Abstract

A factor that limits the use of multiphoton microscopy (MPM) in clinical and preclinical studies is the lack of a compact and flexible probe. We report on a miniaturized MPM probe employing a microelectromechanical system (MEMS) scanning mirror and a double-clad photonic crystal fiber (DCPCF). The use of a MEMS mirror and a DCPCF provides many advantages, such as size reduction, rapid and precise scanning, efficient delivery of short pulses, and high collection efficiency of fluorescent signals. The completed probe was 1 cm in outer diameter and 14cm in length. The developed probe was integrated into an MPM system and used to image fluorescent beads, paper, and biological specimens.

© 2008 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
    [CrossRef] [PubMed]
  2. W. R. Zipfel, R. M. Williams, and W. W. Webb, Nat. Biotechnol. 21, 1369 (2003).
    [CrossRef] [PubMed]
  3. F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, Neuron 31, 903 (2001).
    [CrossRef] [PubMed]
  4. J. C. Jung and M. J. Schnitzer, Opt. Lett. 28, 902 (2003).
    [CrossRef] [PubMed]
  5. B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, and M. J. Schnitzer, Opt. Lett. 30, 2272 (2005).
    [CrossRef] [PubMed]
  6. M. T. Myaing, D. J. MacDonald, and X. Li, Opt. Lett. 31, 1076 (2006).
    [CrossRef] [PubMed]
  7. W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, and M. J. Schnitzer, Opt. Lett. 31, 2018 (2006).
    [CrossRef] [PubMed]
  8. L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, J. Biomed. Opt. 12, 040501-1 (2007).
  9. W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. Chen, Appl. Phys. Lett. 88, 163901 (2006).
    [CrossRef]
  10. W. Jung, D. T. McCormick, Y. Ahn, A. Sepehr, M. Brenner, B. Wong, N. C. Tien, and Z. Chen, Opt. Lett. 32, 3239 (2007).
    [CrossRef] [PubMed]
  11. J. Y. Ye, M. T. Myaing, T. B. Norris, T. Thomas, and J. Baker, Jr., Opt. Lett. 27, 1412 (2002).
    [CrossRef]
  12. 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]

2007

2006

2005

2003

2002

2001

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

1990

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

Ahn, Y.

Anderson, E. P.

Baker, J.

Baker, J. R.

Barretto, R. P. J.

Bouwmans, G.

Brenner, M.

Chen, Z.

W. Jung, D. T. McCormick, Y. Ahn, A. Sepehr, M. Brenner, B. Wong, N. C. Tien, and Z. Chen, Opt. Lett. 32, 3239 (2007).
[CrossRef] [PubMed]

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. Chen, Appl. Phys. Lett. 88, 163901 (2006).
[CrossRef]

Cocker, E. D.

Cranfield, C.

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, J. Biomed. Opt. 12, 040501-1 (2007).

Denk, W.

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

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, J. Biomed. Opt. 12, 040501-1 (2007).

Gu, M.

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, J. Biomed. Opt. 12, 040501-1 (2007).

Helmchen, F.

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

Jain, A.

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, J. Biomed. Opt. 12, 040501-1 (2007).

Jung, J. C.

Jung, W.

W. Jung, D. T. McCormick, Y. Ahn, A. Sepehr, M. Brenner, B. Wong, N. C. Tien, and Z. Chen, Opt. Lett. 32, 3239 (2007).
[CrossRef] [PubMed]

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. Chen, Appl. Phys. Lett. 88, 163901 (2006).
[CrossRef]

Knight, J. C.

Ko, T. H.

Lee, D.

Li, X.

MacDonald, D. J.

McCormick, D. T.

W. Jung, D. T. McCormick, Y. Ahn, A. Sepehr, M. Brenner, B. Wong, N. C. Tien, and Z. Chen, Opt. Lett. 32, 3239 (2007).
[CrossRef] [PubMed]

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. Chen, Appl. Phys. Lett. 88, 163901 (2006).
[CrossRef]

Myaing, M. T.

Norris, T. B.

Piyawattanametha, W.

Ra, H.

Russell, P. St. J.

Schnitzer, M. J.

Sepehr, A.

Solgaard, O.

Strickler, J. H.

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

Tank, D. W.

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

Thomas, T.

Tien, N. C.

W. Jung, D. T. McCormick, Y. Ahn, A. Sepehr, M. Brenner, B. Wong, N. C. Tien, and Z. Chen, Opt. Lett. 32, 3239 (2007).
[CrossRef] [PubMed]

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. Chen, Appl. Phys. Lett. 88, 163901 (2006).
[CrossRef]

Wadsworth, W. J.

Wang, L.

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. Chen, Appl. Phys. Lett. 88, 163901 (2006).
[CrossRef]

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]

Wong, B.

Xie, H.

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, J. Biomed. Opt. 12, 040501-1 (2007).

Ye, J. Y.

Zhang, J.

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. Chen, Appl. Phys. Lett. 88, 163901 (2006).
[CrossRef]

Zipfel, W. R.

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

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (3)

Fig. 1
Fig. 1

Schematic and photographs of the developed MPM probe. A, Photograph and schematic of two-axis MEMS mirror. The 2 mm mirror was fabricated in a separate process and later bonded to the actuator. B, Photograph of GRIN lens assembled with DCPCF. C, MEMS mirror and pigtailed GRIN lens mounted to custom-made packaging. Photograph depicts the inner portion of the probe prior to integration with the outer housing. D, Photograph of completed probe. Submarine-shaped probe compared for size to a U.S. quarter coin. The distance of the aspheric lens to the MEMS devices is adjustable.

Fig. 2
Fig. 2

Schematic of MPM incorporated with probe: F, filter; DM, dichroic mirror; CL, coupling lens; DCPCF, double-clad photonic crystal fiber. To compensate the positive dispersion owing to 1 m DCPCF, prechirping units using a grating pair were used. The MEMS mirror was controlled by a sychnonized signal generated by the imaging computer: A, measurement of laser pulse duration ( 190 fs ) ; B, pulse duration after prechirping units. Broadened pulse (more than 2 ps ) was minimized up to 260 fs .

Fig. 3
Fig. 3

In-vitro MPM images using the compact probe. The excitation power at the sample was 15 mW . A, Image of 6 μ m fluorescent beads. B, Image of paper. Each fiber is clearly visualized. C, Image of chondrocyte in a articular cartilage. D, Image of chondrocytes by commercial MPM system.

Metrics