Abstract

Signal generation in three-photon microscopy is proportional to the inverse-squared of the pulse width. Group velocity dispersion is anomalous for water as well as many glasses near the 1,700 nm excitation window, which makes dispersion compensation using glass prism pairs impractical. We show that the high normal dispersion of a silicon wafer can be conveniently used to compensate the dispersion of a 1,700 nm excitation three-photon microscope. We achieved over a factor of two reduction in pulse width at the sample, which corresponded to over a 4x increase in the generated three-photon signal. This signal increase was demonstrated during in vivo experiments near the surface of the mouse brain as well as 900 μm below the surface.

© 2015 Optical Society of America

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References

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    [Crossref]
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    [Crossref] [PubMed]
  3. M. Müller, J. Squier, R. Wolleschensky, U. Simon, and G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
    [Crossref] [PubMed]
  4. P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
    [Crossref]
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    [Crossref] [PubMed]
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2014 (1)

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20(2), 6800311 (2014).

2013 (1)

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

2012 (2)

2011 (1)

D. Entenberg, J. Wyckoff, B. Gligorijevic, E. T. Roussos, V. V. Verkhusha, J. W. Pollard, and J. Condeelis, “Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging,” Nat. Protoc. 6(10), 1500–1520 (2011).
[Crossref] [PubMed]

2009 (2)

2008 (1)

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

2001 (1)

I. Walmsley, L. Waxer, and C. Dorrer, “The role of dispersion in ultrafast optics,” Rev. Sci. Instrum. 72(1), 1–29 (2001).
[Crossref]

1998 (2)

M. Müller, J. Squier, R. Wolleschensky, U. Simon, and G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[Crossref] [PubMed]

R. E. Sherriff, “Analytic expressions for group-delay dispersion and cubic dispersion in arbitrary prism sequences,” J. Opt. Soc. Am. B 15(3), 1224–1230 (1998).
[Crossref]

1984 (1)

1968 (1)

H. C. Agrawal, J. M. Davis, and W. A. Himwich, “Developmental changes in mouse brain: weight, water content and free amino acids,” J. Neurochem. 15(9), 917–923 (1968).
[Crossref] [PubMed]

1965 (1)

1957 (1)

Agrawal, H. C.

H. C. Agrawal, J. M. Davis, and W. A. Himwich, “Developmental changes in mouse brain: weight, water content and free amino acids,” J. Neurochem. 15(9), 917–923 (1968).
[Crossref] [PubMed]

Andegeko, Y.

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Arkhipov, S. N.

Brakenhoff, G. J.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, and G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[Crossref] [PubMed]

Charan, K.

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20(2), 6800311 (2014).

Chong, A.

Clark, C. G.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Condeelis, J.

D. Entenberg, J. Wyckoff, B. Gligorijevic, E. T. Roussos, V. V. Verkhusha, J. W. Pollard, and J. Condeelis, “Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging,” Nat. Protoc. 6(10), 1500–1520 (2011).
[Crossref] [PubMed]

Dantus, M.

B. Nie, I. Saytashev, A. Chong, H. Liu, S. N. Arkhipov, F. W. Wise, and M. Dantus, “Multimodal microscopy with sub-30 fs Yb fiber laser oscillator,” Biomed. Opt. Express 3(7), 1750–1756 (2012).
[Crossref] [PubMed]

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Davis, J. M.

H. C. Agrawal, J. M. Davis, and W. A. Himwich, “Developmental changes in mouse brain: weight, water content and free amino acids,” J. Neurochem. 15(9), 917–923 (1968).
[Crossref] [PubMed]

Dorrer, C.

I. Walmsley, L. Waxer, and C. Dorrer, “The role of dispersion in ultrafast optics,” Rev. Sci. Instrum. 72(1), 1–29 (2001).
[Crossref]

Entenberg, D.

D. Entenberg, J. Wyckoff, B. Gligorijevic, E. T. Roussos, V. V. Verkhusha, J. W. Pollard, and J. Condeelis, “Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging,” Nat. Protoc. 6(10), 1500–1520 (2011).
[Crossref] [PubMed]

Erny, C.

Fork, R. L.

Gallmann, L.

Giessen, H.

Gissibl, T.

Gligorijevic, B.

D. Entenberg, J. Wyckoff, B. Gligorijevic, E. T. Roussos, V. V. Verkhusha, J. W. Pollard, and J. Condeelis, “Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging,” Nat. Protoc. 6(10), 1500–1520 (2011).
[Crossref] [PubMed]

Gordon, J. P.

Haag, M.

Heese, C.

Himwich, W. A.

H. C. Agrawal, J. M. Davis, and W. A. Himwich, “Developmental changes in mouse brain: weight, water content and free amino acids,” J. Neurochem. 15(9), 917–923 (1968).
[Crossref] [PubMed]

Horton, N. G.

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20(2), 6800311 (2014).

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Huber, R.

Kedenburg, S.

Keller, U.

Kobat, D.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Krauss, G.

Leitenstorfer, A.

Liu, H.

Lozovoy, V. V.

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Malitson, I. H.

Martinez, O. E.

Müller, M.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, and G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[Crossref] [PubMed]

Nie, B.

Pollard, J. W.

D. Entenberg, J. Wyckoff, B. Gligorijevic, E. T. Roussos, V. V. Verkhusha, J. W. Pollard, and J. Condeelis, “Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging,” Nat. Protoc. 6(10), 1500–1520 (2011).
[Crossref] [PubMed]

Roussos, E. T.

