Abstract

We present the application of wide-field time-resolved fluorescence imaging methods for the study of solvent interactions and mixing in microfluidic devices. Time-resolved imaging of fluorescence polarization anisotropy allows us to image the local viscosity of fluorescein in three dimensions in order to directly monitor solvent mixing within a microfluidic channel. This provides a viscosity image acquisition time of the order of minutes, and has been applied to a steady-state laminar flow configuration. To image dynamic fluid mixing in real-time, we demonstrate high-speed fluorescence lifetime imaging at 12.3 Hz applied to DASPI, which directly exhibits a solvent viscosity-dependant fluorescence lifetime. These two methods facilitate a high degree of quantification of microfluidic flow in 3-D and/or at high speed, providing a tool for studying fluid dynamics and for developing enhanced microfluidic assays.

© 2005 Optical Society of America

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  1. D. R. Reyes, D. Iossifidis, P. A. Auroux, and A. Manz, “Micro total analysis systems. 1. Introduction, theory, and technology,” Anal. Chem. 74, 2623–2636 (2002)
    [Crossref] [PubMed]
  2. P. A. Auroux, D. Iossifidis, D. R. Reyes, and A. Manz, “Micro total analysis systems. 2. Analytical standard operations and applications,” Anal. Chem. 74, 2637–2652 (2002)
    [Crossref] [PubMed]
  3. T. Vilkner, D. Janasek, and A. Manz, “Micro total analysis systems. Recent developments,” Anal. Chem. 76, 3373–3385 (2004)
    [Crossref] [PubMed]
  4. E. Verpoorte, “Chip vision - optics for microchips,” Lab Chip 3, 42N–52N (2003)
  5. A. E. Kamholz, B. H. Weigl, B. A. Finlayson, and P. Yager, “Quantitative analysis of molecular interaction in a microfluidic channel: The T-sensor,” Anal. Chem. 71, 5340–5347 (1999)
    [Crossref] [PubMed]
  6. A. Hatch, A. E. Kamholz, K. R. Hawkins, M. S. Munson, E. A. Schilling, B. H. Weigl, and P. Yager, “A rapid diffusion immunoassay in a T-sensor,” Nat. Biotechnol. 19, 461–465 (2001)
    [Crossref] [PubMed]
  7. D. Ross, M. Gaitan, and L. E. Locascio, “Temperature measurement in microfluidic systems using a temperature-dependent fluorescent dye,” Anal. Chem. 73, 4117–4123 (2001)
    [Crossref] [PubMed]
  8. R. P. Hertzberg and A. J. Pope, “High-throughput screening: new technology for the 21st century,” Curr. Opin. Chem. Biol. 4, 445–451 (2000)
    [Crossref] [PubMed]
  9. K. Suhling, J. Siegel, P. M. P. Lanigan, S. Leveque-Fort, S. E. D. Webb, D. Phillips, D. M. Davis, and P. M. W. French, “Time-resolved fluorescence anisotropy imaging applied to live cells,” Opt. Lett. 29, 584–586 (2004)
    [Crossref] [PubMed]
  10. A. H. A. Clayton, Q. S. Hanley, D. J. Arndt-Jovin, V. Subramaniam, and T. M. Jovin, “Dynamic fluorescence anisotropy imaging microscopy in the frequency domain (rFLIM),” Biophys. J. 83, 1631–1649 (2002)
    [Crossref] [PubMed]
  11. G. H. Patterson and D. W. Piston, “Photobleaching in two-photon excitation microscopy,” Biophys. J. 78, 2159–2162 (2000)
    [Crossref] [PubMed]
  12. 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]
  13. R. K. P. Benninger, B. Onfelt, M. A. A. Neil, D. M. Davis, and P. M. W. French, “Fluorescence imaging of two-photon linear dichroism: Cholesterol depletion disrupts molecular orientation in cell membranes,” Biophys. J. 88, 609–622 (2005)
    [Crossref]
  14. J. Siegel, K. Suhling, S. Lévêque-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]
  15. M. Tramier, K. Kemnitz, C. Durieux, J. Coppey, P. Denjean, R. B. Pansu, and M. Coppey-Moisan, “Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells,” Biophys. J. 78, 2614–2627 (2000)
    [Crossref] [PubMed]
  16. D. Axelrod, “Carbocyanine dye orientation in red cell membrane studied by microscopic fluorescence polarization,” Biophys. J. 26, 557–573 (1979)
    [Crossref] [PubMed]
  17. C. Z. Wan and C. K. Johnson, “Time-Resolved Anisotropic 2-Photon Spectroscopy,” Chem. Phys. 179, 513–531 (1994)
    [Crossref]
  18. A. V. Agronskaia, L. Tertoolen, and H. C. Gerritsen, “High frame rate fluorescence lifetime imaging,” J. Phys. D. 36, 1655–1662 (2003)
    [Crossref]
  19. K. Dowling, M. J. Dayel, S. C. W. Hyde, P. M. W. French, M. J. Lever, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High resolution time-domain fluorescence lifetime imaging for biomedical applications,” J. Mod. Opt. 46, 199–209 (1999)
  20. J. R. Lakowicz, Principles of Fluorescence Spectroscopy 2nd edition (Kluwer Academic/Plenum Publishers: New York,1999)
  21. J. R. Taylor, M. C. Adams, and W. Sibbett, “Investigation of viscosity dependent fluorescence lifetime using a synchronously operated picosecond streak camera,” Appl. Phys. 21, 13–17 (1980)
    [Crossref]
  22. M. J. Cole, J. Siegel, S. E. D. Webb, R. Jones, K. Dowling, P. M. W. French, M. J. Lever, L. O. D. Sucharov, M. A. A. Neil, R. Juskaitis, and T. Wilson, “Whole-field optically sectioned fluorescence lifetime imaging,” Opt. Lett. 25, 1361–1363 (2000)
    [Crossref]
  23. D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.
  24. K. Dowling, S. C. W. Hyde, J. C. Dainty, P. M. W. French, and J. D. Hares, “2-D fluorescence lifetime imaging using a time-gated image intensifier,” Opt. Commun. 135, 27–31 (1997)
    [Crossref]
  25. 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, art. no.-180 (2004)
    [Crossref]

