Abstract

We describe the application of wide-field frequency domain Fluorescence Lifetime Imaging Microscopy (FLIM) to imaging in microfluidic devices. FLIM is performed using low cost, intensity modulated Light Emitting Diodes (LEDs) for illumination. The use of lifetime imaging for quantitative analysis within such devices is demonstrated by mapping the molecular diffusion of iodide ions across a microchannel.

© 2006 Optical Society of America

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  1. D.J. Beebe, G.A. Mensing and G.M. Walker, "Physics and Applications of Microfluidics in Biology," Annu. Rev. Biomed. Eng. 4,261-286 (2002).
    [CrossRef] [PubMed]
  2. S.C. Jakeway, A.J. de Mello and E.L. Russell, "Miniaturized total analysis systems for biological analysis," Fresenius J. Anal. Chem. 366,525-539 (2000).
    [CrossRef]
  3. T. Chovan and A. Guttman, "Microfabricated devices in biotechnology and biochemical processing," Trends Biotechnol. 20,116-122 (2002).
    [CrossRef] [PubMed]
  4. A.J. Tüd˝os, G.A.J. Besselink and R.B.M. Schasfoort, "Trends in miniaturized total analysis systems for point-of-care testing in clinical chemistry," Lab. Chip 1,83-96 (2001).
    [CrossRef]
  5. E. Verpoorte, "Microfluidic chips for clinical and forensic analysis," Electrophoresis 23, 677-712 (2002).
    [CrossRef] [PubMed]
  6. Y. Huang, E.L. Mather, J.L. Bell and M. Madou, "MEMS-based sample preparation for molecular diagnostics," Anal. Bioanal. Chem. 372,49-65 (2002).
    [CrossRef] [PubMed]
  7. T. Vo-Dinh and B. Cullum, "Biosensors and biochips: advances in biological and medical diagnostics," Fresenius J. Anal. Chem. 366,540-551 (2000).
    [CrossRef]
  8. Y. Sato, G. Irisawa, M. Ishizuka, K. Hishida and M. Maeda, "Visualization of convective mixing in microchannel by fluorescence imaging," Meas. Sci. Technol. 14,114-122 (2003).
    [CrossRef]
  9. R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref and D.J. Beebe, "Passive mixing in a three-dimensional serpentine microchannel," J. Microelectromech. Syst. 9,190-197 (2000).
    [CrossRef]
  10. R.F. Ismagilov, A.D. Stroock, P.J.A. Kenis, G. Whitesides and H.A. Stone, "Experimental and theoretical scaling laws for transverse diffusive broadening in two-phase laminar flows in microchannels," Appl. Phys. Lett. 76,2376-2378 (2000).
    [CrossRef]
  11. C. Xi, D.L. Marks, D.S. Parikh, L. Raskin and S.A Boppart, "Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography," P. Natl. Acad. Sci. USA 101,7516-7521 (2004).
    [CrossRef]
  12. R.K.P. Benninger, O. Hofmann, J. McGinty, J. Requejo-Isidro, I. Munro, M.A.A. Neil, A.J. deMello and P.M.W. French, "Time-resolved fluorescence imaging of solvent interactions in microfluidic devices," Opt. Express 13,6275-6285 (2005).
    [CrossRef] [PubMed]
  13. S.W. Magennis, E.M. Graham and A.C. Jones, "Quantitative Spatial Mapping of Mixing in Microfluidic Systems," Angewandte Chemie International Edition 44,6512-6516 (2005).
    [CrossRef]
  14. J. R. Lakowicz and K. W. Berndt, "Lifetime-Selective Fluorescence Imaging Using An Rf Phase- Sensitive Camera," Rev. Sci. Instrum. 62,1727-1734 (1991).
    [CrossRef]
  15. G. Marriott, R.M. Clegg, D.J. Arndt-Jovin and T.M. Jovin, "Time resolved imaging microscopy. Phosphorescence and delayed fluorescence imaging," Biophys. J. 60,1374-1387 (1991).
    [CrossRef] [PubMed]
  16. Q. S. Hanley and A. H. A. Clayton, "AB-plot assisted determination of fluorophore mixtures in a fluorescence lifetime microscope using spectra or quenchers," J. Microscopy 218,62-67 (2005).
    [CrossRef]
  17. D. A. Jeong, G. Markle, F. Owen, A. Pease and R. Von Bünau Grenville, "The future of optical lithography," Solid State Technol. 37,39-47 (1994).
  18. M. D. Levenson, "Extending optical lithography to the gigabit era," Solid State Technol. 38, 57-66 (1995).
  19. L. Geppert, "Semiconductor lithography for the next millennium," IEEE Spectrum 33, 33-38 (1996).
    [CrossRef]
  20. S. Okazaki, "Resolution limits of optical lithography," J. Vac. Sci. Technol. B 9,2829-2833 (1991).
    [CrossRef]
  21. LK van Geest and KWJ Stoop, "FLIM on a wide field fluorescence microscope," Lett. Peptide Sci. 10,501-510 (2003).
    [CrossRef]
  22. RobertM. Clegg, Thomas M. Jovin Theodorus and W J Gadella Jr, "Fluorescence lifetime imaging microscopy: Pixel-by-pixel analysis of phase-modulation data," Bioimaging 2,139-159 (1994).
    [CrossRef]
  23. J.M. Harris and F.E. Lytle, "Measurement of subnanosecond fluorescence decays by sampled single-photon detection," Rev. Sci. Instrum. 48,1470-1476 (1977).
    [CrossRef]
  24. Q. S. Hanley, V. Subramaniam and D. J. Arndt-Jovin, "Fluorescence lifetime imaging: multi-point calibration, minimum resolvable differences, and artifact suppression," Cytometry 43,248-260 (2001).
    [CrossRef] [PubMed]
  25. A. Squire and P.I.H. Bastiaens, "Three dimensional image restoration in fluorescence lifetime imaging microscopy," J. Mircoscopy 193,36-49 (1999).
    [CrossRef]
  26. 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]
  27. A. Elder, J. Frank, J. Swartling, X. Dai and C.F. Kaminski, "Calibration of a wide-field frequency-domain fluorescence lifetime microscopy system using light emitting diodes as light sources," J. Microscopy2006 (accepted for publication).
    [CrossRef]
  28. A. C. Mitchell, J. E. Wall and J. G. Murray, "Direct modulation of the effective sensitivity of a CCD detector: a new approach to time-resolved fluorescence imaging," J. Microsc. Oxf. 206,225-232 (2002).
    [CrossRef]

