Abstract

Fluorescence lifetime of dye molecules is a sensitive reporter on local microenvironment which is generally independent of fluorophores concentration and can be used as a means of discrimination between molecules with spectrally overlapping emission. It is therefore a potentially powerful multiplexed detection modality in biosensing but requires extremely low light level operation typical of biological analyte concentrations, long data acquisition periods and on-chip processing capability to realize these advantages. We report here fluorescence lifetime data obtained using a CMOS-SPAD imager in conjunction with DNA microarrays and TIRF excitation geometry. This enables acquisition of single photon arrival time histograms for a 320 pixel FLIM map within less than 26 seconds exposure time. From this, we resolve distinct lifetime signatures corresponding to dye-labelled HCV and quantum-dot-labelled HCMV nucleic acid targets at concentrations as low as 10 nM.

© 2010 OSA

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    [CrossRef] [PubMed]

2010 (4)

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

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 013μm CMOS low dark-count single-photon avalanche diode array,” Opt. Express 18(10), 10257–10269 (2010).
[CrossRef] [PubMed]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

D. U. Li, B. Rae, R. Andrews, J. Arlt, and R. Henderson, “Hardware implementation algorithm and error analysis of high-speed fluorescence lifetime sensing systems using center-of-mass method,” J. Biomed. Opt. 15(1), 017006 (2010).
[CrossRef] [PubMed]

2009 (3)

A. Al Salman, A. Tortschanoff, G. Van der Zwan, F. van Mourik, and M. Chergui, “A model for the multi-exponential excited-state decay of CdSe nanocrystals,” Chem. Phys. 357(1-3), 96–101 (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(5), 543–557 (2009).
[CrossRef] [PubMed]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

2008 (3)

D. E. Schwartz, E. Charbon, and K. L. Shepard, “A single-photon avalanche diode array for fluorescence lifetime imaging microscopy,” IEEE J. Solid-state Circuits 43(11), 2546–2557 (2008).
[CrossRef]

D. E. Schwartz, P. Gong, and K. L. Shepard, “Time-resolved Förster-resonance-energy-transfer DNA assay on an active CMOS microarray,” Biosens. Bioelectron. 24(3), 383–390 (2008).
[CrossRef] [PubMed]

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, “A 128 x 128 Single-photon image sensor with column-level 10-bit time-to-digital converter array,” IEEE J. Solid-state Circuits 43(12), 2977–2989 (2008).
[CrossRef]

2007 (3)

2006 (3)

C. Situma, M. Hashimoto, and S. A. Soper, “Merging microfluidics with microarray-based bioassays,” Biomol. Eng. 23(5), 213–231 (2006).
[CrossRef] [PubMed]

J. Petrik, “Diagnostic applications of microarrays,” Transfus. Med. 16(4), 233–247 (2006).
[CrossRef] [PubMed]

M. Schäferling and S. Nagl, “Optical technologies for the read out and quality control of DNA and protein microarrays,” Anal. Bioanal. Chem. 385(3), 500–517 (2006).
[CrossRef] [PubMed]

2005 (2)

S. Nagl, M. Schaeferling, and O. S. Wolfbeis, “Fluorescence analysis in microarray technology,” Mikrochim. Acta 151(1-2), 1–21 (2005).
[CrossRef]

K. Suhling, P. M. W. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[CrossRef] [PubMed]

2000 (1)

1992 (1)

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

Achilefu, S.

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

Al Salman, A.

A. Al Salman, A. Tortschanoff, G. Van der Zwan, F. van Mourik, and M. Chergui, “A model for the multi-exponential excited-state decay of CdSe nanocrystals,” Chem. Phys. 357(1-3), 96–101 (2009).
[CrossRef]

Andrews, R.

D. U. Li, B. Rae, R. Andrews, J. Arlt, and R. Henderson, “Hardware implementation algorithm and error analysis of high-speed fluorescence lifetime sensing systems using center-of-mass method,” J. Biomed. Opt. 15(1), 017006 (2010).
[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(5), 543–557 (2009).
[CrossRef] [PubMed]

Apanasovich, V. V.