2005 (1)

R. K. P. Benninger, B. Onfelt, M. A. A. Neil, D. M. Davis, and P. M. W. French, “Fluorescence imaging of two-photon linear dichroism: Cholesterol depletion disrupts molecular orientation in cell membranes,” Biophys. J. 88, 609–622 (2005)
[Crossref]

2004 (4)

T. Vilkner, D. Janasek, and A. Manz, “Micro total analysis systems. Recent developments,” Anal. Chem. 76, 3373–3385 (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, art. no.-180 (2004)
[Crossref]

K. Suhling, J. Siegel, P. M. P. Lanigan, S. Leveque-Fort, S. E. D. Webb, D. Phillips, D. M. Davis, and P. M. W. French, “Time-resolved fluorescence anisotropy imaging applied to live cells,” Opt. Lett. 29, 584–586 (2004)
[Crossref] [PubMed]

J. Requejo-Isidro, J. McGinty, I. Munro, D. S. Elson, N. P. Galletly, M. J. Lever, M. A. A. Neil, G. W. H. Stamp, P. M. W. French, P. A. Kellett, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High-speed wide-field time-gated endoscopic fluorescence- lifetime imaging,” Opt. Lett. 29, 2249–2251 (2004)
[Crossref] [PubMed]

2003 (3)

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

E. Verpoorte, “Chip vision - optics for microchips,” Lab Chip 3, 42N–52N (2003)

J. Siegel, K. Suhling, S. Lévêque-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 (3)

D. R. Reyes, D. Iossifidis, P. A. Auroux, and A. Manz, “Micro total analysis systems. 1. Introduction, theory, and technology,” Anal. Chem. 74, 2623–2636 (2002)
[Crossref] [PubMed]

P. A. Auroux, D. Iossifidis, D. R. Reyes, and A. Manz, “Micro total analysis systems. 2. Analytical standard operations and applications,” Anal. Chem. 74, 2637–2652 (2002)
[Crossref] [PubMed]

A. H. A. Clayton, Q. S. Hanley, D. J. Arndt-Jovin, V. Subramaniam, and T. M. Jovin, “Dynamic fluorescence anisotropy imaging microscopy in the frequency domain (rFLIM),” Biophys. J. 83, 1631–1649 (2002)
[Crossref] [PubMed]

2001 (2)

A. Hatch, A. E. Kamholz, K. R. Hawkins, M. S. Munson, E. A. Schilling, B. H. Weigl, and P. Yager, “A rapid diffusion immunoassay in a T-sensor,” Nat. Biotechnol. 19, 461–465 (2001)
[Crossref] [PubMed]

D. Ross, M. Gaitan, and L. E. Locascio, “Temperature measurement in microfluidic systems using a temperature-dependent fluorescent dye,” Anal. Chem. 73, 4117–4123 (2001)
[Crossref] [PubMed]

2000 (4)

