Abstract

We demonstrate an opto-fluidic detection system based on an array of astigmatic diffractive microlenses integrated into a microfluidic flow focus device. Each astigmatic microlens produces a line excitation across the channel and collects fluorescence emission from the linear detection regions. The linear excitation spot results in uniform excitation across the channel and high time resolution in the direction of the flow. Collected fluorescence from each integrated microlens is relayed to a sub-region on a fast CMOS camera. By analyzing the signal from individual microlenses, we demonstrate counting and resolution of 500 nm and 1.1 μm beads at rates of up to 8,300 per second at multiple locations. In addition, a cross-correlation analysis of the signals from different microlenses yields the velocity dispersion of beads traveling through the channel at peak speeds as high as 560 mm/s. Arrays of specifically designed diffractive optics promise to increase the resolution and functionality of opto-fluidic analysis such as flow cytometry and fluorescence cross-correlation spectroscopy.

© 2011 OSA

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  3. D. P. Schrum, C. T. Culbertson, S. C. Jacobson, and J. M. Ramsey, “Microchip flow cytometry using electrokinetic focusing,” Anal. Chem. 73, 5334–5338 (2001).
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  5. J. F. Dishinger and R. T. Kennedy, “Multiplexed detection and applications for separations on parallel microchips,” Electrophoresis 29(16), 3296–3305 (2008).
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]
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  10. S. Camou, H. Fujita, and T. Fujii, “PDMS 2D optical lens integrated with microfluidic channels: principle and characterization,” Lab Chip 3, 40–45 (2003).
    [CrossRef]
  11. J. Seo and L. P. Lee, “Disposable integrated microfluidics with self-aligned planar microlenses,” Sens. Act. B 99, 615–622 (2004).
    [CrossRef]
  12. K. J. Liu and T. H. Wang, “Cylindrical illumination confocal spectroscopy: rectifying the limitations of confocal single molecule spectroscopy through one-dimensional beam shaping,” Biophys. J. 95(6), 2964–2975 (2008).
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  13. H. Farhoosh, M. R. Feldman, S. H. Lee, C. C. Guest, Y. Fainman, and R. Eschbach, “Comparison of binary encoding schemes for electron-beam fabrication of computer generated holograms,” Appl. Opt. 26(20), 4361–4372 (1987).
    [CrossRef] [PubMed]
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  18. E. Schonbrun, W. N. Ye, and K. B. Crozier, “Scanning microscopy using a short-focal-length Fresnel zone plate,” Opt. Lett. 34(14), 2228–2230 (2009).
    [CrossRef] [PubMed]
  19. J. G. Santiago, S. T. Wereley, C. D. Meinhart, D. J. Beebe, and R. J. Adrian, “A particle imaging velocimetry system for microfludics,” Exp. Fluids 25(4), 316–319 (1998).
    [CrossRef]
  20. M. Gösch, H. Blom, J. Holm, T. Heino, and R. Rigler, “Hydrodynamic flow profiling in microchannel structures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72(14), 3260–3265 (2000).
    [CrossRef] [PubMed]
  21. M. Brinkmeier, K. Dorre, J. Stephan, and M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71(3), 609–616 (1999).
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  22. D. Di Carlo, “Inertial microfluidics,” Lab Chip 9(21), 3038–3046 (2009).
    [CrossRef] [PubMed]

2010

E. Schonbrun, A. R. Abate, P. E. Steinvurzel, D. A. Weitz, and K. B. Crozier, “High-throughput fluorescence detection using an integrated zone-plate array,” Lab Chip 10(7), 852–856 (2010).
[CrossRef] [PubMed]

2009

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

E. Schonbrun, W. N. Ye, and K. B. Crozier, “Scanning microscopy using a short-focal-length Fresnel zone plate,” Opt. Lett. 34(14), 2228–2230 (2009).
[CrossRef] [PubMed]

D. Di Carlo, “Inertial microfluidics,” Lab Chip 9(21), 3038–3046 (2009).
[CrossRef] [PubMed]

2008

K. J. Liu and T. H. Wang, “Cylindrical illumination confocal spectroscopy: rectifying the limitations of confocal single molecule spectroscopy through one-dimensional beam shaping,” Biophys. J. 95(6), 2964–2975 (2008).
[CrossRef] [PubMed]

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem. 391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

J. F. Dishinger and R. T. Kennedy, “Multiplexed detection and applications for separations on parallel microchips,” Electrophoresis 29(16), 3296–3305 (2008).
[CrossRef] [PubMed]

2006

C. Simonnet and A. Groisman, “High-throughput and high-resolution flow cytometry in molded microfluidic devices,” Anal. Chem. 78(16), 5653–5663 (2006).
[CrossRef] [PubMed]