2005 (3)

S.W. Magennis, E.M. Graham and A.C. Jones, "Quantitative Spatial Mapping of Mixing in Microfluidic Systems," Angewandte Chemie International Edition 44,6512-6516 (2005).
[CrossRef]

Q. S. Hanley and A. H. A. Clayton, "AB-plot assisted determination of fluorophore mixtures in a fluorescence lifetime microscope using spectra or quenchers," J. Microscopy 218,62-67 (2005).
[CrossRef]

R.K.P. Benninger, O. Hofmann, J. McGinty, J. Requejo-Isidro, I. Munro, M.A.A. Neil, A.J. deMello and P.M.W. French, "Time-resolved fluorescence imaging of solvent interactions in microfluidic devices," Opt. Express 13,6275-6285 (2005).
[CrossRef] [PubMed]

2004 (1)

C. Xi, D.L. Marks, D.S. Parikh, L. Raskin and S.A Boppart, "Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography," P. Natl. Acad. Sci. USA 101,7516-7521 (2004).
[CrossRef]

2003 (2)

Y. Sato, G. Irisawa, M. Ishizuka, K. Hishida and M. Maeda, "Visualization of convective mixing in microchannel by fluorescence imaging," Meas. Sci. Technol. 14,114-122 (2003).
[CrossRef]

LK van Geest and KWJ Stoop, "FLIM on a wide field fluorescence microscope," Lett. Peptide Sci. 10,501-510 (2003).
[CrossRef]

2002 (5)

