design, is employed to accurately match the wavelength of the soliton PCF output with the two-photon absorption spectrum of dye or fluorescent protein biomarker molecules, enhancing their TPL response and allowing the laser damage of biotissues to be avoided.

© 2009 Optical Society of America

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2008 (1)

2006 (1)

A. M. Zheltikov, Phys. Usp. 49, 605 (2006).
[CrossRef]

2005 (3)

S. Konorov, A. Zheltikov, and M. Scalora, Opt. Express 13, 3454 (2005).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, Nat. Methods 2, 941 (2005).
[CrossRef] [PubMed]

F. Helmchen and W. Denk, Nat. Methods 2, 932 (2005).
[CrossRef] [PubMed]

2003 (4)

P. St. J. Russell, Science 299, 358 (2003).
[CrossRef] [PubMed]

M. T. Myaing, J. Y. Ye, T. B. Norris, T. Thomas, J. R. Baker Jr., W. J. Wadsworth, G. Bouwmans, J. C. Knight, and P. St. J. Russell, Opt. Lett. 28, 1224 (2003).
[CrossRef] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, Nat. Biotechnol. 21, 1369 (2003).
[CrossRef] [PubMed]

D. V. Skryabin, F. Luan, J. C. Knight, and P. St. J. Russell, Science 301, 1705 (2003).
[CrossRef] [PubMed]

1998 (1)

J. L. Dynes and J. Ngai, Neuron 20, 1081 (1998).
[CrossRef] [PubMed]

1995 (1)

N. Akhmediev and M. Karlsson, Phys. Rev. A 51, 2602 (1995).
[CrossRef] [PubMed]

1994 (1)

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, Science 263, 802 (1994).
[CrossRef] [PubMed]

1990 (1)

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

Agrawal, G. P.

G. P. Agrawal, Nonlinear Fiber Optics (Academic, 2001).

Akhmediev, N.

N. Akhmediev and M. Karlsson, Phys. Rev. A 51, 2602 (1995).
[CrossRef] [PubMed]

Baker, J. R.

Bouwmans, G.

Chai, L.

Chalfie, M.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, Science 263, 802 (1994).
[CrossRef] [PubMed]

Cheung, E. L. M.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, Nat. Methods 2, 941 (2005).
[CrossRef] [PubMed]

Cocker, E. D.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, Nat. Methods 2, 941 (2005).
[CrossRef] [PubMed]

Denk, W.

F. Helmchen and W. Denk, Nat. Methods 2, 932 (2005).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

Dynes, J. L.

J. L. Dynes and J. Ngai, Neuron 20, 1081 (1998).
[CrossRef] [PubMed]

Euskirchen, G.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, Science 263, 802 (1994).
[CrossRef] [PubMed]

Fang, X.-H.

Flusberg, B. A.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, Nat. Methods 2, 941 (2005).
[CrossRef] [PubMed]

Helmchen, F.

F. Helmchen and W. Denk, Nat. Methods 2, 932 (2005).
[CrossRef] [PubMed]

Hu, M.-L.

Jung, J. C.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, Nat. Methods 2, 941 (2005).
[CrossRef] [PubMed]

Karlsson, M.

N. Akhmediev and M. Karlsson, Phys. Rev. A 51, 2602 (1995).
[CrossRef] [PubMed]

Knight, J. C.

Konorov, S.

Li, Y.-F.

Liu, B.-W.

Luan, F.

D. V. Skryabin, F. Luan, J. C. Knight, and P. St. J. Russell, Science 301, 1705 (2003).
[CrossRef] [PubMed]

Luo, J.

Myaing, M. T.

Ngai, J.

J. L. Dynes and J. Ngai, Neuron 20, 1081 (1998).
[CrossRef] [PubMed]

Norris, T. B.

Piyawattanametha, W.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, Nat. Methods 2, 941 (2005).
[CrossRef] [PubMed]

Prasher, D. C.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, Science 263, 802 (1994).
[CrossRef] [PubMed]

Russell, P. St. J.

