Abstract

We demonstrate that an ultra-fast CMOS camera combined with a photon counting image intensifier can be used to determine photon arrival times well below the exposure time of the camera. We can obtain a time resolution down to around 1% of the exposure time, i.e. of the order of 40 ns with microsecond exposure times. This is achieved by exploiting the invariant phosphor decay of the image intensifier’s phosphor screen: Developing a suitable mathematical framework, we show that the relative intensities of the phosphor decay in successive frames following the photon detection uniquely determine the photon arrival time. This approach opens a way to measuring fast luminescence decays in parallel in many pixels. Possible applications include oxygen and ion concentration imaging using probes with luminescence lifetimes in the range of 100 ns to microseconds.

© 2010 Optical Society of America

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  48. Z. Petrášek, and P. Schwille, "Fluctuations as a source of information in fluorescence microscopy," J. R. Soc. Interface 6, S15-S25 (2009).
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    [CrossRef]

2010 (5)

D.-U. Li, J. Arlt, J. Richardson, R. Walker, A. Buts, D. Stoppa, E. Charbon, and R. Henderson, "Real-time fluorescence lifetime imaging system with a 32×32 0.13μm CMOS low dark-count single-photon avalanche diode array," Opt. Express 18, 10527-102692 (2010).

J. C. G. Bunzli, "Lanthanide luminescence for biomedical analyses and imaging," Chem. Rev. 110, 2729-2755 (2010).
[CrossRef] [PubMed]

M. P. Coogan, J. B. Court, V. L. Gray, A. J. Hayes, S. H. Lloyd, C. O. Millet, S. J. A. Pope, and D. Lloyd, "Probing intracellular oxygen by quenched phosphorescence lifetimes of nanoparticles containing polyacrylamideembedded [Ru(dpp(SO3Na)2)3]Cl2," Photochem. Photobiol. Sci. 9, 103-109 (2010).
[CrossRef] [PubMed]

N. A. Hosny, D. A. Lee, and K. M. M., "Extracellular oxygen concentration mapping with a confocal multiphoton laser scanning microscope and TCSPC card," Proc. SPIE 7569, 756932 (2010).
[CrossRef]

G. Bub, M. Tecza, M. Helmes, P. Lee, and P. Kohl, "Temporal pixel multiplexing for simultaneous high-speed, high-resolution imaging," Nat. Methods 7, 209-211 (2010).
[CrossRef] [PubMed]

2009 (8)

Z. Petrášek, and P. Schwille, "Fluctuations as a source of information in fluorescence microscopy," J. R. Soc. Interface 6, S15-S25 (2009).
[CrossRef]

S. Tisa, F. Guerrieri, and F. Zappa, "Monolithic array of 32 SPAD pixels for single-photon imaging at high frame rates," Nucl. Instrum. Methods Phys. Res., Sect. A 610, 24-27 (2009).
[CrossRef]

X. Michalet, R. A. Colyer, J. Antelman, O. H. W. Siegmund, A. Tremsin, J. V. Vallerga, and S. Weiss, "Single quantum dot imaging with a photon counting camera," Curr. Pharm. Biotechnol. 10, 543-558 (2009).
[CrossRef] [PubMed]

Y. Prokazov, E. Turbin, M. Vitali, A. Herzog, B. Michaelis, W. Zuschratter, and K. Kemnitz, "Reborn quadrant anode image sensor," Nucl. Instrum. Methods Phys. Res., Sect. A 604, 221-223 (2009).
[CrossRef]

Z. Petrášek, H. J. Eckert, and K. Kemnitz, "Wide-field photon counting fluorescence lifetime imaging microscopy: application to photosynthesizing systems," Photosynth. Res. 102, 157-168 (2009).
[CrossRef]

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, 28-36 (2009).
[CrossRef] [PubMed]

A. S. Tremsin, O. H. W. Siegmund, J. V. Vallerga, R. Raffanti, S. Weiss, and X. Michalet, "High speed multichannel charge sensitive data acquisition system with self-triggered event timing," IEEE Trans. Nucl. Sci. 56, 1148-1152 (2009).
[CrossRef]

Y. Yamaguchi, K. Hashino, M. Ito, K. Ikawa, T. Nishioka, and K. Matsumoto, "Sodium dodecyl sulfate polyacrylamide slab gel electrophoresis and hydroxyethyl cellurose gel capillary electrophoresis of luminescent lanthanide chelate-labeled proteins with time-resolved detection," Anal. Sci. 25, 327-332 (2009).
[CrossRef] [PubMed]

2008 (4)

J. A. Spitz, R. Yasukuni, N. Sandeau, M. Takano, J. J. Vachon, R. Meallet-Renault, and R. B. Pansu, "Scanningless wide-field single-photon counting device for fluorescence intensity, lifetime and time-resolved anisotropy imaging microscopy," J. Microsc. 229, 104-114 (2008).
[CrossRef] [PubMed]

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, ""A 128×128 Single-Photon Image Sensor With Column-Level 10-Bit Time-to-Digital Converter Array," IEEE J. Sol.- St. Circ. 43, 2977-2989 (2008).
[CrossRef]

A. J. Berglund, M. D. McMahon, J. J. McClelland, and J. A. Liddle, "Fast, bias-free algorithm for tracking single particles with variable size and shape," Opt. Express 16, 14064-14075 (2008).
[CrossRef] [PubMed]

S. W. Botchway, M. Charnley, J. W. Haycock, A. W. Parker, D. L. Rochester, J. A. Weinstein, and J. A. G. Williams, "Time-resolved and two-photon emission imaging microscopy of live cells with inert platinum complexes," Proc. Natl. Acad. Sci. U.S.A. 105, 16071-16076 (2008).
[CrossRef] [PubMed]

2007 (3)

F. Festy, S. M. Ameer-Beg, T. Ng, and K. Suhling, "Imaging proteins in vivo using fluorescence lifetime microscopy," Mol. Biosyst. 3, 381-391 (2007).
[CrossRef] [PubMed]

X. Michalet, O. H. W. Siegmund, J. V. Vallerga, P. Jelinsky, J. E. Millaud, and S. Weiss, "Detectors for single molecule fluorescence imaging and spectroscopy," J. Mod. Opt. 54, 239-281 (2007).
[CrossRef] [PubMed]

J. B. Hutchings, J. Postma, D. Asquin, and D. Leahy, "Photon event centroiding with UV photon-counting detectors," Publ. Astron. Soc. Pac. 119, 1152-1162 (2007).
[CrossRef]

2006 (1)

T. Nishioka, J. L. Yuan, Y. Yamamoto, K. Sumitomo, Z. Wang, K. Hashino, C. Hosoya, K. Ikawa, G. L. Wang, and K. Matsumoto, "New luminescent europium(III) chelates for DNA labeling," Inorg. Chem. 45, 4088-4096 (2006).
[CrossRef] [PubMed]

2005 (5)

I. Hemmilä, and V. Laitala, "Progress in lanthanides as luminescent probes," J. Fluoresc. 15, 529-542 (2005).
[CrossRef] [PubMed]

M. H. V. Werts, "Making sense of lanthanide luminescence," Sci. Prog. 88, 101-131 (2005).
[CrossRef]

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

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

G. S. Buller, R. D. Harkins, A. McCarthy, P. A. Hiskett, G. R. MacKinnon, G. R. Smith, R. Sung, A. M. Wallace, R. A. Lamb, K. D. Ridley, and J. G. Rarity, "Multiple wavelength time-of-flight sensor based on time-correlated single-photon counting," Rev. Sci. Instrum. 76, 083112 (2005).
[CrossRef]

