Abstract

We investigate the temporal information of nonlinear donor fluorescence in the FRET frustration microscopy. The arrival time of the donor fluorescence varies with the distribution of the excitation laser. The differences of the arrival times between different positions in the excitation spot can be further enhanced in the case of adding a depletion beam upon the FRET probes. The spatial information is encoded in the temporal dynamics of the fluorescent photons from donor molecules and time-gating in detection can be used to increase the spatial resolution.

© 2015 Optical Society of America

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References

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  1. S. W. Hell, “Far-field optical nanoscopy,” Science 316(5828), 1153–1158 (2007).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref]
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2013 (2)

G. Vicidomini, A. Schönle, H. Ta, K. Y. Han, G. Moneron, C. Eggeling, and S. W. Hell, “STED Nanoscopy with Time-Gated Detection: Theoretical and Experimental Aspects,” PLoS ONE 8(1), e54421 (2013).
[Crossref] [PubMed]

F. Xu, L. Wei, Z. Chen, and W. Min, “Frustrated FRET for high-contrast high-resolution two-photon imaging,” Opt. Express 21(12), 14097–14108 (2013).
[Crossref] [PubMed]

2012 (1)

I. V. Gopich and A. Szabo, “Theory of the energy transfer efficiency and fluorescence lifetime distribution in single-molecule FRET,” Proc. Natl. Acad. Sci. U.S.A. 109(20), 7747–7752 (2012).
[Crossref] [PubMed]

2011 (3)

C. G. Galbraith and J. A. Galbraith, “Super-resolution microscopy at a glance,” J. Cell Sci. 124(10), 1607–1611 (2011).
[Crossref] [PubMed]

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

J. R. Moffitt, C. Osseforth, and J. Michaelis, “Time-gating improves the spatial resolution of STED microscopy,” Opt. Express 19(5), 4242–4254 (2011).
[Crossref] [PubMed]

2010 (2)

2009 (1)

2008 (1)

M. Beutler, K. Makrogianneli, R. J. Vermeij, M. Keppler, T. Ng, T. M. Jovin, and R. Heintzmann, “satFRET: estimation of Förster resonance energy transfer by acceptor saturation,” Eur. Biophys. J. 38(1), 69–82 (2008).
[Crossref] [PubMed]

2007 (1)

S. W. Hell, “Far-field optical nanoscopy,” Science 316(5828), 1153–1158 (2007).
[Crossref] [PubMed]

1999 (1)

A. Schonle, P. E. Hanninen, and S. W. Hell, “Nonlinear fluorescence through intermolecular energy transfer and resolution increase in fluorescence microscopy,” Ann. Phys. 8(2), 115–133 (1999).
[Crossref]

1996 (1)

P. E. Hanninen, L. Lehtela, and S. W. Hell, “Two- and multiphoton excitation of conjugate-dyes using a continuous wave laser,” Opt. Commun. 130(1–3), 29–33 (1996).
[Crossref]

1948 (1)

T. Förster, “Zwischenmolekulare Energiewanderung und Fluoreszenz,” Ann. Phys. 437(1–2), 55–75 (1948).
[Crossref]

Beutler, M.

M. Beutler, K. Makrogianneli, R. J. Vermeij, M. Keppler, T. Ng, T. M. Jovin, and R. Heintzmann, “satFRET: estimation of Förster resonance energy transfer by acceptor saturation,” Eur. Biophys. J. 38(1), 69–82 (2008).
[Crossref] [PubMed]

Chen, J.

Chen, Z.

Cheng, Y.

Cordes, T.

J. Vogelsang, T. Cordes, C. Forthmann, C. Steinhauer, and P. Tinnefeld, “Intrinsically Resolution Enhancing Probes for Confocal Microscopy,” Nano Lett. 10(2), 672–679 (2010).
[Crossref] [PubMed]

Deng, S.

Eggeling, C.

G. Vicidomini, A. Schönle, H. Ta, K. Y. Han, G. Moneron, C. Eggeling, and S. W. Hell, “STED Nanoscopy with Time-Gated Detection: Theoretical and Experimental Aspects,” PLoS ONE 8(1), e54421 (2013).
[Crossref] [PubMed]

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

Engelhardt, J.

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

Fan, C.

Förster, T.

