Abstract

We discuss a Hadamard-transform-based fluorescence-lifetime-imaging (HT-FLI) technique for fluorescence-lifetime-imaging microscopy (FLIM). The HT-FLI uses a Fourier-transform phase-modulation fluorometer (FT-PMF) for fluorescence-lifetime measurements, where the modulation frequency of the excitation light is swept linearly in frequency from zero to a specific maximum during a fixed duration of time. Thereafter, fluorescence lifetimes are derived through Fourier transforms for the fluorescence and reference waveforms. The FT-PMF enables the analysis of multi-component samples simultaneously. HT imaging uses electronic exchange of HT illumination mask patterns, and a high-speed, high-sensitivity photomultiplier, to eliminate frame-rate issues that accompany two-dimensional image detectors.

© 2016 Optical Society of America

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References

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    [Crossref] [PubMed]
  3. H. Wallrabe and A. Periasamy, “Imaging protein molecules using FRET and FLIM microscopy,” Curr. Opin. Biotechnol. 16(1), 19–27 (2005).
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    [Crossref]
  5. X. F. Wang, T. Uchida, and S. Minami, “A fluorescence lifetime distribution measurement system based on phase-resolved detection using an image dissector tube,” Appl. Spectrosc. 43(5), 840–845 (1989).
    [Crossref]
  6. I. Bugiel, K. Koonig, and H. Wabnitz, “Investigation of cells by fluorescence laser scanning microscopy with subnanosecond time resolution,” Lasers Life Sci. 3(1), 47–53 (1989).
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    [Crossref]

2015 (1)

T. Mizuno, S. Nakao, Y. Mizutani, and T. Iwata, “Photon-counting 1.0 GHz-phase-modulation fluorometer,” Rev. Sci. Instrum. 86(4), 043110 (2015).
[Crossref] [PubMed]

2009 (1)

J. A. Levitt, D. R. Matthews, S. M. Ameer-Beg, and K. Suhling, “Fluorescence lifetime and polarization-resolved imaging in cell biology,” Curr. Opin. Biotechnol. 20(1), 28–36 (2009).
[Crossref] [PubMed]

2005 (3)

H. Wallrabe and A. Periasamy, “Imaging protein molecules using FRET and FLIM microscopy,” Curr. Opin. Biotechnol. 16(1), 19–27 (2005).
[Crossref] [PubMed]

T. Iwata, H. Shibata, and T. Araki, “Construction of a Fourier-transform phase-modulation fluorometer,” Meas. Sci. Technol. 16(11), 2351–2356 (2005).
[Crossref]

K. Hassler, T. Anhut, and T. Lasser, “Time-resolved Hadamard fluorescence imaging,” Appl. Opt. 44(35), 7564–7572 (2005).
[Crossref] [PubMed]

2004 (1)

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(8), 795–801 (2004).
[Crossref] [PubMed]

2002 (1)

D. Magde, R. Wong, and P. G. Seybold, “Fluorescence quantum yields and their relation to lifetimes of rhodamine 6G and fluorescein in nine solvents: Improved absolute standards for quantum yields,” Photochem. Photobiol. 75(4), 327–334 (2002).
[Crossref] [PubMed]

1999 (4)

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[Crossref]

P. Harms, J. Sipior, N. Ram, G. M. Carter, and G. Rao, “Low cost phase-modulation measurements of nanosecond fluorescence lifetimes using a lock-in amplifier,” Rev. Sci. Instrum. 70(2), 1535–1539 (1999).
[Crossref]

Q. S. Hanley, P. J. Verveer, and T. M. Jovin, “Spectral imaging in a programmable array microscope by Hadamard transform fluorescence spectroscopy,” Appl. Spectrosc. 53(1), 1–10 (1999).
[Crossref]

A. Squire and P. I. H. Bastiaens, “Three dimensional image restoration in fluorescence lifetime imaging microscopy,” J. Microsc. 193(1), 36–49 (1999).
[Crossref] [PubMed]

1993 (1)

T. W. J. Gadella, T. M. Jovin, and R. M. Clegg, “Fluorescence lifetime imaging microscopy (FLIM): Spatial resolution of microstructures on the nanosecond time scale,” Biophys. Chem. 48(2), 221–239 (1993).
[Crossref]

1992 (1)

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

1991 (2)

J. R. Lakowicz and K. W. Berndt, “Lifetime-selective fluorescence imaging using an rf phase-sensitive camera,” Rev. Sci. Instrum. 62(7), 1727–1734 (1991).
[Crossref]

