Abstract

A new integration based fluorescence lifetime imaging microscopy (FLIM) called IEM has been proposed to implement lifetime extraction [J. Opt. Soc. Am. A 25, 1190 (2008) ]. A real-time hardware implementation of the IEM FLIM algorithm suitable for single photon avalanche diode arrays in nanometer-scale CMOS technology is now proposed. The problems of reduced pixel readout bandwidth and background noise are studied and a calibration method suitable for FPGA implementation is introduced. In particular, the relationship between signal-to-noise ratio and background noise is considered based on statistics theory and compared with a rapid lifetime determination method and maximum-likelihood estimator with–without background correction. The results are also compared with Monte Carlo simulations giving good agreement. The performance of the proposed methods has been tested on monoexponential decay experimental data. The high flexibility, wide range, and hardware friendliness make IEM the best candidate for system-on-chip integration to our knowledge.

© 2009 Optical Society of America

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  26. M. Ghioni, A. Gulinatti, I. Rech, F. Zappa, and S. Cova, “Progress in silicon single-photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 13, 852-862 (2007).
    [CrossRef]
  27. M. Gersbach, C. Niclass, J. Richardson, R. Henderson, L. Grant, and E. Charbon, “A single photon detector implemented in a 130 nm CMOS imaging process,” in Proceedings of the 38th European Solid-State Device Research Conference (2008), pp. 270-273.
    [CrossRef]
  28. M. A. Marwick and A. G. Anreou, “Single photon avalanche photodetector with integrated quenching fabricated in TSMC 0.18 μm1.8 V CMOS process,” Electron. Lett. 44, 643-644 (2008).
    [CrossRef]
  29. M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett. 200, 199-204 (1992).
    [CrossRef]
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    [CrossRef]
  31. J. Philips and K. Carlsson, “Theoretical investigation of the signal-to-noise ratio in fluorescence lifetime imaging,” J. Opt. Soc. Am. A 20, 368-379 (2003).
    [CrossRef]

2008

D.-A. Mendels, E. M. Graham, S. W. Magennis, A. C. Jones, and F. Mendels, “Quantitative comparison of thermal and solutal transport in a T-mixer by FLIM and CFD,” Microfluid. Nanofluid. 5, 603-617 (2008).

D.-U. Li, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip time-correlated fluorescence lifetime extraction algorithms and error analysis,” J. Opt. Soc. Am. A 25, 1190-1198 (2008).
[CrossRef]

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71, 201-213 (2008).
[CrossRef]

M. A. Marwick and A. G. Anreou, “Single photon avalanche photodetector with integrated quenching fabricated in TSMC 0.18 μm1.8 V CMOS process,” Electron. Lett. 44, 643-644 (2008).
[CrossRef]

2007

C. Niclass, M. Gersbach, R. Henderson, L. Grant, and E. Charbon, “A single photon avalanche diode implemented in 130-nm CMOS technology,” IEEE J. Sel. Top. Quantum Electron. 13, 863-869 (2007).
[CrossRef]

M. Ghioni, A. Gulinatti, I. Rech, F. Zappa, and S. Cova, “Progress in silicon single-photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 13, 852-862 (2007).
[CrossRef]

2006

2005

R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones, “Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M. Hhal-DNA complexes,” Nucleic Acids Res. 33, 6953-6960 (2005).
[CrossRef] [PubMed]

J. A. Jo, Q. Fang, and L. Marcu, “Ultrafast method for the analysis of fluorescence lifetime imaging microscopy data based on the Laguerre expansion technique,” IEEE J. Sel. Top. Quantum Electron. 11, 835-845 (2005).
[CrossRef]

2004

S. Pelet, M. J. R. Previte, L. H. Laiho, and P. T. C. So, “A fast global fitting algorithm for fluorescence lifetime imaging microscopy based on image segmentation,” Biophys. J. 87, 2807-2817 (2004).
[CrossRef] [PubMed]

C. Moore, S. P. Chan, J. N. Demas, and B. A. Degraff, “Comparison of methods for rapid evaluation of lifetime of exponential decays,” Appl. Spectrosc. 58, 603-607 (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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

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).
[CrossRef] [PubMed]

D. Halmer, G. von Basum, P. Hering, and M. Mürtz, “Fast exponential fitting algorithm for real-time instrumental use,” Rev. Sci. Instrum. 75, 2187-2191 (2004).
[CrossRef]

C. Niclass, A. Rochas, P. A. Besse, and E. Charbon, “Toward a 3-D camera based on single photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 10, 796-802 (2004).
[CrossRef]

2003

J. Philips and K. Carlsson, “Theoretical investigation of the signal-to-noise ratio in fluorescence lifetime imaging,” J. Opt. Soc. Am. A 20, 368-379 (2003).
[CrossRef]

A. V. Agronskaia, L. Tertoolen, and H. C. Gerritsen, “High frame rate fluorescence lifetime imaging,” J. Phys. D 36, 1655-1662 (2003).
[CrossRef]

2002

W. Trabesinger, C. G. Hübner, B. Hecht, and U. P. Wild, “Continuous real-time measurement of fluorescence lifetimes,” Rev. Sci. Instrum. 73, 3122-3124 (2002).
[CrossRef]

1999

J. Mizeret, T. Stepinac, M. Hansroul, A. Studzinski, H. van den Bergh, and G. Wagnières, “Instrumentation for real-time fluorescence lifetime imaging in endoscopy,” Rev. Sci. Instrum. 70, 4689-4701 (1999).
[CrossRef]