2004 (2)

M. Peter, and S. M. Ameer-Beg, "Imaging molecular interactions by multiphoton FLIM," Biol. Cell 96, 231-236 (2004).
[CrossRef] [PubMed]

D. S. Elson, I. Munro, J. Requejo-Isidro, J. McGinty, C. Dunsby, N. Galletly, G. W. Stamp, M. A. A. Neil, M. J. Lever, P. A. Kellett, A. Dymoke-Bradshaw, J. Hares, and P. M. W. French, "Real-time time-domain fluorescence lifetime imaging including single-shot acquisition with a segmented optical image intensifier," N. J. Phys. 6, 180 (2004).
[CrossRef]

2003 (1)

J. Siegel, K. Suhling, S. Leveque-Fort, S. E. D. Webb, D. M. Davis, D. Phillips, Y. Sabharwal, and P. M. W. French, "Wide-field time-resolved fluorescence anisotropy imaging (TR-FAIM): Imaging the rotational mobility of a fluorophore," Rev. Sci. Instrum. 74, 182-192 (2003).
[CrossRef]

2002 (5)

K. Suhling, R. W. Airey, and B. L. Morgan, "Minimization of fixed pattern noise in photon event counting imaging," Rev. Sci. Instrum. 73, 2917-2922 (2002).
[CrossRef]

P. R. Selvin, "Principles and biophysical applications of lanthanide-based probes," Annu. Rev. Biophys. Biomol. Struct. 31, 275-302 (2002).
[CrossRef] [PubMed]

J. E. Lees, and G. W. Fraser, "Efficiency enhancements for MCP-based beta autoradiography imaging," Nucl. Instrum. Methods Phys. Res., Sect. A 477, 239-243 (2002).
[CrossRef]

A. C. Mitchell, J. E. Wall, J. G. Murray, and C. G. Morgan, "Direct modulation of the effective sensitivity of a ccd detector: a new approach to time-resolved fluorescence imaging," J. Microsc. 206, 225-232 (2002).
[CrossRef] [PubMed]

O. Jagutzki, A. Cerezo, A. Czasch, R. Dörner, M. Hattaß, M. Huang, V. Mergel, U. Spillmann, K. Ullmann-Pfleger, T. Weber, H. Schmidt-Böcking, and G. D. W. Smith, "Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode," IEEE Trans. Nucl. Sci. 49, 2477-2483 (2002).
[CrossRef]

2001 (1)

K. Suhling, G. Hungerford, R. W. Airey, and B. L. Morgan, "A position-sensitive photon event counting detector applied to fluorescence imaging of dyes in sol-gel matrices," Meas. Sci. Technol. 12, 131-141 (2001).
[CrossRef]

2000 (1)

F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, "A 32-channel time-resolved instrument for medical optical tomography," Rev. Sci. Instrum. 71, 256-265 (2000).
[CrossRef]

1999 (1)

K. Suhling, R. Airey, and B. Morgan, ""Optimisation of centroiding algorithms for photon event counting imaging," Nucl. Instrum. Methods Phys. Res., Sect. A 437, 393-418 (1999).
[CrossRef]

1998 (2)

J. G. Mainprize, and M. J. Yaffe, "The effect of phosphor persistence on image quality in digital x-ray scanning systems," Med. Phys. 25, 2440-2454 (1998).
[CrossRef]

G. Vereb, E. Jares-Erijman, P. R. Selvin, and T. M. Jovin, "Temporally and spectrally resolved imaging microscopy of lanthanide chelates," Biophys. J. 74, 2210-2222 (1998).
[CrossRef] [PubMed]

1997 (1)

P. D. Read, M. K. Carter, C. D. Pike, R. A. Harrison, B. J. Kent, B. M. Swinyard, B. E. Patchett, R. M. Redfern, A. Shearer, and M. Colhoun, "Uses of microchannel plate intensified detectors for imaging applications in the X-ray, EUV and visible wavelength regions,"Nucl. Instrum. Methods Phys. Res., Sect. A 392, 359-363 (1997).
[CrossRef]

1996 (2)

W. K. Young, B. Vojnovic, and P. Wardman, "Measurement of oxygen tension in tumours by time-resolved fluorescence," Br. J. Cancer 74, S256-S259 (1996).

G. Hungerford, and D. J. S. Birch, "Single-photon timing detectors for fluorescence lifetime spectroscopy," Meas. Sci. Technol. 7, 121-135 (1996).
[CrossRef]

1995 (2)

C. L. Joseph, "UV image sensors and associated technologies," Exp. Astron. 6, 97-127 (1995).
[CrossRef]

Z. Bajzer, A. Zelić, and F. G. Prendergast, "Analytical approach to the recovery of short fluorescence lifetimes from fluorescence decay curves," Biophys. J. 69, 1148-1161 (1995).
[CrossRef] [PubMed]

1992 (2)

H. W. Kröger, G. K. Schmidt, and N. Pailer, "Faint object camera - European contribution to the Hubble Space Telescope," ACTA Aeronaut. Astronaut. Sinica 26, 827-834 (1992).

N. A. Sharp, "Millisecond time resolution with the kitt peak photon-counting array," Publ. Astron. Soc. Pac. 104, 263-269 (1992).
[CrossRef]

1991 (1)

G. Marriott, R. M. Clegg, D. J. Arndt-Jovin, and T. M. Jovin, "Time resolved imaging microscopy - phosphorescence and delayed fluorescence imaging," Biophys. J. 60, 1374-1387 (1991).
[CrossRef] [PubMed]

Ahr, L.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

Airey, R.

K. Suhling, R. Airey, and B. Morgan, ""Optimisation of centroiding algorithms for photon event counting imaging," Nucl. Instrum. Methods Phys. Res., Sect. A 437, 393-418 (1999).
[CrossRef]

Airey, R. W.

K. Suhling, R. W. Airey, and B. L. Morgan, "Minimization of fixed pattern noise in photon event counting imaging," Rev. Sci. Instrum. 73, 2917-2922 (2002).
[CrossRef]

K. Suhling, G. Hungerford, R. W. Airey, and B. L. Morgan, "A position-sensitive photon event counting detector applied to fluorescence imaging of dyes in sol-gel matrices," Meas. Sci. Technol. 12, 131-141 (2001).
[CrossRef]

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, 28-36 (2009).
[CrossRef] [PubMed]

F. Festy, S. M. Ameer-Beg, T. Ng, and K. Suhling, "Imaging proteins in vivo using fluorescence lifetime microscopy," Mol. Biosyst. 3, 381-391 (2007).
[CrossRef] [PubMed]

M. Peter, and S. M. Ameer-Beg, "Imaging molecular interactions by multiphoton FLIM," Biol. Cell 96, 231-236 (2004).
[CrossRef] [PubMed]

Antelman, J.

X. Michalet, R. A. Colyer, J. Antelman, O. H. W. Siegmund, A. Tremsin, J. V. Vallerga, and S. Weiss, "Single quantum dot imaging with a photon counting camera," Curr. Pharm. Biotechnol. 10, 543-558 (2009).
[CrossRef] [PubMed]

Arlt, J.

D.-U. Li, J. Arlt, J. Richardson, R. Walker, A. Buts, D. Stoppa, E. Charbon, and R. Henderson, "Real-time fluorescence lifetime imaging system with a 32×32 0.13μm CMOS low dark-count single-photon avalanche diode array," Opt. Express 18, 10527-102692 (2010).