X. F. Wang, T. Uchida, D. M. Coleman, and S. Minami, “A two-dimensional fluorescence lifetime imaging system using a gated image intensifier,” Appl. Spectrosc. 45(3), 360–366 (1991).
[Crossref]

1989 (2)

X. F. Wang, T. Uchida, and S. Minami, “A fluorescence lifetime distribution measurement system based on phase-resolved detection using an image dissector tube,” Appl. Spectrosc. 43(5), 840–845 (1989).
[Crossref]

I. Bugiel, K. Koonig, and H. Wabnitz, “Investigation of cells by fluorescence laser scanning microscopy with subnanosecond time resolution,” Lasers Life Sci. 3(1), 47–53 (1989).

1976 (1)

Ameer-Beg, S. M.

J. A. Levitt, D. R. Matthews, S. M. Ameer-Beg, and K. Suhling, “Fluorescence lifetime and polarization-resolved imaging in cell biology,” Curr. Opin. Biotechnol. 20(1), 28–36 (2009).
[Crossref] [PubMed]

Anhut, T.

Araki, T.

T. Iwata, H. Shibata, and T. Araki, “Construction of a Fourier-transform phase-modulation fluorometer,” Meas. Sci. Technol. 16(11), 2351–2356 (2005).
[Crossref]

Bastiaens, P. I. H.

A. Squire and P. I. H. Bastiaens, “Three dimensional image restoration in fluorescence lifetime imaging microscopy,” J. Microsc. 193(1), 36–49 (1999).
[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(8), 795–801 (2004).
[Crossref] [PubMed]

Berndt, K. W.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

J. R. Lakowicz and K. W. Berndt, “Lifetime-selective fluorescence imaging using an rf phase-sensitive camera,” Rev. Sci. Instrum. 62(7), 1727–1734 (1991).
[Crossref]

Bugiel, I.

I. Bugiel, K. Koonig, and H. Wabnitz, “Investigation of cells by fluorescence laser scanning microscopy with subnanosecond time resolution,” Lasers Life Sci. 3(1), 47–53 (1989).

Carter, G. M.

P. Harms, J. Sipior, N. Ram, G. M. Carter, and G. Rao, “Low cost phase-modulation measurements of nanosecond fluorescence lifetimes using a lock-in amplifier,” Rev. Sci. Instrum. 70(2), 1535–1539 (1999).
[Crossref]

Clegg, R. M.

T. W. J. Gadella, T. M. Jovin, and R. M. Clegg, “Fluorescence lifetime imaging microscopy (FLIM): Spatial resolution of microstructures on the nanosecond time scale,” Biophys. Chem. 48(2), 221–239 (1993).
[Crossref]

Coleman, D. M.

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(8), 795–801 (2004).
[Crossref] [PubMed]

Decker, J. A.

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(8), 795–801 (2004).
[Crossref] [PubMed]

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(8), 795–801 (2004).
[Crossref] [PubMed]

Gadella, T. W. J.

T. W. J. Gadella, T. M. Jovin, and R. M. Clegg, “Fluorescence lifetime imaging microscopy (FLIM): Spatial resolution of microstructures on the nanosecond time scale,” Biophys. Chem. 48(2), 221–239 (1993).
[Crossref]

Hanley, Q. S.

Harms, P.

P. Harms, J. Sipior, N. Ram, G. M. Carter, and G. Rao, “Low cost phase-modulation measurements of nanosecond fluorescence lifetimes using a lock-in amplifier,” Rev. Sci. Instrum. 70(2), 1535–1539 (1999).
[Crossref]

Harwit, M.

Hassler, K.

Iwata, T.

T. Mizuno, S. Nakao, Y. Mizutani, and T. Iwata, “Photon-counting 1.0 GHz-phase-modulation fluorometer,” Rev. Sci. Instrum. 86(4), 043110 (2015).
[Crossref] [PubMed]

T. Iwata, H. Shibata, and T. Araki, “Construction of a Fourier-transform phase-modulation fluorometer,” Meas. Sci. Technol. 16(11), 2351–2356 (2005).
[Crossref]

Johnson, M.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

Jovin, T. M.