R. P. Hertzberg and A. J. Pope, “High-throughput screening: new technology for the 21st century,” Curr. Opin. Chem. Biol. 4, 445–451 (2000)
[Crossref] [PubMed]

G. H. Patterson and D. W. Piston, “Photobleaching in two-photon excitation microscopy,” Biophys. J. 78, 2159–2162 (2000)
[Crossref] [PubMed]

M. J. Cole, J. Siegel, S. E. D. Webb, R. Jones, K. Dowling, P. M. W. French, M. J. Lever, L. O. D. Sucharov, M. A. A. Neil, R. Juskaitis, and T. Wilson, “Whole-field optically sectioned fluorescence lifetime imaging,” Opt. Lett. 25, 1361–1363 (2000)
[Crossref]

M. Tramier, K. Kemnitz, C. Durieux, J. Coppey, P. Denjean, R. B. Pansu, and M. Coppey-Moisan, “Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells,” Biophys. J. 78, 2614–2627 (2000)
[Crossref] [PubMed]

1999 (2)

A. E. Kamholz, B. H. Weigl, B. A. Finlayson, and P. Yager, “Quantitative analysis of molecular interaction in a microfluidic channel: The T-sensor,” Anal. Chem. 71, 5340–5347 (1999)
[Crossref] [PubMed]

K. Dowling, M. J. Dayel, S. C. W. Hyde, P. M. W. French, M. J. Lever, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High resolution time-domain fluorescence lifetime imaging for biomedical applications,” J. Mod. Opt. 46, 199–209 (1999)

1997 (1)

K. Dowling, S. C. W. Hyde, J. C. Dainty, P. M. W. French, and J. D. Hares, “2-D fluorescence lifetime imaging using a time-gated image intensifier,” Opt. Commun. 135, 27–31 (1997)
[Crossref]

1994 (1)

C. Z. Wan and C. K. Johnson, “Time-Resolved Anisotropic 2-Photon Spectroscopy,” Chem. Phys. 179, 513–531 (1994)
[Crossref]

1980 (1)

J. R. Taylor, M. C. Adams, and W. Sibbett, “Investigation of viscosity dependent fluorescence lifetime using a synchronously operated picosecond streak camera,” Appl. Phys. 21, 13–17 (1980)
[Crossref]

1979 (1)

D. Axelrod, “Carbocyanine dye orientation in red cell membrane studied by microscopic fluorescence polarization,” Biophys. J. 26, 557–573 (1979)
[Crossref] [PubMed]

Adams, M. C.

J. R. Taylor, M. C. Adams, and W. Sibbett, “Investigation of viscosity dependent fluorescence lifetime using a synchronously operated picosecond streak camera,” Appl. Phys. 21, 13–17 (1980)
[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]

Arndt-Jovin, D. J.

A. H. A. Clayton, Q. S. Hanley, D. J. Arndt-Jovin, V. Subramaniam, and T. M. Jovin, “Dynamic fluorescence anisotropy imaging microscopy in the frequency domain (rFLIM),” Biophys. J. 83, 1631–1649 (2002)
[Crossref] [PubMed]

Auksorius, E.

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Auroux, P. A.

D. R. Reyes, D. Iossifidis, P. A. Auroux, and A. Manz, “Micro total analysis systems. 1. Introduction, theory, and technology,” Anal. Chem. 74, 2623–2636 (2002)
[Crossref] [PubMed]

P. A. Auroux, D. Iossifidis, D. R. Reyes, and A. Manz, “Micro total analysis systems. 2. Analytical standard operations and applications,” Anal. Chem. 74, 2637–2652 (2002)
[Crossref] [PubMed]

Axelrod, D.

D. Axelrod, “Carbocyanine dye orientation in red cell membrane studied by microscopic fluorescence polarization,” Biophys. J. 26, 557–573 (1979)
[Crossref] [PubMed]

Benninger, R. K. P.

R. K. P. Benninger, B. Onfelt, M. A. A. Neil, D. M. Davis, and P. M. W. French, “Fluorescence imaging of two-photon linear dichroism: Cholesterol depletion disrupts molecular orientation in cell membranes,” Biophys. J. 88, 609–622 (2005)
[Crossref]

Beule, P. A. A. De

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Clayton, A. H. A.

A. H. A. Clayton, Q. S. Hanley, D. J. Arndt-Jovin, V. Subramaniam, and T. M. Jovin, “Dynamic fluorescence anisotropy imaging microscopy in the frequency domain (rFLIM),” Biophys. J. 83, 1631–1649 (2002)
[Crossref] [PubMed]

Cole, M. J.

Coppey, J.