T. Förster, “Zwischenmolekulare Energiewanderung und Fluoreszenz,” Ann. Phys. 437(1–2), 55–75 (1948).
[Crossref]

Forthmann, C.

J. Vogelsang, T. Cordes, C. Forthmann, C. Steinhauer, and P. Tinnefeld, “Intrinsically Resolution Enhancing Probes for Confocal Microscopy,” Nano Lett. 10(2), 672–679 (2010).
[Crossref] [PubMed]

Galbraith, C. G.

C. G. Galbraith and J. A. Galbraith, “Super-resolution microscopy at a glance,” J. Cell Sci. 124(10), 1607–1611 (2011).
[Crossref] [PubMed]

Galbraith, J. A.

C. G. Galbraith and J. A. Galbraith, “Super-resolution microscopy at a glance,” J. Cell Sci. 124(10), 1607–1611 (2011).
[Crossref] [PubMed]

Gopich, I. V.

I. V. Gopich and A. Szabo, “Theory of the energy transfer efficiency and fluorescence lifetime distribution in single-molecule FRET,” Proc. Natl. Acad. Sci. U.S.A. 109(20), 7747–7752 (2012).
[Crossref] [PubMed]

Han, K. Y.

G. Vicidomini, A. Schönle, H. Ta, K. Y. Han, G. Moneron, C. Eggeling, and S. W. Hell, “STED Nanoscopy with Time-Gated Detection: Theoretical and Experimental Aspects,” PLoS ONE 8(1), e54421 (2013).
[Crossref] [PubMed]

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

Hanninen, P. E.

A. Schonle, P. E. Hanninen, and S. W. Hell, “Nonlinear fluorescence through intermolecular energy transfer and resolution increase in fluorescence microscopy,” Ann. Phys. 8(2), 115–133 (1999).
[Crossref]

P. E. Hanninen, L. Lehtela, and S. W. Hell, “Two- and multiphoton excitation of conjugate-dyes using a continuous wave laser,” Opt. Commun. 130(1–3), 29–33 (1996).
[Crossref]

Heintzmann, R.

M. Beutler, K. Makrogianneli, R. J. Vermeij, M. Keppler, T. Ng, T. M. Jovin, and R. Heintzmann, “satFRET: estimation of Förster resonance energy transfer by acceptor saturation,” Eur. Biophys. J. 38(1), 69–82 (2008).
[Crossref] [PubMed]

Hell, S. W.

G. Vicidomini, A. Schönle, H. Ta, K. Y. Han, G. Moneron, C. Eggeling, and S. W. Hell, “STED Nanoscopy with Time-Gated Detection: Theoretical and Experimental Aspects,” PLoS ONE 8(1), e54421 (2013).
[Crossref] [PubMed]

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

S. W. Hell, “Far-field optical nanoscopy,” Science 316(5828), 1153–1158 (2007).
[Crossref] [PubMed]

A. Schonle, P. E. Hanninen, and S. W. Hell, “Nonlinear fluorescence through intermolecular energy transfer and resolution increase in fluorescence microscopy,” Ann. Phys. 8(2), 115–133 (1999).
[Crossref]

P. E. Hanninen, L. Lehtela, and S. W. Hell, “Two- and multiphoton excitation of conjugate-dyes using a continuous wave laser,” Opt. Commun. 130(1–3), 29–33 (1996).
[Crossref]

Huang, Q.

Jovin, T. M.

M. Beutler, K. Makrogianneli, R. J. Vermeij, M. Keppler, T. Ng, T. M. Jovin, and R. Heintzmann, “satFRET: estimation of Förster resonance energy transfer by acceptor saturation,” Eur. Biophys. J. 38(1), 69–82 (2008).
[Crossref] [PubMed]

Keppler, M.

M. Beutler, K. Makrogianneli, R. J. Vermeij, M. Keppler, T. Ng, T. M. Jovin, and R. Heintzmann, “satFRET: estimation of Förster resonance energy transfer by acceptor saturation,” Eur. Biophys. J. 38(1), 69–82 (2008).
[Crossref] [PubMed]

Lehtela, L.

P. E. Hanninen, L. Lehtela, and S. W. Hell, “Two- and multiphoton excitation of conjugate-dyes using a continuous wave laser,” Opt. Commun. 130(1–3), 29–33 (1996).
[Crossref]

Makrogianneli, K.