Arndt-Jovin, D. J.

G. Marriott, R. M. Clegg, D. J. Arndt-Jovin, and T. M. Jovin, "Time resolved imaging microscopy - phosphorescence and delayed fluorescence imaging," Biophys. J. 60, 1374-1387 (1991).
[CrossRef] [PubMed]

Asquin, D.

J. B. Hutchings, J. Postma, D. Asquin, and D. Leahy, "Photon event centroiding with UV photon-counting detectors," Publ. Astron. Soc. Pac. 119, 1152-1162 (2007).
[CrossRef]

Bajzer, Z.

Z. Bajzer, A. Zelić, and F. G. Prendergast, "Analytical approach to the recovery of short fluorescence lifetimes from fluorescence decay curves," Biophys. J. 69, 1148-1161 (1995).
[CrossRef] [PubMed]

Berglund, A. J.

Bingham, R. E.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

Birch, D. J. S.

G. Hungerford, and D. J. S. Birch, "Single-photon timing detectors for fluorescence lifetime spectroscopy," Meas. Sci. Technol. 7, 121-135 (1996).
[CrossRef]

Botchway, S. W.

S. W. Botchway, M. Charnley, J. W. Haycock, A. W. Parker, D. L. Rochester, J. A. Weinstein, and J. A. G. Williams, "Time-resolved and two-photon emission imaging microscopy of live cells with inert platinum complexes," Proc. Natl. Acad. Sci. U.S.A. 105, 16071-16076 (2008).
[CrossRef] [PubMed]

Boyd, P. T.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

Breeveld, A. A.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

Broos, P. S.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

Bub, G.

G. Bub, M. Tecza, M. Helmes, P. Lee, and P. Kohl, "Temporal pixel multiplexing for simultaneous high-speed, high-resolution imaging," Nat. Methods 7, 209-211 (2010).
[CrossRef] [PubMed]

Buller, G. S.

G. S. Buller, R. D. Harkins, A. McCarthy, P. A. Hiskett, G. R. MacKinnon, G. R. Smith, R. Sung, A. M. Wallace, R. A. Lamb, K. D. Ridley, and J. G. Rarity, "Multiple wavelength time-of-flight sensor based on time-correlated single-photon counting," Rev. Sci. Instrum. 76, 083112 (2005).
[CrossRef]

Bunzli, J. C. G.

J. C. G. Bunzli, "Lanthanide luminescence for biomedical analyses and imaging," Chem. Rev. 110, 2729-2755 (2010).
[CrossRef] [PubMed]

Buts, A.

D.-U. Li, J. Arlt, J. Richardson, R. Walker, A. Buts, D. Stoppa, E. Charbon, and R. Henderson, "Real-time fluorescence lifetime imaging system with a 32×32 0.13μm CMOS low dark-count single-photon avalanche diode array," Opt. Express 18, 10527-102692 (2010).

Carter, M. J.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

Carter, M. K.

P. D. Read, M. K. Carter, C. D. Pike, R. A. Harrison, B. J. Kent, B. M. Swinyard, B. E. Patchett, R. M. Redfern, A. Shearer, and M. Colhoun, "Uses of microchannel plate intensified detectors for imaging applications in the X-ray, EUV and visible wavelength regions,"Nucl. Instrum. Methods Phys. Res., Sect. A 392, 359-363 (1997).
[CrossRef]

Cerezo, A.

O. Jagutzki, A. Cerezo, A. Czasch, R. Dörner, M. Hattaß, M. Huang, V. Mergel, U. Spillmann, K. Ullmann-Pfleger, T. Weber, H. Schmidt-Böcking, and G. D. W. Smith, "Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode," IEEE Trans. Nucl. Sci. 49, 2477-2483 (2002).
[CrossRef]

Charbon, E.

D.-U. Li, J. Arlt, J. Richardson, R. Walker, A. Buts, D. Stoppa, E. Charbon, and R. Henderson, "Real-time fluorescence lifetime imaging system with a 32×32 0.13μm CMOS low dark-count single-photon avalanche diode array," Opt. Express 18, 10527-102692 (2010).

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, ""A 128×128 Single-Photon Image Sensor With Column-Level 10-Bit Time-to-Digital Converter Array," IEEE J. Sol.- St. Circ. 43, 2977-2989 (2008).
[CrossRef]

Charnley, M.

S. W. Botchway, M. Charnley, J. W. Haycock, A. W. Parker, D. L. Rochester, J. A. Weinstein, and J. A. G. Williams, "Time-resolved and two-photon emission imaging microscopy of live cells with inert platinum complexes," Proc. Natl. Acad. Sci. U.S.A. 105, 16071-16076 (2008).
[CrossRef] [PubMed]

Clegg, R. M.

G. Marriott, R. M. Clegg, D. J. Arndt-Jovin, and T. M. Jovin, "Time resolved imaging microscopy - phosphorescence and delayed fluorescence imaging," Biophys. J. 60, 1374-1387 (1991).
[CrossRef] [PubMed]

Colhoun, M.

P. D. Read, M. K. Carter, C. D. Pike, R. A. Harrison, B. J. Kent, B. M. Swinyard, B. E. Patchett, R. M. Redfern, A. Shearer, and M. Colhoun, "Uses of microchannel plate intensified detectors for imaging applications in the X-ray, EUV and visible wavelength regions,"Nucl. Instrum. Methods Phys. Res., Sect. A 392, 359-363 (1997).
[CrossRef]

Colyer, R. A.

X. Michalet, R. A. Colyer, J. Antelman, O. H. W. Siegmund, A. Tremsin, J. V. Vallerga, and S. Weiss, "Single quantum dot imaging with a photon counting camera," Curr. Pharm. Biotechnol. 10, 543-558 (2009).
[CrossRef] [PubMed]

Coogan, M. P.

M. P. Coogan, J. B. Court, V. L. Gray, A. J. Hayes, S. H. Lloyd, C. O. Millet, S. J. A. Pope, and D. Lloyd, "Probing intracellular oxygen by quenched phosphorescence lifetimes of nanoparticles containing polyacrylamideembedded [Ru(dpp(SO3Na)2)3]Cl2," Photochem. Photobiol. Sci. 9, 103-109 (2010).
[CrossRef] [PubMed]

Court, J. B.

M. P. Coogan, J. B. Court, V. L. Gray, A. J. Hayes, S. H. Lloyd, C. O. Millet, S. J. A. Pope, and D. Lloyd, "Probing intracellular oxygen by quenched phosphorescence lifetimes of nanoparticles containing polyacrylamideembedded [Ru(dpp(SO3Na)2)3]Cl2," Photochem. Photobiol. Sci. 9, 103-109 (2010).
[CrossRef] [PubMed]

Czasch, A.

O. Jagutzki, A. Cerezo, A. Czasch, R. Dörner, M. Hattaß, M. Huang, V. Mergel, U. Spillmann, K. Ullmann-Pfleger, T. Weber, H. Schmidt-Böcking, and G. D. W. Smith, "Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode," IEEE Trans. Nucl. Sci. 49, 2477-2483 (2002).
[CrossRef]

Davis, D. M.

J. Siegel, K. Suhling, S. Leveque-Fort, S. E. D. Webb, D. M. Davis, D. Phillips, Y. Sabharwal, and P. M. W. French, "Wide-field time-resolved fluorescence anisotropy imaging (TR-FAIM): Imaging the rotational mobility of a fluorophore," Rev. Sci. Instrum. 74, 182-192 (2003).
[CrossRef]

Delpy, D. T.

