Abstract

We show theoretically and experimentally that simultaneous spatial and temporal focusing can scan the temporal focal plane axially by adjusting the group velocity dispersion in the excitation beam path. When the group velocity dispersion is small, the pulse width at the temporal focal plane is transform-limited, and the amount of shift depends linearly upon the dispersion. By adding a meter of large mode area fiber into the system, we demonstrate this axial scanning capability in a fiber delivery configuration. Because a transform-limited pulse width is automatically recovered at the temporal focal plane, simultaneous spatial and temporal focusing negates the need for any dispersion pre-compensation, further facilitating its integration into a fiber delivery system. A highly promising application for simultaneous spatial and temporal focusing is an axial scanning multiphoton fluorescence fiber probe without any moving parts at the distal end and without dispersion pre-compensation.

© 2006 Optical Society of America

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2006

2005

2004

2003

2002

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, "Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues," IEEE Trans. Biomed. Eng. 49,1168-1172 (2002).
[CrossRef] [PubMed]

D. Bird, and M. Gu, "Fibre-optic two-photon scanning fluorescence microscopy," J. Microsc. 208,35-48 (2002).
[CrossRef] [PubMed]

D. G. Ouzounov, K. D. Moll, M. A. Foster, W. R. Zipfel, W. W. Webb, and A. L. Gaeta, "Delivery of nanojoule femtosecond pulses through large-core microstructured fibers," Opt. Lett. 27, 1513-1515 (2002).
[CrossRef]

2001

C. Liang, M. R. Descour, K. B. Sung, and R. Richards-Kortum, "Fiber confocal reflectance microscope (FCRM) for in-vivo imaging," Opt. Express 9,821-830 (2001).
[CrossRef] [PubMed]

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31,903-912 (2001).
[CrossRef] [PubMed]

2000

A. R. Rouse, and A. F. Gmitro, "Multispectral imaging with a confocal microendoscope," Opt. Lett. 25,1708-1710 (2000).
[CrossRef]

B. Berge, and J. Peseux, "Variable focal lens controlled by an external voltage: An application of electrowetting," Eur. Phys. J. E 3,159-163 (2000).
[CrossRef]

1999

U. Hofmann, S. Muehlmann, M. Witt, K. Dorschel, R. Schutz, and B. Wagner, "Electrostatically driven micromirrors for a miniaturized confocal laser scanning microscope," Proceedings of SPIE 3878,29-38 (1999).
[CrossRef]

1996

1993

1991

L. Giniunas, R. Juskaitis, and S. V. Shatalin, "Scanning Fiberoptic Microscope," Electron. Lett. 27,724-726 (1991).
[CrossRef]

1990

1986

Anderson, E. P.

Berge, B.

B. Berge, and J. Peseux, "Variable focal lens controlled by an external voltage: An application of electrowetting," Eur. Phys. J. E 3,159-163 (2000).
[CrossRef]

Bird, D.

D. Bird, and M. Gu, "Two-photon fluorescence endoscopy with a micro-optic scanning head," Opt. Lett. 28,1552-1554 (2003).
[CrossRef] [PubMed]

D. Bird, and M. Gu, "Fibre-optic two-photon scanning fluorescence microscopy," J. Microsc. 208,35-48 (2002).
[CrossRef] [PubMed]

Cheung, T. H.

Christie, R.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc.National Academy of Sciences of the United States of America 100,7075-7080 (2003).
[CrossRef]

Cocker, E. D.

Collier, T.

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, "Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues," IEEE Trans. Biomed. Eng. 49,1168-1172 (2002).
[CrossRef] [PubMed]

Cranfield, C.

Denk, W.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31,903-912 (2001).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, "2-Photon Laser Scanning Fluorescence Microscopy," Science 248,73-76 (1990).
[CrossRef] [PubMed]

Descour, M.

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, "Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues," IEEE Trans. Biomed. Eng. 49,1168-1172 (2002).
[CrossRef] [PubMed]

Descour, M. R.

Dickensheets, D. L.

Dombeck, D. A.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91,1908-1912 (2004).
[CrossRef]

Dorschel, K.

U. Hofmann, S. Muehlmann, M. Witt, K. Dorschel, R. Schutz, and B. Wagner, "Electrostatically driven micromirrors for a miniaturized confocal laser scanning microscope," Proceedings of SPIE 3878,29-38 (1999).
[CrossRef]

Durst, M.