M. Beutler, K. Makrogianneli, R. J. Vermeij, M. Keppler, T. Ng, T. M. Jovin, and R. Heintzmann, “satFRET: estimation of Förster resonance energy transfer by acceptor saturation,” Eur. Biophys. J. 38(1), 69–82 (2008).
[Crossref] [PubMed]

Michaelis, J.

Min, W.

Moffitt, J. R.

Moneron, G.

G. Vicidomini, A. Schönle, H. Ta, K. Y. Han, G. Moneron, C. Eggeling, and S. W. Hell, “STED Nanoscopy with Time-Gated Detection: Theoretical and Experimental Aspects,” PLoS ONE 8(1), e54421 (2013).
[Crossref] [PubMed]

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

Ng, T.

M. Beutler, K. Makrogianneli, R. J. Vermeij, M. Keppler, T. Ng, T. M. Jovin, and R. Heintzmann, “satFRET: estimation of Förster resonance energy transfer by acceptor saturation,” Eur. Biophys. J. 38(1), 69–82 (2008).
[Crossref] [PubMed]

Osseforth, C.

Reuss, M.

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

Schonle, A.

A. Schonle, P. E. Hanninen, and S. W. Hell, “Nonlinear fluorescence through intermolecular energy transfer and resolution increase in fluorescence microscopy,” Ann. Phys. 8(2), 115–133 (1999).
[Crossref]

Schönle, A.

G. Vicidomini, A. Schönle, H. Ta, K. Y. Han, G. Moneron, C. Eggeling, and S. W. Hell, “STED Nanoscopy with Time-Gated Detection: Theoretical and Experimental Aspects,” PLoS ONE 8(1), e54421 (2013).
[Crossref] [PubMed]

Steinhauer, C.

J. Vogelsang, T. Cordes, C. Forthmann, C. Steinhauer, and P. Tinnefeld, “Intrinsically Resolution Enhancing Probes for Confocal Microscopy,” Nano Lett. 10(2), 672–679 (2010).
[Crossref] [PubMed]

Szabo, A.

I. V. Gopich and A. Szabo, “Theory of the energy transfer efficiency and fluorescence lifetime distribution in single-molecule FRET,” Proc. Natl. Acad. Sci. U.S.A. 109(20), 7747–7752 (2012).
[Crossref] [PubMed]

Ta, H.

G. Vicidomini, A. Schönle, H. Ta, K. Y. Han, G. Moneron, C. Eggeling, and S. W. Hell, “STED Nanoscopy with Time-Gated Detection: Theoretical and Experimental Aspects,” PLoS ONE 8(1), e54421 (2013).
[Crossref] [PubMed]

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

Tinnefeld, P.

J. Vogelsang, T. Cordes, C. Forthmann, C. Steinhauer, and P. Tinnefeld, “Intrinsically Resolution Enhancing Probes for Confocal Microscopy,” Nano Lett. 10(2), 672–679 (2010).
[Crossref] [PubMed]

Vermeij, R. J.

M. Beutler, K. Makrogianneli, R. J. Vermeij, M. Keppler, T. Ng, T. M. Jovin, and R. Heintzmann, “satFRET: estimation of Förster resonance energy transfer by acceptor saturation,” Eur. Biophys. J. 38(1), 69–82 (2008).
[Crossref] [PubMed]

Vicidomini, G.

G. Vicidomini, A. Schönle, H. Ta, K. Y. Han, G. Moneron, C. Eggeling, and S. W. Hell, “STED Nanoscopy with Time-Gated Detection: Theoretical and Experimental Aspects,” PLoS ONE 8(1), e54421 (2013).
[Crossref] [PubMed]

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

Vogelsang, J.

J. Vogelsang, T. Cordes, C. Forthmann, C. Steinhauer, and P. Tinnefeld, “Intrinsically Resolution Enhancing Probes for Confocal Microscopy,” Nano Lett. 10(2), 672–679 (2010).
[Crossref] [PubMed]

Wei, L.

Westphal, V.

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

Xu, F.