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

E. Verpoorte, "Microfluidic chips for clinical and forensic analysis," Electrophoresis 23, 677-712 (2002).
[CrossRef] [PubMed]

Y. Huang, E.L. Mather, J.L. Bell and M. Madou, "MEMS-based sample preparation for molecular diagnostics," Anal. Bioanal. Chem. 372,49-65 (2002).
[CrossRef] [PubMed]

D.J. Beebe, G.A. Mensing and G.M. Walker, "Physics and Applications of Microfluidics in Biology," Annu. Rev. Biomed. Eng. 4,261-286 (2002).
[CrossRef] [PubMed]

T. Chovan and A. Guttman, "Microfabricated devices in biotechnology and biochemical processing," Trends Biotechnol. 20,116-122 (2002).
[CrossRef] [PubMed]

2001 (2)

A.J. Tüd˝os, G.A.J. Besselink and R.B.M. Schasfoort, "Trends in miniaturized total analysis systems for point-of-care testing in clinical chemistry," Lab. Chip 1,83-96 (2001).
[CrossRef]

Q. S. Hanley, V. Subramaniam and D. J. Arndt-Jovin, "Fluorescence lifetime imaging: multi-point calibration, minimum resolvable differences, and artifact suppression," Cytometry 43,248-260 (2001).
[CrossRef] [PubMed]

2000 (5)

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]

S.C. Jakeway, A.J. de Mello and E.L. Russell, "Miniaturized total analysis systems for biological analysis," Fresenius J. Anal. Chem. 366,525-539 (2000).
[CrossRef]

T. Vo-Dinh and B. Cullum, "Biosensors and biochips: advances in biological and medical diagnostics," Fresenius J. Anal. Chem. 366,540-551 (2000).
[CrossRef]

R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref and D.J. Beebe, "Passive mixing in a three-dimensional serpentine microchannel," J. Microelectromech. Syst. 9,190-197 (2000).
[CrossRef]

R.F. Ismagilov, A.D. Stroock, P.J.A. Kenis, G. Whitesides and H.A. Stone, "Experimental and theoretical scaling laws for transverse diffusive broadening in two-phase laminar flows in microchannels," Appl. Phys. Lett. 76,2376-2378 (2000).
[CrossRef]

1999 (1)

A. Squire and P.I.H. Bastiaens, "Three dimensional image restoration in fluorescence lifetime imaging microscopy," J. Mircoscopy 193,36-49 (1999).
[CrossRef]

1996 (1)

L. Geppert, "Semiconductor lithography for the next millennium," IEEE Spectrum 33, 33-38 (1996).
[CrossRef]

1995 (1)

M. D. Levenson, "Extending optical lithography to the gigabit era," Solid State Technol. 38, 57-66 (1995).

1994 (2)

D. A. Jeong, G. Markle, F. Owen, A. Pease and R. Von Bünau Grenville, "The future of optical lithography," Solid State Technol. 37,39-47 (1994).

RobertM. Clegg, Thomas M. Jovin Theodorus and W J Gadella Jr, "Fluorescence lifetime imaging microscopy: Pixel-by-pixel analysis of phase-modulation data," Bioimaging 2,139-159 (1994).
[CrossRef]

1991 (3)

J. R. Lakowicz and K. W. Berndt, "Lifetime-Selective Fluorescence Imaging Using An Rf Phase- Sensitive Camera," Rev. Sci. Instrum. 62,1727-1734 (1991).
[CrossRef]

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

S. Okazaki, "Resolution limits of optical lithography," J. Vac. Sci. Technol. B 9,2829-2833 (1991).
[CrossRef]

1977 (1)

J.M. Harris and F.E. Lytle, "Measurement of subnanosecond fluorescence decays by sampled single-photon detection," Rev. Sci. Instrum. 48,1470-1476 (1977).
[CrossRef]

Adrian, R.J.

R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref and D.J. Beebe, "Passive mixing in a three-dimensional serpentine microchannel," J. Microelectromech. Syst. 9,190-197 (2000).
[CrossRef]

Aref, H.

