Abstract

We report on the development of a miniature, flexible, fiber-optic scanning endoscope for two-photon fluorescence imaging. The endoscope uses a tubular piezoelectric actuator for achieving two-dimensional beam scanning and a double-clad fiber for delivery of the excitation light and collection of two-photon fluorescence. Real-time imaging of fluorescent beads and cancer cells has been performed.

© 2006 Optical Society of America

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2005

2004

2003

2002

E. J. Seibel and Q. Y. J. Smithwick, Lasers Surg. Med. 30, 177 (2002).
[CrossRef] [PubMed]

2001

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, Neuron 31, 903 (2001).
[CrossRef] [PubMed]

S. W. Clark, F. O. Ilday, and F. W. Wise, Opt. Lett. 26, 1320 (2001).
[CrossRef]

1997

W. Denk and K. Svoboda, Neuron 18, 351 (1997).
[CrossRef] [PubMed]

1990

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

1987

O. E. Martinez, IEEE J. Quantum Electron. 23, 59 (1987).
[CrossRef]

Anderson, E. P.

Baker, J. R.

Bird, D.

Bouwmans, G.

Chen, Y.

Clark, S. W.

Cobb, M. J.

Cocker, E. D.

Denk, W.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, Neuron 31, 903 (2001).
[CrossRef] [PubMed]

W. Denk and K. Svoboda, Neuron 18, 351 (1997).
[CrossRef] [PubMed]

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

Fee, M. S.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, Neuron 31, 903 (2001).
[CrossRef] [PubMed]

Flusberg, B. A.

Fu, L.

Gan, X. S.

Gobel, W.

Gu, M.

Helmchen, F.

Ilday, F. O.

Kerr, J. N. D.

Kimmey, M. B.

Knight, J. C.

Li, X. D.

Liu, X. M.

Lung, J. C.

Martinez, O. E.

O. E. Martinez, IEEE J. Quantum Electron. 23, 59 (1987).
[CrossRef]

Myaing, M. T.

Nimmerjahn, A.

Norris, T. B.

Russell, P. St. J.

Schnitzer, M. J.

Seibel, E. J.

E. J. Seibel and Q. Y. J. Smithwick, Lasers Surg. Med. 30, 177 (2002).
[CrossRef] [PubMed]

Smithwick, Q. Y. J.

E. J. Seibel and Q. Y. J. Smithwick, Lasers Surg. Med. 30, 177 (2002).
[CrossRef] [PubMed]

Strickler, J. H.

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

Svoboda, K.

W. Denk and K. Svoboda, Neuron 18, 351 (1997).
[CrossRef] [PubMed]

Tank, D. W.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, Neuron 31, 903 (2001).
[CrossRef] [PubMed]

Thomas, T.

Wadsworth, W. J.

Webb, W. W.

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

Wise, F. W.

Ye, J. Y.

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Figures (3)

Fig. 1
Fig. 1

(a) Schematic of the miniature beam scanning head. (b) Shape of the amplitude-modulated drive waveforms for the ± x and ± y electrodes. (c) The resultant spiral scan pattern.

Fig. 2
Fig. 2

(a) Cross-sectional structure of the double-clad fiber. Excitation light propagates in the core while fluorescence is collected by the core and the inner cladding. (b) Schematic of the fiber-optic scanning TPF endoscope imaging system. The TPF signal excited at the sample is collected by the GRIN lens and fiber and then directed toward the PMT by the dichroic mirror. The piezoelectric transducer (PZT) tube, fiber tip, and GRIN lens are encased in hypodermic tubing with an overall outer diameter of 2.4 mm . PM, pick-off mirrors; DM, dichroic mirror; CL, coupling lens; DAQ, signal digitizer and data acquisition.

Fig. 3
Fig. 3

TPF images of (a) 6 μ m and (b) 2.2 μ m fluorescent beads. The blurriness of the 2.2 μ m beads indicates that we are reaching the lateral resolution limit of the current endoscope. (c) TPF image of fixed breast cancer cells (SK-BR-3) acquired with the scanning fiber-optic endoscope. 5-carboxyrhodamine 6G labeled monoclonal anti-Her2 antibodies were attached to the cell surfaces. The excitation power in the core of the fiber was 10 mW . The image sharpness degrades near the outer edge since the cells on a flat cover glass are out of focus.

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