Abstract

The first, to our knowledge, miniature dual-axes confocal microscope has been developed, with an outer diameter of 10mm, for subsurface imaging of biological tissues with 57μm resolution. Depth-resolved en face images are obtained at 30framespersecond, with a field of view of 800×100μm, by employing a two-dimensional scanning microelectromechanical systems mirror. Reflectance and fluorescence images are obtained with a laser source at 785nm, demonstrating the ability to perform real-time optical biopsy.

© 2007 Optical Society of America

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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
  5. J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
    [CrossRef]
  6. H. Ra, Y. Taguchi, D. Lee, W. Piyawattanametha, and O. Solgaard, presented at the IEEE International Conference on Micro Electro Mechanical Systems, Turkey, January 22-26, 2006.
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    [CrossRef]
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  9. H. Ra, W. Piyawattanametha, Y. Taguchi, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, August 21-24, 2006.

2006 (2)

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

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, 13 (2006).
[CrossRef]

2003 (1)

2002 (1)

1999 (1)

1995 (1)

E. H. Stelzer, S. Lindek, S. Albrecht, R. Pick, G. Ritter, N. Salmon, and R. Stricker, J. Microsc. 179, 1 (1995).
[CrossRef]

Albrecht, S.

E. H. Stelzer, S. Lindek, S. Albrecht, R. Pick, G. Ritter, N. Salmon, and R. Stricker, J. Microsc. 179, 1 (1995).
[CrossRef]

Barretto, R. P. J.

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, 13 (2006).
[CrossRef]

Chan, N. Y.

Cocker, E. D.

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, 13 (2006).
[CrossRef]

Contag, C. H.

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

T. D. Wang, M. J. Mandella, C. H. Contag, N. Y. Chan, and G. S. Kino, Opt. Lett. 28, 414 (2003).
[CrossRef] [PubMed]

Crawford, J. H.

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

Descour, M. R.

Flusberg, B. A.

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, 13 (2006).
[CrossRef]

Friedland, S.

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

Hsiung, P.

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

Kino, G. S.

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

T. D. Wang, M. J. Mandella, C. H. Contag, N. Y. Chan, and G. S. Kino, Opt. Lett. 28, 414 (2003).
[CrossRef] [PubMed]

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

Ko, T. H.

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, 13 (2006).
[CrossRef]

Lee, D.

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, 13 (2006).
[CrossRef]

H. Ra, Y. Taguchi, D. Lee, W. Piyawattanametha, and O. Solgaard, presented at the IEEE International Conference on Micro Electro Mechanical Systems, Turkey, January 22-26, 2006.

Liang, C.

Lindek, S.

E. H. Stelzer, S. Lindek, S. Albrecht, R. Pick, G. Ritter, N. Salmon, and R. Stricker, J. Microsc. 179, 1 (1995).
[CrossRef]

Liu, J. T. C.

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

Mandella, M. J.

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

T. D. Wang, M. J. Mandella, C. H. Contag, N. Y. Chan, and G. S. Kino, Opt. Lett. 28, 414 (2003).
[CrossRef] [PubMed]

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

Pick, R.

E. H. Stelzer, S. Lindek, S. Albrecht, R. Pick, G. Ritter, N. Salmon, and R. Stricker, J. Microsc. 179, 1 (1995).
[CrossRef]

Piyawattanametha, W.

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, 13 (2006).
[CrossRef]

H. Ra, Y. Taguchi, D. Lee, W. Piyawattanametha, and O. Solgaard, presented at the IEEE International Conference on Micro Electro Mechanical Systems, Turkey, January 22-26, 2006.

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

H. Ra, W. Piyawattanametha, Y. Taguchi, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, August 21-24, 2006.

Ra, H.

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, 13 (2006).
[CrossRef]

H. Ra, Y. Taguchi, D. Lee, W. Piyawattanametha, and O. Solgaard, presented at the IEEE International Conference on Micro Electro Mechanical Systems, Turkey, January 22-26, 2006.

H. Ra, W. Piyawattanametha, Y. Taguchi, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, August 21-24, 2006.

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

Ragomentich, F.

Richards-Kortum, R. R.

Ritter, G.

E. H. Stelzer, S. Lindek, S. Albrecht, R. Pick, G. Ritter, N. Salmon, and R. Stricker, J. Microsc. 179, 1 (1995).
[CrossRef]

Salmon, N.

E. H. Stelzer, S. Lindek, S. Albrecht, R. Pick, G. Ritter, N. Salmon, and R. Stricker, J. Microsc. 179, 1 (1995).
[CrossRef]

Schnitzer, M. J.

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, 13 (2006).
[CrossRef]

Soetikno, R.

