Abstract

We present a new high-speed lifetime measurement scheme of analog mean-delay (AMD) method which is suitable for studying dynamical time-resolved spectroscopy and high-speed fluorescence lifetime imaging microscopy (FLIM). In our lifetime measurement method, the time-domain intensity signal of a fluorescence decay is acquired as an analog waveform. And the lifetime information is extracted from the mean temporal delay of the acquired signal. Since this method does not rely on the single-photon counting technique, the signals of multiple fluorescence photons can be acquired simultaneously. The measurement speed can be increased easily by raising the fluorescence intensity without a photon-rate limit. We have investigated various characteristics of our method in lifetime accuracy and precision as well as measurement speed. It has been found that our method can provide excellent measurement performances in various aspects. We have demonstrated a high-speed measurement with a high photon detection rate of ~108 photons per second with a nearly shot noise-limited photon economy. A fluorescence lifetime of 3.2 ns was accurately determined with a standard deviation of 3% from the data acquired within 17.8 μs at a rate of 56,300 lifetime determinations per second.

© 2009 Optical Society of America

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  1. H. C. Gerristen, A. Draaijer, D. J. van den Heuvel, and A. V. Agronskaia, "Fluorescence lifetime imaging in scanning microscopy" in Handbook of Biological Confocal Microscopy, 3rd Ed., J. B. Pawley, ed. (Springer, New York, 2006).
  2. D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
    [CrossRef] [PubMed]
  3. Klaus Suhling, Paul M. W. French, and D. Phillips, "Time-resolved fluorescence microscopy," Photochem. Photobiol. Sci. 4, 13-22 (2005).
    [CrossRef]
  4. P. Herman, H.-J. Lin, and J. R. Lakowicz, "Lifetime-based imaging" in Biomedical Photonics Handbook, T. Vo-Dinh, ed. (CRC Press, Boca Raton, 2003).
    [CrossRef]
  5. E. A. Jares-Erijman and T. M. Jovin, "FRET imaging," Nat. Biotechnol. 21, 1387-1395 (2003).
    [CrossRef] [PubMed]
  6. D. K. Nair, M. Jose, T. Kuner, W. Zuschratter, and R. Hartig, "FRET-FLIM at nanometer spectral resolution from living cells," Opt. Express 14, 12217-12229 (2006), http://www.opticsinfobase.org/abstract.cfm?URI=oe-14-25-12217.
    [CrossRef] [PubMed]
  7. W. Zhong, M. Wu, C. Chang, K. A. Merrick, S. D. Merajver, and M. Mycek, "Picosecond-resolution fluorescence lifetime imaging microscopy: a useful tool for sensing molecular interactions in vivo via FRET," Opt. Express 15, 18220-18235 (2007), http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-15-26-18220.
    [CrossRef] [PubMed]
  8. D. M. Grant, J. McGinty, E. J. McGhee, T. D. Bunney, D. M. Owen, C. B. Talbot, W. Zhang, S. Kumar, I. Munro, P. M. Lanigan, G. T. Kennedy, C. Dunsby, A. I. Magee, P. Courtney, M. Katan, M. A. A. Neil, and P. M. W. French, "High speed optically sectioned fluorescence lifetime imaging permits study of live cell signaling events," Opt. Express 15, 15656-15673 (2007), http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-15-24-15656.
    [CrossRef] [PubMed]
  9. K. Cralsson and J. Philip, "Theoretical investigation of the signal-to-noise ratio for different fluorescence lifetime imaging techniques," Proc. SPIE 4622, 70-78 (2002).
  10. H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, "Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution," J. Microsc. 206, 218-224 (2002).
    [CrossRef] [PubMed]
