Abstract

We demonstrate the application of focus-tunable acousto-optic lens technology in confocal microscopy for a high-speed axial scanning of the object. The advantages of the proposed approach include high axial scan rate, no mechanical sample movement, no additional non-symmetric aberrations, and the control of the effective depth of focus. The acousto-optic lens operating at the focus tuning rate of 300 kHz is developed and implemented in scanning laser confocal microscopy. The performance of the instrumentation is presented using test targets. Rapid focus tuning may enhance in vivo three-dimensional imaging in confocal microscopy.

© 2018 Optical Society of America

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References

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    [Crossref]
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    [Crossref]
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    [Crossref]
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    [Crossref]
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    [Crossref]

2017 (3)

K. B. Yushkov and V. Y. Molchanov, “Hyperspectral imaging acousto-optic system with spatial filtering for optical phase visualization,” J. Biomed. Opt. 22, 066017 (2017).
[Crossref]

M. Duocastella, G. Sancataldo, P. Saggau, P. Ramoino, P. Bianchini, and A. Diaspro, “Fast inertia-free volumetric light-sheet microscope,” ACS Photon. 4, 1797–1804 (2017).
[Crossref]

M. Hofer, N. K. Balla, and S. Brasselet, “High-speed polarization-resolved coherent Raman scattering imaging,” Optica 4, 795–801 (2017).
[Crossref]

2016 (2)

2015 (3)

2014 (3)

2013 (4)

S. Choi, P. Kim, R. Boutilier, M. Y. Kim, Y. J. Lee, and H. Lee, “Development of a high speed laser scanning confocal microscope with an acquisition rate up to 200 frames per second,” Opt. Express 21, 23611–23618 (2013).
[Crossref]

K. C. Heo, S. H. Yu, J. H. Kwon, and J. S. Gwag, “Thermally tunable-focus lenticular lens using liquid crystal,” Appl. Opt. 52, 8460–8464 (2013).
[Crossref]

D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
[Crossref]

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

2012 (1)

2010 (1)

2008 (3)

A. Mermillod-Blondin, E. McLeod, and C. B. Arnold, “High-speed varifocal imaging with a tunable acoustic gradient index of refraction lens,” Opt. Lett. 33, 2146–2148 (2008).
[Crossref]

C. A. Lopez and A. H. Hirsa, “Fast focusing using a pinned-contact oscillating liquid lens,” Nat. Photonics 2, 610–613 (2008).
[Crossref]

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, “Three-dimensional random access multiphoton microscopy for functional imaging of neuronal activity,” Nat. Neurosci. 11, 713–720 (2008).
[Crossref]

2007 (2)

E. McLeod and C. B. Arnold, “Mechanics and refractive power optimization of tunable acoustic gradient lenses,” J. Appl. Phys. 102, 033104 (2007).
[Crossref]

I. Grulkowski, D. Jankowski, and P. Kwiek, “Acousto-optic interaction of a Gaussian laser beam with an ultrasonic wave of cylindrical symmetry,” Appl. Opt. 46, 5870–5876 (2007).
[Crossref]

2006 (3)

H. Ren, D. Fox, P. A. Anderson, B. Wu, and S.-T. Wu, “Tunable-focus liquid lens controlled using a servo motor,” Opt. Express 14, 8031–8036 (2006).
[Crossref]

I. Grulkowski and P. Kwiek, “Experimental study of light diffraction by standing ultrasonic wave with cylindrical symmetry,” Opt. Commun. 267, 14–19 (2006).
[Crossref]

V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt. 11, 034003 (2006).
[Crossref]

2003 (1)

V. Iyer, B. E. Losavio, and P. Saggau, “Compensation of spatial and temporal dispersion for acousto-optic multiphoton laser-scanning microscopy,” J. Biomed. Opt. 8, 460–471 (2003).
[Crossref]

2001 (1)

Akemann, W.

Anderson, P. A.

Angus Silver, R.

Arnold, C. B.

A. Mermillod-Blondin, E. McLeod, and C. B. Arnold, “High-speed varifocal imaging with a tunable acoustic gradient index of refraction lens,” Opt. Lett. 33, 2146–2148 (2008).
[Crossref]

E. McLeod and C. B. Arnold, “Mechanics and refractive power optimization of tunable acoustic gradient lenses,” J. Appl. Phys. 102, 033104 (2007).
[Crossref]

Balla, N. K.