S. Laptenok, K. M. Mullen, J. W. Borst, I. H. M. van Stokkum, V. V. Apanasovich, and A. Visser, “Fluorescence Lifetime Imaging Microscopy (FLIM) data analysis with TIMP,” J. Stat. Softw. 18, 18 (2007).

Arlt, J.

D. U. Li, B. Rae, R. Andrews, J. Arlt, and R. Henderson, “Hardware implementation algorithm and error analysis of high-speed fluorescence lifetime sensing systems using center-of-mass method,” J. Biomed. Opt. 15(1), 017006 (2010).
[CrossRef] [PubMed]

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 013μm CMOS low dark-count single-photon avalanche diode array,” Opt. Express 18(10), 10257–10269 (2010).
[CrossRef] [PubMed]

Bachmann, T. T.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Battaglia, C.

Berezin, M. Y.

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

Berndt, K. W.

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

Borst, J. W.

S. Laptenok, K. M. Mullen, J. W. Borst, I. H. M. van Stokkum, V. V. Apanasovich, and A. Visser, “Fluorescence Lifetime Imaging Microscopy (FLIM) data analysis with TIMP,” J. Stat. Softw. 18, 18 (2007).

Buts, A.

Campbell, C. J.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

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 013μm CMOS low dark-count single-photon avalanche diode array,” Opt. Express 18(10), 10257–10269 (2010).
[CrossRef] [PubMed]

D. E. Schwartz, E. Charbon, and K. L. Shepard, “A single-photon avalanche diode array for fluorescence lifetime imaging microscopy,” IEEE J. Solid-state Circuits 43(11), 2546–2557 (2008).
[CrossRef]

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, “A 128 x 128 Single-photon image sensor with column-level 10-bit time-to-digital converter array,” IEEE J. Solid-state Circuits 43(12), 2977–2989 (2008).
[CrossRef]

Chergui, M.

A. Al Salman, A. Tortschanoff, G. Van der Zwan, F. van Mourik, and M. Chergui, “A model for the multi-exponential excited-state decay of CdSe nanocrystals,” Chem. Phys. 357(1-3), 96–101 (2009).
[CrossRef]

Ciani, I.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

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(5), 543–557 (2009).
[CrossRef] [PubMed]

Comelli, D.

Consolandi, C.

Crain, J.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Cubeddu, R.

D’Andrea, C.

De Bellis, G.

Donati, S.

Ember, S. W. J.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Esposito, A.

Favi, C.

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, “A 128 x 128 Single-photon image sensor with column-level 10-bit time-to-digital converter array,” IEEE J. Solid-state Circuits 43(12), 2977–2989 (2008).
[CrossRef]

French, P. M. W.

K. Suhling, P. M. W. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[CrossRef] [PubMed]

Gerritsen, H. C.

Gersbach, M.

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, “A 128 x 128 Single-photon image sensor with column-level 10-bit time-to-digital converter array,” IEEE J. Solid-state Circuits 43(12), 2977–2989 (2008).
[CrossRef]

Ghazal, P.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Giraud, G.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Gong, P.

D. E. Schwartz, P. Gong, and K. L. Shepard, “Time-resolved Förster-resonance-energy-transfer DNA assay on an active CMOS microarray,” Biosens. Bioelectron. 24(3), 383–390 (2008).
[CrossRef] [PubMed]

Hashimoto, M.

C. Situma, M. Hashimoto, and S. A. Soper, “Merging microfluidics with microarray-based bioassays,” Biomol. Eng. 23(5), 213–231 (2006).
[CrossRef] [PubMed]

Henderson, R.

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 013μm CMOS low dark-count single-photon avalanche diode array,” Opt. Express 18(10), 10257–10269 (2010).
[CrossRef] [PubMed]

D. U. Li, B. Rae, R. Andrews, J. Arlt, and R. Henderson, “Hardware implementation algorithm and error analysis of high-speed fluorescence lifetime sensing systems using center-of-mass method,” J. Biomed. Opt. 15(1), 017006 (2010).
[CrossRef] [PubMed]

Johnson, M.

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

Khondoker, M. R.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Kluter, T.

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, “A 128 x 128 Single-photon image sensor with column-level 10-bit time-to-digital converter array,” IEEE J. Solid-state Circuits 43(12), 2977–2989 (2008).
[CrossRef]

Lakowicz, J. R.