F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, "A 32-channel time-resolved instrument for medical optical tomography," Rev. Sci. Instrum. 71, 256-265 (2000).
[CrossRef]

Dörner, R.

O. Jagutzki, A. Cerezo, A. Czasch, R. Dörner, M. Hattaß, M. Huang, V. Mergel, U. Spillmann, K. Ullmann-Pfleger, T. Weber, H. Schmidt-Böcking, and G. D. W. Smith, "Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode," IEEE Trans. Nucl. Sci. 49, 2477-2483 (2002).
[CrossRef]

Dunsby, C.

D. S. Elson, I. Munro, J. Requejo-Isidro, J. McGinty, C. Dunsby, N. Galletly, G. W. Stamp, M. A. A. Neil, M. J. Lever, P. A. Kellett, A. Dymoke-Bradshaw, J. Hares, and P. M. W. French, "Real-time time-domain fluorescence lifetime imaging including single-shot acquisition with a segmented optical image intensifier," N. J. Phys. 6, 180 (2004).
[CrossRef]

Dymoke-Bradshaw, A.

D. S. Elson, I. Munro, J. Requejo-Isidro, J. McGinty, C. Dunsby, N. Galletly, G. W. Stamp, M. A. A. Neil, M. J. Lever, P. A. Kellett, A. Dymoke-Bradshaw, J. Hares, and P. M. W. French, "Real-time time-domain fluorescence lifetime imaging including single-shot acquisition with a segmented optical image intensifier," N. J. Phys. 6, 180 (2004).
[CrossRef]

Eckert, H. J.

Z. Petrášek, H. J. Eckert, and K. Kemnitz, "Wide-field photon counting fluorescence lifetime imaging microscopy: application to photosynthesizing systems," Photosynth. Res. 102, 157-168 (2009).
[CrossRef]

Elson, D. S.

D. S. Elson, I. Munro, J. Requejo-Isidro, J. McGinty, C. Dunsby, N. Galletly, G. W. Stamp, M. A. A. Neil, M. J. Lever, P. A. Kellett, A. Dymoke-Bradshaw, J. Hares, and P. M. W. French, "Real-time time-domain fluorescence lifetime imaging including single-shot acquisition with a segmented optical image intensifier," N. J. Phys. 6, 180 (2004).
[CrossRef]

Favi, C.

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, ""A 128×128 Single-Photon Image Sensor With Column-Level 10-Bit Time-to-Digital Converter Array," IEEE J. Sol.- St. Circ. 43, 2977-2989 (2008).
[CrossRef]

Festy, F.

F. Festy, S. M. Ameer-Beg, T. Ng, and K. Suhling, "Imaging proteins in vivo using fluorescence lifetime microscopy," Mol. Biosyst. 3, 381-391 (2007).
[CrossRef] [PubMed]

Fraser, G. W.

J. E. Lees, and G. W. Fraser, "Efficiency enhancements for MCP-based beta autoradiography imaging," Nucl. Instrum. Methods Phys. Res., Sect. A 477, 239-243 (2002).
[CrossRef]

French, P. M. W.

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

D. S. Elson, I. Munro, J. Requejo-Isidro, J. McGinty, C. Dunsby, N. Galletly, G. W. Stamp, M. A. A. Neil, M. J. Lever, P. A. Kellett, A. Dymoke-Bradshaw, J. Hares, and P. M. W. French, "Real-time time-domain fluorescence lifetime imaging including single-shot acquisition with a segmented optical image intensifier," N. J. Phys. 6, 180 (2004).
[CrossRef]

J. Siegel, K. Suhling, S. Leveque-Fort, S. E. D. Webb, D. M. Davis, D. Phillips, Y. Sabharwal, and P. M. W. French, "Wide-field time-resolved fluorescence anisotropy imaging (TR-FAIM): Imaging the rotational mobility of a fluorophore," Rev. Sci. Instrum. 74, 182-192 (2003).
[CrossRef]

Fry, M. E.

F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, "A 32-channel time-resolved instrument for medical optical tomography," Rev. Sci. Instrum. 71, 256-265 (2000).
[CrossRef]

Galletly, N.

D. S. Elson, I. Munro, J. Requejo-Isidro, J. McGinty, C. Dunsby, N. Galletly, G. W. Stamp, M. A. A. Neil, M. J. Lever, P. A. Kellett, A. Dymoke-Bradshaw, J. Hares, and P. M. W. French, "Real-time time-domain fluorescence lifetime imaging including single-shot acquisition with a segmented optical image intensifier," N. J. Phys. 6, 180 (2004).
[CrossRef]

Gersbach, M.

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, ""A 128×128 Single-Photon Image Sensor With Column-Level 10-Bit Time-to-Digital Converter Array," IEEE J. Sol.- St. Circ. 43, 2977-2989 (2008).
[CrossRef]

Gray, V. L.

M. P. Coogan, J. B. Court, V. L. Gray, A. J. Hayes, S. H. Lloyd, C. O. Millet, S. J. A. Pope, and D. Lloyd, "Probing intracellular oxygen by quenched phosphorescence lifetimes of nanoparticles containing polyacrylamideembedded [Ru(dpp(SO3Na)2)3]Cl2," Photochem. Photobiol. Sci. 9, 103-109 (2010).
[CrossRef] [PubMed]

Guerrieri, F.

S. Tisa, F. Guerrieri, and F. Zappa, "Monolithic array of 32 SPAD pixels for single-photon imaging at high frame rates," Nucl. Instrum. Methods Phys. Res., Sect. A 610, 24-27 (2009).
[CrossRef]

Hancock, B. K.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

Hares, J.

D. S. Elson, I. Munro, J. Requejo-Isidro, J. McGinty, C. Dunsby, N. Galletly, G. W. Stamp, M. A. A. Neil, M. J. Lever, P. A. Kellett, A. Dymoke-Bradshaw, J. Hares, and P. M. W. French, "Real-time time-domain fluorescence lifetime imaging including single-shot acquisition with a segmented optical image intensifier," N. J. Phys. 6, 180 (2004).
[CrossRef]

Harkins, R. D.

G. S. Buller, R. D. Harkins, A. McCarthy, P. A. Hiskett, G. R. MacKinnon, G. R. Smith, R. Sung, A. M. Wallace, R. A. Lamb, K. D. Ridley, and J. G. Rarity, "Multiple wavelength time-of-flight sensor based on time-correlated single-photon counting," Rev. Sci. Instrum. 76, 083112 (2005).
[CrossRef]

Harrison, R. A.

P. D. Read, M. K. Carter, C. D. Pike, R. A. Harrison, B. J. Kent, B. M. Swinyard, B. E. Patchett, R. M. Redfern, A. Shearer, and M. Colhoun, "Uses of microchannel plate intensified detectors for imaging applications in the X-ray, EUV and visible wavelength regions,"Nucl. Instrum. Methods Phys. Res., Sect. A 392, 359-363 (1997).
[CrossRef]

Hashino, K.

Y. Yamaguchi, K. Hashino, M. Ito, K. Ikawa, T. Nishioka, and K. Matsumoto, "Sodium dodecyl sulfate polyacrylamide slab gel electrophoresis and hydroxyethyl cellurose gel capillary electrophoresis of luminescent lanthanide chelate-labeled proteins with time-resolved detection," Anal. Sci. 25, 327-332 (2009).
[CrossRef] [PubMed]

T. Nishioka, J. L. Yuan, Y. Yamamoto, K. Sumitomo, Z. Wang, K. Hashino, C. Hosoya, K. Ikawa, G. L. Wang, and K. Matsumoto, "New luminescent europium(III) chelates for DNA labeling," Inorg. Chem. 45, 4088-4096 (2006).
[CrossRef] [PubMed]

Hattaß, M.