M. Tramier, K. Kemnitz, C. Durieux, J. Coppey, P. Denjean, R. B. Pansu, and M. Coppey-Moisan, “Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells,” Biophys. J. 78, 2614–2627 (2000)
[Crossref] [PubMed]

Coppey-Moisan, M.

M. Tramier, K. Kemnitz, C. Durieux, J. Coppey, P. Denjean, R. B. Pansu, and M. Coppey-Moisan, “Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells,” Biophys. J. 78, 2614–2627 (2000)
[Crossref] [PubMed]

Courtney, P.

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Dainty, J. C.

K. Dowling, S. C. W. Hyde, J. C. Dainty, P. M. W. French, and J. D. Hares, “2-D fluorescence lifetime imaging using a time-gated image intensifier,” Opt. Commun. 135, 27–31 (1997)
[Crossref]

Davis, D. M.

R. K. P. Benninger, B. Onfelt, M. A. A. Neil, D. M. Davis, and P. M. W. French, “Fluorescence imaging of two-photon linear dichroism: Cholesterol depletion disrupts molecular orientation in cell membranes,” Biophys. J. 88, 609–622 (2005)
[Crossref]

K. Suhling, J. Siegel, P. M. P. Lanigan, S. Leveque-Fort, S. E. D. Webb, D. Phillips, D. M. Davis, and P. M. W. French, “Time-resolved fluorescence anisotropy imaging applied to live cells,” Opt. Lett. 29, 584–586 (2004)
[Crossref] [PubMed]

J. Siegel, K. Suhling, S. Lévêque-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]

Dayel, M. J.

K. Dowling, M. J. Dayel, S. C. W. Hyde, P. M. W. French, M. J. Lever, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High resolution time-domain fluorescence lifetime imaging for biomedical applications,” J. Mod. Opt. 46, 199–209 (1999)

Denjean, P.

M. Tramier, K. Kemnitz, C. Durieux, J. Coppey, P. Denjean, R. B. Pansu, and M. Coppey-Moisan, “Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells,” Biophys. J. 78, 2614–2627 (2000)
[Crossref] [PubMed]

Dowling, K.

M. J. Cole, J. Siegel, S. E. D. Webb, R. Jones, K. Dowling, P. M. W. French, M. J. Lever, L. O. D. Sucharov, M. A. A. Neil, R. Juskaitis, and T. Wilson, “Whole-field optically sectioned fluorescence lifetime imaging,” Opt. Lett. 25, 1361–1363 (2000)
[Crossref]

K. Dowling, M. J. Dayel, S. C. W. Hyde, P. M. W. French, M. J. Lever, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High resolution time-domain fluorescence lifetime imaging for biomedical applications,” J. Mod. Opt. 46, 199–209 (1999)

K. Dowling, S. C. W. Hyde, J. C. Dainty, P. M. W. French, and J. D. Hares, “2-D fluorescence lifetime imaging using a time-gated image intensifier,” Opt. Commun. 135, 27–31 (1997)
[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,” New J. Phys. 6, art. no.-180 (2004)
[Crossref]

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Durieux, C.

M. Tramier, K. Kemnitz, C. Durieux, J. Coppey, P. Denjean, R. B. Pansu, and M. Coppey-Moisan, “Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells,” Biophys. J. 78, 2614–2627 (2000)
[Crossref] [PubMed]

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, art. no.-180 (2004)
[Crossref]

Dymoke-Bradshaw, A. K. L.

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]

K. Dowling, M. J. Dayel, S. C. W. Hyde, P. M. W. French, M. J. Lever, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High resolution time-domain fluorescence lifetime imaging for biomedical applications,” J. Mod. Opt. 46, 199–209 (1999)

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, art. no.-180 (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. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Finlayson, B. A.

A. E. Kamholz, B. H. Weigl, B. A. Finlayson, and P. Yager, “Quantitative analysis of molecular interaction in a microfluidic channel: The T-sensor,” Anal. Chem. 71, 5340–5347 (1999)
[Crossref] [PubMed]

French, P. M. W.