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

2004

Y. C. Tung, M. Zhang, C. T. Lin, K. Kurabayashi, and S. J. Skerlos, “PDMS-based optofluidic micro flow cytometer with two-color, multi-angle fluorescence detection capability using PIN photodiodes,” Sens. Act. B 98(2–3), 356–367 (2004).
[CrossRef]

J. Seo and L. P. Lee, “Disposable integrated microfluidics with self-aligned planar microlenses,” Sens. Act. B 99, 615–622 (2004).
[CrossRef]

2003

S. Camou, H. Fujita, and T. Fujii, “PDMS 2D optical lens integrated with microfluidic channels: principle and characterization,” Lab Chip 3, 40–45 (2003).
[CrossRef]

2001

M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, and G. M. Whitesides, “An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications,” Anal. Chem. 73(18), 4491–4498 (2001).
[CrossRef] [PubMed]

D. P. Schrum, C. T. Culbertson, S. C. Jacobson, and J. M. Ramsey, “Microchip flow cytometry using electrokinetic focusing,” Anal. Chem. 73, 5334–5338 (2001).

2000

M. Gösch, H. Blom, J. Holm, T. Heino, and R. Rigler, “Hydrodynamic flow profiling in microchannel structures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72(14), 3260–3265 (2000).
[CrossRef] [PubMed]

1999

M. Brinkmeier, K. Dorre, J. Stephan, and M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71(3), 609–616 (1999).
[CrossRef] [PubMed]

1998

J. G. Santiago, S. T. Wereley, C. D. Meinhart, D. J. Beebe, and R. J. Adrian, “A particle imaging velocimetry system for microfludics,” Exp. Fluids 25(4), 316–319 (1998).
[CrossRef]

1996

H. J. Tiziani, R. Achi, R. N. Kramer, and L. Wiegers, “Theoretical analysis of confocal microscopy with microlenses,” Appl. Opt. 35(1), 120–125 (1996).
[CrossRef] [PubMed]

1987

H. Farhoosh, M. R. Feldman, S. H. Lee, C. C. Guest, Y. Fainman, and R. Eschbach, “Comparison of binary encoding schemes for electron-beam fabrication of computer generated holograms,” Appl. Opt. 26(20), 4361–4372 (1987).
[CrossRef] [PubMed]

1984

D. Psaltis, E. G. Paek, and S. S. Venkatesh, “Optical image correlation with a binary spatial light modulator,” Opt. Eng. 23, 698 (1984).

Abate, A. R.

E. Schonbrun, A. R. Abate, P. E. Steinvurzel, D. A. Weitz, and K. B. Crozier, “High-throughput fluorescence detection using an integrated zone-plate array,” Lab Chip 10(7), 852–856 (2010).
[CrossRef] [PubMed]

Achi, R.

H. J. Tiziani, R. Achi, R. N. Kramer, and L. Wiegers, “Theoretical analysis of confocal microscopy with microlenses,” Appl. Opt. 35(1), 120–125 (1996).
[CrossRef] [PubMed]

Adrian, R. J.

J. G. Santiago, S. T. Wereley, C. D. Meinhart, D. J. Beebe, and R. J. Adrian, “A particle imaging velocimetry system for microfludics,” Exp. Fluids 25(4), 316–319 (1998).
[CrossRef]

Anderson, G. P.

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

Ateya, D. A.

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem. 391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Beebe, D. J.

J. G. Santiago, S. T. Wereley, C. D. Meinhart, D. J. Beebe, and R. J. Adrian, “A particle imaging velocimetry system for microfludics,” Exp. Fluids 25(4), 316–319 (1998).
[CrossRef]

Bilenberg, B.

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

Blom, H.

M. Gösch, H. Blom, J. Holm, T. Heino, and R. Rigler, “Hydrodynamic flow profiling in microchannel structures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72(14), 3260–3265 (2000).
[CrossRef] [PubMed]

Bøggild, P.

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

Brinkmeier, M.

M. Brinkmeier, K. Dorre, J. Stephan, and M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71(3), 609–616 (1999).
[CrossRef] [PubMed]

Camou, S.

S. Camou, H. Fujita, and T. Fujii, “PDMS 2D optical lens integrated with microfluidic channels: principle and characterization,” Lab Chip 3, 40–45 (2003).
[CrossRef]

Chabinyc, M. L.

M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, and G. M. Whitesides, “An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications,” Anal. Chem. 73(18), 4491–4498 (2001).
[CrossRef] [PubMed]

Chiu, D. T.

M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, and G. M. Whitesides, “An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications,” Anal. Chem. 73(18), 4491–4498 (2001).
[CrossRef] [PubMed]

Christian, J. F.