Bansal, V.

V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt. 11, 034003 (2006).
[Crossref]

Bianchini, P.

M. Duocastella, G. Sancataldo, P. Saggau, P. Ramoino, P. Bianchini, and A. Diaspro, “Fast inertia-free volumetric light-sheet microscope,” ACS Photon. 4, 1797–1804 (2017).
[Crossref]

Bourdieu, L.

Boutilier, R.

Brasselet, S.

Burmak, L. I.

Chen, H.

Chen, S.-C.

Choi, S.

Csakanyi, A.

P. A. Maak, J. B. Rozsa, G. Katona, E. S. Vizi, M. Veress, A. Csakanyi, and G. Szalay, “Focusing system comprising acousto-optic deflectors for focusing an electromagnetic beam,” U.S. patentUS8559085 B2 (15October2013).

Czarske, J. W.

Dan, D.

D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
[Crossref]

Davidson, N.

Diaspro, A.

M. Duocastella, G. Sancataldo, P. Saggau, P. Ramoino, P. Bianchini, and A. Diaspro, “Fast inertia-free volumetric light-sheet microscope,” ACS Photon. 4, 1797–1804 (2017).
[Crossref]

M. Duocastella, G. Vicidomini, and A. Diaspro, “Simultaneous multiplane confocal microscopy using acoustic tunable lenses,” Opt. Express 22, 19293–19301 (2014).
[Crossref]

Dieudonné, S.

Duemani Reddy, G.

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, “Three-dimensional random access multiphoton microscopy for functional imaging of neuronal activity,” Nat. Neurosci. 11, 713–720 (2008).
[Crossref]

Duocastella, M.

M. Duocastella, G. Sancataldo, P. Saggau, P. Ramoino, P. Bianchini, and A. Diaspro, “Fast inertia-free volumetric light-sheet microscope,” ACS Photon. 4, 1797–1804 (2017).
[Crossref]

M. Duocastella, G. Vicidomini, and A. Diaspro, “Simultaneous multiplane confocal microscopy using acoustic tunable lenses,” Opt. Express 22, 19293–19301 (2014).
[Crossref]

Eliceiri, K. W.

S. W. Paddock and K. W. Eliceiri, “Laser scanning confocal microscopy: history, applications, and related optical sectioning techniques,” in Confocal Microscopy: Methods in Molecular Biology (Methods and Protocols), S. W. Paddock, ed. (Humana, 2014).

Evans, G. J.

Fink, R.

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, “Three-dimensional random access multiphoton microscopy for functional imaging of neuronal activity,” Nat. Neurosci. 11, 713–720 (2008).
[Crossref]

Finkeldey, M.

Fischer, A.

Fox, D.

Friedman, N.

Gao, P.

D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
[Crossref]

Gerhardt, N. C.

Griffiths, V. A.

Grulkowski, I.

Gu, C.

Gwag, J. S.

Gweon, D.

Hayashi, S.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

Heo, K. C.

Hirsa, A. H.

C. A. Lopez and A. H. Hirsa, “Fast focusing using a pinned-contact oscillating liquid lens,” Nat. Photonics 2, 610–613 (2008).
[Crossref]

Hofer, M.

Hofmann, M. R.

Iyer, V.

V. Iyer, B. E. Losavio, and P. Saggau, “Compensation of spatial and temporal dispersion for acousto-optic multiphoton laser-scanning microscopy,” J. Biomed. Opt. 8, 460–471 (2003).
[Crossref]

Jankowski, D.

Jeong, H.-J.

Jiang, J.

Kang, J.

Kaplan, A.

Katona, G.

P. A. Maak, J. B. Rozsa, G. Katona, E. S. Vizi, M. Veress, A. Csakanyi, and G. Szalay, “Focusing system comprising acousto-optic deflectors for focusing an electromagnetic beam,” U.S. patentUS8559085 B2 (15October2013).

Ke, Y.

Kelleher, K.

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, “Three-dimensional random access multiphoton microscopy for functional imaging of neuronal activity,” Nat. Neurosci. 11, 713–720 (2008).
[Crossref]

Kim, M. Y.

Kim, P.

Kirkby, P. A.