R. K. P. Benninger, B. Onfelt, M. A. A. Neil, D. M. Davis, and P. M. W. French, “Fluorescence imaging of two-photon linear dichroism: Cholesterol depletion disrupts molecular orientation in cell membranes,” Biophys. J. 88, 609–622 (2005)
[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]

K. Suhling, J. Siegel, P. M. P. Lanigan, S. Leveque-Fort, S. E. D. Webb, D. Phillips, D. M. Davis, and P. M. W. French, “Time-resolved fluorescence anisotropy imaging applied to live cells,” Opt. Lett. 29, 584–586 (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, art. no.-180 (2004)
[Crossref]

J. Siegel, K. Suhling, S. Lévêque-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]

M. J. Cole, J. Siegel, S. E. D. Webb, R. Jones, K. Dowling, P. M. W. French, M. J. Lever, L. O. D. Sucharov, M. A. A. Neil, R. Juskaitis, and T. Wilson, “Whole-field optically sectioned fluorescence lifetime imaging,” Opt. Lett. 25, 1361–1363 (2000)
[Crossref]

K. Dowling, M. J. Dayel, S. C. W. Hyde, P. M. W. French, M. J. Lever, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High resolution time-domain fluorescence lifetime imaging for biomedical applications,” J. Mod. Opt. 46, 199–209 (1999)

K. Dowling, S. C. W. Hyde, J. C. Dainty, P. M. W. French, and J. D. Hares, “2-D fluorescence lifetime imaging using a time-gated image intensifier,” Opt. Commun. 135, 27–31 (1997)
[Crossref]

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Gaitan, M.

D. Ross, M. Gaitan, and L. E. Locascio, “Temperature measurement in microfluidic systems using a temperature-dependent fluorescent dye,” Anal. Chem. 73, 4117–4123 (2001)
[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, art. no.-180 (2004)
[Crossref]

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

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]

Grant, D.

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Hanley, Q. S.

A. H. A. Clayton, Q. S. Hanley, D. J. Arndt-Jovin, V. Subramaniam, and T. M. Jovin, “Dynamic fluorescence anisotropy imaging microscopy in the frequency domain (rFLIM),” Biophys. J. 83, 1631–1649 (2002)
[Crossref] [PubMed]

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, art. no.-180 (2004)
[Crossref]

Hares, J. D.

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]

K. Dowling, M. J. Dayel, S. C. W. Hyde, P. M. W. French, M. J. Lever, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High resolution time-domain fluorescence lifetime imaging for biomedical applications,” J. Mod. Opt. 46, 199–209 (1999)

K. Dowling, S. C. W. Hyde, J. C. Dainty, P. M. W. French, and J. D. Hares, “2-D fluorescence lifetime imaging using a time-gated image intensifier,” Opt. Commun. 135, 27–31 (1997)
[Crossref]

Hatch, A.

A. Hatch, A. E. Kamholz, K. R. Hawkins, M. S. Munson, E. A. Schilling, B. H. Weigl, and P. Yager, “A rapid diffusion immunoassay in a T-sensor,” Nat. Biotechnol. 19, 461–465 (2001)
[Crossref] [PubMed]

Hawkins, K. R.

A. Hatch, A. E. Kamholz, K. R. Hawkins, M. S. Munson, E. A. Schilling, B. H. Weigl, and P. Yager, “A rapid diffusion immunoassay in a T-sensor,” Nat. Biotechnol. 19, 461–465 (2001)
[Crossref] [PubMed]

Hertzberg, R. P.

R. P. Hertzberg and A. J. Pope, “High-throughput screening: new technology for the 21st century,” Curr. Opin. Chem. Biol. 4, 445–451 (2000)
[Crossref] [PubMed]

Hyde, S. C. W.

K. Dowling, M. J. Dayel, S. C. W. Hyde, P. M. W. French, M. J. Lever, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High resolution time-domain fluorescence lifetime imaging for biomedical applications,” J. Mod. Opt. 46, 199–209 (1999)

K. Dowling, S. C. W. Hyde, J. C. Dainty, P. M. W. French, and J. D. Hares, “2-D fluorescence lifetime imaging using a time-gated image intensifier,” Opt. Commun. 135, 27–31 (1997)
[Crossref]

Iossifidis, D.

P. A. Auroux, D. Iossifidis, D. R. Reyes, and A. Manz, “Micro total analysis systems. 2. Analytical standard operations and applications,” Anal. Chem. 74, 2637–2652 (2002)
[Crossref] [PubMed]

D. R. Reyes, D. Iossifidis, P. A. Auroux, and A. Manz, “Micro total analysis systems. 1. Introduction, theory, and technology,” Anal. Chem. 74, 2623–2636 (2002)
[Crossref] [PubMed]

Janasek, D.

T. Vilkner, D. Janasek, and A. Manz, “Micro total analysis systems. Recent developments,” Anal. Chem. 76, 3373–3385 (2004)
[Crossref] [PubMed]

Johnson, C. K.

C. Z. Wan and C. K. Johnson, “Time-Resolved Anisotropic 2-Photon Spectroscopy,” Chem. Phys. 179, 513–531 (1994)
[Crossref]

Jones, R.

Jovin, T. M.