  11. T. H. Chia, A. Williamson, D. D. Spencer, and M. J. Levene, "Multiphoton fluorescence lifetime imaging of intrinsic fluorescence in human and rat brain tissue reveals spatially distinct NADH binding," Opt. Express 16, 4237-4249 (2008), http://www.opticsinfobase.org/abstract.cfm?URI=oe-16-6-4237.
    [CrossRef] [PubMed]
  12. W. Becker, A. Bergmann, M. A. Hink, K. König, K. Benndorf, and C. Biskup, "Fluorescence lifetime imaging by time-correlated single-photon counting," Microsc. Res. Tech. 63, 58-66 (2003).
    [CrossRef] [PubMed]
  13. W. Becker and A. Bergmann, "Timing stability of TCSPC experiments," Proc. SPIE 6372, 637209 (2006).
    [CrossRef]
  14. A. Schönle, M. Glatz, and S. W. Hell, "Four-dimensional multiphoton microscopy with time-correlated single-photon counting," Appl. Opt. 39, 6306-6311 (2000), http://www.opticsinfobase.org/ao/abstract.cfm?URI=ao-39-34-6306.
    [CrossRef]
  15. D. McLoskey, D. J. S. Birch, A. Sanderson, K. Suhling, E. Welch, and P. J. Hicks, "Multiplexed single-photon counting. I. A time-correlated fluorescence lifetime camera," Rev. Sci. Instrum. 67, 2228-2237 (1996).
    [CrossRef]
  16. R. V. Krishnan, H. Saitoh, H. Terada, V. E. Centonze, and B. Herman, "Development of a multiphoton fluorescence lifetime imaging microscopy system using a streak camera," Rev. Sci. Instrum. 74, 2714-2721 (2003).
    [CrossRef]
  17. C. J. de Grauw and H. C. Gerritsen, "Multiple time-gate module for fluorescence lifetime imaging," Appl. Spectrosc. 55, 670-678 (2001), http://www.opticsinfobase.org/as/abstract.cfm?URI=as-55-6-670.
    [CrossRef]
  18. E.-S. Kwak, T. J. Kang, and D. A. Vanden Bout, "Fluorescence lifetime imaging with near-field scanning optical microscopy," Anal. Chem. 73, 3257 -3262 (2001).
    [CrossRef] [PubMed]
  19. J. Requejo-Isidro, J. McGinty, I. Munro, D. S. Elson, N. P. Galletly, M. J. Lever, M. A. A. Neil, G. W. H. Stamp, P. M. W. French, P. A. Kellett, J. D. Hares, and A. K. L. Dymoke-Bradshaw, "High-speed wide-field time-gated endoscopic fluorescence-lifetime imaging," Opt. Lett. 29, 2249-2251 (2004), http://www.opticsinfobase.org/ol/abstract.cfm?URI=ol-29-19-2249.
    [CrossRef]
  20. A. Esposito, T. Oggier, H. Gerritsen, F. Lustenberger, and F. Wouters, "All-solid-state lock-in imaging for wide-field fluorescence lifetime sensing," Opt. Express 13, 9812-9821 (2005), http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-13-24-9812.
    [CrossRef] [PubMed]
  21. A. I. Zverev, Handbook of Filter Synthesis (John Wiley & Sons, Hoboken, 2005).
  22. ISS, Inc, "Lifetime data of selected fluorophores," http://www.iss.com/resources/fluorophores.html.
  23. H. Stark and J. W. Woods, Probability and Random Processes with Applications to Signal Processing, 3rd Ed., (Prentice-Hall, Upper Saddle River, 2002).
  24. S. Moon and D. Y. Kim, "Analog single-photon counter for high-speed scanning microscopy," Opt. Express 16, 13990-14003 (2008), http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-16-18-13990.
    [CrossRef] [PubMed]

2008 (2)

2007 (2)

2006 (2)

2005 (2)

2004 (2)

J. Requejo-Isidro, J. McGinty, I. Munro, D. S. Elson, N. P. Galletly, M. J. Lever, M. A. A. Neil, G. W. H. Stamp, P. M. W. French, P. A. Kellett, J. D. Hares, and A. K. L. Dymoke-Bradshaw, "High-speed wide-field time-gated endoscopic fluorescence-lifetime imaging," Opt. Lett. 29, 2249-2251 (2004), http://www.opticsinfobase.org/ol/abstract.cfm?URI=ol-29-19-2249.
[CrossRef]

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

2003 (3)

W. Becker, A. Bergmann, M. A. Hink, K. König, K. Benndorf, and C. Biskup, "Fluorescence lifetime imaging by time-correlated single-photon counting," Microsc. Res. Tech. 63, 58-66 (2003).
[CrossRef] [PubMed]