Kondo, T.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

Konno, D.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

Konstantinou, G.

Koukourakis, N.

Kubitscheck, U.

U. Kubitscheck, Fluorescence Microscopy: From Principles to Biological Applications (Wiley, 2017).

Kwiek, P.

I. Grulkowski, D. Jankowski, and P. Kwiek, “Acousto-optic interaction of a Gaussian laser beam with an ultrasonic wave of cylindrical symmetry,” Appl. Opt. 46, 5870–5876 (2007).
[Crossref]

I. Grulkowski and P. Kwiek, “Experimental study of light diffraction by standing ultrasonic wave with cylindrical symmetry,” Opt. Commun. 267, 14–19 (2006).
[Crossref]

Kwon, J. H.

Lee, H.

Lee, Y. J.

Léger, J.-F.

Lei, M.

D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
[Crossref]

Leithold, C.

Lin, H.-C.

Lin, Y.-H.

Lopez, C. A.

C. A. Lopez and A. H. Hirsa, “Fast focusing using a pinned-contact oscillating liquid lens,” Nat. Photonics 2, 610–613 (2008).
[Crossref]

Losavio, B. E.

V. Iyer, B. E. Losavio, and P. Saggau, “Compensation of spatial and temporal dispersion for acousto-optic multiphoton laser-scanning microscopy,” J. Biomed. Opt. 8, 460–471 (2003).
[Crossref]

Maak, P. A.

P. A. Maak, J. B. Rozsa, G. Katona, E. S. Vizi, M. Veress, A. Csakanyi, and G. Szalay, “Focusing system comprising acousto-optic deflectors for focusing an electromagnetic beam,” U.S. patentUS8559085 B2 (15October2013).

Machikhin, A. S.

Mathieu, B.

Matsuzaki, F.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

McLeod, E.

A. Mermillod-Blondin, E. McLeod, and C. B. Arnold, “High-speed varifocal imaging with a tunable acoustic gradient index of refraction lens,” Opt. Lett. 33, 2146–2148 (2008).
[Crossref]

E. McLeod and C. B. Arnold, “Mechanics and refractive power optimization of tunable acoustic gradient lenses,” J. Appl. Phys. 102, 033104 (2007).
[Crossref]

Mermillod-Blondin, A.

Mitchell, J. E.

Molchanov, V. Y.

K. B. Yushkov and V. Y. Molchanov, “Hyperspectral imaging acousto-optic system with spatial filtering for optical phase visualization,” J. Biomed. Opt. 22, 066017 (2017).
[Crossref]

Naga Srinivas Nadella, K. M.

Nakayama, H.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

Onami, S.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

Paddock, S. W.

S. W. Paddock and K. W. Eliceiri, “Laser scanning confocal microscopy: history, applications, and related optical sectioning techniques,” in Confocal Microscopy: Methods in Molecular Biology (Methods and Protocols), S. W. Paddock, ed. (Humana, 2014).

Patel, S.

V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt. 11, 034003 (2006).
[Crossref]

Pawley, J. B.

J. B. Pawley, “Fundamental limits in confocal microscopy,” in Handbook of Biological Confocal Microscopy (Springer, 2006), pp. 20–42.

Pozhar, V. E.

Qi, Y.

D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
[Crossref]

Ramoino, P.

M. Duocastella, G. Sancataldo, P. Saggau, P. Ramoino, P. Bianchini, and A. Diaspro, “Fast inertia-free volumetric light-sheet microscope,” ACS Photon. 4, 1797–1804 (2017).
[Crossref]

Ren, H.

Rozsa, J. B.

P. A. Maak, J. B. Rozsa, G. Katona, E. S. Vizi, M. Veress, A. Csakanyi, and G. Szalay, “Focusing system comprising acousto-optic deflectors for focusing an electromagnetic beam,” U.S. patentUS8559085 B2 (15October2013).

Saggau, P.

M. Duocastella, G. Sancataldo, P. Saggau, P. Ramoino, P. Bianchini, and A. Diaspro, “Fast inertia-free volumetric light-sheet microscope,” ACS Photon. 4, 1797–1804 (2017).
[Crossref]

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, “Three-dimensional random access multiphoton microscopy for functional imaging of neuronal activity,” Nat. Neurosci. 11, 713–720 (2008).
[Crossref]

V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt. 11, 034003 (2006).
[Crossref]

V. Iyer, B. E. Losavio, and P. Saggau, “Compensation of spatial and temporal dispersion for acousto-optic multiphoton laser-scanning microscopy,” J. Biomed. Opt. 8, 460–471 (2003).
[Crossref]

Sancataldo, G.