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

Laptenok, S.

S. Laptenok, K. M. Mullen, J. W. Borst, I. H. M. van Stokkum, V. V. Apanasovich, and A. Visser, “Fluorescence Lifetime Imaging Microscopy (FLIM) data analysis with TIMP,” J. Stat. Softw. 18, 18 (2007).

Li, D. U.

D. U. Li, B. Rae, R. Andrews, J. Arlt, and R. Henderson, “Hardware implementation algorithm and error analysis of high-speed fluorescence lifetime sensing systems using center-of-mass method,” J. Biomed. Opt. 15(1), 017006 (2010).
[CrossRef] [PubMed]

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 013μm CMOS low dark-count single-photon avalanche diode array,” Opt. Express 18(10), 10257–10269 (2010).
[CrossRef] [PubMed]

Martini, G.

Michalet, X.

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(5), 543–557 (2009).
[CrossRef] [PubMed]

Mount, A. R.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Mullen, K. M.

S. Laptenok, K. M. Mullen, J. W. Borst, I. H. M. van Stokkum, V. V. Apanasovich, and A. Visser, “Fluorescence Lifetime Imaging Microscopy (FLIM) data analysis with TIMP,” J. Stat. Softw. 18, 18 (2007).

Nagl, S.

M. Schäferling and S. Nagl, “Optical technologies for the read out and quality control of DNA and protein microarrays,” Anal. Bioanal. Chem. 385(3), 500–517 (2006).
[CrossRef] [PubMed]

S. Nagl, M. Schaeferling, and O. S. Wolfbeis, “Fluorescence analysis in microarray technology,” Mikrochim. Acta 151(1-2), 1–21 (2005).
[CrossRef]

Niclass, C.

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, “A 128 x 128 Single-photon image sensor with column-level 10-bit time-to-digital converter array,” IEEE J. Solid-state Circuits 43(12), 2977–2989 (2008).
[CrossRef]

Norgia, M.

Nowaczyk, K.

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

Petrik, J.

J. Petrik, “Diagnostic applications of microarrays,” Transfus. Med. 16(4), 233–247 (2006).
[CrossRef] [PubMed]

Phillips, D.

K. Suhling, P. M. W. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[CrossRef] [PubMed]

Pifferi, A.

Rae, B.

D. U. Li, B. Rae, R. Andrews, J. Arlt, and R. Henderson, “Hardware implementation algorithm and error analysis of high-speed fluorescence lifetime sensing systems using center-of-mass method,” J. Biomed. Opt. 15(1), 017006 (2010).
[CrossRef] [PubMed]

Richardson, J.

Ross, A. J.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Rossi-Bernardi, L.

Salani, G.

Schaeferling, M.

S. Nagl, M. Schaeferling, and O. S. Wolfbeis, “Fluorescence analysis in microarray technology,” Mikrochim. Acta 151(1-2), 1–21 (2005).
[CrossRef]

Schäferling, M.

M. Schäferling and S. Nagl, “Optical technologies for the read out and quality control of DNA and protein microarrays,” Anal. Bioanal. Chem. 385(3), 500–517 (2006).
[CrossRef] [PubMed]

Schulze, H.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Schwartz, D. E.

D. E. Schwartz, E. Charbon, and K. L. Shepard, “A single-photon avalanche diode array for fluorescence lifetime imaging microscopy,” IEEE J. Solid-state Circuits 43(11), 2546–2557 (2008).
[CrossRef]

D. E. Schwartz, P. Gong, and K. L. Shepard, “Time-resolved Förster-resonance-energy-transfer DNA assay on an active CMOS microarray,” Biosens. Bioelectron. 24(3), 383–390 (2008).
[CrossRef] [PubMed]

Shepard, K. L.

D. E. Schwartz, E. Charbon, and K. L. Shepard, “A single-photon avalanche diode array for fluorescence lifetime imaging microscopy,” IEEE J. Solid-state Circuits 43(11), 2546–2557 (2008).
[CrossRef]

D. E. Schwartz, P. Gong, and K. L. Shepard, “Time-resolved Förster-resonance-energy-transfer DNA assay on an active CMOS microarray,” Biosens. Bioelectron. 24(3), 383–390 (2008).
[CrossRef] [PubMed]

Siegmund, O. H. W.