Q. S. Hanley, P. J. Verveer, and T. M. Jovin, “Spectral imaging in a programmable array microscope by Hadamard transform fluorescence spectroscopy,” Appl. Spectrosc. 53(1), 1–10 (1999).
[Crossref]

T. W. J. Gadella, T. M. Jovin, and R. M. Clegg, “Fluorescence lifetime imaging microscopy (FLIM): Spatial resolution of microstructures on the nanosecond time scale,” Biophys. Chem. 48(2), 221–239 (1993).
[Crossref]

Koonig, K.

I. Bugiel, K. Koonig, and H. Wabnitz, “Investigation of cells by fluorescence laser scanning microscopy with subnanosecond time resolution,” Lasers Life Sci. 3(1), 47–53 (1989).

Lakowicz, J. R.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

J. R. Lakowicz and K. W. Berndt, “Lifetime-selective fluorescence imaging using an rf phase-sensitive camera,” Rev. Sci. Instrum. 62(7), 1727–1734 (1991).
[Crossref]

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(8), 795–801 (2004).
[Crossref] [PubMed]

Lasser, T.

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(8), 795–801 (2004).
[Crossref] [PubMed]

Levitt, J. A.

J. A. Levitt, D. R. Matthews, S. M. Ameer-Beg, and K. Suhling, “Fluorescence lifetime and polarization-resolved imaging in cell biology,” Curr. Opin. Biotechnol. 20(1), 28–36 (2009).
[Crossref] [PubMed]

Magde, D.

D. Magde, R. Wong, and P. G. Seybold, “Fluorescence quantum yields and their relation to lifetimes of rhodamine 6G and fluorescein in nine solvents: Improved absolute standards for quantum yields,” Photochem. Photobiol. 75(4), 327–334 (2002).
[Crossref] [PubMed]

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[Crossref]

Matthews, D. R.

J. A. Levitt, D. R. Matthews, S. M. Ameer-Beg, and K. Suhling, “Fluorescence lifetime and polarization-resolved imaging in cell biology,” Curr. Opin. Biotechnol. 20(1), 28–36 (2009).
[Crossref] [PubMed]

McGinty, 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(8), 795–801 (2004).
[Crossref] [PubMed]

Minami, S.

Mizuno, T.

T. Mizuno, S. Nakao, Y. Mizutani, and T. Iwata, “Photon-counting 1.0 GHz-phase-modulation fluorometer,” Rev. Sci. Instrum. 86(4), 043110 (2015).
[Crossref] [PubMed]

Mizutani, Y.

T. Mizuno, S. Nakao, Y. Mizutani, and T. Iwata, “Photon-counting 1.0 GHz-phase-modulation fluorometer,” Rev. Sci. Instrum. 86(4), 043110 (2015).
[Crossref] [PubMed]

Munro, I.

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(8), 795–801 (2004).
[Crossref] [PubMed]

Nakao, S.

T. Mizuno, S. Nakao, Y. Mizutani, and T. Iwata, “Photon-counting 1.0 GHz-phase-modulation fluorometer,” Rev. Sci. Instrum. 86(4), 043110 (2015).
[Crossref] [PubMed]

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(8), 795–801 (2004).
[Crossref] [PubMed]

Nowaczyk, K.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

Paganetti, R.

Periasamy, A.

H. Wallrabe and A. Periasamy, “Imaging protein molecules using FRET and FLIM microscopy,” Curr. Opin. Biotechnol. 16(1), 19–27 (2005).
[Crossref] [PubMed]

Phillips, 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(8), 795–801 (2004).
[Crossref] [PubMed]

Ram, N.

P. Harms, J. Sipior, N. Ram, G. M. Carter, and G. Rao, “Low cost phase-modulation measurements of nanosecond fluorescence lifetimes using a lock-in amplifier,” Rev. Sci. Instrum. 70(2), 1535–1539 (1999).
[Crossref]

Rao, G.

P. Harms, J. Sipior, N. Ram, G. M. Carter, and G. Rao, “Low cost phase-modulation measurements of nanosecond fluorescence lifetimes using a lock-in amplifier,” Rev. Sci. Instrum. 70(2), 1535–1539 (1999).
[Crossref]

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(8), 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(8), 795–801 (2004).
[Crossref] [PubMed]

Rojas, G. E.

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[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(8), 795–801 (2004).
[Crossref] [PubMed]

Seybold, P. G.

D. Magde, R. Wong, and P. G. Seybold, “Fluorescence quantum yields and their relation to lifetimes of rhodamine 6G and fluorescein in nine solvents: Improved absolute standards for quantum yields,” Photochem. Photobiol. 75(4), 327–334 (2002).
[Crossref] [PubMed]

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[Crossref]

Shibata, H.