A. A. Istratov and O. F. Vyvenko, “Exponential analysis in physical phenomena” Rev. Sci. Instrum. 70, 1233-1257 (1999).
[CrossRef]

P. I. H. Bastiaens and A. Squire, “Fluorescence lifetime imaging microscopy: spatial resolution of biochemical processes in the cell,” Trends Cell Biol. 9, 48-52 (1999).
[CrossRef] [PubMed]

1997

P. C. Schneider and R. M. Clegg, “Rapid acquisition, analysis, and display of fluorescence lifetime-resolved images for real-time applications,” Rev. Sci. Instrum. 68, 4107-4119 (1997).
[CrossRef]

1992

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett. 200, 199-204 (1992).
[CrossRef]

1989

R. M. Ballew and J. N. Demas, “An error analysis of the rapid lifetime determination method for the evaluation of single exponential decays,” Anal. Chem. 61, 30-33 (1989).
[CrossRef]

1984

H. P. Good, A. J. Kallir, and U. P. Wild, “Comparison of fluorescence lifetime fitting techniques,” J. Phys. Chem. 88, 5435-5441 (1984).
[CrossRef]

1981

P. Hall and B. Selinger, “Better estimates of exponential decay parameters,” J. Phys. Chem. 85, 2941-2946 (1981).
[CrossRef]

Agronskaia, A. V.

A. V. Agronskaia, L. Tertoolen, and H. C. Gerritsen, “High frame rate fluorescence lifetime imaging,” J. Phys. D 36, 1655-1662 (2003).
[CrossRef]

Anreou, A. G.

M. A. Marwick and A. G. Anreou, “Single photon avalanche photodetector with integrated quenching fabricated in TSMC 0.18 μm1.8 V CMOS process,” Electron. Lett. 44, 643-644 (2008).
[CrossRef]

Ballew, R. M.

R. M. Ballew and J. N. Demas, “An error analysis of the rapid lifetime determination method for the evaluation of single exponential decays,” Anal. Chem. 61, 30-33 (1989).
[CrossRef]

Bastiaens, P. I. H.

P. I. H. Bastiaens and A. Squire, “Fluorescence lifetime imaging microscopy: spatial resolution of biochemical processes in the cell,” Trends Cell Biol. 9, 48-52 (1999).
[CrossRef] [PubMed]

Becker, W.

W. Becker, Advanced Time-Correlated Single Photon Counting Techniques (Springer, 2005).
[CrossRef]

Besse, P. A.

C. Niclass, A. Rochas, P. A. Besse, and E. Charbon, “Toward a 3-D camera based on single photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 10, 796-802 (2004).
[CrossRef]

Bonnist, E.

D.-U. Li, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip time-correlated fluorescence lifetime extraction algorithms and error analysis,” J. Opt. Soc. Am. A 25, 1190-1198 (2008).
[CrossRef]

D.-U. Li, B. Rae, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip fluorescence lifetime extraction using synchronous gating scheme-theoretical error analysis and practical implementation,” in Proceedings of the International Conference on Bioinspired Systems and Signal Processing (2008), pp. 171-176.

Brennan, C. M.

Carlsson, K.

Chan, S. P.

Charbon, E.

C. Niclass, M. Gersbach, R. Henderson, L. Grant, and E. Charbon, “A single photon avalanche diode implemented in 130-nm CMOS technology,” IEEE J. Sel. Top. Quantum Electron. 13, 863-869 (2007).
[CrossRef]

C. Niclass, A. Rochas, P. A. Besse, and E. Charbon, “Toward a 3-D camera based on single photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 10, 796-802 (2004).
[CrossRef]

M. Gersbach, C. Niclass, J. Richardson, R. Henderson, L. Grant, and E. Charbon, “A single photon detector implemented in a 130 nm CMOS imaging process,” in Proceedings of the 38th European Solid-State Device Research Conference (2008), pp. 270-273.
[CrossRef]

B. Rae, C. Griffin, K. Muir, J. Girkin, E. Gu, D. Renshaw, E. Charbon, M. Dawson, and R. Henderson, “A microsystem for time-resolved fluorescence analysis using CMOS single-photon avalanche diodes and micro-LEDs,” in Proceedings of the IEEE International Conference on Solid State Circuits (IEEE, 2008), pp. 166-167.

Clegg, R. M.

P. C. Schneider and R. M. Clegg, “Rapid acquisition, analysis, and display of fluorescence lifetime-resolved images for real-time applications,” Rev. Sci. Instrum. 68, 4107-4119 (1997).
[CrossRef]

Colyer, R. A.

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71, 201-213 (2008).
[CrossRef]

Cova, S.

M. Ghioni, A. Gulinatti, I. Rech, F. Zappa, and S. Cova, “Progress in silicon single-photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 13, 852-862 (2007).
[CrossRef]

Daujotyte, D.

R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones, “Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M. Hhal-DNA complexes,” Nucleic Acids Res. 33, 6953-6960 (2005).
[CrossRef] [PubMed]

Dawson, M.

B. Rae, C. Griffin, K. Muir, J. Girkin, E. Gu, D. Renshaw, E. Charbon, M. Dawson, and R. Henderson, “A microsystem for time-resolved fluorescence analysis using CMOS single-photon avalanche diodes and micro-LEDs,” in Proceedings of the IEEE International Conference on Solid State Circuits (IEEE, 2008), pp. 166-167.

Degraff, B. A.

Demas, J. N.