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

Solgaard, O.

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, 13 (2006).
[CrossRef]

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

H. Ra, Y. Taguchi, D. Lee, W. Piyawattanametha, and O. Solgaard, presented at the IEEE International Conference on Micro Electro Mechanical Systems, Turkey, January 22-26, 2006.

H. Ra, W. Piyawattanametha, Y. Taguchi, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, August 21-24, 2006.

Stelzer, E. H.

E. H. Stelzer, S. Lindek, S. Albrecht, R. Pick, G. Ritter, N. Salmon, and R. Stricker, J. Microsc. 179, 1 (1995).
[CrossRef]

Stricker, R.

E. H. Stelzer, S. Lindek, S. Albrecht, R. Pick, G. Ritter, N. Salmon, and R. Stricker, J. Microsc. 179, 1 (1995).
[CrossRef]

Sung, K.

Taguchi, Y.

H. Ra, Y. Taguchi, D. Lee, W. Piyawattanametha, and O. Solgaard, presented at the IEEE International Conference on Micro Electro Mechanical Systems, Turkey, January 22-26, 2006.

H. Ra, W. Piyawattanametha, Y. Taguchi, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, August 21-24, 2006.

Wang, T. D.

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

T. D. Wang, M. J. Mandella, C. H. Contag, N. Y. Chan, and G. S. Kino, Opt. Lett. 28, 414 (2003).
[CrossRef] [PubMed]

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

Webb, R. H.

Wong, L. K.

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

Appl. Opt. (2)

J. Biomed. Opt. (1)

J. T. C. Liu, M. J. Mandella, S. Friedland, R. Soetikno, J. H. Crawford, C. H. Contag, G. S. Kino, and T. D. Wang, J. Biomed. Opt. 11, 054109 (2006).
[CrossRef]

J. Microsc. (1)

E. H. Stelzer, S. Lindek, S. Albrecht, R. Pick, G. Ritter, N. Salmon, and R. Stricker, J. Microsc. 179, 1 (1995).
[CrossRef]

Opt. Lett. (2)

T. D. Wang, M. J. Mandella, C. H. Contag, N. Y. Chan, and G. S. Kino, Opt. Lett. 28, 414 (2003).
[CrossRef] [PubMed]

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, 13 (2006).
[CrossRef]

Other (3)

W. Piyawattanametha, J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, P. Hsiung, T. D. Wang, G. S. Kino, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, Montana, August 21-24, 2006.

H. Ra, W. Piyawattanametha, Y. Taguchi, and O. Solgaard, presented at the IEEE International Conference on Optical Micro Electro Mechanical Systems, August 21-24, 2006.

H. Ra, Y. Taguchi, D. Lee, W. Piyawattanametha, and O. Solgaard, presented at the IEEE International Conference on Micro Electro Mechanical Systems, Turkey, January 22-26, 2006.

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Figures (4)

Fig. 1
Fig. 1

Miniature dual-axes confocal scan head optics. (1) Collimated illumination beam. (2) Collimated collection beam. (3) MEMS 2D scanner. (4) Parabolic reflecting surface. (5) Index-matching hemisphere.

Fig. 2
Fig. 2

Miniature dual-axes microscope package design drawings. The outer diameter for this device is 10 mm , with all essential optics and optical paths contained within the central 5 mm diameter. (1) Fibered collimators. (2) Risley alignment prisms. (3) MEMS PCB. (4) Parabolic reflector. (5) Axial sliding mechanism to control imaging depth. (6) Removable end cap holding the parabolic reflector.

Fig. 3
Fig. 3

Scanning electron microscopy image of the 2D scanner. Dimensions of the MEMS chip are 3.2 mm × 2.9 mm , with each mirror surface measuring 650 μ m × 600 μ m . (1) Outer torsional spring. (2) Outer axis electrostatic comb actuators. (3) Inner torsional spring. (4) Inner axis electrostatic comb actuators.

Fig. 4
Fig. 4

(a) Dual-axes reflectance image of a USAF target, obtained at 30 frames/s, demonstrating resolvable lines in element 4 of group 7 ( 5.5 μ m period). FOV = 350 μ m × 100 μ m . (b) Dual-axes fluorescence image of normal colonic mucosa at 785 nm , showing circular crypts and surrounding colonocytes. The image is an average of five frames acquired at 30 frames per second. Imaging depth = 20 μ m at the image center. FOV = 800 μ m × 100 μ m .

Equations (2)

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Δ x d = 0.466 λ n α cos θ = 2.2 , Δ y d = 0.466 λ n α = 2.0 ,
Δ z d = 0.466 λ n α sin θ = 5.0 .

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