T. Iwata, H. Shibata, and T. Araki, “Construction of a Fourier-transform phase-modulation fluorometer,” Meas. Sci. Technol. 16(11), 2351–2356 (2005).
[Crossref]

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(8), 795–801 (2004).
[Crossref] [PubMed]

Sipior, J.

P. Harms, J. Sipior, N. Ram, G. M. Carter, and G. Rao, “Low cost phase-modulation measurements of nanosecond fluorescence lifetimes using a lock-in amplifier,” Rev. Sci. Instrum. 70(2), 1535–1539 (1999).
[Crossref]

Squire, A.

A. Squire and P. I. H. Bastiaens, “Three dimensional image restoration in fluorescence lifetime imaging microscopy,” J. Microsc. 193(1), 36–49 (1999).
[Crossref] [PubMed]

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(8), 795–801 (2004).
[Crossref] [PubMed]

Suhling, K.

J. A. Levitt, D. R. Matthews, S. M. Ameer-Beg, and K. Suhling, “Fluorescence lifetime and polarization-resolved imaging in cell biology,” Curr. Opin. Biotechnol. 20(1), 28–36 (2009).
[Crossref] [PubMed]

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(8), 795–801 (2004).
[Crossref] [PubMed]

Swift, R. D.

Szmacinski, H.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

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(8), 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(8), 795–801 (2004).
[Crossref] [PubMed]

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(8), 795–801 (2004).
[Crossref] [PubMed]

Uchida, T.

Verveer, P. J.

Wabnitz, H.

I. Bugiel, K. Koonig, and H. Wabnitz, “Investigation of cells by fluorescence laser scanning microscopy with subnanosecond time resolution,” Lasers Life Sci. 3(1), 47–53 (1989).

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(8), 795–801 (2004).
[Crossref] [PubMed]

Wallrabe, H.

H. Wallrabe and A. Periasamy, “Imaging protein molecules using FRET and FLIM microscopy,” Curr. Opin. Biotechnol. 16(1), 19–27 (2005).
[Crossref] [PubMed]

Wang, X. F.

Wattson, R. B.

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(8), 795–801 (2004).
[Crossref] [PubMed]

Wong, R.

D. Magde, R. Wong, and P. G. Seybold, “Fluorescence quantum yields and their relation to lifetimes of rhodamine 6G and fluorescein in nine solvents: Improved absolute standards for quantum yields,” Photochem. Photobiol. 75(4), 327–334 (2002).
[Crossref] [PubMed]

Anal. Biochem. (1)

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

Appl. Opt. (2)

Appl. Spectrosc. (3)

Biophys. Chem. (1)

T. W. J. Gadella, T. M. Jovin, and R. M. Clegg, “Fluorescence lifetime imaging microscopy (FLIM): Spatial resolution of microstructures on the nanosecond time scale,” Biophys. Chem. 48(2), 221–239 (1993).
[Crossref]

Curr. Opin. Biotechnol. (2)

J. A. Levitt, D. R. Matthews, S. M. Ameer-Beg, and K. Suhling, “Fluorescence lifetime and polarization-resolved imaging in cell biology,” Curr. Opin. Biotechnol. 20(1), 28–36 (2009).
[Crossref] [PubMed]

H. Wallrabe and A. Periasamy, “Imaging protein molecules using FRET and FLIM microscopy,” Curr. Opin. Biotechnol. 16(1), 19–27 (2005).
[Crossref] [PubMed]

J. Microsc. (1)

A. Squire and P. I. H. Bastiaens, “Three dimensional image restoration in fluorescence lifetime imaging microscopy,” J. Microsc. 193(1), 36–49 (1999).
[Crossref] [PubMed]

Lasers Life Sci. (1)

I. Bugiel, K. Koonig, and H. Wabnitz, “Investigation of cells by fluorescence laser scanning microscopy with subnanosecond time resolution,” Lasers Life Sci. 3(1), 47–53 (1989).