D. Entenberg, J. Wyckoff, B. Gligorijevic, E. T. Roussos, V. V. Verkhusha, J. W. Pollard, and J. Condeelis, “Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging,” Nat. Protoc. 6(10), 1500–1520 (2011).
[Crossref] [PubMed]

Salzberg, C. D.

Saytashev, I.

Schaffer, C. B.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Scheu, R.

Sell, A.

Sherriff, R. E.

Simon, U.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, and G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[Crossref] [PubMed]

Squier, J.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, and G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[Crossref] [PubMed]

Verkhusha, V. V.

D. Entenberg, J. Wyckoff, B. Gligorijevic, E. T. Roussos, V. V. Verkhusha, J. W. Pollard, and J. Condeelis, “Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging,” Nat. Protoc. 6(10), 1500–1520 (2011).
[Crossref] [PubMed]

Vieweg, M.

Villa, J. J.

Walmsley, I.

I. Walmsley, L. Waxer, and C. Dorrer, “The role of dispersion in ultrafast optics,” Rev. Sci. Instrum. 72(1), 1–29 (2001).
[Crossref]

Wang, K.

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20(2), 6800311 (2014).

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Waxer, L.

I. Walmsley, L. Waxer, and C. Dorrer, “The role of dispersion in ultrafast optics,” Rev. Sci. Instrum. 72(1), 1–29 (2001).
[Crossref]

Weisel, L. R.

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Wise, F. W.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

B. Nie, I. Saytashev, A. Chong, H. Liu, S. N. Arkhipov, F. W. Wise, and M. Dantus, “Multimodal microscopy with sub-30 fs Yb fiber laser oscillator,” Biomed. Opt. Express 3(7), 1750–1756 (2012).
[Crossref] [PubMed]

Wolleschensky, R.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, and G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[Crossref] [PubMed]

Wyckoff, J.

D. Entenberg, J. Wyckoff, B. Gligorijevic, E. T. Roussos, V. V. Verkhusha, J. W. Pollard, and J. Condeelis, “Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging,” Nat. Protoc. 6(10), 1500–1520 (2011).
[Crossref] [PubMed]

Xi, P.

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Xu, C.

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20(2), 6800311 (2014).

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

IEEE J. Sel. Top. Quantum Electron. (1)

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20(2), 6800311 (2014).

J. Microsc. (1)

M. Müller, J. Squier, R. Wolleschensky, U. Simon, and G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[Crossref] [PubMed]

J. Neurochem. (1)

H. C. Agrawal, J. M. Davis, and W. A. Himwich, “Developmental changes in mouse brain: weight, water content and free amino acids,” J. Neurochem. 15(9), 917–923 (1968).
[Crossref] [PubMed]

J. Opt. Soc. Am. (2)

J. Opt. Soc. Am. B (1)

Nat. Photonics (1)

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Nat. Protoc. (1)

D. Entenberg, J. Wyckoff, B. Gligorijevic, E. T. Roussos, V. V. Verkhusha, J. W. Pollard, and J. Condeelis, “Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging,” Nat. Protoc. 6(10), 1500–1520 (2011).
[Crossref] [PubMed]

Opt. Commun. (1)

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Opt. Express (2)

Opt. Lett. (1)

Opt. Mater. Express (1)

Rev. Sci. Instrum. (1)

I. Walmsley, L. Waxer, and C. Dorrer, “The role of dispersion in ultrafast optics,” Rev. Sci. Instrum. 72(1), 1–29 (2001).
[Crossref]

Other (3)

C. Xu and W. W. Webb, “Multiphoton excitation of molecular fluorophores and nonlinear laser microscopy,” in Topics in Fluorescence Spectroscopy, J. R. Lakowicz, ed. (Plenum, 1997), Vol. 5, pp. 471–540.

G. P. Agrawal, Nonlinear Fiber Optics (Academic, 2001).

Schott optical glass data sheets, http://www.schott.com/advanced_optics/us/abbe_datasheets/schott_datasheet_all_us.pdf

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Figures (5)

Fig. 1
Fig. 1 Material GVD vs. wavelength near 1,700 nm for common optical materials. The vertical line at 1.7 μm denotes our excitation wavelength. Note the different scales used for Si and H2O.
Fig. 2
Fig. 2 Experimental setup. The PC Rod shifts the wavelength of the laser from 1.55 um to 1.7 μm through soliton self-frequency shift [7]. Dispersive elements (H2O, D2O, microscope optics, and Si wafers) were independently added to the beam path.
Fig. 3
Fig. 3 Spectrum of pulse and second-order interferometric autocorrelations after various optical elements. (a) Pulse spectrum after the PC rod. (b)-(h) Second-order interferometric autocorrelations: (b) immediately after the collimating lens following the PC rod, (c) after 2 mm H2O, (d) after 1 cm D2O, (e) after microscope and 1 mm H2O, (f) after microscope, 1 mm H2O, and 3 mm Si, (g) after microscope and 2 mm H2O, (h) after microscope, 2 mm H2O, and 3 mm Si. The intensity FWHM of the pulse, assuming a sech2 pulse, is also displayed in each panel.
Fig. 4
Fig. 4 In vivo three-photon microscopy of Texas Red-labeled blood vessel within an intact mouse brain. (a) and (c) were recorded without the Si wafer, while (b) and (d) were recorded after insertion of the 3 mm wafer at the Brewster angle. The brightness of the images reflects the signal level. Scale bar, 50 μm.
Fig. 5
Fig. 5 TOD of common optical materials.

Tables (1)

Tables Icon

Table 1 Calculated GVD and TOD of various materials at 1,700 nm. The bold values are calculations at 1,600 nm

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