Eickhoff, V. C.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, V. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65,1180-1186 (2005).
[CrossRef] [PubMed]

Eliceiri, K. W.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, V. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65,1180-1186 (2005).
[CrossRef] [PubMed]

Fee, M. S.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31,903-912 (2001).
[CrossRef] [PubMed]

Flusberg, B. A.

Follen, M.

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, "Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues," IEEE Trans. Biomed. Eng. 49,1168-1172 (2002).
[CrossRef] [PubMed]

Foster, M. A.

Fu, L.

Gaeta, A. L.

Gendron-Fitzpatrick, A.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, V. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65,1180-1186 (2005).
[CrossRef] [PubMed]

Gibson, G. M.

Giniunas, L.

L. Giniunas, R. Juskaitis, and S. V. Shatalin, "Scanning Fiberoptic Microscope," Electron. Lett. 27,724-726 (1991).
[CrossRef]

Girkin, J. M.

Gmitro, A. F.

Gobel, W.

Gu, M.

Helmchen, F.

Hendriks, B. H. W.

S. Kuiper, and B. H. W. Hendriks, "Variable-focus liquid lens for miniature cameras," Appl. Phys. Lett. 85,1128-1130 (2004).
[CrossRef]

Hofmann, U.

U. Hofmann, S. Muehlmann, M. Witt, K. Dorschel, R. Schutz, and B. Wagner, "Electrostatically driven micromirrors for a miniaturized confocal laser scanning microscope," Proceedings of SPIE 3878,29-38 (1999).
[CrossRef]

Hyman, B. T.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc.National Academy of Sciences of the United States of America 100,7075-7080 (2003).
[CrossRef]

Jain, A.

Jung, J. C.

Juskaitis, R.

L. Giniunas, R. Juskaitis, and S. V. Shatalin, "Scanning Fiberoptic Microscope," Electron. Lett. 27,724-726 (1991).
[CrossRef]

Kano, A.

Kasischke, K. A.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91,1908-1912 (2004).
[CrossRef]

Kerr, J. N. D.

Kim, D.

D. Kim, K. H. Kim, S. Yazdanfar, and P. T. C. So, "Optical biopsy in high-speed handheld miniaturized multifocal multiphoton microscopy," Proceedings of SPIE 5700,14-22 (2005).
[CrossRef]

Kim, K. H.

D. Kim, K. H. Kim, S. Yazdanfar, and P. T. C. So, "Optical biopsy in high-speed handheld miniaturized multifocal multiphoton microscopy," Proceedings of SPIE 5700,14-22 (2005).
[CrossRef]

Kino, G. S.

Kroto, S. M.

Kuiper, S.

S. Kuiper, and B. H. W. Hendriks, "Variable-focus liquid lens for miniature cameras," Appl. Phys. Lett. 85,1128-1130 (2004).
[CrossRef]

Leaird, D. E.

Levene, M. J.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91,1908-1912 (2004).
[CrossRef]

Liang, C.

Liang, C. N.

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, "Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues," IEEE Trans. Biomed. Eng. 49,1168-1172 (2002).
[CrossRef] [PubMed]

Lung, J. C.

Makita, S.

Martinez, O. E.

Moll, K. D.

Molloy, R. P.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91,1908-1912 (2004).
[CrossRef]

Muehlmann, S.

U. Hofmann, S. Muehlmann, M. Witt, K. Dorschel, R. Schutz, and B. Wagner, "Electrostatically driven micromirrors for a miniaturized confocal laser scanning microscope," Proceedings of SPIE 3878,29-38 (1999).
[CrossRef]

Nelson, K. A.

Nikitin, A. Y.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc.National Academy of Sciences of the United States of America 100,7075-7080 (2003).
[CrossRef]

Nimmerjahn, A.

Oron, D.

Ouzounov, D. G.

Padgett, M. J.

Patel, J. S.

Patterson, B. A.

Peseux, J.

B. Berge, and J. Peseux, "Variable focal lens controlled by an external voltage: An application of electrowetting," Eur. Phys. J. E 3,159-163 (2000).
[CrossRef]

Poland, S. P.

Qu, J. N. Y.

Ramanujam, N.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, V. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65,1180-1186 (2005).
[CrossRef] [PubMed]

Richards-Kortum, R.

