Abstract

We present an interferometric confocal microscope using an array of 1200 vertical cavity surface emitting lasers (VCSELs) coupled to a multimode fiber. Spatial coherence gating provides ~18,000 continuous virtual pinholes, allowing an entire en face plane to be imaged in a snapshot. This approach maintains the same optical sectioning as a scanning confocal microscope without moving parts, while the high power of the VCSEL array (5mW per laser) enables high-speed image acquisition with integration times as short as 100 μs. Interferometric detection also recovers the phase of the image, enabling quantitative phase measurements and improving the contrast when imaging phase objects.

© 2014 Optical Society of America

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  1. R. H. Webb, Rep. Prog. Phys. 59, 427 (1996).
    [CrossRef]
  2. G. S. Kino and T. R. Corle, Confocal Scanning Optical Microscopy and Related Imaging Systems (Academic, 1996).
  3. M. Rajadhyaksha, R. R. Anderson, and R. H. Webb, Appl. Opt. 38, 2105 (1999).
    [CrossRef]
  4. J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, O. Solgaard, G. S. Kino, W. Piyawattanametha, C. H. Contag, and T. D. Wang, Opt. Lett. 32, 256 (2007).
    [CrossRef]
  5. M. Petráň, M. Hadravský, M. D. Egger, and R. Galambos, J. Opt. Soc. Am. 58, 661 (1968).
    [CrossRef]
  6. A. Egner, V. Andresen, and S. W. Hell, J. Microsc. 206, 24 (2002).
    [CrossRef]
  7. T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
    [CrossRef]
  8. P. J. Dwyer, C. A. DiMarzio, and M. Rajadhyaksha, Appl. Opt. 46, 1843 (2007).
    [CrossRef]
  9. B. Larson, S. Abeytunge, and M. Rajadhyaksha, Biomed. Opt. Express 2, 2055 (2011).
    [CrossRef]
  10. K.-B. Im, S. Han, H. Park, D. Kim, and B.-M. Kim, Opt. Express 13, 5151 (2005).
    [CrossRef]
  11. D. Wang, Y. Chen, Y. Wang, and J. T. C. Liu, Opt. Lett. 38, 5280 (2013).
    [CrossRef]
  12. G. J. Tearney, R. H. Webb, and B. E. Bouma, Opt. Lett. 23, 1152 (1998).
    [CrossRef]
  13. A. Safrani and I. Abdulhalim, Opt. Lett. 37, 458 (2012).
    [CrossRef]
  14. M. G. Somekh, C. W. See, and J. Goh, Opt. Commun. 174, 75 (2000).
    [CrossRef]
  15. M. C. Pitter, C. W. See, and M. G. Somekh, Opt. Lett. 29, 1200 (2004).
    [CrossRef]
  16. Y. Choi, T. D. Yang, K. J. Lee, and W. Choi, Opt. Lett. 36, 2465 (2011).
    [CrossRef]
  17. A. Dubois, L. Vabre, A.-C. Boccara, and E. Beaurepaire, Appl. Opt. 41, 805 (2002).
    [CrossRef]
  18. J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
    [CrossRef]
  19. A.-H. Dhalla, J. V. Migacz, and J. A. Izatt, Opt. Lett. 35, 2305 (2010).
    [CrossRef]
  20. L. Wang, T. Tschudi, T. Halldórsson, and P. R. Pétursson, Appl. Opt. 37, 1770 (1998).
    [CrossRef]
  21. A. Mermillod-Blondin, H. Mentzel, and A. Rosenfeld, Opt. Lett. 38, 4112 (2013).
    [CrossRef]
  22. T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, Opt. Lett. 30, 1165 (2005).
    [CrossRef]

2013 (3)

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

A. Mermillod-Blondin, H. Mentzel, and A. Rosenfeld, Opt. Lett. 38, 4112 (2013).
[CrossRef]

D. Wang, Y. Chen, Y. Wang, and J. T. C. Liu, Opt. Lett. 38, 5280 (2013).
[CrossRef]

2012 (1)