Ann. Phys. (2)

T. Förster, “Zwischenmolekulare Energiewanderung und Fluoreszenz,” Ann. Phys. 437(1–2), 55–75 (1948).
[Crossref]

A. Schonle, P. E. Hanninen, and S. W. Hell, “Nonlinear fluorescence through intermolecular energy transfer and resolution increase in fluorescence microscopy,” Ann. Phys. 8(2), 115–133 (1999).
[Crossref]

Eur. Biophys. J. (1)

M. Beutler, K. Makrogianneli, R. J. Vermeij, M. Keppler, T. Ng, T. M. Jovin, and R. Heintzmann, “satFRET: estimation of Förster resonance energy transfer by acceptor saturation,” Eur. Biophys. J. 38(1), 69–82 (2008).
[Crossref] [PubMed]

J. Cell Sci. (1)

C. G. Galbraith and J. A. Galbraith, “Super-resolution microscopy at a glance,” J. Cell Sci. 124(10), 1607–1611 (2011).
[Crossref] [PubMed]

Nano Lett. (1)

J. Vogelsang, T. Cordes, C. Forthmann, C. Steinhauer, and P. Tinnefeld, “Intrinsically Resolution Enhancing Probes for Confocal Microscopy,” Nano Lett. 10(2), 672–679 (2010).
[Crossref] [PubMed]

Nat. Methods (1)

G. Vicidomini, G. Moneron, K. Y. Han, V. Westphal, H. Ta, M. Reuss, J. Engelhardt, C. Eggeling, and S. W. Hell, “Sharper low-power STED nanoscopy by time gating,” Nat. Methods 8(7), 571–573 (2011).
[Crossref] [PubMed]

Opt. Commun. (1)

P. E. Hanninen, L. Lehtela, and S. W. Hell, “Two- and multiphoton excitation of conjugate-dyes using a continuous wave laser,” Opt. Commun. 130(1–3), 29–33 (1996).
[Crossref]

Opt. Express (2)

Opt. Lett. (2)

PLoS ONE (1)

G. Vicidomini, A. Schönle, H. Ta, K. Y. Han, G. Moneron, C. Eggeling, and S. W. Hell, “STED Nanoscopy with Time-Gated Detection: Theoretical and Experimental Aspects,” PLoS ONE 8(1), e54421 (2013).
[Crossref] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

I. V. Gopich and A. Szabo, “Theory of the energy transfer efficiency and fluorescence lifetime distribution in single-molecule FRET,” Proc. Natl. Acad. Sci. U.S.A. 109(20), 7747–7752 (2012).
[Crossref] [PubMed]

Science (1)

S. W. Hell, “Far-field optical nanoscopy,” Science 316(5828), 1153–1158 (2007).
[Crossref] [PubMed]

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Figures (4)

Fig. 1
Fig. 1 Temporal information in saturated FRET microscopy. (a) The normalized intensity distribution of excitation beam. (b) The decay rates of donor spontaneous emission from the donor molecules at the locations denoted by the circles in (a). The fluorescence is normalized by the total number of fluorescence ( F inf = F ( t = ) ) . The x axis unit in (a) is the excitation wavelength λ = 488 n m .
Fig. 2
Fig. 2 Improving spatial resolution by time-gating. (a) Timing diagram for satFRET microscopy with time-gated detection. The spontaneous emission is collected during a time window (green) starting tg after the completion of excitation pulse (blue) and lasting until the beginning of the next excitation pulse. Normalized transverse PSF (b-d) and the longitudinal PSF (e-g) for conventional microscopy (b, e), satFRET microscopy (c, f) and time-gated satFRET microscopy(d, g). The comparison between the PSF profiles along the X (h) and Z axial (i) for satFRET microscopy with (green line) and without (red line) time-gating. (j) The N-fold resolution improvement of time-gated satFRET microscopy compared to the conventional microscope as the function of tg. The excitation wavelength λ = 488 n m is used.
Fig. 3
Fig. 3 Temporal information in FRET assisted STED microscopy. The fluorescence as a function of time (b) emitted from the donor molecules at the locations denoted by the circles in (a). The fluorescence is normalized by the total number of fluorescence ( F inf = F ( t = ) ) . The x axis unit in (a) is the excitation wavelength λ = 488 n m .
Fig. 4
Fig. 4 Improving spatial resolution of FRET assisted STED microscopy with time-gating. (a) Timing diagram for time-gating. The normalized PSFs on the focal plane for FRET associated STED microscopy without (b) and with the time-gating (c). (d) The intensity profiles with different gating-time tg (0, purple; 0.5τ, blue; τ, red; 2τ, black). (e) The N-fold improvement of resolution over that of a conventional microscope as a function of the strength of the STED beam with different gating-time (0, purple; 0.5τ, blue; τ, red; 2τ, black). (f) The N-fold improvement of resolution over that of a conventional microscope as a function of tg with different STED beam power ( ξ = 40 , purple; ξ = 20 , blue; ξ = 10 , red). The excitation wavelength λ = 488 n m is used.