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, "Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues," IEEE Trans. Biomed. Eng. 49,1168-1172 (2002).
[CrossRef] [PubMed]

C. Liang, M. R. Descour, K. B. Sung, and R. Richards-Kortum, "Fiber confocal reflectance microscope (FCRM) for in-vivo imaging," Opt. Express 9,821-830 (2001).
[CrossRef] [PubMed]

Rouse, A. R.

Ruprecht, A. K.

Schnitzer, M. J.

Schutz, R.

U. Hofmann, S. Muehlmann, M. Witt, K. Dorschel, R. Schutz, and B. Wagner, "Electrostatically driven micromirrors for a miniaturized confocal laser scanning microscope," Proceedings of SPIE 3878,29-38 (1999).
[CrossRef]

Shatalin, S. V.

L. Giniunas, R. Juskaitis, and S. V. Shatalin, "Scanning Fiberoptic Microscope," Electron. Lett. 27,724-726 (1991).
[CrossRef]

Silberberg, Y.

Skala, M. C.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, V. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65,1180-1186 (2005).
[CrossRef] [PubMed]

So, P. T. C.

D. Kim, K. H. Kim, S. Yazdanfar, and P. T. C. So, "Optical biopsy in high-speed handheld miniaturized multifocal multiphoton microscopy," Proceedings of SPIE 5700,14-22 (2005).
[CrossRef]

Squirrell, J. M.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, V. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65,1180-1186 (2005).
[CrossRef] [PubMed]

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, "2-Photon Laser Scanning Fluorescence Microscopy," Science 248,73-76 (1990).
[CrossRef] [PubMed]

Suchowski, H.

H. Suchowski, D. Oron, and Y. Silberberg, "Generation of a dark nonlinear focus by spatio-temporal coherent control," Opt. Commun. 264,482-487 (2006).
[CrossRef]

Sung, K. B.

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, "Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues," IEEE Trans. Biomed. Eng. 49,1168-1172 (2002).
[CrossRef] [PubMed]

C. Liang, M. R. Descour, K. B. Sung, and R. Richards-Kortum, "Fiber confocal reflectance microscope (FCRM) for in-vivo imaging," Opt. Express 9,821-830 (2001).
[CrossRef] [PubMed]

Tal, E.

Tank, D. W.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31,903-912 (2001).
[CrossRef] [PubMed]

Tiziani, H. J.

Udovich, J. A.

van Howe, J.

Vrotsos, K. M.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, V. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65,1180-1186 (2005).
[CrossRef] [PubMed]

Wagner, B.

U. Hofmann, S. Muehlmann, M. Witt, K. Dorschel, R. Schutz, and B. Wagner, "Electrostatically driven micromirrors for a miniaturized confocal laser scanning microscope," Proceedings of SPIE 3878,29-38 (1999).
[CrossRef]

Webb, W. W.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91,1908-1912 (2004).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc.National Academy of Sciences of the United States of America 100,7075-7080 (2003).
[CrossRef]

D. G. Ouzounov, K. D. Moll, M. A. Foster, W. R. Zipfel, W. W. Webb, and A. L. Gaeta, "Delivery of nanojoule femtosecond pulses through large-core microstructured fibers," Opt. Lett. 27, 1513-1515 (2002).
[CrossRef]

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[CrossRef]

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[CrossRef]

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Figures (7)

Fig. 1.
Fig. 1.

A typical SSTF setup

Fig. 2.
Fig. 2.

A ray-tracing representation of the focal volume shows intuitively the fundamental scanning limit, where s is the lateral spot size of a monochromatic beam and Zmax is the length of the geometrical overlap.

Fig. 3.
Fig. 3.

SSTF setup composed of a mode-locked Ti:Sapphire laser tuned to 775 nm, a 1200 lines/mm grating, a 4× beam shrinker, a Zeiss Apochromat 10×/0.45 objective lens, and, for fiber delivery experiments, one meter of large mode area fiber coupled by two 0.1 NA objective lenses.

Fig. 4.
Fig. 4.