2011 (2)

2010 (1)

2009 (1)

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

2007 (2)

2005 (2)

2004 (1)

2002 (2)

2000 (1)

M. G. Somekh, C. W. See, and J. Goh, Opt. Commun. 174, 75 (2000).
[CrossRef]

1999 (1)

1998 (2)

1996 (1)

R. H. Webb, Rep. Prog. Phys. 59, 427 (1996).
[CrossRef]

1968 (1)

Abdulhalim, I.

Abeytunge, S.

Anderson, R. R.

Andresen, V.

A. Egner, V. Andresen, and S. W. Hell, J. Microsc. 206, 24 (2002).
[CrossRef]

Beaurepaire, E.

Boccara, A.-C.

Bouma, B. E.

Chen, Y.

Choi, W.

Choi, Y.

Contag, C. H.

Corle, T. R.

G. S. Kino and T. R. Corle, Confocal Scanning Optical Microscopy and Related Imaging Systems (Academic, 1996).

D’Asaro, L. A.

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

Dasari, R. R.

Dhalla, A.-H.

DiMarzio, C. A.

Dubois, A.

Dwyer, P. J.

Egger, M. D.

Egner, A.

A. Egner, V. Andresen, and S. W. Hell, J. Microsc. 206, 24 (2002).
[CrossRef]

Feld, M. S.

Fujita, K.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Galambos, R.

Ghosh, C. L.

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

Goh, J.

M. G. Somekh, C. W. See, and J. Goh, Opt. Commun. 174, 75 (2000).
[CrossRef]

Hadravský, M.

Halldórsson, T.

Han, S.

Hayashi, S.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Hell, S. W.

A. Egner, V. Andresen, and S. W. Hell, J. Microsc. 206, 24 (2002).
[CrossRef]

Ikeda, T.

Im, K.-B.

Izatt, J. A.

Khalfin, V.

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

Kim, B.-M.

Kim, D.

Kino, G. S.

J. T. C. Liu, M. J. Mandella, H. Ra, L. K. Wong, O. Solgaard, G. S. Kino, W. Piyawattanametha, C. H. Contag, and T. D. Wang, Opt. Lett. 32, 256 (2007).
[CrossRef]

G. S. Kino and T. R. Corle, Confocal Scanning Optical Microscopy and Related Imaging Systems (Academic, 1996).

Kondo, T.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Konno, D.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Kosugi, Y.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Larson, B.

Lee, K. J.

Liu, J. T. C.

Mandella, M. J.

Matsuzaki, F.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Mentzel, H.

Mermillod-Blondin, A.

Migacz, J. V.

Miglo, A.

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

Mimori-Kiyosue, Y.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Nakayama, H.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Onami, S.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Park, H.

Petrán, M.

Pétursson, P. R.

Pitter, M. C.

Piyawattanametha, W.

Popescu, G.

Pradhan, P.

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

Ra, H.

Rajadhyaksha, M.

Rosenfeld, A.

Safrani, A.

See, C. W.

M. C. Pitter, C. W. See, and M. G. Somekh, Opt. Lett. 29, 1200 (2004).
[CrossRef]

M. G. Somekh, C. W. See, and J. Goh, Opt. Commun. 174, 75 (2000).
[CrossRef]

Seurin, J.-F.

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

Shimozawa, T.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Shitamukai, A.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Solgaard, O.

Somekh, M. G.

M. C. Pitter, C. W. See, and M. G. Somekh, Opt. Lett. 29, 1200 (2004).
[CrossRef]

M. G. Somekh, C. W. See, and J. Goh, Opt. Commun. 174, 75 (2000).
[CrossRef]

Takayama, J.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Tearney, G. J.

Tschudi, T.

Vabre, L.

Wang, D.

Wang, L.