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(5), 543–557 (2009).
[CrossRef] [PubMed]

Situma, C.

C. Situma, M. Hashimoto, and S. A. Soper, “Merging microfluidics with microarray-based bioassays,” Biomol. Eng. 23(5), 213–231 (2006).
[CrossRef] [PubMed]

Soper, S. A.

C. Situma, M. Hashimoto, and S. A. Soper, “Merging microfluidics with microarray-based bioassays,” Biomol. Eng. 23(5), 213–231 (2006).
[CrossRef] [PubMed]

Stoppa, D.

Suhling, K.

K. Suhling, P. M. W. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[CrossRef] [PubMed]

Szmacinski, H.

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

Taroni, P.

Terry, J. G.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Tlili, C.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Torricelli, A.

Tortschanoff, A.

A. Al Salman, A. Tortschanoff, G. Van der Zwan, F. van Mourik, and M. Chergui, “A model for the multi-exponential excited-state decay of CdSe nanocrystals,” Chem. Phys. 357(1-3), 96–101 (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(5), 543–557 (2009).
[CrossRef] [PubMed]

Valentini, G.

Vallerga, J. V.

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(5), 543–557 (2009).
[CrossRef] [PubMed]

Van der Zwan, G.

A. Al Salman, A. Tortschanoff, G. Van der Zwan, F. van Mourik, and M. Chergui, “A model for the multi-exponential excited-state decay of CdSe nanocrystals,” Chem. Phys. 357(1-3), 96–101 (2009).
[CrossRef]

van Mourik, F.

A. Al Salman, A. Tortschanoff, G. Van der Zwan, F. van Mourik, and M. Chergui, “A model for the multi-exponential excited-state decay of CdSe nanocrystals,” Chem. Phys. 357(1-3), 96–101 (2009).
[CrossRef]

van Stokkum, I. H. M.

S. Laptenok, K. M. Mullen, J. W. Borst, I. H. M. van Stokkum, V. V. Apanasovich, and A. Visser, “Fluorescence Lifetime Imaging Microscopy (FLIM) data analysis with TIMP,” J. Stat. Softw. 18, 18 (2007).

Visser, A.

S. Laptenok, K. M. Mullen, J. W. Borst, I. H. M. van Stokkum, V. V. Apanasovich, and A. Visser, “Fluorescence Lifetime Imaging Microscopy (FLIM) data analysis with TIMP,” J. Stat. Softw. 18, 18 (2007).

Walker, R.

Walton, A. J.

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

Weiss, S.

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(5), 543–557 (2009).
[CrossRef] [PubMed]

Wolfbeis, O. S.

S. Nagl, M. Schaeferling, and O. S. Wolfbeis, “Fluorescence analysis in microarray technology,” Mikrochim. Acta 151(1-2), 1–21 (2005).
[CrossRef]

Wouters, F. S.

Anal. Bioanal. Chem. (1)

M. Schäferling and S. Nagl, “Optical technologies for the read out and quality control of DNA and protein microarrays,” Anal. Bioanal. Chem. 385(3), 500–517 (2006).
[CrossRef] [PubMed]

Anal. Biochem. (1)

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

Biomol. Eng. (1)

C. Situma, M. Hashimoto, and S. A. Soper, “Merging microfluidics with microarray-based bioassays,” Biomol. Eng. 23(5), 213–231 (2006).
[CrossRef] [PubMed]

Biosens. Bioelectron. (1)

D. E. Schwartz, P. Gong, and K. L. Shepard, “Time-resolved Förster-resonance-energy-transfer DNA assay on an active CMOS microarray,” Biosens. Bioelectron. 24(3), 383–390 (2008).
[CrossRef] [PubMed]

Chem. Phys. (1)

A. Al Salman, A. Tortschanoff, G. Van der Zwan, F. van Mourik, and M. Chergui, “A model for the multi-exponential excited-state decay of CdSe nanocrystals,” Chem. Phys. 357(1-3), 96–101 (2009).
[CrossRef]

Chem. Phys. Lett. (1)