O. Jagutzki, A. Cerezo, A. Czasch, R. Dörner, M. Hattaß, M. Huang, V. Mergel, U. Spillmann, K. Ullmann-Pfleger, T. Weber, H. Schmidt-Böcking, and G. D. W. Smith, "Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode," IEEE Trans. Nucl. Sci. 49, 2477-2483 (2002).
[CrossRef]

Haycock, J. W.

S. W. Botchway, M. Charnley, J. W. Haycock, A. W. Parker, D. L. Rochester, J. A. Weinstein, and J. A. G. Williams, "Time-resolved and two-photon emission imaging microscopy of live cells with inert platinum complexes," Proc. Natl. Acad. Sci. U.S.A. 105, 16071-16076 (2008).
[CrossRef] [PubMed]

Hayes, A. J.

M. P. Coogan, J. B. Court, V. L. Gray, A. J. Hayes, S. H. Lloyd, C. O. Millet, S. J. A. Pope, and D. Lloyd, "Probing intracellular oxygen by quenched phosphorescence lifetimes of nanoparticles containing polyacrylamideembedded [Ru(dpp(SO3Na)2)3]Cl2," Photochem. Photobiol. Sci. 9, 103-109 (2010).
[CrossRef] [PubMed]

Hebden, J. C.

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Y. Prokazov, E. Turbin, M. Vitali, A. Herzog, B. Michaelis, W. Zuschratter, and K. Kemnitz, "Reborn quadrant anode image sensor," Nucl. Instrum. Methods Phys. Res., Sect. A 604, 221-223 (2009).
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P. D. Read, M. K. Carter, C. D. Pike, R. A. Harrison, B. J. Kent, B. M. Swinyard, B. E. Patchett, R. M. Redfern, A. Shearer, and M. Colhoun, "Uses of microchannel plate intensified detectors for imaging applications in the X-ray, EUV and visible wavelength regions,"Nucl. Instrum. Methods Phys. Res., Sect. A 392, 359-363 (1997).
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G. S. Buller, R. D. Harkins, A. McCarthy, P. A. Hiskett, G. R. MacKinnon, G. R. Smith, R. Sung, A. M. Wallace, R. A. Lamb, K. D. Ridley, and J. G. Rarity, "Multiple wavelength time-of-flight sensor based on time-correlated single-photon counting," Rev. Sci. Instrum. 76, 083112 (2005).
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J. Siegel, K. Suhling, S. Leveque-Fort, S. E. D. Webb, D. M. Davis, D. Phillips, Y. Sabharwal, and P. M. W. French, "Wide-field time-resolved fluorescence anisotropy imaging (TR-FAIM): Imaging the rotational mobility of a fluorophore," Rev. Sci. Instrum. 74, 182-192 (2003).
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J. A. Spitz, R. Yasukuni, N. Sandeau, M. Takano, J. J. Vachon, R. Meallet-Renault, and R. B. Pansu, "Scanningless wide-field single-photon counting device for fluorescence intensity, lifetime and time-resolved anisotropy imaging microscopy," J. Microsc. 229, 104-114 (2008).
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Siegel, J.

J. Siegel, K. Suhling, S. Leveque-Fort, S. E. D. Webb, D. M. Davis, D. Phillips, Y. Sabharwal, and P. M. W. French, "Wide-field time-resolved fluorescence anisotropy imaging (TR-FAIM): Imaging the rotational mobility of a fluorophore," Rev. Sci. Instrum. 74, 182-192 (2003).
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A. S. Tremsin, O. H. W. Siegmund, J. V. Vallerga, R. Raffanti, S. Weiss, and X. Michalet, "High speed multichannel charge sensitive data acquisition system with self-triggered event timing," IEEE Trans. Nucl. Sci. 56, 1148-1152 (2009).
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[CrossRef] [PubMed]

X. Michalet, O. H. W. Siegmund, J. V. Vallerga, P. Jelinsky, J. E. Millaud, and S. Weiss, "Detectors for single molecule fluorescence imaging and spectroscopy," J. Mod. Opt. 54, 239-281 (2007).
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Smith, G. D. W.

O. Jagutzki, A. Cerezo, A. Czasch, R. Dörner, M. Hattaß, M. Huang, V. Mergel, U. Spillmann, K. Ullmann-Pfleger, T. Weber, H. Schmidt-Böcking, and G. D. W. Smith, "Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode," IEEE Trans. Nucl. Sci. 49, 2477-2483 (2002).
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Smith, G. R.

G. S. Buller, R. D. Harkins, A. McCarthy, P. A. Hiskett, G. R. MacKinnon, G. R. Smith, R. Sung, A. M. Wallace, R. A. Lamb, K. D. Ridley, and J. G. Rarity, "Multiple wavelength time-of-flight sensor based on time-correlated single-photon counting," Rev. Sci. Instrum. 76, 083112 (2005).
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Smith, K.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
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Smith, P. J.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
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Soto, J. C.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
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Spillmann, U.

O. Jagutzki, A. Cerezo, A. Czasch, R. Dörner, M. Hattaß, M. Huang, V. Mergel, U. Spillmann, K. Ullmann-Pfleger, T. Weber, H. Schmidt-Böcking, and G. D. W. Smith, "Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode," IEEE Trans. Nucl. Sci. 49, 2477-2483 (2002).
[CrossRef]

Spitz, J. A.

J. A. Spitz, R. Yasukuni, N. Sandeau, M. Takano, J. J. Vachon, R. Meallet-Renault, and R. B. Pansu, "Scanningless wide-field single-photon counting device for fluorescence intensity, lifetime and time-resolved anisotropy imaging microscopy," J. Microsc. 229, 104-114 (2008).
[CrossRef] [PubMed]

Stamp, G. W.

D. S. Elson, I. Munro, J. Requejo-Isidro, J. McGinty, C. Dunsby, N. Galletly, G. W. Stamp, M. A. A. Neil, M. J. Lever, P. A. Kellett, A. Dymoke-Bradshaw, J. Hares, and P. M. W. French, "Real-time time-domain fluorescence lifetime imaging including single-shot acquisition with a segmented optical image intensifier," N. J. Phys. 6, 180 (2004).
[CrossRef]

Still, M. D.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

Stock, J.

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
[CrossRef]

Stoppa, D.

D.-U. Li, J. Arlt, J. Richardson, R. Walker, A. Buts, D. Stoppa, E. Charbon, and R. Henderson, "Real-time fluorescence lifetime imaging system with a 32×32 0.13μm CMOS low dark-count single-photon avalanche diode array," Opt. Express 18, 10527-102692 (2010).

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, 28-36 (2009).
[CrossRef] [PubMed]

F. Festy, S. M. Ameer-Beg, T. Ng, and K. Suhling, "Imaging proteins in vivo using fluorescence lifetime microscopy," Mol. Biosyst. 3, 381-391 (2007).
[CrossRef] [PubMed]

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

J. Siegel, K. Suhling, S. Leveque-Fort, S. E. D. Webb, D. M. Davis, D. Phillips, Y. Sabharwal, and P. M. W. French, "Wide-field time-resolved fluorescence anisotropy imaging (TR-FAIM): Imaging the rotational mobility of a fluorophore," Rev. Sci. Instrum. 74, 182-192 (2003).
[CrossRef]

K. Suhling, R. W. Airey, and B. L. Morgan, "Minimization of fixed pattern noise in photon event counting imaging," Rev. Sci. Instrum. 73, 2917-2922 (2002).
[CrossRef]

K. Suhling, G. Hungerford, R. W. Airey, and B. L. Morgan, "A position-sensitive photon event counting detector applied to fluorescence imaging of dyes in sol-gel matrices," Meas. Sci. Technol. 12, 131-141 (2001).
[CrossRef]

K. Suhling, R. Airey, and B. Morgan, ""Optimisation of centroiding algorithms for photon event counting imaging," Nucl. Instrum. Methods Phys. Res., Sect. A 437, 393-418 (1999).
[CrossRef]

Sumitomo, K.