R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref and D.J. Beebe, "Passive mixing in a three-dimensional serpentine microchannel," J. Microelectromech. Syst. 9,190-197 (2000).
[CrossRef]

Arndt-Jovin, D. J.

Q. S. Hanley, V. Subramaniam and D. J. Arndt-Jovin, "Fluorescence lifetime imaging: multi-point calibration, minimum resolvable differences, and artifact suppression," Cytometry 43,248-260 (2001).
[CrossRef] [PubMed]

Arndt-Jovin, D.J.

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

Bastiaens, P.I.H.

A. Squire and P.I.H. Bastiaens, "Three dimensional image restoration in fluorescence lifetime imaging microscopy," J. Mircoscopy 193,36-49 (1999).
[CrossRef]

Beebe, D.J.

D.J. Beebe, G.A. Mensing and G.M. Walker, "Physics and Applications of Microfluidics in Biology," Annu. Rev. Biomed. Eng. 4,261-286 (2002).
[CrossRef] [PubMed]

R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref and D.J. Beebe, "Passive mixing in a three-dimensional serpentine microchannel," J. Microelectromech. Syst. 9,190-197 (2000).
[CrossRef]

Bell, J.L.

Y. Huang, E.L. Mather, J.L. Bell and M. Madou, "MEMS-based sample preparation for molecular diagnostics," Anal. Bioanal. Chem. 372,49-65 (2002).
[CrossRef] [PubMed]

Benninger, R.K.P.

Berndt, K. W.

J. R. Lakowicz and K. W. Berndt, "Lifetime-Selective Fluorescence Imaging Using An Rf Phase- Sensitive Camera," Rev. Sci. Instrum. 62,1727-1734 (1991).
[CrossRef]

Besselink, G.A.J.

A.J. Tüd˝os, G.A.J. Besselink and R.B.M. Schasfoort, "Trends in miniaturized total analysis systems for point-of-care testing in clinical chemistry," Lab. Chip 1,83-96 (2001).
[CrossRef]

Boppart, S.A

C. Xi, D.L. Marks, D.S. Parikh, L. Raskin and S.A Boppart, "Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography," P. Natl. Acad. Sci. USA 101,7516-7521 (2004).
[CrossRef]

Chovan, T.

T. Chovan and A. Guttman, "Microfabricated devices in biotechnology and biochemical processing," Trends Biotechnol. 20,116-122 (2002).
[CrossRef] [PubMed]

Clayton, A. H. A.

Q. S. Hanley and A. H. A. Clayton, "AB-plot assisted determination of fluorophore mixtures in a fluorescence lifetime microscope using spectra or quenchers," J. Microscopy 218,62-67 (2005).
[CrossRef]

Clegg, R.M.

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

Cole, M.J.

Cullum, B.

T. Vo-Dinh and B. Cullum, "Biosensors and biochips: advances in biological and medical diagnostics," Fresenius J. Anal. Chem. 366,540-551 (2000).
[CrossRef]

de Mello, A.J.

S.C. Jakeway, A.J. de Mello and E.L. Russell, "Miniaturized total analysis systems for biological analysis," Fresenius J. Anal. Chem. 366,525-539 (2000).
[CrossRef]

deMello, A.J.

Dowling, K.

French, P.M.W.

Geppert, L.

L. Geppert, "Semiconductor lithography for the next millennium," IEEE Spectrum 33, 33-38 (1996).
[CrossRef]

Graham, E.M.

S.W. Magennis, E.M. Graham and A.C. Jones, "Quantitative Spatial Mapping of Mixing in Microfluidic Systems," Angewandte Chemie International Edition 44,6512-6516 (2005).
[CrossRef]

Guttman, A.

T. Chovan and A. Guttman, "Microfabricated devices in biotechnology and biochemical processing," Trends Biotechnol. 20,116-122 (2002).
[CrossRef] [PubMed]

Hanley, Q. S.