(a) The shift of the temporal focal plane position is plotted versus GVD varied by adjusting the prism pair. The squares represent peak positions of axial traces taken for various prism positions. The solid line is the expected linear relationship. In (b), the data points represent the pulse width at the sample for various GVD values. The triangles demonstrate the recovery of the pulse width for a 1200 lines per millimeter grating and a 4× beam shrinker. The squares show that the pulse broadens with added GVD when the grating is changed to 600 lines per millimeter and the beam shrinker is reduced to 2×. The solid red line is the predicted pulse width for the broadening case.

Fig. 5.
Fig. 5.

Scanning of a #1 cover glass coated on both sides with a thin Rhodamine B film. The blue curve is an axial trace obtained by scanning the sample with a translation stage. The red circles represent data taken of the axial scan by tuning the GVD at a fixed sample position.

Fig. 6.
Fig. 6.

Autocorrelation traces for a system without dispersion compensation where the pulse has propagated through one meter of large mode area fiber. The laser has a center wavelength of 775 nm and a spectral width of 8 nm. In plot (a), the pulse is at the output of the large mode area fiber, and in (b), at the temporal focal plane of the SSTF setup.

Fig. 7.
Fig. 7.

Axial scan data obtained by GVD tuning for (a) wide-field and (b) line-scanning SSTF.

Equations (23)

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A 1 ( x , ω ) = A 0 e ω 2 Ω 2 e ( x α ω ) 2 s 2 e i β ω 2
T P E ( z ) = I 2 ( x , z , t ) d x d t = C [ ( 1 + β Ω 2 z f z M ) 2 + ( f z + β Ω 2 z R z R ) 2 ] 1 2
T P E ( z ) C [ 1 + ( f z + β Ω 2 z R z R ) 2 ] 1 2 .
Δ z shift = β Ω 2 z R .
τ = τ 0 · [ 1 + ( β Ω 2 ) 2 z R z M ] 1 2 .
β Ω 2 max = ( z M z R ) 1 2 = ( s 2 + α 2 Ω 2 s 2 ) 1 2 α Ω s .
τ = τ 0 · [ 1 + ( β Ω 2 β Ω 2 max ) 2 ] 1 2 .
Δ z max = β Ω 2 max · z R = ( z M z R ) 1 2 α Ω s z R .
U 1 ( x ) = e ikf i λ f U 0 ( ξ ) e i k 2 f ( x ξ ) 2 d ξ .
A 2 ( x , ω ) = A 0 e ikf i λ f e ω 2 Ω 2 e i β ω 2 e ( ξ α ω ) 2 s 2 e i k 2 f ( x ξ ) 2 d ξ
= A 0 e ikf e ω 2 Ω 2 e i β ω 2 1 ( 1 + i 2 f k s 2 ) 1 2 e k ( x α ω ) 2 2 if + k s 2
A 3 ( x , ω ) = A 0 e ikf e ω 2 Ω 2 e i β ω 2 1 ( 1 + i 2 f k s 2 ) 1 2 e k ( x α ω ) 2 2 if + k s 2 e i k 2 f x 2 .
A 4 ( x , z , ω ) = A 0 e ik ( z + f ) e ω 2 Ω 2 e i β ω 2 1 ( 1 + i 2 f k s 2 ) 1 2 1 ( 1 + i 2 z k s 1 2 ) 1 2 · . . .
. . . · e ( x ( f z ) f α ω ) 2 s 2 2 e i k α ω x f e i k α 2 ω 2 ( z f ) 2 f 2
A 5 ( x , z , t ) = A 4 ( x , z , ω ) · e i ω t d ω
= κ · e x 2 s 2 2 e Ω 2 4 ( 1 + χ ) ( t + γ x ) 2
κ = A 0 Ω i π f z M 1 [ f z z M 1 + i ( f z z R + β Ω 2 ) ] 1 2 ,
γ = k 0 α f 1 + i ( z f ) z M ,
χ = i ( z f ) z B 1 + i ( z f ) z M i β Ω 2 ,
z M = 2 f 2 k 0 s 2 , z R = 2 f 2 k 0 s 2 + α 2 Ω 2 , and z B = 2 f 2 k 0 α 2 Ω 2 .
I ( x , z , t ) = A 5 2 = κ e x 2 s 2 2 e Ω 2 4 ( 1 + χ ) ( t + γ x ) 2 2 .
τ = τ 0 [ 1 + ( β Ω 2 ) 2 z R z M ] 1 2
s 3 = s 3 ( 0 ) [ 1 + ( β Ω 2 ) 2 z R z M ] 1 2

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