T. Nishioka, J. L. Yuan, Y. Yamamoto, K. Sumitomo, Z. Wang, K. Hashino, C. Hosoya, K. Ikawa, G. L. Wang, and K. Matsumoto, "New luminescent europium(III) chelates for DNA labeling," Inorg. Chem. 45, 4088-4096 (2006).
[CrossRef] [PubMed]

Sung, R.

G. S. Buller, R. D. Harkins, A. McCarthy, P. A. Hiskett, G. R. MacKinnon, G. R. Smith, R. Sung, A. M. Wallace, R. A. Lamb, K. D. Ridley, and J. G. Rarity, "Multiple wavelength time-of-flight sensor based on time-correlated single-photon counting," Rev. Sci. Instrum. 76, 083112 (2005).
[CrossRef]

Swinyard, B. M.

P. D. Read, M. K. Carter, C. D. Pike, R. A. Harrison, B. J. Kent, B. M. Swinyard, B. E. Patchett, R. M. Redfern, A. Shearer, and M. Colhoun, "Uses of microchannel plate intensified detectors for imaging applications in the X-ray, EUV and visible wavelength regions,"Nucl. Instrum. Methods Phys. Res., Sect. A 392, 359-363 (1997).
[CrossRef]

Takano, M.

J. A. Spitz, R. Yasukuni, N. Sandeau, M. Takano, J. J. Vachon, R. Meallet-Renault, and R. B. Pansu, "Scanningless wide-field single-photon counting device for fluorescence intensity, lifetime and time-resolved anisotropy imaging microscopy," J. Microsc. 229, 104-114 (2008).
[CrossRef] [PubMed]

Tecza, M.

G. Bub, M. Tecza, M. Helmes, P. Lee, and P. Kohl, "Temporal pixel multiplexing for simultaneous high-speed, high-resolution imaging," Nat. Methods 7, 209-211 (2010).
[CrossRef] [PubMed]

Tisa, S.

S. Tisa, F. Guerrieri, and F. Zappa, "Monolithic array of 32 SPAD pixels for single-photon imaging at high frame rates," Nucl. Instrum. Methods Phys. Res., Sect. A 610, 24-27 (2009).
[CrossRef]

Tremsin, A.

X. Michalet, R. A. Colyer, J. Antelman, O. H. W. Siegmund, A. Tremsin, J. V. Vallerga, and S. Weiss, "Single quantum dot imaging with a photon counting camera," Curr. Pharm. Biotechnol. 10, 543-558 (2009).
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A. S. Tremsin, O. H. W. Siegmund, J. V. Vallerga, R. Raffanti, S. Weiss, and X. Michalet, "High speed multichannel charge sensitive data acquisition system with self-triggered event timing," IEEE Trans. Nucl. Sci. 56, 1148-1152 (2009).
[CrossRef]

Turbin, E.

Y. Prokazov, E. Turbin, M. Vitali, A. Herzog, B. Michaelis, W. Zuschratter, and K. Kemnitz, "Reborn quadrant anode image sensor," Nucl. Instrum. Methods Phys. Res., Sect. A 604, 221-223 (2009).
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O. Jagutzki, A. Cerezo, A. Czasch, R. Dörner, M. Hattaß, M. Huang, V. Mergel, U. Spillmann, K. Ullmann-Pfleger, T. Weber, H. Schmidt-Böcking, and G. D. W. Smith, "Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode," IEEE Trans. Nucl. Sci. 49, 2477-2483 (2002).
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J. A. Spitz, R. Yasukuni, N. Sandeau, M. Takano, J. J. Vachon, R. Meallet-Renault, and R. B. Pansu, "Scanningless wide-field single-photon counting device for fluorescence intensity, lifetime and time-resolved anisotropy imaging microscopy," J. Microsc. 229, 104-114 (2008).
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X. Michalet, R. A. Colyer, J. Antelman, O. H. W. Siegmund, A. Tremsin, J. V. Vallerga, and S. Weiss, "Single quantum dot imaging with a photon counting camera," Curr. Pharm. Biotechnol. 10, 543-558 (2009).
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A. S. Tremsin, O. H. W. Siegmund, J. V. Vallerga, R. Raffanti, S. Weiss, and X. Michalet, "High speed multichannel charge sensitive data acquisition system with self-triggered event timing," IEEE Trans. Nucl. Sci. 56, 1148-1152 (2009).
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X. Michalet, O. H. W. Siegmund, J. V. Vallerga, P. Jelinsky, J. E. Millaud, and S. Weiss, "Detectors for single molecule fluorescence imaging and spectroscopy," J. Mod. Opt. 54, 239-281 (2007).
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G. Vereb, E. Jares-Erijman, P. R. Selvin, and T. M. Jovin, "Temporally and spectrally resolved imaging microscopy of lanthanide chelates," Biophys. J. 74, 2210-2222 (1998).
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Y. Prokazov, E. Turbin, M. Vitali, A. Herzog, B. Michaelis, W. Zuschratter, and K. Kemnitz, "Reborn quadrant anode image sensor," Nucl. Instrum. Methods Phys. Res., Sect. A 604, 221-223 (2009).
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W. K. Young, B. Vojnovic, and P. Wardman, "Measurement of oxygen tension in tumours by time-resolved fluorescence," Br. J. Cancer 74, S256-S259 (1996).

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D.-U. Li, J. Arlt, J. Richardson, R. Walker, A. Buts, D. Stoppa, E. Charbon, and R. Henderson, "Real-time fluorescence lifetime imaging system with a 32×32 0.13μm CMOS low dark-count single-photon avalanche diode array," Opt. Express 18, 10527-102692 (2010).

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A. C. Mitchell, J. E. Wall, J. G. Murray, and C. G. Morgan, "Direct modulation of the effective sensitivity of a ccd detector: a new approach to time-resolved fluorescence imaging," J. Microsc. 206, 225-232 (2002).
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G. S. Buller, R. D. Harkins, A. McCarthy, P. A. Hiskett, G. R. MacKinnon, G. R. Smith, R. Sung, A. M. Wallace, R. A. Lamb, K. D. Ridley, and J. G. Rarity, "Multiple wavelength time-of-flight sensor based on time-correlated single-photon counting," Rev. Sci. Instrum. 76, 083112 (2005).
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T. Nishioka, J. L. Yuan, Y. Yamamoto, K. Sumitomo, Z. Wang, K. Hashino, C. Hosoya, K. Ikawa, G. L. Wang, and K. Matsumoto, "New luminescent europium(III) chelates for DNA labeling," Inorg. Chem. 45, 4088-4096 (2006).
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T. Nishioka, J. L. Yuan, Y. Yamamoto, K. Sumitomo, Z. Wang, K. Hashino, C. Hosoya, K. Ikawa, G. L. Wang, and K. Matsumoto, "New luminescent europium(III) chelates for DNA labeling," Inorg. Chem. 45, 4088-4096 (2006).
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W. K. Young, B. Vojnovic, and P. Wardman, "Measurement of oxygen tension in tumours by time-resolved fluorescence," Br. J. Cancer 74, S256-S259 (1996).