Q. S. Hanley and A. H. A. Clayton, "AB-plot assisted determination of fluorophore mixtures in a fluorescence lifetime microscope using spectra or quenchers," J. Microscopy 218,62-67 (2005).
[CrossRef]

Q. S. Hanley, V. Subramaniam and D. J. Arndt-Jovin, "Fluorescence lifetime imaging: multi-point calibration, minimum resolvable differences, and artifact suppression," Cytometry 43,248-260 (2001).
[CrossRef] [PubMed]

Harris, J.M.

J.M. Harris and F.E. Lytle, "Measurement of subnanosecond fluorescence decays by sampled single-photon detection," Rev. Sci. Instrum. 48,1470-1476 (1977).
[CrossRef]

Hishida, K.

Y. Sato, G. Irisawa, M. Ishizuka, K. Hishida and M. Maeda, "Visualization of convective mixing in microchannel by fluorescence imaging," Meas. Sci. Technol. 14,114-122 (2003).
[CrossRef]

Hofmann, O.

Huang, Y.

Y. Huang, E.L. Mather, J.L. Bell and M. Madou, "MEMS-based sample preparation for molecular diagnostics," Anal. Bioanal. Chem. 372,49-65 (2002).
[CrossRef] [PubMed]

Irisawa, G.

Y. Sato, G. Irisawa, M. Ishizuka, K. Hishida and M. Maeda, "Visualization of convective mixing in microchannel by fluorescence imaging," Meas. Sci. Technol. 14,114-122 (2003).
[CrossRef]

Ishizuka, M.

Y. Sato, G. Irisawa, M. Ishizuka, K. Hishida and M. Maeda, "Visualization of convective mixing in microchannel by fluorescence imaging," Meas. Sci. Technol. 14,114-122 (2003).
[CrossRef]

Ismagilov, R.F.

R.F. Ismagilov, A.D. Stroock, P.J.A. Kenis, G. Whitesides and H.A. Stone, "Experimental and theoretical scaling laws for transverse diffusive broadening in two-phase laminar flows in microchannels," Appl. Phys. Lett. 76,2376-2378 (2000).
[CrossRef]

Jakeway, S.C.

S.C. Jakeway, A.J. de Mello and E.L. Russell, "Miniaturized total analysis systems for biological analysis," Fresenius J. Anal. Chem. 366,525-539 (2000).
[CrossRef]

Jeong, D. A.

D. A. Jeong, G. Markle, F. Owen, A. Pease and R. Von Bünau Grenville, "The future of optical lithography," Solid State Technol. 37,39-47 (1994).

Jones, A.C.

S.W. Magennis, E.M. Graham and A.C. Jones, "Quantitative Spatial Mapping of Mixing in Microfluidic Systems," Angewandte Chemie International Edition 44,6512-6516 (2005).
[CrossRef]

Jones, R.

Jovin, T.M.

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

Juskaitis, R.

Kenis, P.J.A.

R.F. Ismagilov, A.D. Stroock, P.J.A. Kenis, G. Whitesides and H.A. Stone, "Experimental and theoretical scaling laws for transverse diffusive broadening in two-phase laminar flows in microchannels," Appl. Phys. Lett. 76,2376-2378 (2000).
[CrossRef]

Lakowicz, J. R.

J. R. Lakowicz and K. W. Berndt, "Lifetime-Selective Fluorescence Imaging Using An Rf Phase- Sensitive Camera," Rev. Sci. Instrum. 62,1727-1734 (1991).
[CrossRef]

Levenson, M. D.

M. D. Levenson, "Extending optical lithography to the gigabit era," Solid State Technol. 38, 57-66 (1995).

Lever, M.J.

Liu, R.H.

R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref and D.J. Beebe, "Passive mixing in a three-dimensional serpentine microchannel," J. Microelectromech. Syst. 9,190-197 (2000).
[CrossRef]

Lytle, F.E.

J.M. Harris and F.E. Lytle, "Measurement of subnanosecond fluorescence decays by sampled single-photon detection," Rev. Sci. Instrum. 48,1470-1476 (1977).
[CrossRef]

Madou, M.

Y. Huang, E.L. Mather, J.L. Bell and M. Madou, "MEMS-based sample preparation for molecular diagnostics," Anal. Bioanal. Chem. 372,49-65 (2002).
[CrossRef] [PubMed]

Maeda, M.