E. A. Jares-Erijman and T. M. Jovin, "FRET imaging," Nat. Biotechnol. 21, 1387-1395 (2003).
[CrossRef] [PubMed]

R. V. Krishnan, H. Saitoh, H. Terada, V. E. Centonze, and B. Herman, "Development of a multiphoton fluorescence lifetime imaging microscopy system using a streak camera," Rev. Sci. Instrum. 74, 2714-2721 (2003).
[CrossRef]

2002 (2)

K. Cralsson and J. Philip, "Theoretical investigation of the signal-to-noise ratio for different fluorescence lifetime imaging techniques," Proc. SPIE 4622, 70-78 (2002).

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, "Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution," J. Microsc. 206, 218-224 (2002).
[CrossRef] [PubMed]

2001 (2)

E.-S. Kwak, T. J. Kang, and D. A. Vanden Bout, "Fluorescence lifetime imaging with near-field scanning optical microscopy," Anal. Chem. 73, 3257 -3262 (2001).
[CrossRef] [PubMed]

C. J. de Grauw and H. C. Gerritsen, "Multiple time-gate module for fluorescence lifetime imaging," Appl. Spectrosc. 55, 670-678 (2001), http://www.opticsinfobase.org/as/abstract.cfm?URI=as-55-6-670.
[CrossRef]

2000 (1)

1996 (1)

D. McLoskey, D. J. S. Birch, A. Sanderson, K. Suhling, E. Welch, and P. J. Hicks, "Multiplexed single-photon counting. I. A time-correlated fluorescence lifetime camera," Rev. Sci. Instrum. 67, 2228-2237 (1996).
[CrossRef]

Agronskaia, A. V.

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, "Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution," J. Microsc. 206, 218-224 (2002).
[CrossRef] [PubMed]

Asselbergs, M. A. H.

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, "Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution," J. Microsc. 206, 218-224 (2002).
[CrossRef] [PubMed]

Becker, W.

W. Becker and A. Bergmann, "Timing stability of TCSPC experiments," Proc. SPIE 6372, 637209 (2006).
[CrossRef]

W. Becker, A. Bergmann, M. A. Hink, K. König, K. Benndorf, and C. Biskup, "Fluorescence lifetime imaging by time-correlated single-photon counting," Microsc. Res. Tech. 63, 58-66 (2003).
[CrossRef] [PubMed]

Benndorf, K.

W. Becker, A. Bergmann, M. A. Hink, K. König, K. Benndorf, and C. Biskup, "Fluorescence lifetime imaging by time-correlated single-photon counting," Microsc. Res. Tech. 63, 58-66 (2003).
[CrossRef] [PubMed]

Benninger, R.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Bergmann, A.

W. Becker and A. Bergmann, "Timing stability of TCSPC experiments," Proc. SPIE 6372, 637209 (2006).
[CrossRef]

W. Becker, A. Bergmann, M. A. Hink, K. König, K. Benndorf, and C. Biskup, "Fluorescence lifetime imaging by time-correlated single-photon counting," Microsc. Res. Tech. 63, 58-66 (2003).
[CrossRef] [PubMed]

Birch, D. J. S.

D. McLoskey, D. J. S. Birch, A. Sanderson, K. Suhling, E. Welch, and P. J. Hicks, "Multiplexed single-photon counting. I. A time-correlated fluorescence lifetime camera," Rev. Sci. Instrum. 67, 2228-2237 (1996).
[CrossRef]

Biskup, C.

W. Becker, A. Bergmann, M. A. Hink, K. König, K. Benndorf, and C. Biskup, "Fluorescence lifetime imaging by time-correlated single-photon counting," Microsc. Res. Tech. 63, 58-66 (2003).
[CrossRef] [PubMed]

Bunney, T. D.

Centonze, V. E.

R. V. Krishnan, H. Saitoh, H. Terada, V. E. Centonze, and B. Herman, "Development of a multiphoton fluorescence lifetime imaging microscopy system using a streak camera," Rev. Sci. Instrum. 74, 2714-2721 (2003).
[CrossRef]

Chang, C.