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J. Siegel, K. Suhling, S. Leveque-Fort, S. E. D. Webb, D. M. Davis, D. Phillips, Y. Sabharwal, and P. M. W. French, "Wide-field time-resolved fluorescence anisotropy imaging (TR-FAIM): Imaging the rotational mobility of a fluorophore," Rev. Sci. Instrum. 74, 182-192 (2003).
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O. Jagutzki, A. Cerezo, A. Czasch, R. Dörner, M. Hattaß, M. Huang, V. Mergel, U. Spillmann, K. Ullmann-Pfleger, T. Weber, H. Schmidt-Böcking, and G. D. W. Smith, "Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode," IEEE Trans. Nucl. Sci. 49, 2477-2483 (2002).
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S. W. Botchway, M. Charnley, J. W. Haycock, A. W. Parker, D. L. Rochester, J. A. Weinstein, and J. A. G. Williams, "Time-resolved and two-photon emission imaging microscopy of live cells with inert platinum complexes," Proc. Natl. Acad. Sci. U.S.A. 105, 16071-16076 (2008).
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X. Michalet, R. A. Colyer, J. Antelman, O. H. W. Siegmund, A. Tremsin, J. V. Vallerga, and S. Weiss, "Single quantum dot imaging with a photon counting camera," Curr. Pharm. Biotechnol. 10, 543-558 (2009).
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A. S. Tremsin, O. H. W. Siegmund, J. V. Vallerga, R. Raffanti, S. Weiss, and X. Michalet, "High speed multichannel charge sensitive data acquisition system with self-triggered event timing," IEEE Trans. Nucl. Sci. 56, 1148-1152 (2009).
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X. Michalet, O. H. W. Siegmund, J. V. Vallerga, P. Jelinsky, J. E. Millaud, and S. Weiss, "Detectors for single molecule fluorescence imaging and spectroscopy," J. Mod. Opt. 54, 239-281 (2007).
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M. H. V. Werts, "Making sense of lanthanide luminescence," Sci. Prog. 88, 101-131 (2005).
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S. W. Botchway, M. Charnley, J. W. Haycock, A. W. Parker, D. L. Rochester, J. A. Weinstein, and J. A. G. Williams, "Time-resolved and two-photon emission imaging microscopy of live cells with inert platinum complexes," Proc. Natl. Acad. Sci. U.S.A. 105, 16071-16076 (2008).
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J. G. Mainprize, and M. J. Yaffe, "The effect of phosphor persistence on image quality in digital x-ray scanning systems," Med. Phys. 25, 2440-2454 (1998).
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Y. Yamaguchi, K. Hashino, M. Ito, K. Ikawa, T. Nishioka, and K. Matsumoto, "Sodium dodecyl sulfate polyacrylamide slab gel electrophoresis and hydroxyethyl cellurose gel capillary electrophoresis of luminescent lanthanide chelate-labeled proteins with time-resolved detection," Anal. Sci. 25, 327-332 (2009).
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T. Nishioka, J. L. Yuan, Y. Yamamoto, K. Sumitomo, Z. Wang, K. Hashino, C. Hosoya, K. Ikawa, G. L. Wang, and K. Matsumoto, "New luminescent europium(III) chelates for DNA labeling," Inorg. Chem. 45, 4088-4096 (2006).
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J. A. Spitz, R. Yasukuni, N. Sandeau, M. Takano, J. J. Vachon, R. Meallet-Renault, and R. B. Pansu, "Scanningless wide-field single-photon counting device for fluorescence intensity, lifetime and time-resolved anisotropy imaging microscopy," J. Microsc. 229, 104-114 (2008).
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W. K. Young, B. Vojnovic, and P. Wardman, "Measurement of oxygen tension in tumours by time-resolved fluorescence," Br. J. Cancer 74, S256-S259 (1996).

Yuan, J. L.

T. Nishioka, J. L. Yuan, Y. Yamamoto, K. Sumitomo, Z. Wang, K. Hashino, C. Hosoya, K. Ikawa, G. L. Wang, and K. Matsumoto, "New luminescent europium(III) chelates for DNA labeling," Inorg. Chem. 45, 4088-4096 (2006).
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S. Tisa, F. Guerrieri, and F. Zappa, "Monolithic array of 32 SPAD pixels for single-photon imaging at high frame rates," Nucl. Instrum. Methods Phys. Res., Sect. A 610, 24-27 (2009).
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Z. Bajzer, A. Zelić, and F. G. Prendergast, "Analytical approach to the recovery of short fluorescence lifetimes from fluorescence decay curves," Biophys. J. 69, 1148-1161 (1995).
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Y. Prokazov, E. Turbin, M. Vitali, A. Herzog, B. Michaelis, W. Zuschratter, and K. Kemnitz, "Reborn quadrant anode image sensor," Nucl. Instrum. Methods Phys. Res., Sect. A 604, 221-223 (2009).
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G. Vereb, E. Jares-Erijman, P. R. Selvin, and T. M. Jovin, "Temporally and spectrally resolved imaging microscopy of lanthanide chelates," Biophys. J. 74, 2210-2222 (1998).
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W. K. Young, B. Vojnovic, and P. Wardman, "Measurement of oxygen tension in tumours by time-resolved fluorescence," Br. J. Cancer 74, S256-S259 (1996).

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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, 28-36 (2009).
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Curr. Pharm. Biotechnol. (1)

X. Michalet, R. A. Colyer, J. Antelman, O. H. W. Siegmund, A. Tremsin, J. V. Vallerga, and S. Weiss, "Single quantum dot imaging with a photon counting camera," Curr. Pharm. Biotechnol. 10, 543-558 (2009).
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A. S. Tremsin, O. H. W. Siegmund, J. V. Vallerga, R. Raffanti, S. Weiss, and X. Michalet, "High speed multichannel charge sensitive data acquisition system with self-triggered event timing," IEEE Trans. Nucl. Sci. 56, 1148-1152 (2009).
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Inorg. Chem. (1)

T. Nishioka, J. L. Yuan, Y. Yamamoto, K. Sumitomo, Z. Wang, K. Hashino, C. Hosoya, K. Ikawa, G. L. Wang, and K. Matsumoto, "New luminescent europium(III) chelates for DNA labeling," Inorg. Chem. 45, 4088-4096 (2006).
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A. C. Mitchell, J. E. Wall, J. G. Murray, and C. G. Morgan, "Direct modulation of the effective sensitivity of a ccd detector: a new approach to time-resolved fluorescence imaging," J. Microsc. 206, 225-232 (2002).
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J. A. Spitz, R. Yasukuni, N. Sandeau, M. Takano, J. J. Vachon, R. Meallet-Renault, and R. B. Pansu, "Scanningless wide-field single-photon counting device for fluorescence intensity, lifetime and time-resolved anisotropy imaging microscopy," J. Microsc. 229, 104-114 (2008).
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J. Mod. Opt. (1)

X. Michalet, O. H. W. Siegmund, J. V. Vallerga, P. Jelinsky, J. E. Millaud, and S. Weiss, "Detectors for single molecule fluorescence imaging and spectroscopy," J. Mod. Opt. 54, 239-281 (2007).
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F. Festy, S. M. Ameer-Beg, T. Ng, and K. Suhling, "Imaging proteins in vivo using fluorescence lifetime microscopy," Mol. Biosyst. 3, 381-391 (2007).
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K. Suhling, R. Airey, and B. Morgan, ""Optimisation of centroiding algorithms for photon event counting imaging," Nucl. Instrum. Methods Phys. Res., Sect. A 437, 393-418 (1999).
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Y. Prokazov, E. Turbin, M. Vitali, A. Herzog, B. Michaelis, W. Zuschratter, and K. Kemnitz, "Reborn quadrant anode image sensor," Nucl. Instrum. Methods Phys. Res., Sect. A 604, 221-223 (2009).
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Opt. Express (2)

D.-U. Li, J. Arlt, J. Richardson, R. Walker, A. Buts, D. Stoppa, E. Charbon, and R. Henderson, "Real-time fluorescence lifetime imaging system with a 32×32 0.13μm CMOS low dark-count single-photon avalanche diode array," Opt. Express 18, 10527-102692 (2010).