Y. Sato, G. Irisawa, M. Ishizuka, K. Hishida and M. Maeda, "Visualization of convective mixing in microchannel by fluorescence imaging," Meas. Sci. Technol. 14,114-122 (2003).
[CrossRef]

Magennis, S.W.

S.W. Magennis, E.M. Graham and A.C. Jones, "Quantitative Spatial Mapping of Mixing in Microfluidic Systems," Angewandte Chemie International Edition 44,6512-6516 (2005).
[CrossRef]

Markle, G.

D. A. Jeong, G. Markle, F. Owen, A. Pease and R. Von Bünau Grenville, "The future of optical lithography," Solid State Technol. 37,39-47 (1994).

Marks, D.L.

C. Xi, D.L. Marks, D.S. Parikh, L. Raskin and S.A Boppart, "Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography," P. Natl. Acad. Sci. USA 101,7516-7521 (2004).
[CrossRef]

Marriott, G.

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

Mather, E.L.

Y. Huang, E.L. Mather, J.L. Bell and M. Madou, "MEMS-based sample preparation for molecular diagnostics," Anal. Bioanal. Chem. 372,49-65 (2002).
[CrossRef] [PubMed]

McGinty, J.

Mensing, G.A.

D.J. Beebe, G.A. Mensing and G.M. Walker, "Physics and Applications of Microfluidics in Biology," Annu. Rev. Biomed. Eng. 4,261-286 (2002).
[CrossRef] [PubMed]

Mitchell, A. C.

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

Munro, I.

Murray, J. G.

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

Neil, M.A.A.

Okazaki, S.

S. Okazaki, "Resolution limits of optical lithography," J. Vac. Sci. Technol. B 9,2829-2833 (1991).
[CrossRef]

Olsen, M.G.

R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref and D.J. Beebe, "Passive mixing in a three-dimensional serpentine microchannel," J. Microelectromech. Syst. 9,190-197 (2000).
[CrossRef]

Owen, F.

D. A. Jeong, G. Markle, F. Owen, A. Pease and R. Von Bünau Grenville, "The future of optical lithography," Solid State Technol. 37,39-47 (1994).

Parikh, D.S.

C. Xi, D.L. Marks, D.S. Parikh, L. Raskin and S.A Boppart, "Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography," P. Natl. Acad. Sci. USA 101,7516-7521 (2004).
[CrossRef]

Pease, A.

D. A. Jeong, G. Markle, F. Owen, A. Pease and R. Von Bünau Grenville, "The future of optical lithography," Solid State Technol. 37,39-47 (1994).

Raskin, L.

C. Xi, D.L. Marks, D.S. Parikh, L. Raskin and S.A Boppart, "Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography," P. Natl. Acad. Sci. USA 101,7516-7521 (2004).
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R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref and D.J. Beebe, "Passive mixing in a three-dimensional serpentine microchannel," J. Microelectromech. Syst. 9,190-197 (2000).
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LK van Geest and KWJ Stoop, "FLIM on a wide field fluorescence microscope," Lett. Peptide Sci. 10,501-510 (2003).
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R.H. Liu, M.A. Stremler, K.V. Sharp, M.G. Olsen, J.G. Santiago, R.J. Adrian, H. Aref and D.J. Beebe, "Passive mixing in a three-dimensional serpentine microchannel," J. Microelectromech. Syst. 9,190-197 (2000).
[CrossRef]

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R.F. Ismagilov, A.D. Stroock, P.J.A. Kenis, G. Whitesides and H.A. Stone, "Experimental and theoretical scaling laws for transverse diffusive broadening in two-phase laminar flows in microchannels," Appl. Phys. Lett. 76,2376-2378 (2000).
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[CrossRef]

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Xi, C.