Scalora, M.

Schnitzer, M. J.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, Nat. Methods 2, 941 (2005).
[CrossRef] [PubMed]

Skryabin, D. V.

D. V. Skryabin, F. Luan, J. C. Knight, and P. St. J. Russell, Science 301, 1705 (2003).
[CrossRef] [PubMed]

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

Thomas, T.

Tong, W.

Tu, Y.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, Science 263, 802 (1994).
[CrossRef] [PubMed]

Voronin, A. A.

Wadsworth, W. J.

Wang, C.-Y.

Ward, W. W.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, Science 263, 802 (1994).
[CrossRef] [PubMed]

Webb, W. W.

W. R. Zipfel, R. M. Williams, and W. W. Webb, Nat. Biotechnol. 21, 1369 (2003).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

Williams, R. M.

W. R. Zipfel, R. M. Williams, and W. W. Webb, Nat. Biotechnol. 21, 1369 (2003).
[CrossRef] [PubMed]

Ye, J. Y.

Zheltikov, A.

Zheltikov, A. M.

Zipfel, W. R.

W. R. Zipfel, R. M. Williams, and W. W. Webb, Nat. Biotechnol. 21, 1369 (2003).
[CrossRef] [PubMed]

Nat. Biotechnol. (1)

W. R. Zipfel, R. M. Williams, and W. W. Webb, Nat. Biotechnol. 21, 1369 (2003).
[CrossRef] [PubMed]

Nat. Methods (2)

F. Helmchen and W. Denk, Nat. Methods 2, 932 (2005).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, Nat. Methods 2, 941 (2005).
[CrossRef] [PubMed]

Neuron (1)

J. L. Dynes and J. Ngai, Neuron 20, 1081 (1998).
[CrossRef] [PubMed]

Opt. Express (2)

Opt. Lett. (1)

Phys. Rev. A (1)

N. Akhmediev and M. Karlsson, Phys. Rev. A 51, 2602 (1995).
[CrossRef] [PubMed]

Phys. Usp. (1)

A. M. Zheltikov, Phys. Usp. 49, 605 (2006).
[CrossRef]

Science (4)

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

P. St. J. Russell, Science 299, 358 (2003).
[CrossRef] [PubMed]

D. V. Skryabin, F. Luan, J. C. Knight, and P. St. J. Russell, Science 301, 1705 (2003).
[CrossRef] [PubMed]

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, Science 263, 802 (1994).
[CrossRef] [PubMed]

Other (1)

G. P. Agrawal, Nonlinear Fiber Optics (Academic, 2001).

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Figures (2)

Fig. 1
Fig. 1

(a) Scanning electron microscope image of the dual-cladding PCF. (b), (c) Spectrally and (d) temporally resolved output of the dual-cladding, two-zero GVD point PCF calculated with the use of the GNSE as a function of (b) the input energy and (c), (d) propagation distance z along the fiber. (b) Fiber length is 50 cm ; (c), (d) the input pulse energy is 265 pJ .

Fig. 2
Fig. 2

(a) Decaying kinetics of the fluorescent response of EGFP from the brain of a transgenic mouse in open-skull experiments. The inset shows the spectrum of PCF output measured for three different input energies of Ti:sapphire laser pulses: (triangles) 150 pJ , (rectangles) 250 pJ , and (filled circles) 400 pJ . (b) Spectrally resolved fluorescent response of enhanced green fluorescent protein (EGFP) in brain of a transgenic mouse (filled circles), DsRed2 fluorescent protein in the tail of a Xenopus laevis tadpole (rectangles), and AlexaFluor 555 dye in stained mouse brain (triangles). The inset shows the fluorescent response of AlexaFluor 488 dye (filled circles) excited via TPA by the frequency-shifted soliton output of a highly nonlinear PCF (triangles). The spectrum of the laser pulse is shown by the dash-dotted line in the inset.

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