Chia, T. H.

Courtney, P.

Cralsson, K.

K. Cralsson and J. Philip, "Theoretical investigation of the signal-to-noise ratio for different fluorescence lifetime imaging techniques," Proc. SPIE 4622, 70-78 (2002).

Davis, D.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

de Grauw, C. J.

Dunsby, C.

Dymoke-Bradshaw, A. K. L.

Elson, D.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Elson, D. S.

Esposito, A.

French, P.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

French, P. M. W.

French, Paul M. W.

Klaus Suhling, Paul M. W. French, and D. Phillips, "Time-resolved fluorescence microscopy," Photochem. Photobiol. Sci. 4, 13-22 (2005).
[CrossRef]

Galletly, N. P.

Gerritsen, H.

Gerritsen, H. C.

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, "Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution," J. Microsc. 206, 218-224 (2002).
[CrossRef] [PubMed]

C. J. de Grauw and H. C. Gerritsen, "Multiple time-gate module for fluorescence lifetime imaging," Appl. Spectrosc. 55, 670-678 (2001), http://www.opticsinfobase.org/as/abstract.cfm?URI=as-55-6-670.
[CrossRef]

Glatz, M.

Grant, D. M.

Hares, J. D.

Hartig, R.

Hell, S. W.

Herman, B.

R. V. Krishnan, H. Saitoh, H. Terada, V. E. Centonze, and B. Herman, "Development of a multiphoton fluorescence lifetime imaging microscopy system using a streak camera," Rev. Sci. Instrum. 74, 2714-2721 (2003).
[CrossRef]

Hicks, P. J.

D. McLoskey, D. J. S. Birch, A. Sanderson, K. Suhling, E. Welch, and P. J. Hicks, "Multiplexed single-photon counting. I. A time-correlated fluorescence lifetime camera," Rev. Sci. Instrum. 67, 2228-2237 (1996).
[CrossRef]

Hink, M. A.

W. Becker, A. Bergmann, M. A. Hink, K. König, K. Benndorf, and C. Biskup, "Fluorescence lifetime imaging by time-correlated single-photon counting," Microsc. Res. Tech. 63, 58-66 (2003).
[CrossRef] [PubMed]

Jares-Erijman, E. A.

E. A. Jares-Erijman and T. M. Jovin, "FRET imaging," Nat. Biotechnol. 21, 1387-1395 (2003).
[CrossRef] [PubMed]

Jose, M.

Jovin, T. M.

E. A. Jares-Erijman and T. M. Jovin, "FRET imaging," Nat. Biotechnol. 21, 1387-1395 (2003).
[CrossRef] [PubMed]

Kang, T. J.

E.-S. Kwak, T. J. Kang, and D. A. Vanden Bout, "Fluorescence lifetime imaging with near-field scanning optical microscopy," Anal. Chem. 73, 3257 -3262 (2001).
[CrossRef] [PubMed]

Katan, M.

Kellett, P. A.

Kennedy, G. T.

Kim, D. Y.

König, K.

W. Becker, A. Bergmann, M. A. Hink, K. König, K. Benndorf, and C. Biskup, "Fluorescence lifetime imaging by time-correlated single-photon counting," Microsc. Res. Tech. 63, 58-66 (2003).
[CrossRef] [PubMed]

Krishnan, R. V.

R. V. Krishnan, H. Saitoh, H. Terada, V. E. Centonze, and B. Herman, "Development of a multiphoton fluorescence lifetime imaging microscopy system using a streak camera," Rev. Sci. Instrum. 74, 2714-2721 (2003).
[CrossRef]

Kumar, S.

Kuner, T.

Kwak, E.-S.

E.-S. Kwak, T. J. Kang, and D. A. Vanden Bout, "Fluorescence lifetime imaging with near-field scanning optical microscopy," Anal. Chem. 73, 3257 -3262 (2001).
[CrossRef] [PubMed]

Lanigan, P.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Lanigan, P. M.

Levene, M. J.

Lever, J.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Lever, M. J.

Lustenberger, F.

Magee, A. I.

McGhee, E. J.