C. Moore, S. P. Chan, J. N. Demas, and B. A. Degraff, “Comparison of methods for rapid evaluation of lifetime of exponential decays,” Appl. Spectrosc. 58, 603-607 (2004).
[CrossRef] [PubMed]

R. M. Ballew and J. N. Demas, “An error analysis of the rapid lifetime determination method for the evaluation of single exponential decays,” Anal. Chem. 61, 30-33 (1989).
[CrossRef]

Dryden, D. T. F.

R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones, “Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M. Hhal-DNA complexes,” Nucleic Acids Res. 33, 6953-6960 (2005).
[CrossRef] [PubMed]

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,” New J. Phys. 6, 1-13 (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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

Dymoke-Bradshaw, A. K. L.

Elder, A. D.

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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

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).
[CrossRef] [PubMed]

Fang, Q.

J. A. Jo, Q. Fang, and L. Marcu, “Ultrafast method for the analysis of fluorescence lifetime imaging microscopy data based on the Laguerre expansion technique,” IEEE J. Sel. Top. Quantum Electron. 11, 835-845 (2005).
[CrossRef]

Fisher, A. C.

Frank, J. H.

French, P. M. 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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

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).
[CrossRef] [PubMed]

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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

Galletly, N. P.

Gerritsen, H. C.

A. V. Agronskaia, L. Tertoolen, and H. C. Gerritsen, “High frame rate fluorescence lifetime imaging,” J. Phys. D 36, 1655-1662 (2003).
[CrossRef]

Gersbach, M.

C. Niclass, M. Gersbach, R. Henderson, L. Grant, and E. Charbon, “A single photon avalanche diode implemented in 130-nm CMOS technology,” IEEE J. Sel. Top. Quantum Electron. 13, 863-869 (2007).
[CrossRef]

M. Gersbach, C. Niclass, J. Richardson, R. Henderson, L. Grant, and E. Charbon, “A single photon detector implemented in a 130 nm CMOS imaging process,” in Proceedings of the 38th European Solid-State Device Research Conference (2008), pp. 270-273.
[CrossRef]

Ghioni, M.

M. Ghioni, A. Gulinatti, I. Rech, F. Zappa, and S. Cova, “Progress in silicon single-photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 13, 852-862 (2007).
[CrossRef]

Girkin, J.

B. Rae, C. Griffin, K. Muir, J. Girkin, E. Gu, D. Renshaw, E. Charbon, M. Dawson, and R. Henderson, “A microsystem for time-resolved fluorescence analysis using CMOS single-photon avalanche diodes and micro-LEDs,” in Proceedings of the IEEE International Conference on Solid State Circuits (IEEE, 2008), pp. 166-167.

Good, H. P.

H. P. Good, A. J. Kallir, and U. P. Wild, “Comparison of fluorescence lifetime fitting techniques,” J. Phys. Chem. 88, 5435-5441 (1984).
[CrossRef]

Graham, E. M.

D.-A. Mendels, E. M. Graham, S. W. Magennis, A. C. Jones, and F. Mendels, “Quantitative comparison of thermal and solutal transport in a T-mixer by FLIM and CFD,” Microfluid. Nanofluid. 5, 603-617 (2008).

Grant, L.

C. Niclass, M. Gersbach, R. Henderson, L. Grant, and E. Charbon, “A single photon avalanche diode implemented in 130-nm CMOS technology,” IEEE J. Sel. Top. Quantum Electron. 13, 863-869 (2007).
[CrossRef]

M. Gersbach, C. Niclass, J. Richardson, R. Henderson, L. Grant, and E. Charbon, “A single photon detector implemented in a 130 nm CMOS imaging process,” in Proceedings of the 38th European Solid-State Device Research Conference (2008), pp. 270-273.
[CrossRef]

Gratton, E.

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71, 201-213 (2008).
[CrossRef]

Grazulis, S.

R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones, “Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M. Hhal-DNA complexes,” Nucleic Acids Res. 33, 6953-6960 (2005).
[CrossRef] [PubMed]

Griffin, C.

B. Rae, C. Griffin, K. Muir, J. Girkin, E. Gu, D. Renshaw, E. Charbon, M. Dawson, and R. Henderson, “A microsystem for time-resolved fluorescence analysis using CMOS single-photon avalanche diodes and micro-LEDs,” in Proceedings of the IEEE International Conference on Solid State Circuits (IEEE, 2008), pp. 166-167.

Gu, E.

B. Rae, C. Griffin, K. Muir, J. Girkin, E. Gu, D. Renshaw, E. Charbon, M. Dawson, and R. Henderson, “A microsystem for time-resolved fluorescence analysis using CMOS single-photon avalanche diodes and micro-LEDs,” in Proceedings of the IEEE International Conference on Solid State Circuits (IEEE, 2008), pp. 166-167.

Gulinatti, A.

M. Ghioni, A. Gulinatti, I. Rech, F. Zappa, and S. Cova, “Progress in silicon single-photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 13, 852-862 (2007).
[CrossRef]

Hall, P.

P. Hall and B. Selinger, “Better estimates of exponential decay parameters,” J. Phys. Chem. 85, 2941-2946 (1981).
[CrossRef]

Halmer, D.

D. Halmer, G. von Basum, P. Hering, and M. Mürtz, “Fast exponential fitting algorithm for real-time instrumental use,” Rev. Sci. Instrum. 75, 2187-2191 (2004).
[CrossRef]

Hansroul, M.

J. Mizeret, T. Stepinac, M. Hansroul, A. Studzinski, H. van den Bergh, and G. Wagnières, “Instrumentation for real-time fluorescence lifetime imaging in endoscopy,” Rev. Sci. Instrum. 70, 4689-4701 (1999).
[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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

Hares, J. D.

Hecht, B.