Meas. Sci. Technol. (1)

T. Iwata, H. Shibata, and T. Araki, “Construction of a Fourier-transform phase-modulation fluorometer,” Meas. Sci. Technol. 16(11), 2351–2356 (2005).
[Crossref]

Photochem. Photobiol. (2)

D. Magde, R. Wong, and P. G. Seybold, “Fluorescence quantum yields and their relation to lifetimes of rhodamine 6G and fluorescein in nine solvents: Improved absolute standards for quantum yields,” Photochem. Photobiol. 75(4), 327–334 (2002).
[Crossref] [PubMed]

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[Crossref]

Photochem. Photobiol. Sci. (1)

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(8), 795–801 (2004).
[Crossref] [PubMed]

Rev. Sci. Instrum. (3)

T. Mizuno, S. Nakao, Y. Mizutani, and T. Iwata, “Photon-counting 1.0 GHz-phase-modulation fluorometer,” Rev. Sci. Instrum. 86(4), 043110 (2015).
[Crossref] [PubMed]

P. Harms, J. Sipior, N. Ram, G. M. Carter, and G. Rao, “Low cost phase-modulation measurements of nanosecond fluorescence lifetimes using a lock-in amplifier,” Rev. Sci. Instrum. 70(2), 1535–1539 (1999).
[Crossref]

J. R. Lakowicz and K. W. Berndt, “Lifetime-selective fluorescence imaging using an rf phase-sensitive camera,” Rev. Sci. Instrum. 62(7), 1727–1734 (1991).
[Crossref]

Other (2)

M. Harwit and N. L. Sloane, Hadamard Transform Optics (Academic Press, 1979).

J. R. Lakowicz, Principles of Fluorescence Spectroscopy, 3rd ed. (Springer, 2006).

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Figures (7)

Fig. 1
Fig. 1 Schematic of the FT-PMF working principle.
Fig. 2
Fig. 2 (a) Schematic of the HTI system, (b) generation of an N × 1 object column vector g from an n × n object matrix (G), where N = n2, (c) an N × 1 observation vector y is obtained by multiplying an N × N mask matrix (M) with g: y = Mg, and (d) generation of n illumination mask pattern n × n matrices from (M).
Fig. 3
Fig. 3 Schematic of HT-FLI; (a) cyclic Hadamard mask patterns; (b) chirped excitation waveforms; (c) fluorescence waveforms; (d) N pairs of real and imaginary spectra; (e) k(<<N) pairs of real and imaginary images obtained from (d) by an inverse Hadamard transform; (f) amplitude ratio m and phase difference θ images calculated from (e); (g) shading image corresponding to each fluorescence lifetime.
Fig. 4
Fig. 4 Schematic of an n × n LED array driver (upper part). CSR; cyclic shift register used to generate Hadamard illumination mask patterns. AWG; arbitrary waveform generator for chirped sinusoidal waveform generation and its operating timing diagram (lower part); (A) master clock for pattern exchange. (B) settling time Td for preparing Hadamard illumination mask patterns and dwell time T for frequency chirping, (C) start pulse for the chirped waveform, (D) frequency-chirped excitation waveform, and (E) resulting fluorescence waveform.
Fig. 5
Fig. 5 (a) Schematic of two single-component samples with a fluorescence lifetime that varies spatially (R6G: 10-μM rhodamine 6G in ethanol; RB: 10-μM rhodamine B in ethanol) (b) Schematic of a two-component mixture of R6G and RB with volume ratios of (iii) 3:1, (vi) 1:1, and (v) 1:3, respectively. (c) Fluorescence excitation spectra of (i) R6G, (ii) RB, and (iii) 1:1 mixed solution. (d) Corresponding emission spectra.
Fig. 6
Fig. 6 (a) A dc (f = 0) fluorescence image obtained with HT-FLI for the two-cell sample shown in Fig. 5(a). (b) Amplitude ratio m and phase difference θ as a function of the modulation frequency f derived at a position X marked in (a), and (c) at a position Y marked in (a). (d) Initial amplitude ratio image a2/a1 calculated for each pixel. (e) a1 shading image for τ ¯ 1 = 4.2 ± 0.21 ns. (f) a2 shading image for τ ¯ 2 = 2.5 ± 0.13 ns.
Fig. 7
Fig. 7 (a) A dc (f = 0) fluorescence intensity image obtained from HT-FLI for the multi-component cells in Fig. 5(b). (b) Amplitude ratio m and phase difference θ as a function of the modulation frequency f derived at a position X, marked in (a), (c) for position Y, and (d) for position Z. (e) Initial amplitude ratio a2/a1 calculated for each pixel. (f) a1 shading image for τ ¯ 1 = 4.2 ± 0.21 ns, and (g) a2 shading image for τ ¯ 2 = 2.5 ± 0.13 ns.

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