McGinty, J.

McLoskey, D.

D. McLoskey, D. J. S. Birch, A. Sanderson, K. Suhling, E. Welch, and P. J. Hicks, "Multiplexed single-photon counting. I. A time-correlated fluorescence lifetime camera," Rev. Sci. Instrum. 67, 2228-2237 (1996).
[CrossRef]

Merajver, S. D.

Merrick, K. A.

Moon, S.

Munro, I.

Mycek, M.

Nair, D. K.

Neil, M.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Neil, M. A. A.

Oggier, T.

Owen, D. M.

Philip, J.

K. Cralsson and J. Philip, "Theoretical investigation of the signal-to-noise ratio for different fluorescence lifetime imaging techniques," Proc. SPIE 4622, 70-78 (2002).

Phillips, D.

Klaus Suhling, Paul M. W. French, and D. Phillips, "Time-resolved fluorescence microscopy," Photochem. Photobiol. Sci. 4, 13-22 (2005).
[CrossRef]

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Reavell, F.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Requejo-Isidro, J.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

J. Requejo-Isidro, J. McGinty, I. Munro, D. S. Elson, N. P. Galletly, M. J. Lever, M. A. A. Neil, G. W. H. Stamp, P. M. W. French, P. A. Kellett, J. D. Hares, and A. K. L. Dymoke-Bradshaw, "High-speed wide-field time-gated endoscopic fluorescence-lifetime imaging," Opt. Lett. 29, 2249-2251 (2004), http://www.opticsinfobase.org/ol/abstract.cfm?URI=ol-29-19-2249.
[CrossRef]

Saitoh, H.

R. V. Krishnan, H. Saitoh, H. Terada, V. E. Centonze, and B. Herman, "Development of a multiphoton fluorescence lifetime imaging microscopy system using a streak camera," Rev. Sci. Instrum. 74, 2714-2721 (2003).
[CrossRef]

Sanderson, A.

D. McLoskey, D. J. S. Birch, A. Sanderson, K. Suhling, E. Welch, and P. J. Hicks, "Multiplexed single-photon counting. I. A time-correlated fluorescence lifetime camera," Rev. Sci. Instrum. 67, 2228-2237 (1996).
[CrossRef]

Sandison, A.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Schönle, A.

Siegel, J.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Spencer, D. D.

Stamp, G.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Stamp, G. W. H.

Suhling, K.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

D. McLoskey, D. J. S. Birch, A. Sanderson, K. Suhling, E. Welch, and P. J. Hicks, "Multiplexed single-photon counting. I. A time-correlated fluorescence lifetime camera," Rev. Sci. Instrum. 67, 2228-2237 (1996).
[CrossRef]

Suhling, Klaus

Klaus Suhling, Paul M. W. French, and D. Phillips, "Time-resolved fluorescence microscopy," Photochem. Photobiol. Sci. 4, 13-22 (2005).
[CrossRef]

Tadrous, P.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Talbot, C.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Talbot, C. B.

Terada, H.

R. V. Krishnan, H. Saitoh, H. Terada, V. E. Centonze, and B. Herman, "Development of a multiphoton fluorescence lifetime imaging microscopy system using a streak camera," Rev. Sci. Instrum. 74, 2714-2721 (2003).
[CrossRef]

Treanor, B.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Van Sark, W. G. J. H. M.

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, "Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution," J. Microsc. 206, 218-224 (2002).
[CrossRef] [PubMed]

Vanden Bout, D. A.

E.-S. Kwak, T. J. Kang, and D. A. Vanden Bout, "Fluorescence lifetime imaging with near-field scanning optical microscopy," Anal. Chem. 73, 3257 -3262 (2001).
[CrossRef] [PubMed]

Wallace, A.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Webb, S.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Welch, E.

D. McLoskey, D. J. S. Birch, A. Sanderson, K. Suhling, E. Welch, and P. J. Hicks, "Multiplexed single-photon counting. I. A time-correlated fluorescence lifetime camera," Rev. Sci. Instrum. 67, 2228-2237 (1996).
[CrossRef]

Williamson, A.

Wouters, F.

Wu, M.

Zhang, W.