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Solution state hybridization detection using time-resolved fluorescence anisotropy of quantum dot-DNA bioconjugates,” Chem. Phys. Lett. 484(4-6), 309–314 (2010).
[CrossRef]

Chem. Rev. (1)

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

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(5), 543–557 (2009).
[CrossRef] [PubMed]

IEEE J. Solid-state Circuits (2)

D. E. Schwartz, E. Charbon, and K. L. Shepard, “A single-photon avalanche diode array for fluorescence lifetime imaging microscopy,” IEEE J. Solid-state Circuits 43(11), 2546–2557 (2008).
[CrossRef]

C. Niclass, C. Favi, T. Kluter, M. Gersbach, and E. Charbon, “A 128 x 128 Single-photon image sensor with column-level 10-bit time-to-digital converter array,” IEEE J. Solid-state Circuits 43(12), 2977–2989 (2008).
[CrossRef]

Int. J. Mol. Sci. (1)

G. Giraud, H. Schulze, T. T. Bachmann, C. J. Campbell, A. R. Mount, P. Ghazal, M. R. Khondoker, A. J. Ross, S. W. J. Ember, I. Ciani, C. Tlili, A. J. Walton, J. G. Terry, and J. Crain, “Fluorescence lifetime imaging of quantum dot labeled DNA microarrays,” Int. J. Mol. Sci. 10(4), 1930–1941 (2009).
[CrossRef] [PubMed]

J. Biomed. Opt. (1)

D. U. Li, B. Rae, R. Andrews, J. Arlt, and R. Henderson, “Hardware implementation algorithm and error analysis of high-speed fluorescence lifetime sensing systems using center-of-mass method,” J. Biomed. Opt. 15(1), 017006 (2010).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A (1)

J. Stat. Softw. (1)

S. Laptenok, K. M. Mullen, J. W. Borst, I. H. M. van Stokkum, V. V. Apanasovich, and A. Visser, “Fluorescence Lifetime Imaging Microscopy (FLIM) data analysis with TIMP,” J. Stat. Softw. 18, 18 (2007).

Mikrochim. Acta (1)

S. Nagl, M. Schaeferling, and O. S. Wolfbeis, “Fluorescence analysis in microarray technology,” Mikrochim. Acta 151(1-2), 1–21 (2005).
[CrossRef]

Opt. Express (2)

Opt. Lett. (1)

Photochem. Photobiol. Sci. (1)

K. Suhling, P. M. W. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[CrossRef] [PubMed]

Transfus. Med. (1)

J. Petrik, “Diagnostic applications of microarrays,” Transfus. Med. 16(4), 233–247 (2006).
[CrossRef] [PubMed]

Other (2)

M. Gersbach, Single-photon detector arrays for time-resolved fluorescence imaging (Thesis, Ecole Polytechnique Federale de Lausanne, Lausanne, 2009).

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, "A 32x32 50ps resolution 10 bit time to digital converter array in 130nm CMOS for time correlated imaging," in Proceedings of IEEE 2009 Custom Integrated Circuits Conference (IEEE, New York, 2009), pp. 77–80.

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Figures (3)

Fig. 1
Fig. 1

Experimental setup of the TIRF-SPAD imager setup. (see text for details).

Fig. 2
Fig. 2

Decays histograms (circles) with corresponding fit (solid lines) obtained for three individual pixels associated with the three categories of microspots, (a) HCV, (b) HCMV-HCV mixture and (c) HCMV.

Fig. 3
Fig. 3

(Left) FLIM map of DNA microarray spotted with a series of four sub-arrays corresponding to four subframes of 16x20 pixels each: (a) HCV probes, (b) HCMV probes, (c) four spots containing a mixture of 50% HCV and 50% HCMV probes, (d) HCV probes (top left), HCMV probes (bottom right) and 50% probe mixture (diagonal). The array was hybridized with a solution containing 10 nM of Alexa430 labeled HCV complementary target and 10nM of Qdot525 labeled HCMV complementary target. (Right) Fluorescence lifetime histograms and Gaussian fit, extracted from the four sub-arrays. Note that (d) used a bi-exponential model with τ1 = 4.2 ns & τ2 = 22.0 ns fixed.

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