W. Trabesinger, C. G. Hübner, B. Hecht, and U. P. Wild, “Continuous real-time measurement of fluorescence lifetimes,” Rev. Sci. Instrum. 73, 3122-3124 (2002).
[CrossRef]

Henderson, R.

D.-U. Li, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip time-correlated fluorescence lifetime extraction algorithms and error analysis,” J. Opt. Soc. Am. A 25, 1190-1198 (2008).
[CrossRef]

C. Niclass, M. Gersbach, R. Henderson, L. Grant, and E. Charbon, “A single photon avalanche diode implemented in 130-nm CMOS technology,” IEEE J. Sel. Top. Quantum Electron. 13, 863-869 (2007).
[CrossRef]

M. Gersbach, C. Niclass, J. Richardson, R. Henderson, L. Grant, and E. Charbon, “A single photon detector implemented in a 130 nm CMOS imaging process,” in Proceedings of the 38th European Solid-State Device Research Conference (2008), pp. 270-273.
[CrossRef]

D.-U. Li, B. Rae, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip fluorescence lifetime extraction using synchronous gating scheme-theoretical error analysis and practical implementation,” in Proceedings of the International Conference on Bioinspired Systems and Signal Processing (2008), pp. 171-176.

B. Rae, C. Griffin, K. Muir, J. Girkin, E. Gu, D. Renshaw, E. Charbon, M. Dawson, and R. Henderson, “A microsystem for time-resolved fluorescence analysis using CMOS single-photon avalanche diodes and micro-LEDs,” in Proceedings of the IEEE International Conference on Solid State Circuits (IEEE, 2008), pp. 166-167.

Hering, P.

D. Halmer, G. von Basum, P. Hering, and M. Mürtz, “Fast exponential fitting algorithm for real-time instrumental use,” Rev. Sci. Instrum. 75, 2187-2191 (2004).
[CrossRef]

Hübner, C. G.

W. Trabesinger, C. G. Hübner, B. Hecht, and U. P. Wild, “Continuous real-time measurement of fluorescence lifetimes,” Rev. Sci. Instrum. 73, 3122-3124 (2002).
[CrossRef]

Istratov, A. A.

A. A. Istratov and O. F. Vyvenko, “Exponential analysis in physical phenomena” Rev. Sci. Instrum. 70, 1233-1257 (1999).
[CrossRef]

Jo, J. A.

J. A. Jo, Q. Fang, and L. Marcu, “Ultrafast method for the analysis of fluorescence lifetime imaging microscopy data based on the Laguerre expansion technique,” IEEE J. Sel. Top. Quantum Electron. 11, 835-845 (2005).
[CrossRef]

Jones, A. C.

D.-A. Mendels, E. M. Graham, S. W. Magennis, A. C. Jones, and F. Mendels, “Quantitative comparison of thermal and solutal transport in a T-mixer by FLIM and CFD,” Microfluid. Nanofluid. 5, 603-617 (2008).

R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones, “Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M. Hhal-DNA complexes,” Nucleic Acids Res. 33, 6953-6960 (2005).
[CrossRef] [PubMed]

Kallir, A. J.

H. P. Good, A. J. Kallir, and U. P. Wild, “Comparison of fluorescence lifetime fitting techniques,” J. Phys. Chem. 88, 5435-5441 (1984).
[CrossRef]

Kaminski, C. F.

Kellett, P. 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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

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).
[CrossRef] [PubMed]

Klimasauskas, S.

R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones, “Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M. Hhal-DNA complexes,” Nucleic Acids Res. 33, 6953-6960 (2005).
[CrossRef] [PubMed]

Köllner, M.

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett. 200, 199-204 (1992).
[CrossRef]

Laiho, L. H.

S. Pelet, M. J. R. Previte, L. H. Laiho, and P. T. C. So, “A fast global fitting algorithm for fluorescence lifetime imaging microscopy based on image segmentation,” Biophys. J. 87, 2807-2817 (2004).
[CrossRef] [PubMed]

Lee, C.

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71, 201-213 (2008).
[CrossRef]

Lever, M. J.

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).
[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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

Li, D.-U.

D.-U. Li, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip time-correlated fluorescence lifetime extraction algorithms and error analysis,” J. Opt. Soc. Am. A 25, 1190-1198 (2008).
[CrossRef]

D.-U. Li, B. Rae, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip fluorescence lifetime extraction using synchronous gating scheme-theoretical error analysis and practical implementation,” in Proceedings of the International Conference on Bioinspired Systems and Signal Processing (2008), pp. 171-176.

Magennis, S. W.

D.-A. Mendels, E. M. Graham, S. W. Magennis, A. C. Jones, and F. Mendels, “Quantitative comparison of thermal and solutal transport in a T-mixer by FLIM and CFD,” Microfluid. Nanofluid. 5, 603-617 (2008).

R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones, “Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M. Hhal-DNA complexes,” Nucleic Acids Res. 33, 6953-6960 (2005).
[CrossRef] [PubMed]

Marcu, L.

J. A. Jo, Q. Fang, and L. Marcu, “Ultrafast method for the analysis of fluorescence lifetime imaging microscopy data based on the Laguerre expansion technique,” IEEE J. Sel. Top. Quantum Electron. 11, 835-845 (2005).
[CrossRef]

Marwick, M. A.

M. A. Marwick and A. G. Anreou, “Single photon avalanche photodetector with integrated quenching fabricated in TSMC 0.18 μm1.8 V CMOS process,” Electron. Lett. 44, 643-644 (2008).
[CrossRef]

Matthews, S. M.

McGinty, 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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

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).
[CrossRef] [PubMed]

Mendels, D.-A.