Equations (9)

Equations on this page are rendered with MathJax. Learn more.

N d a t = K f D N D a + K f A N d A K e x c N d a N D a t = K e x c N d a + K f A N D A ( K f D + K T ) N D a N D A t = K e x c N d A ( K f A + K f D ) N D A N d A t = K f D N D A + K T N D a ( K f A + K e x c ) N d A
N D a 0 = 1 1 + K T K f A + K f D + K T K e x c K T ( K e x c + K f A + K f D ) N D A 0 = N D a 0 K T K e x c K f A ( K e x c + K f A + K f D ) N D 0 = N D a 0 + N D A 0
N D a ( r , t ) t = ( K f D + K T ) N D a ( r , t ) + K f A N D A ( r , t ) N D A ( r , t ) t = ( K f D + K f A ) N D A ( r , t )
F D a ( r , t ) t = K f D N D a ( r , t ) F D A ( r , t ) t = K f D N D A ( r , t )
F D ( r , t ) = F D A + F D a = N D 0 ( r ) [ N D A 0 ( r ) N D 0 ( r ) K f D K f D + K f A ( 1 exp ( t ( K f D + K f A ) ) ) + K f D K f D + K T ( 1 N D A 0 ( r ) N D 0 ( r ) K T K T K f A ) ( 1 exp ( t ( K f D + K T ) ) ) + N D A 0 ( r ) N D 0 ( r ) K f A K f D + K f A K f D K T K f A ( 1 exp ( t ( K f D + K f A ) ) ) ]
F ( r ) = F D ( r , ) F D ( r , t g ) = N D 0 ( r ) [ N D A 0 ( r ) N D 0 ( r ) K f D K f D + K f A exp ( t g ( K f D + K f A ) ) + K f D K f D + K T ( 1 N D A 0 ( r ) N D 0 ( r ) K T K T K f A ) exp ( t g ( K f D + K T ) ) + N D A 0 ( r ) N D 0 ( r ) K f A K f D + K f A K f D K T K f A exp ( t g ( K f D + K f A ) ) ]
N' D 0 ( r ) = N ' D a 0 ( r ) + N ' D A 0 ( r ) = 1 1 + K T K f A + K s + K f D + K T K e x c ( K f A + K s ) K e x c K T K e x c ( K f A + K s ) ( K e x c + K f A + K s + K f D ) [ 1 + K T K e x c ( K f A + K s ) ( K e x c + K f A + K s + K f D ) ]
F ' D ( r , t ) = N ' D 0 ( r ) [ N ' D A 0 ( r ) N ' D 0 ( r ) K f D K f D + K f A + K s ( 1 exp ( t ( K f D + K f A + K s ) ) ) + K f D K f D + K T ( 1 N ' D A 0 ( r ) N ' D 0 ( r ) K T K T K f A K s ) ( 1 exp ( t ( K f D + K T ) ) ) + N ' D A 0 ( r ) N ' D 0 ( r ) K f A + K s K f D + K f A + K s K f D K T K f A K s ( 1 exp ( t ( K f D + K f A + K s ) ) ) ]
F ' ( r ) = F ' D ( r , ) F ' D ( r , t g ) = N ' D 0 ( r ) [ N ' D A 0 ( r ) N ' D 0 ( r ) K f D K f D + K f A + K s exp ( t g ( K f D + K f A + K s ) ) + K f D K f D + K T ( 1 N ' D A 0 ( r ) N ' D 0 ( r ) K T K T K f A K s ) exp ( t g ( K f D + K T ) ) + N ' D A 0 ( r ) N ' D 0 ( r ) K f A + K s K f D + K f A + K s K f D K T K f A K s exp ( t g ( K f D + K f A + K s ) ) ]

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