A. H. A. Clayton, Q. S. Hanley, D. J. Arndt-Jovin, V. Subramaniam, and T. M. Jovin, “Dynamic fluorescence anisotropy imaging microscopy in the frequency domain (rFLIM),” Biophys. J. 83, 1631–1649 (2002)
[Crossref] [PubMed]

Juskaitis, R.

Kamholz, A. E.

A. Hatch, A. E. Kamholz, K. R. Hawkins, M. S. Munson, E. A. Schilling, B. H. Weigl, and P. Yager, “A rapid diffusion immunoassay in a T-sensor,” Nat. Biotechnol. 19, 461–465 (2001)
[Crossref] [PubMed]

A. E. Kamholz, B. H. Weigl, B. A. Finlayson, and P. Yager, “Quantitative analysis of molecular interaction in a microfluidic channel: The T-sensor,” Anal. Chem. 71, 5340–5347 (1999)
[Crossref] [PubMed]

Kellett, P. A.

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, art. no.-180 (2004)
[Crossref]

Kemnitz, K.

M. Tramier, K. Kemnitz, C. Durieux, J. Coppey, P. Denjean, R. B. Pansu, and M. Coppey-Moisan, “Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells,” Biophys. J. 78, 2614–2627 (2000)
[Crossref] [PubMed]

Lakowicz, J. R.

J. R. Lakowicz, Principles of Fluorescence Spectroscopy 2nd edition (Kluwer Academic/Plenum Publishers: New York,1999)

Lanigan, P. M. P.

K. Suhling, J. Siegel, P. M. P. Lanigan, S. Leveque-Fort, S. E. D. Webb, D. Phillips, D. M. Davis, and P. M. W. French, “Time-resolved fluorescence anisotropy imaging applied to live cells,” Opt. Lett. 29, 584–586 (2004)
[Crossref] [PubMed]

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Leveque-Fort, S.

Lévêque-Fort, S.

J. Siegel, K. Suhling, S. Lévêque-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]

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, art. no.-180 (2004)
[Crossref]

M. J. Cole, J. Siegel, S. E. D. Webb, R. Jones, K. Dowling, P. M. W. French, M. J. Lever, L. O. D. Sucharov, M. A. A. Neil, R. Juskaitis, and T. Wilson, “Whole-field optically sectioned fluorescence lifetime imaging,” Opt. Lett. 25, 1361–1363 (2000)
[Crossref]

K. Dowling, M. J. Dayel, S. C. W. Hyde, P. M. W. French, M. J. Lever, J. D. Hares, and A. K. L. Dymoke-Bradshaw, “High resolution time-domain fluorescence lifetime imaging for biomedical applications,” J. Mod. Opt. 46, 199–209 (1999)

Locascio, L. E.

D. Ross, M. Gaitan, and L. E. Locascio, “Temperature measurement in microfluidic systems using a temperature-dependent fluorescent dye,” Anal. Chem. 73, 4117–4123 (2001)
[Crossref] [PubMed]

Manz, A.

T. Vilkner, D. Janasek, and A. Manz, “Micro total analysis systems. Recent developments,” Anal. Chem. 76, 3373–3385 (2004)
[Crossref] [PubMed]

D. R. Reyes, D. Iossifidis, P. A. Auroux, and A. Manz, “Micro total analysis systems. 1. Introduction, theory, and technology,” Anal. Chem. 74, 2623–2636 (2002)
[Crossref] [PubMed]

P. A. Auroux, D. Iossifidis, D. R. Reyes, and A. Manz, “Micro total analysis systems. 2. Analytical standard operations and applications,” Anal. Chem. 74, 2637–2652 (2002)
[Crossref] [PubMed]

McGinty, 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, art. no.-180 (2004)
[Crossref]

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

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, art. no.-180 (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. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Munson, M. S.

A. Hatch, A. E. Kamholz, K. R. Hawkins, M. S. Munson, E. A. Schilling, B. H. Weigl, and P. Yager, “A rapid diffusion immunoassay in a T-sensor,” Nat. Biotechnol. 19, 461–465 (2001)
[Crossref] [PubMed]

Neil, M. A. A.

R. K. P. Benninger, B. Onfelt, M. A. A. Neil, D. M. Davis, and P. M. W. French, “Fluorescence imaging of two-photon linear dichroism: Cholesterol depletion disrupts molecular orientation in cell membranes,” Biophys. J. 88, 609–622 (2005)
[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. 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, art. no.-180 (2004)
[Crossref]

M. J. Cole, J. Siegel, S. E. D. Webb, R. Jones, K. Dowling, P. M. W. French, M. J. Lever, L. O. D. Sucharov, M. A. A. Neil, R. Juskaitis, and T. Wilson, “Whole-field optically sectioned fluorescence lifetime imaging,” Opt. Lett. 25, 1361–1363 (2000)
[Crossref]

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Onfelt, B.