M. Duocastella, G. Sancataldo, P. Saggau, P. Ramoino, P. Bianchini, and A. Diaspro, “Fast inertia-free volumetric light-sheet microscope,” ACS Photon. 4, 1797–1804 (2017).
[Crossref]

Shimozawa, T.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

Shitamukai, A.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

Stürmer, M.

Szalay, G.

P. A. Maak, J. B. Rozsa, G. Katona, E. S. Vizi, M. Veress, A. Csakanyi, and G. Szalay, “Focusing system comprising acousto-optic deflectors for focusing an electromagnetic beam,” U.S. patentUS8559085 B2 (15October2013).

Szulzycki, K.

Takayama, J.

T. Shimozawa, K. Yamagata, T. Kondo, S. Hayashi, A. Shitamukai, D. Konno, F. Matsuzaki, J. Takayama, S. Onami, and H. Nakayama, “Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging,” Proc. Natl. Acad. Sci. USA 110, 3399–3404 (2013).
[Crossref]

Ventalon, C.

Veress, M.

P. A. Maak, J. B. Rozsa, G. Katona, E. S. Vizi, M. Veress, A. Csakanyi, and G. Szalay, “Focusing system comprising acousto-optic deflectors for focusing an electromagnetic beam,” U.S. patentUS8559085 B2 (15October2013).

Vicidomini, G.

Viskovatykh, A. V.

Vizi, E. S.

P. A. Maak, J. B. Rozsa, G. Katona, E. S. Vizi, M. Veress, A. Csakanyi, and G. Szalay, “Focusing system comprising acousto-optic deflectors for focusing an electromagnetic beam,” U.S. patentUS8559085 B2 (15October2013).

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D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
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Wu, B.

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D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
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D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
[Crossref]

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D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
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D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
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D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
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D. Dan, M. Lei, B. Yao, W. Wang, M. Winterhalder, A. Zumbusch, Y. Qi, L. Xia, S. Yan, Y. Yang, P. Gao, T. Ye, and W. Zhao, “DMD-based LED-illumination super-resolution and optical sectioning microscopy,” Sci. Rep. 3, 1116 (2013).
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Supplementary Material (2)

NameDescription
» Visualization 1       Spatio-temporal wavefront modulation behind the acousto-optic lens
» Visualization 2       Image of the USAF resolution target using confocal microscopy with high-speed acousto-optic lens

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Figures (5)

Fig. 1.
Fig. 1. Operation of focus tunable AOL. (a) Scheme of AOL compounded with 4× objective for tuning the focal plane. (b) Dynamics of phase and intensity at the exit plane of the AOL studied with a wavefront sensor (Visualization 1). (c) Theoretical focus tuning in the proposed system for Raman–Nath parameter v=8.
Fig. 2.
Fig. 2. Experimental setup. C, collimator; BS, beam-splitter; PH, pinhole; PMT, photomultiplier tube; Sc, galvanometric scanners; AOL, acousto-optic lens; OBJ, objective (offset) lens; S, sample; GEN, dual-channel function generator; L1, collecting lens; ADC, analog-to-digital converter (acquisition card); COMP, computer.
Fig. 3.
Fig. 3. USAF target imaging with confocal microscopy equipped with the AOL. Images acquired (a) without and (b) with axial scanning (Visualization 2). (c) Cross sections of the bars belonging to the second element of the sixth group.
Fig. 4.
Fig. 4. Modulation transfer function of the confocal microscope (a) without and (b) with axial scanning.
Fig. 5.
Fig. 5. Depth-of-field target imaging with confocal microscopy equipped with the AOL. Images acquired (a) without and (b) with axial scanning. (c) Light intensity profiles along red and blue vertical lines.

Equations (4)

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n(r,t)=n0+δnJ0(Kr)cos(Ωt),
1fAOL(t)=1fOBJ+K2v2k·cos(Ωt),
C(fx)=ImaxIminImax+Imin,
FR=2facqNxNy,

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