Wang, T. D.

Wang, Y.

Watanabe, T. M.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Webb, R. H.

Wong, L. K.

Wynn, J. D.

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

Xu, G.

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

Yamagata, K.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Yang, T. D.

Appl. Opt. (4)

Biomed. Opt. Express (1)

J. Microsc. (1)

A. Egner, V. Andresen, and S. W. Hell, J. Microsc. 206, 24 (2002).
[CrossRef]

J. Opt. Soc. Am. (1)

Opt. Commun. (1)

M. G. Somekh, C. W. See, and J. Goh, Opt. Commun. 174, 75 (2000).
[CrossRef]

Opt. Express (1)

Opt. Lett. (9)

Proc. Natl. Acad. Sci. USA (1)

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, H. Nakayama, Y. Kosugi, T. M. Watanabe, K. Fujita, and Y. Mimori-Kiyosue, Proc. Natl. Acad. Sci. USA 110, 3399 (2013).
[CrossRef]

Proc. SPIE (1)

J.-F. Seurin, G. Xu, V. Khalfin, A. Miglo, J. D. Wynn, P. Pradhan, C. L. Ghosh, and L. A. D’Asaro, Proc. SPIE 7229, 722903 (2009).
[CrossRef]

Rep. Prog. Phys. (1)

R. H. Webb, Rep. Prog. Phys. 59, 427 (1996).
[CrossRef]

Other (1)

G. S. Kino and T. R. Corle, Confocal Scanning Optical Microscopy and Related Imaging Systems (Academic, 1996).

Supplementary Material (1)

» Media 1: AVI (1413 KB)     

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Figures (4)

Fig. 1.
Fig. 1.

(a) Schematic of the full-field confocal microscope. (b) Top view of the VCSEL array while lasing—each dot is a separate laser. The scale bar is 100 μm. (c) Magnified view of the VCSEL array—each circle is an independent laser. The scale bar is 20 μm. The VCSEL array was coupled to a 1 m long multimode fiber, which scrambled the modes, providing a uniform illumination source. The emission leaving the multimode fiber was imaged using 20× (NA=0.4) objectives onto the sample and reference arms through a beam splitter. The beam splitter was offset from the optical axis of the sample arm in order to introduce interference fringes in the detected signal. A charge-coupled device (CCD) camera was then used to record the interference pattern.

Fig. 2.
Fig. 2.

(a) Unprocessed interference pattern measured on the CCD camera shown in Fig. 1. High-contrast fringes are visible across the image. (b) Spatial Fourier transform of the image in (a). A Hann window, indicated by the black circle, was used to select the off-axis component. This component was then shifted back to the center of Fourier space. The (c) amplitude and (d) phase of the field from the sample are recovered after inverse Fourier transform of the filtered image in (b). (e) Magnified view of the region indicated in (a) showing high-contrast interference fringes. (f) Magnified view of the region indicated in (c); features separated by 2.19 μm are clearly distinguishable. (g) Step height of the Air Force chart features extracted from the phase image along the cross-section line shown in (d).

Fig. 3.
Fig. 3.

(a) Axial PSF was recorded by scanning a mirror through the focal plane and recording the intensity of the confocal image as a function of the mirror position. The confocal microscope shows a sharp axial response with FWHM 8μm, compared with the conventional microscope in which the recorded intensity decays slowly with defocus. (b) The lateral PSF was estimated by examining the sharpness of the edge in the image of the resolution chart shown in Fig. 2(c). The half-width at half-maximum is 1.2μm.

Fig. 4.
Fig. 4.

Images of lens paper at two focal planes separated by 28 μm. The conventional microscope images were recorded by blocking the reference arm. Unlike the conventional microscope, the optical sectioning ability of the confocal microscope enables imaging of different planes while rejecting out-of-plane light. (Media 1) The supplementary video shows the conventional microscope and confocal images as the lens paper is scanned through the focal plane.

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