R. K. P. Benninger, B. Onfelt, M. A. A. Neil, D. M. Davis, and P. M. W. French, “Fluorescence imaging of two-photon linear dichroism: Cholesterol depletion disrupts molecular orientation in cell membranes,” Biophys. J. 88, 609–622 (2005)
[Crossref]

Pansu, R. B.

M. Tramier, K. Kemnitz, C. Durieux, J. Coppey, P. Denjean, R. B. Pansu, and M. Coppey-Moisan, “Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells,” Biophys. J. 78, 2614–2627 (2000)
[Crossref] [PubMed]

Patterson, G. H.

G. H. Patterson and D. W. Piston, “Photobleaching in two-photon excitation microscopy,” Biophys. J. 78, 2159–2162 (2000)
[Crossref] [PubMed]

Phillips, D.

K. Suhling, J. Siegel, P. M. P. Lanigan, S. Leveque-Fort, S. E. D. Webb, D. Phillips, D. M. Davis, and P. M. W. French, “Time-resolved fluorescence anisotropy imaging applied to live cells,” Opt. Lett. 29, 584–586 (2004)
[Crossref] [PubMed]

J. Siegel, K. Suhling, S. Lévêque-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]

Piston, D. W.

G. H. Patterson and D. W. Piston, “Photobleaching in two-photon excitation microscopy,” Biophys. J. 78, 2159–2162 (2000)
[Crossref] [PubMed]

Pope, A. J.

R. P. Hertzberg and A. J. Pope, “High-throughput screening: new technology for the 21st century,” Curr. Opin. Chem. Biol. 4, 445–451 (2000)
[Crossref] [PubMed]

Requejo-Isidro, 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, art. no.-180 (2004)
[Crossref]

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Reyes, D. R.

P. A. Auroux, D. Iossifidis, D. R. Reyes, and A. Manz, “Micro total analysis systems. 2. Analytical standard operations and applications,” Anal. Chem. 74, 2637–2652 (2002)
[Crossref] [PubMed]

D. R. Reyes, D. Iossifidis, P. A. Auroux, and A. Manz, “Micro total analysis systems. 1. Introduction, theory, and technology,” Anal. Chem. 74, 2623–2636 (2002)
[Crossref] [PubMed]

Ross, D.

D. Ross, M. Gaitan, and L. E. Locascio, “Temperature measurement in microfluidic systems using a temperature-dependent fluorescent dye,” Anal. Chem. 73, 4117–4123 (2001)
[Crossref] [PubMed]

Sabharwal, Y.

J. Siegel, K. Suhling, S. Lévêque-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]

Schilling, E. A.

A. Hatch, A. E. Kamholz, K. R. Hawkins, M. S. Munson, E. A. Schilling, B. H. Weigl, and P. Yager, “A rapid diffusion immunoassay in a T-sensor,” Nat. Biotechnol. 19, 461–465 (2001)
[Crossref] [PubMed]

Schimpf, D. N.

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

Sibbett, W.

J. R. Taylor, M. C. Adams, and W. Sibbett, “Investigation of viscosity dependent fluorescence lifetime using a synchronously operated picosecond streak camera,” Appl. Phys. 21, 13–17 (1980)
[Crossref]

Siegel, J.

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, art. no.-180 (2004)
[Crossref]

Stamp, G. W. H.

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)
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Subramaniam, V.

A. H. A. Clayton, Q. S. Hanley, D. J. Arndt-Jovin, V. Subramaniam, and T. M. Jovin, “Dynamic fluorescence anisotropy imaging microscopy in the frequency domain (rFLIM),” Biophys. J. 83, 1631–1649 (2002)
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K. Suhling, J. Siegel, P. M. P. Lanigan, S. Leveque-Fort, S. E. D. Webb, D. Phillips, D. M. Davis, and P. M. W. French, “Time-resolved fluorescence anisotropy imaging applied to live cells,” Opt. Lett. 29, 584–586 (2004)
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[Crossref]

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[Crossref]

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[Crossref] [PubMed]

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[Crossref] [PubMed]

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A. Hatch, A. E. Kamholz, K. R. Hawkins, M. S. Munson, E. A. Schilling, B. H. Weigl, and P. Yager, “A rapid diffusion immunoassay in a T-sensor,” Nat. Biotechnol. 19, 461–465 (2001)
[Crossref] [PubMed]