D.-A. Mendels, E. M. Graham, S. W. Magennis, A. C. Jones, and F. Mendels, “Quantitative comparison of thermal and solutal transport in a T-mixer by FLIM and CFD,” Microfluid. Nanofluid. 5, 603-617 (2008).

Mendels, F.

D.-A. Mendels, E. M. Graham, S. W. Magennis, A. C. Jones, and F. Mendels, “Quantitative comparison of thermal and solutal transport in a T-mixer by FLIM and CFD,” Microfluid. Nanofluid. 5, 603-617 (2008).

Mizeret, J.

J. Mizeret, T. Stepinac, M. Hansroul, A. Studzinski, H. van den Bergh, and G. Wagnières, “Instrumentation for real-time fluorescence lifetime imaging in endoscopy,” Rev. Sci. Instrum. 70, 4689-4701 (1999).
[CrossRef]

Moore, C.

Muir, K.

B. Rae, C. Griffin, K. Muir, J. Girkin, E. Gu, D. Renshaw, E. Charbon, M. Dawson, and R. Henderson, “A microsystem for time-resolved fluorescence analysis using CMOS single-photon avalanche diodes and micro-LEDs,” in Proceedings of the IEEE International Conference on Solid State Circuits (IEEE, 2008), pp. 166-167.

Munro, I.

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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

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).
[CrossRef] [PubMed]

Mürtz, M.

D. Halmer, G. von Basum, P. Hering, and M. Mürtz, “Fast exponential fitting algorithm for real-time instrumental use,” Rev. Sci. Instrum. 75, 2187-2191 (2004).
[CrossRef]

Neely, R. K.

R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones, “Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M. Hhal-DNA complexes,” Nucleic Acids Res. 33, 6953-6960 (2005).
[CrossRef] [PubMed]

Neil, M. A. 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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

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).
[CrossRef] [PubMed]

Niclass, C.

C. Niclass, M. Gersbach, R. Henderson, L. Grant, and E. Charbon, “A single photon avalanche diode implemented in 130-nm CMOS technology,” IEEE J. Sel. Top. Quantum Electron. 13, 863-869 (2007).
[CrossRef]

C. Niclass, A. Rochas, P. A. Besse, and E. Charbon, “Toward a 3-D camera based on single photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 10, 796-802 (2004).
[CrossRef]

M. Gersbach, C. Niclass, J. Richardson, R. Henderson, L. Grant, and E. Charbon, “A single photon detector implemented in a 130 nm CMOS imaging process,” in Proceedings of the 38th European Solid-State Device Research Conference (2008), pp. 270-273.
[CrossRef]

Pancheri, L.

L. Pancheri and D. Stoppa, “Low-noise CMOS single-photon avalanche diodes with 32 ns dead time,” in Proceedings of the 37th European Solid-State Device Research Conference (2007), pp. 362-365.
[CrossRef]

Pelet, S.

S. Pelet, M. J. R. Previte, L. H. Laiho, and P. T. C. So, “A fast global fitting algorithm for fluorescence lifetime imaging microscopy based on image segmentation,” Biophys. J. 87, 2807-2817 (2004).
[CrossRef] [PubMed]

Philips, J.

Previte, M. J. R.

S. Pelet, M. J. R. Previte, L. H. Laiho, and P. T. C. So, “A fast global fitting algorithm for fluorescence lifetime imaging microscopy based on image segmentation,” Biophys. J. 87, 2807-2817 (2004).
[CrossRef] [PubMed]

Rae, B.

B. Rae, C. Griffin, K. Muir, J. Girkin, E. Gu, D. Renshaw, E. Charbon, M. Dawson, and R. Henderson, “A microsystem for time-resolved fluorescence analysis using CMOS single-photon avalanche diodes and micro-LEDs,” in Proceedings of the IEEE International Conference on Solid State Circuits (IEEE, 2008), pp. 166-167.

D.-U. Li, B. Rae, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip fluorescence lifetime extraction using synchronous gating scheme-theoretical error analysis and practical implementation,” in Proceedings of the International Conference on Bioinspired Systems and Signal Processing (2008), pp. 171-176.

Rech, I.

M. Ghioni, A. Gulinatti, I. Rech, F. Zappa, and S. Cova, “Progress in silicon single-photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 13, 852-862 (2007).
[CrossRef]

Renshaw, D.

D.-U. Li, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip time-correlated fluorescence lifetime extraction algorithms and error analysis,” J. Opt. Soc. Am. A 25, 1190-1198 (2008).
[CrossRef]

D.-U. Li, B. Rae, E. Bonnist, D. Renshaw, and R. Henderson, “On-chip fluorescence lifetime extraction using synchronous gating scheme-theoretical error analysis and practical implementation,” in Proceedings of the International Conference on Bioinspired Systems and Signal Processing (2008), pp. 171-176.

B. Rae, C. Griffin, K. Muir, J. Girkin, E. Gu, D. Renshaw, E. Charbon, M. Dawson, and R. Henderson, “A microsystem for time-resolved fluorescence analysis using CMOS single-photon avalanche diodes and micro-LEDs,” in Proceedings of the IEEE International Conference on Solid State Circuits (IEEE, 2008), pp. 166-167.

Requejo-Isidro, 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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

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).
[CrossRef] [PubMed]

Richardson, J.

M. Gersbach, C. Niclass, J. Richardson, R. Henderson, L. Grant, and E. Charbon, “A single photon detector implemented in a 130 nm CMOS imaging process,” in Proceedings of the 38th European Solid-State Device Research Conference (2008), pp. 270-273.
[CrossRef]

Rochas, A.