C. Xi, D.L. Marks, D.S. Parikh, L. Raskin and S.A Boppart, "Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography," P. Natl. Acad. Sci. USA 101,7516-7521 (2004).
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R.F. Ismagilov, A.D. Stroock, P.J.A. Kenis, G. Whitesides and H.A. Stone, "Experimental and theoretical scaling laws for transverse diffusive broadening in two-phase laminar flows in microchannels," Appl. Phys. Lett. 76,2376-2378 (2000).
[CrossRef]

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[CrossRef] [PubMed]

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Q. S. Hanley, V. Subramaniam and D. J. Arndt-Jovin, "Fluorescence lifetime imaging: multi-point calibration, minimum resolvable differences, and artifact suppression," Cytometry 43,248-260 (2001).
[CrossRef] [PubMed]

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E. Verpoorte, "Microfluidic chips for clinical and forensic analysis," Electrophoresis 23, 677-712 (2002).
[CrossRef] [PubMed]

Fresenius J. Anal. Chem. (2)

S.C. Jakeway, A.J. de Mello and E.L. Russell, "Miniaturized total analysis systems for biological analysis," Fresenius J. Anal. Chem. 366,525-539 (2000).
[CrossRef]

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[CrossRef]

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

Lett. Peptide Sci. (1)

LK van Geest and KWJ Stoop, "FLIM on a wide field fluorescence microscope," Lett. Peptide Sci. 10,501-510 (2003).
[CrossRef]

Meas. Sci. Technol. (1)

Y. Sato, G. Irisawa, M. Ishizuka, K. Hishida and M. Maeda, "Visualization of convective mixing in microchannel by fluorescence imaging," Meas. Sci. Technol. 14,114-122 (2003).
[CrossRef]

Opt. Express (1)

Opt. Lett. (1)

P. Natl. Acad. Sci. USA (1)

C. Xi, D.L. Marks, D.S. Parikh, L. Raskin and S.A Boppart, "Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography," P. Natl. Acad. Sci. USA 101,7516-7521 (2004).
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A. Elder, J. Frank, J. Swartling, X. Dai and C.F. Kaminski, "Calibration of a wide-field frequency-domain fluorescence lifetime microscopy system using light emitting diodes as light sources," J. Microscopy2006 (accepted for publication).
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Supplementary Material (1)

» Media 1: AVI (4783 KB)     

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Figures (6)

Fig. 1.
Fig. 1.

Design of the dual-inlet stamp used to create PDMS microchannel structure.

Fig. 2.
Fig. 2.

Microfabrication of dual inlet channel using photolithography and soft lithography.

Fig. 3.
Fig. 3.

Confocal 3D image of two parallel aqueous streams flowing down a microchannel, just after the inlets. Only the left flow contained fluorescent dye. The signals seen on the right define the channel wall and stem from residual dye attached to the wall from previous experiments. The loss of fluorescence intensity in the upper part of the channel is due to reabsorption and optical distortion near the walls. The wider profile of the upper part of the fluorescent stream is due to small imperfections in the geometry of the microchannel and its inlets.

Fig. 4.
Fig. 4.

Calibration plot to determine the Stern-Vollmer quenching parameters for Rhodamine 6G solutions with KI. Each solution contains a different concentration of KI, but the same ionic strength through addition of KCl. From the gradient and intercept the bimolecular reaction rate constant, kq, is found to be 6.64×109 dm3 mole-1 s-1.

Fig. 5.
Fig. 5.

Lifetime images taken at increasing distances along the length of the channel. The increasing degree of mixing with increasing distance is clearly seen. [Media 1]

Fig. 6.
Fig. 6.

(a) Plot of lifetime profiles perpendicular to the flow direction for 5 different distances down the channel. Initially one sees a sharper gradient, which gradually becomes less distinct. (b) Concentration profiles derived from the lifetime data according to Equation 3.

Equations (5)

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

τ m = 1 2 π f 1 m 2 1
τ ϕ = tan ϕ 2 π f
τ ϕ = 1 2 π f tan ( ( ϕ ϕ ref ) + tan 1 ( 2 π f τ ref ) )
τ m = 1 2 π f ( m ref 2 m 2 ( 1 + ( 2 π f ) 2 τ ref 2 ) 1 ) 1 2
1 τ = d q [ Q ] + 1 τ 0

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