Zhong, W.

Zuschratter, W.

Anal. Chem. (1)

E.-S. Kwak, T. J. Kang, and D. A. Vanden Bout, "Fluorescence lifetime imaging with near-field scanning optical microscopy," Anal. Chem. 73, 3257 -3262 (2001).
[CrossRef] [PubMed]

Appl. Opt. (1)

Appl. Spectrosc. (1)

J. Microsc. (1)

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, "Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution," J. Microsc. 206, 218-224 (2002).
[CrossRef] [PubMed]

Microsc. Res. Tech. (1)

W. Becker, A. Bergmann, M. A. Hink, K. König, K. Benndorf, and C. Biskup, "Fluorescence lifetime imaging by time-correlated single-photon counting," Microsc. Res. Tech. 63, 58-66 (2003).
[CrossRef] [PubMed]

Nat. Biotechnol. (1)

E. A. Jares-Erijman and T. M. Jovin, "FRET imaging," Nat. Biotechnol. 21, 1387-1395 (2003).
[CrossRef] [PubMed]

Opt. Express (6)

D. K. Nair, M. Jose, T. Kuner, W. Zuschratter, and R. Hartig, "FRET-FLIM at nanometer spectral resolution from living cells," Opt. Express 14, 12217-12229 (2006), http://www.opticsinfobase.org/abstract.cfm?URI=oe-14-25-12217.
[CrossRef] [PubMed]

W. Zhong, M. Wu, C. Chang, K. A. Merrick, S. D. Merajver, and M. Mycek, "Picosecond-resolution fluorescence lifetime imaging microscopy: a useful tool for sensing molecular interactions in vivo via FRET," Opt. Express 15, 18220-18235 (2007), http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-15-26-18220.
[CrossRef] [PubMed]

D. M. Grant, J. McGinty, E. J. McGhee, T. D. Bunney, D. M. Owen, C. B. Talbot, W. Zhang, S. Kumar, I. Munro, P. M. Lanigan, G. T. Kennedy, C. Dunsby, A. I. Magee, P. Courtney, M. Katan, M. A. A. Neil, and P. M. W. French, "High speed optically sectioned fluorescence lifetime imaging permits study of live cell signaling events," Opt. Express 15, 15656-15673 (2007), http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-15-24-15656.
[CrossRef] [PubMed]

T. H. Chia, A. Williamson, D. D. Spencer, and M. J. Levene, "Multiphoton fluorescence lifetime imaging of intrinsic fluorescence in human and rat brain tissue reveals spatially distinct NADH binding," Opt. Express 16, 4237-4249 (2008), http://www.opticsinfobase.org/abstract.cfm?URI=oe-16-6-4237.
[CrossRef] [PubMed]

A. Esposito, T. Oggier, H. Gerritsen, F. Lustenberger, and F. Wouters, "All-solid-state lock-in imaging for wide-field fluorescence lifetime sensing," Opt. Express 13, 9812-9821 (2005), http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-13-24-9812.
[CrossRef] [PubMed]

S. Moon and D. Y. Kim, "Analog single-photon counter for high-speed scanning microscopy," Opt. Express 16, 13990-14003 (2008), http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-16-18-13990.
[CrossRef] [PubMed]

Opt. Lett. (1)

Photochem. Photobiol. Sci. (2)

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, "Time-domain fluorescence lifetime imaging applied to biological tissue," Photochem. Photobiol. Sci.  3, 795-801 (2004).
[CrossRef] [PubMed]

Klaus Suhling, Paul M. W. French, and D. Phillips, "Time-resolved fluorescence microscopy," Photochem. Photobiol. Sci. 4, 13-22 (2005).
[CrossRef]

Proc. SPIE (2)

K. Cralsson and J. Philip, "Theoretical investigation of the signal-to-noise ratio for different fluorescence lifetime imaging techniques," Proc. SPIE 4622, 70-78 (2002).