C. Niclass, A. Rochas, P. A. Besse, and E. Charbon, “Toward a 3-D camera based on single photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 10, 796-802 (2004).
[CrossRef]

Schneider, P. C.

P. C. Schneider and R. M. Clegg, “Rapid acquisition, analysis, and display of fluorescence lifetime-resolved images for real-time applications,” Rev. Sci. Instrum. 68, 4107-4119 (1997).
[CrossRef]

Selinger, B.

P. Hall and B. Selinger, “Better estimates of exponential decay parameters,” J. Phys. Chem. 85, 2941-2946 (1981).
[CrossRef]

So, P. T. C.

S. Pelet, M. J. R. Previte, L. H. Laiho, and P. T. C. So, “A fast global fitting algorithm for fluorescence lifetime imaging microscopy based on image segmentation,” Biophys. J. 87, 2807-2817 (2004).
[CrossRef] [PubMed]

Squire, A.

P. I. H. Bastiaens and A. Squire, “Fluorescence lifetime imaging microscopy: spatial resolution of biochemical processes in the cell,” Trends Cell Biol. 9, 48-52 (1999).
[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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

Stamp, G. W. H.

Stepinac, T.

J. Mizeret, T. Stepinac, M. Hansroul, A. Studzinski, H. van den Bergh, and G. Wagnières, “Instrumentation for real-time fluorescence lifetime imaging in endoscopy,” Rev. Sci. Instrum. 70, 4689-4701 (1999).
[CrossRef]

Stoppa, D.

L. Pancheri and D. Stoppa, “Low-noise CMOS single-photon avalanche diodes with 32 ns dead time,” in Proceedings of the 37th European Solid-State Device Research Conference (2007), pp. 362-365.
[CrossRef]

Studzinski, A.

J. Mizeret, T. Stepinac, M. Hansroul, A. Studzinski, H. van den Bergh, and G. Wagnières, “Instrumentation for real-time fluorescence lifetime imaging in endoscopy,” Rev. Sci. Instrum. 70, 4689-4701 (1999).
[CrossRef]

Swartling, J.

Tertoolen, L.

A. V. Agronskaia, L. Tertoolen, and H. C. Gerritsen, “High frame rate fluorescence lifetime imaging,” J. Phys. D 36, 1655-1662 (2003).
[CrossRef]

Trabesinger, W.

W. Trabesinger, C. G. Hübner, B. Hecht, and U. P. Wild, “Continuous real-time measurement of fluorescence lifetimes,” Rev. Sci. Instrum. 73, 3122-3124 (2002).
[CrossRef]

van den Bergh, H.

J. Mizeret, T. Stepinac, M. Hansroul, A. Studzinski, H. van den Bergh, and G. Wagnières, “Instrumentation for real-time fluorescence lifetime imaging in endoscopy,” Rev. Sci. Instrum. 70, 4689-4701 (1999).
[CrossRef]

von Basum, G.

D. Halmer, G. von Basum, P. Hering, and M. Mürtz, “Fast exponential fitting algorithm for real-time instrumental use,” Rev. Sci. Instrum. 75, 2187-2191 (2004).
[CrossRef]

Vyvenko, O. F.

A. A. Istratov and O. F. Vyvenko, “Exponential analysis in physical phenomena” Rev. Sci. Instrum. 70, 1233-1257 (1999).
[CrossRef]

Wagnières, G.

J. Mizeret, T. Stepinac, M. Hansroul, A. Studzinski, H. van den Bergh, and G. Wagnières, “Instrumentation for real-time fluorescence lifetime imaging in endoscopy,” Rev. Sci. Instrum. 70, 4689-4701 (1999).
[CrossRef]

Wild, U. P.

W. Trabesinger, C. G. Hübner, B. Hecht, and U. P. Wild, “Continuous real-time measurement of fluorescence lifetimes,” Rev. Sci. Instrum. 73, 3122-3124 (2002).
[CrossRef]

H. P. Good, A. J. Kallir, and U. P. Wild, “Comparison of fluorescence lifetime fitting techniques,” J. Phys. Chem. 88, 5435-5441 (1984).
[CrossRef]

Wolfrum, J.

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett. 200, 199-204 (1992).
[CrossRef]

Yunus, K.

Zappa, F.

M. Ghioni, A. Gulinatti, I. Rech, F. Zappa, and S. Cova, “Progress in silicon single-photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 13, 852-862 (2007).
[CrossRef]

Anal. Chem.

R. M. Ballew and J. N. Demas, “An error analysis of the rapid lifetime determination method for the evaluation of single exponential decays,” Anal. Chem. 61, 30-33 (1989).
[CrossRef]

Appl. Spectrosc.

Biophys. J.

S. Pelet, M. J. R. Previte, L. H. Laiho, and P. T. C. So, “A fast global fitting algorithm for fluorescence lifetime imaging microscopy based on image segmentation,” Biophys. J. 87, 2807-2817 (2004).
[CrossRef] [PubMed]

Chem. Phys. Lett.

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett. 200, 199-204 (1992).
[CrossRef]

Electron. Lett.

M. A. Marwick and A. G. Anreou, “Single photon avalanche photodetector with integrated quenching fabricated in TSMC 0.18 μm1.8 V CMOS process,” Electron. Lett. 44, 643-644 (2008).
[CrossRef]

IEEE J. Sel. Top. Quantum Electron.