A. J. Berglund, M. D. McMahon, J. J. McClelland, and J. A. Liddle, "Fast, bias-free algorithm for tracking single particles with variable size and shape," Opt. Express 16, 14064-14075 (2008).
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Proc. Natl. Acad. Sci. U.S.A. (1)

S. W. Botchway, M. Charnley, J. W. Haycock, A. W. Parker, D. L. Rochester, J. A. Weinstein, and J. A. G. Williams, "Time-resolved and two-photon emission imaging microscopy of live cells with inert platinum complexes," Proc. Natl. Acad. Sci. U.S.A. 105, 16071-16076 (2008).
[CrossRef] [PubMed]

Proc. SPIE (1)

N. A. Hosny, D. A. Lee, and K. M. M., "Extracellular oxygen concentration mapping with a confocal multiphoton laser scanning microscope and TCSPC card," Proc. SPIE 7569, 756932 (2010).
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Publ. Astron. Soc. Pac. (2)

N. A. Sharp, "Millisecond time resolution with the kitt peak photon-counting array," Publ. Astron. Soc. Pac. 104, 263-269 (1992).
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J. B. Hutchings, J. Postma, D. Asquin, and D. Leahy, "Photon event centroiding with UV photon-counting detectors," Publ. Astron. Soc. Pac. 119, 1152-1162 (2007).
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Rev. Sci. Instrum. (4)

F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, "A 32-channel time-resolved instrument for medical optical tomography," Rev. Sci. Instrum. 71, 256-265 (2000).
[CrossRef]

G. S. Buller, R. D. Harkins, A. McCarthy, P. A. Hiskett, G. R. MacKinnon, G. R. Smith, R. Sung, A. M. Wallace, R. A. Lamb, K. D. Ridley, and J. G. Rarity, "Multiple wavelength time-of-flight sensor based on time-correlated single-photon counting," Rev. Sci. Instrum. 76, 083112 (2005).
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K. Suhling, R. W. Airey, and B. L. Morgan, "Minimization of fixed pattern noise in photon event counting imaging," Rev. Sci. Instrum. 73, 2917-2922 (2002).
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J. Siegel, K. Suhling, S. Leveque-Fort, S. E. D. Webb, D. M. Davis, D. Phillips, Y. Sabharwal, and P. M. W. French, "Wide-field time-resolved fluorescence anisotropy imaging (TR-FAIM): Imaging the rotational mobility of a fluorophore," Rev. Sci. Instrum. 74, 182-192 (2003).
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Sci. Prog. (1)

M. H. V. Werts, "Making sense of lanthanide luminescence," Sci. Prog. 88, 101-131 (2005).
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Space Sci. Rev. (1)

P. W. A. Roming, T. E. Kennedy, K. O. Mason, J. A. Nousek, L. Ahr, R. E. Bingham, P. S. Broos, M. J. Carter, B. K. Hancock, H. E. Huckle, S. D. Hunsberger, H. Kawakami, R. Killough, T. S. Koch, M. K. Mclelland, K. Smith, P. J. Smith, J. C. Soto, P. T. Boyd, A. A. Breeveld, S. T. Holland, M. Ivanushkina, M. S. Pryzby, M. D. Still, and J. Stock, "The swift ultra-violet/optical telescope," Space Sci. Rev. 120, 95-142 (2005).
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Other (2)

D. V. O’Connor, and D. Phillips, Time-Correlated Single Photon Counting (Academic Press, 1984). ISBN 0125241402.

W. Becker, Advanced Time-Correlated Single Photon Counting Techniques, Springer Series in Chemical Physics (Springer, 2005). ISBN 3540260471.
[CrossRef]

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Figures (5)

Fig. 1
Fig. 1

The detection timing diagram. The camera exposure period T, determined by the shutter frequency 1/T, consists of the dead time (0, zT) and the active time (zT,T). The photon event at time xT relative to the beginning of the exposure period, together with the phosphor decay f(t), determines the intensities Im detected in the frames m, (m ≥ 1). x thus determines the sub-exposure arrival time of a photon event, and can be calculated from the intensities of the photon event in subsequent frames. The exposure time in our case is 4μs.

Fig. 2
Fig. 2

Event identification and decay extraction. A: An example of two events arriving in frame 1 as imaged in frames 0 to 6. The first event, in sequence I, reaches the maximum intensity in the first frame that is above the threshold level, while the second event, in sequence II, reaches its maximum in the second frame. B: The sum of frames 0 to 22 of the two events shown in A, together with the centroid position marked by a red cross. C: The intensity of the two events extracted from a 3 × 3 pixel region in every frame. Each time channel corresponds to 4 μs. D: An average decay of all events in one measurement, together with the standard deviation σ in every data point. The intensities in each set of frames in A and in both images in B have been scaled to use the whole gray scale for better visibility.

Fig. 3
Fig. 3

Timing of photon events with the camera exposure period T = 4μs, and the excitation frequency 20 kHz. The events occurring in even and odd frames are displayed in blue and red, respectively. The drift of x vs. the frame number, marked by solid lines, is caused by the ratio between the camera frame rate and the laser trigger not being exactly 12.5. The horizontal line at x = 0.174 marks the end of the dead time.

Fig. 4
Fig. 4

The experimentally determined dependence of the timing uncertainty σx (standard deviation of x) on the position x of the photon event relative to the beginning of the camera exposure period. The line is a fit to the events with x > 0.6.

Fig. 5
Fig. 5

For the highest timing uncertainty, the optimum delay between the camera shutter and the excitation trigger should be chosen. By adjusting the delay x0T between the camera shutter and the excitation trigger, the luminescence decay (blue curve) to be measured is positioned towards the end of the exposure period (0, T) where the timing uncertainty is highest (red line).

Equations (9)

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f ( t ) = j a j e t / τ j .
I 1 = β T f ( t x T ) d t = j a j τ j e x T / τ j ( e β / τ j e T / τ j ) ,
I m = ( m 1 ) T + z T m T f ( t x T ) d t = j a j τ j e x T / τ j ( e ( ( m 1 ) T + z T ) / τ j e m T / τ j ) .
I 0 = β 0 f ( t x T ) d t = j a j τ j e x T / τ j ( e β / τ j 1 ) ,
I m = β 1 β 2 f ( t x T ) d t = j a j τ j e x T / τ j ( e β 1 / τ j e β 2 / τ j ) ,
χ 2 = m ( d m A I m ) 2 ,
ρ = ln ( 1 p ) π d 2 n T p π d 2 n T
x = c n f + b ,
χ 2 = k m ( d m , k A k I m , k ) 2 ,

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