W. Becker and A. Bergmann, "Timing stability of TCSPC experiments," Proc. SPIE 6372, 637209 (2006).
[CrossRef]

Rev. Sci. Instrum. (2)

D. McLoskey, D. J. S. Birch, A. Sanderson, K. Suhling, E. Welch, and P. J. Hicks, "Multiplexed single-photon counting. I. A time-correlated fluorescence lifetime camera," Rev. Sci. Instrum. 67, 2228-2237 (1996).
[CrossRef]

R. V. Krishnan, H. Saitoh, H. Terada, V. E. Centonze, and B. Herman, "Development of a multiphoton fluorescence lifetime imaging microscopy system using a streak camera," Rev. Sci. Instrum. 74, 2714-2721 (2003).
[CrossRef]

Other (5)

H. C. Gerristen, A. Draaijer, D. J. van den Heuvel, and A. V. Agronskaia, "Fluorescence lifetime imaging in scanning microscopy" in Handbook of Biological Confocal Microscopy, 3rd Ed., J. B. Pawley, ed. (Springer, New York, 2006).

P. Herman, H.-J. Lin, and J. R. Lakowicz, "Lifetime-based imaging" in Biomedical Photonics Handbook, T. Vo-Dinh, ed. (CRC Press, Boca Raton, 2003).
[CrossRef]

A. I. Zverev, Handbook of Filter Synthesis (John Wiley & Sons, Hoboken, 2005).

ISS, Inc, "Lifetime data of selected fluorophores," http://www.iss.com/resources/fluorophores.html.

H. Stark and J. W. Woods, Probability and Random Processes with Applications to Signal Processing, 3rd Ed., (Prentice-Hall, Upper Saddle River, 2002).

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Figures (4)

Fig. 1.
Fig. 1.

Schematic timing plots of excitation, fluorescence emission and photodetection processes that occur serially in time. For a detected photoelectron, the final temporal delay is a summation of various random variables of time delays.

Fig. 2.
Fig. 2.

Schematic diagram of the experimental setup for fluorescence lifetime measurement.

Fig. 3.
Fig. 3.

Signals acquired at an acquisition rate of 100 MS/s (a), and acquired at 2,000 MS/s (b), respectively, for Alexa Fluor 633. Each pulse is normalized by the peak.

Fig. 4.
Fig. 4.

Effect of the integration window width ΔTw for the iterative algorithm of mean-delay determination on the standard deviation Δτ and the effective number of iterations Niter . The window width is normalized by the FWHM of the IRF, 45.2 ns.

Tables (1)

Tables Icon

Table 1. Fluorescence lifetimes obtained by the analog mean-delay method performed at the two different sampling rates and the phase fluorometry method.

Equations (16)

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

F = Δ τ τ N
i e ( t ) = γ { I ex ( t ) Ψ τ ( t ) I pd ( t ) } ,
i irf ( t ) i e ( t ) | τ = 0 = γ { I ex I pd ( t ) } .
Ψ τ ( t ) = 1 { { i e } ( f ) { i irf } ( f ) }
τ f = 1 2 πf tan ( ϕ ( f ) ϕ irf ( f ) )
T e = ( t ex + T ex ) + ( T re + T fl + t fl ) + ( T pd ) .
T e 0 T e | T re = 0 T fl = 0 = ( t ex + T ex ) + ( t fl ) + ( T pd ) .
T e T e 0 = T re + T fl T fl = τ
τ = T e T e 0 = ( t i e ( t ) dt i e ( t ) dt ) ( t i irf ( t ) dt i irf ( t ) dt )
Δ τ 2 = σ 2 [ T fl ] = σ 2 [ T fl ] N = τ 2 N
Δ t tts 2 = σ 2 [ ( i T pd i ) ]
Δ τ 2 = σ 2 [ ( i = 1 N T e i + j = 1 N d e T d j ) ( N + N d e ) ]
= ( N σ 2 [ T e ] + N d e σ 2 [ T d ] ) ( N + N d e ) 2
σ 2 [ T e ] N + 1 N ( R d ε 12 Δ T w 2 )
Δ τ 2 = 1 N ( τ 2 + Δ t ex 2 + Δ t tts 2 + R d ε 12 Δ T w 2 )
F = 1 + 1 τ 2 { Δ t ex 2 + Δ t tts 2 + ( R d 12 Δ T w T m ) Δ T w 2 }

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