C. Niclass, A. Rochas, P. A. Besse, and E. Charbon, “Toward a 3-D camera based on single photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 10, 796-802 (2004).
[CrossRef]

C. Niclass, M. Gersbach, R. Henderson, L. Grant, and E. Charbon, “A single photon avalanche diode implemented in 130-nm CMOS technology,” IEEE J. Sel. Top. Quantum Electron. 13, 863-869 (2007).
[CrossRef]

M. Ghioni, A. Gulinatti, I. Rech, F. Zappa, and S. Cova, “Progress in silicon single-photon avalanche diodes,” IEEE J. Sel. Top. Quantum Electron. 13, 852-862 (2007).
[CrossRef]

J. A. Jo, Q. Fang, and L. Marcu, “Ultrafast method for the analysis of fluorescence lifetime imaging microscopy data based on the Laguerre expansion technique,” IEEE J. Sel. Top. Quantum Electron. 11, 835-845 (2005).
[CrossRef]

J. Opt. Soc. Am. A

J. Phys. Chem.

P. Hall and B. Selinger, “Better estimates of exponential decay parameters,” J. Phys. Chem. 85, 2941-2946 (1981).
[CrossRef]

H. P. Good, A. J. Kallir, and U. P. Wild, “Comparison of fluorescence lifetime fitting techniques,” J. Phys. Chem. 88, 5435-5441 (1984).
[CrossRef]

J. Phys. D

A. V. Agronskaia, L. Tertoolen, and H. C. Gerritsen, “High frame rate fluorescence lifetime imaging,” J. Phys. D 36, 1655-1662 (2003).
[CrossRef]

Microfluid. Nanofluid.

D.-A. Mendels, E. M. Graham, S. W. Magennis, A. C. Jones, and F. Mendels, “Quantitative comparison of thermal and solutal transport in a T-mixer by FLIM and CFD,” Microfluid. Nanofluid. 5, 603-617 (2008).

Microsc. Res. Tech.

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71, 201-213 (2008).
[CrossRef]

New J. Phys.

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,” New J. Phys. 6, 1-13 (2004).
[CrossRef]

Nucleic Acids Res.

R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones, “Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M. Hhal-DNA complexes,” Nucleic Acids Res. 33, 6953-6960 (2005).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Rev. Sci. Instrum.

W. Trabesinger, C. G. Hübner, B. Hecht, and U. P. Wild, “Continuous real-time measurement of fluorescence lifetimes,” Rev. Sci. Instrum. 73, 3122-3124 (2002).
[CrossRef]

D. Halmer, G. von Basum, P. Hering, and M. Mürtz, “Fast exponential fitting algorithm for real-time instrumental use,” Rev. Sci. Instrum. 75, 2187-2191 (2004).
[CrossRef]

P. C. Schneider and R. M. Clegg, “Rapid acquisition, analysis, and display of fluorescence lifetime-resolved images for real-time applications,” Rev. Sci. Instrum. 68, 4107-4119 (1997).
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Figures (10)

Fig. 1
Fig. 1

(a) Laboratory FLIM. (b) FLIM system-on-chip.

Fig. 2
Fig. 2

Relationship between DCR and signal readout bandwidth.

Fig. 3
Fig. 3

(a) Single-exponential decay and concept of IEM and (b) hardware implementation of IEM.

Fig. 4
Fig. 4

Precision and accuracy curves for the MLE with ( N c = 2 17 , N b = 0 ), ( N c = 2 17 , N b = 10 4 ), and ( N c = 8 × 2 17 , N b = 8 × 10 4 ), respectively.

Fig. 5
Fig. 5

Precision and accuracy curves for the 128-bin IEM and two-gate RLD with (a) N c = 2 17 , N b = 10 2 , and (b) N c = 2 17 , N b = 10 4 .

Fig. 6
Fig. 6

Precision and accuracy curves for the (a) 128-bin IEM and two-gate RLD and (b) 128-bin IEM and 128-bin MLE with different N b N c ratios under N c + N b = 2 17 .

Fig. 7
Fig. 7

Hardware implementation of background noise calibration.

Fig. 8
Fig. 8

Precision and accuracy curves with background correction for the 128-bin IEM, 128-bin MLE, and two-gate RLD with N b N c = 7.63 and N c = 2 17 .

Fig. 9
Fig. 9

Fluorescence histograms detected by two CMOS SPADs.

Fig. 10
Fig. 10

Calculated lifetimes with background correction versus NF for different algorithms with a mean NF of 3400 and MW = ( a ) 17, (b) 85, and (c) 156 ns . Calculated lifetimes with background correction versus NF for different algorithms with a mean NF of 900 and MW = ( d ) 17, (e) 85, and (f) 156 ns .

Equations (32)