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[Crossref] [PubMed]

T. Vilkner, D. Janasek, and A. Manz, “Micro total analysis systems. Recent developments,” Anal. Chem. 76, 3373–3385 (2004)
[Crossref] [PubMed]

A. E. Kamholz, B. H. Weigl, B. A. Finlayson, and P. Yager, “Quantitative analysis of molecular interaction in a microfluidic channel: The T-sensor,” Anal. Chem. 71, 5340–5347 (1999)
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Appl. Phys. (1)

J. R. Taylor, M. C. Adams, and W. Sibbett, “Investigation of viscosity dependent fluorescence lifetime using a synchronously operated picosecond streak camera,” Appl. Phys. 21, 13–17 (1980)
[Crossref]

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A. H. A. Clayton, Q. S. Hanley, D. J. Arndt-Jovin, V. Subramaniam, and T. M. Jovin, “Dynamic fluorescence anisotropy imaging microscopy in the frequency domain (rFLIM),” Biophys. J. 83, 1631–1649 (2002)
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[Crossref]

M. Tramier, K. Kemnitz, C. Durieux, J. Coppey, P. Denjean, R. B. Pansu, and M. Coppey-Moisan, “Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells,” Biophys. J. 78, 2614–2627 (2000)
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[Crossref]

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[Crossref]

Lab Chip (1)

E. Verpoorte, “Chip vision - optics for microchips,” Lab Chip 3, 42N–52N (2003)

Nat. Biotechnol. (1)

A. Hatch, A. E. Kamholz, K. R. Hawkins, M. S. Munson, E. A. Schilling, B. H. Weigl, and P. Yager, “A rapid diffusion immunoassay in a T-sensor,” Nat. Biotechnol. 19, 461–465 (2001)
[Crossref] [PubMed]

New J. Phys. (1)

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, art. no.-180 (2004)
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Rev. Sci. Instrum. (1)

J. Siegel, K. Suhling, S. Lévêque-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]

Other (2)

D. Grant, E. Auksorius, D. N. Schimpf, P. M. P. Lanigan, P. A. A. De Beule, J. McGinty, D. S. Elson, C. Dunsby, J. Requejo-Isidro, I. Munro, N. Galletly, G. W. H. Stamp, P. Courtney, M. A. A. Neil, and P. M. W. French, “An Electronically Tuneable Ultrafast Laser Source applied to Fluorescence Imaging including Wide-Field Optically-Sectioned Fluoescence Lifetime Imaging using a Nipkow Disk Microscope” presented at Focus on Microscopy, Jena, Germany, 20–23 March, 2005.

J. R. Lakowicz, Principles of Fluorescence Spectroscopy 2nd edition (Kluwer Academic/Plenum Publishers: New York,1999)

Supplementary Material (2)

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Figures (8)

Fig. 1.
Fig. 1.

Schematic of rFLIM setup

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Fig. 2.
Fig. 2.

Schematic of high speed FLIM setup

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Fig. 3.
Fig. 3.

(a) Channel schematic, (b) image of correlation time at junction and (c) Sample data points with fit

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Fig. 4.
Fig. 4.

(a) and (b) Images of correlation time at ~0.4cm downstream of the point of confluence at 10 and 1 μl/min flow rate respectively. (c) Comparison of viscosity profiles across channel for the different flow rates.

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Fig. 5.
Fig. 5.

Rendered 3D viscosity profile of flow interface, viewed from above.

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Fig. 6.
Fig. 6.

Comparison of (a) rotational correlation time images, (b) fluorescence lifetime images and (c) profiles across the channel.

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Fig. 7.
Fig. 7.

(3.33MB) Movie of fluorescence lifetime at point of confluence, with color scale attached. Flows were applied through the two side inlets while the center inlet was unused.

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Fig. 8.
Fig. 8.

(3.33MB) Movie of fluorescence lifetime at channel 5cm from mixing point as flow is decreased from 10 to 0 μl/min. Color scale as in fig. 7.

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Equations (7)

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

r ( t ) = ⌊ I ∥ ( t ) − G I ⊥ ( t ) ⌋ [ I ∥ ( t ) + 2 G I ⊥ ( t ) ]
G = ( I VV I VH I HV I HH ) 1 2
I ∥ = K a I x + K b I y + K c I z I ⊥ = K a I x + K b I z + K c I y
r ( t ) = r 0 exp ( − t θ )
θ = V η 3 kT
τ RLD = Δ t ln ( I 1 I 2 )
F ( t ) = I ∥ ( t ) + 2 G I ⊥ ( t )

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