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τ ( f 0 f M 1 ) = t 0 t M 1 f ( t ) d t h j = 0 M 1 C j f j ,
τ IEM h = j = 0 M 1 C j N j N 0 N M 1 = j = 0 M 1 N j ( N 0 + N M 1 ) 2 N 0 N M 1 = N c ( N 0 + N M 1 ) 2 N 0 N M 1 ,
N 0 N M 1 = 2 L ,
τ IEM h = [ ( N 0 + N M 1 ) + 4 i = 1 ( M 1 ) 2 N 2 i 1 + 2 i = 1 ( M 3 ) 2 N 2 i ] 3 ( N 0 N M 1 ) ,
E N j = N c x j ( 1 x ) ( 1 x M ) 1 + N b M 1 = σ N j 2 ,
τ IEM h = j = 0 M 1 C j E N j + j = 0 M 1 C j σ N j E N 0 E N M 1 + σ N 0 σ N M 1 = U ¯ + σ u V + σ v = U ¯ ( 1 + σ u U ¯ ) V ( 1 + σ v V ) U ¯ ( 1 + σ u U ¯ σ v V ) V ,
U ¯ = j = 0 M 1 C j E N j = N c 2 ( 1 + x ) ( 1 x M 1 ) 1 x M + N b ( M 1 ) M = U + B ,
σ u = j = 0 M 1 C j σ N j ,
V = E N 0 E N M 1 = N c ( 1 x ) ( 1 x M 1 ) 1 x M ,
σ v = σ N 0 σ N M 1 ,
τ IEM = h ( 1 + x ) 2 ( 1 x ) ( 1 + B U ) ( 1 + σ u U ¯ σ v V ) = τ [ 1 + 1 12 α 2 + O ( α 4 ) ] ( 1 + B U ) ( 1 + σ u U ¯ σ v V ) τ [ 1 + 1 12 α 2 + B U ( 1 + 1 12 α 2 ) + ( 1 + 1 12 α 2 ) ( 1 + B U ) ( σ u U ¯ σ v V ) ] = τ ( 1 + Δ τ τ + σ τ τ ) ,
Δ τ IEM τ IEM = 1 12 α 2 + B U ( 1 + 1 12 α 2 ) = 1 12 ( h τ ) 2 + N b N c 2 ( M 1 ) ( 1 x M ) M ( 1 + x ) ( 1 x M 1 ) [ 1 + 1 12 ( h τ ) 2 ] ,
σ τ IEM τ IEM = ( 1 + 1 12 α 2 ) ( 1 + B U ) ( σ u U ¯ σ v V ) = [ 1 + 1 12 ( h τ ) 2 ] [ 1 + N b N c 2 ( M 1 ) ( 1 x M ) M ( 1 + x ) ( 1 x M 1 ) ] σ a ,
σ a = σ u U ¯ σ v V = ( 1 2 U ¯ 1 V ) 2 σ N 0 2 + ( 1 U ¯ ) 2 j = 1 M 2 σ N j 2 + ( 1 2 U ¯ + 1 V ) 2 σ N M 1 2 ,
j = 1 M 2 σ N j 2 = N c ( 1 x ) 1 x M ( x + x 2 + + x M 2 ) + M 2 M N b = N c ( x x M 1 ) 1 x M + N b ( M 2 ) M .
Precision τ σ τ 2 + Δ τ 2 .
N c = ( PCR DCR ) T M = T M PCR N b N b N c = DCR PCR DCR = 0.25 ,
N b 0 = T M 0 D C R = N F 0 D C R F R N b = N b 0 T M T M 0 = N b 0 N F N F 0 N b 0 ,
U ¯ cal = N c 2 ( 1 + x ) ( 1 x M 1 ) 1 x M + N b ( M 1 ) M N b 0 N F ( M 1 ) M N F 0 U ,
E D j = N b 0 M 1 = σ D j 2 = N b M 1 .
τ IEM , cal h = j = 0 M 1 C j E N j + j = 0 M 1 C j σ N j ( j = 0 M 1 C j E D j + j = 0 M 1 C j σ D j ) E N 0 E N M 1 + σ N 0 σ N M 1 = U ( 1 + σ u ¯ U ) V ( 1 + σ v V ) ,
σ u ¯ = j = 0 M 1 C j σ N j j = 0 M 1 C j σ D j .
τ IEM , cal = h ( 1 + x ) 2 ( 1 x ) ( 1 + σ u ¯ U σ v V ) τ [ 1 + 1 12 ( h τ ) 2 ] ( 1 + σ u ¯ U σ v V ) = τ ( 1 + Δ τ τ + σ τ τ ) .
Δ τ IEM , cal τ IEM , cal = 1 12 ( h τ ) 2 = Δ τ IEM τ IEM N b = 0 ,
σ τ IEM , cal τ IEM , cal = ( 1 + 1 12 α 2 ) ( σ u ¯ U σ v V ) = [ 1 + 1 12 ( h τ ) 2 ] σ a ¯ ,
σ a ¯ = ( 1 2 U 1 V ) 2 σ N 0 2 + ( σ D 0 2 U ) 2 + ( 1 U ) 2 j = 1 M 2 ( σ N j 2 + σ D j 2 ) + ( 1 2 U + 1 V ) 2 σ N M 1 2 + ( σ D M 1 2 U ) 2 = 2 N c Q ( x ) + Z ( x ) ,
Q ( x ) = ( 1 x M ) ( x + x M ) ( 1 x ) ( 1 x M 1 ) 2 ( 1 + x ) 2 , Z ( x ) = N b N c [ 2 ( M 1 ) ( 1 x ) 2 + x 2 + 1 ] ( 1 x M ) 2 M ( 1 x 2 ) 2 ( 1 x M 1 ) 2 .
σ τ RLD , cal τ RLD , cal = τ w g N c 2 + y + y 1 + N b N c [ ( 1 + y ) 2 + ( 1 + y 1 ) 2 ] ,
σ τ MLE , cal τ MLE , cal = τ h N c ( 1 x ) 2 ( 1 x M ) 2 { 1 x G ( x ) + N b N c 2 P ( x ) x 2 [ G ( x ) ] 2 } ,
x = exp ( t τ ) ,
G ( x ) = 1 M 2 x M 1 + ( 2 M 2 2 ) x M M 2 x M + 1 + x 2 M ,
P ( x ) = [ 1 ( M + 1 ) x M + M x M + 1 ] [ M + ( M + 1 ) x x M + 1 ] + ( 1 x ) 2 ( 1 x M ) 2 6 ( M + 1 ) 1 ( 2 M + 1 ) 1 .

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