M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, and G. M. Whitesides, “An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications,” Anal. Chem. 73(18), 4491–4498 (2001).
[CrossRef] [PubMed]

Crozier, K. B.

E. Schonbrun, A. R. Abate, P. E. Steinvurzel, D. A. Weitz, and K. B. Crozier, “High-throughput fluorescence detection using an integrated zone-plate array,” Lab Chip 10(7), 852–856 (2010).
[CrossRef] [PubMed]

E. Schonbrun, W. N. Ye, and K. B. Crozier, “Scanning microscopy using a short-focal-length Fresnel zone plate,” Opt. Lett. 34(14), 2228–2230 (2009).
[CrossRef] [PubMed]

Culbertson, C. T.

D. P. Schrum, C. T. Culbertson, S. C. Jacobson, and J. M. Ramsey, “Microchip flow cytometry using electrokinetic focusing,” Anal. Chem. 73, 5334–5338 (2001).

Di Carlo, D.

D. Di Carlo, “Inertial microfluidics,” Lab Chip 9(21), 3038–3046 (2009).
[CrossRef] [PubMed]

Dishinger, J. F.

J. F. Dishinger and R. T. Kennedy, “Multiplexed detection and applications for separations on parallel microchips,” Electrophoresis 29(16), 3296–3305 (2008).
[CrossRef] [PubMed]

Dorre, K.

M. Brinkmeier, K. Dorre, J. Stephan, and M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71(3), 609–616 (1999).
[CrossRef] [PubMed]

Eigen, M.

M. Brinkmeier, K. Dorre, J. Stephan, and M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71(3), 609–616 (1999).
[CrossRef] [PubMed]

Erickson, J. S.

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem. 391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Eschbach, R.

H. Farhoosh, M. R. Feldman, S. H. Lee, C. C. Guest, Y. Fainman, and R. Eschbach, “Comparison of binary encoding schemes for electron-beam fabrication of computer generated holograms,” Appl. Opt. 26(20), 4361–4372 (1987).
[CrossRef] [PubMed]

Fainman, Y.

H. Farhoosh, M. R. Feldman, S. H. Lee, C. C. Guest, Y. Fainman, and R. Eschbach, “Comparison of binary encoding schemes for electron-beam fabrication of computer generated holograms,” Appl. Opt. 26(20), 4361–4372 (1987).
[CrossRef] [PubMed]

Farhoosh, H.

H. Farhoosh, M. R. Feldman, S. H. Lee, C. C. Guest, Y. Fainman, and R. Eschbach, “Comparison of binary encoding schemes for electron-beam fabrication of computer generated holograms,” Appl. Opt. 26(20), 4361–4372 (1987).
[CrossRef] [PubMed]

Feldman, M. R.

H. Farhoosh, M. R. Feldman, S. H. Lee, C. C. Guest, Y. Fainman, and R. Eschbach, “Comparison of binary encoding schemes for electron-beam fabrication of computer generated holograms,” Appl. Opt. 26(20), 4361–4372 (1987).
[CrossRef] [PubMed]

Fujii, T.

S. Camou, H. Fujita, and T. Fujii, “PDMS 2D optical lens integrated with microfluidic channels: principle and characterization,” Lab Chip 3, 40–45 (2003).
[CrossRef]

Fujita, H.

S. Camou, H. Fujita, and T. Fujii, “PDMS 2D optical lens integrated with microfluidic channels: principle and characterization,” Lab Chip 3, 40–45 (2003).
[CrossRef]

Golden, J. P.

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem. 391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Gösch, M.

M. Gösch, H. Blom, J. Holm, T. Heino, and R. Rigler, “Hydrodynamic flow profiling in microchannel structures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72(14), 3260–3265 (2000).
[CrossRef] [PubMed]

Groisman, A.

C. Simonnet and A. Groisman, “High-throughput and high-resolution flow cytometry in molded microfluidic devices,” Anal. Chem. 78(16), 5653–5663 (2006).
[CrossRef] [PubMed]

Guest, C. C.

H. Farhoosh, M. R. Feldman, S. H. Lee, C. C. Guest, Y. Fainman, and R. Eschbach, “Comparison of binary encoding schemes for electron-beam fabrication of computer generated holograms,” Appl. Opt. 26(20), 4361–4372 (1987).
[CrossRef] [PubMed]

Heino, T.

M. Gösch, H. Blom, J. Holm, T. Heino, and R. Rigler, “Hydrodynamic flow profiling in microchannel structures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72(14), 3260–3265 (2000).
[CrossRef] [PubMed]

Hilliard, L. R.

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem. 391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Holm, J.

M. Gösch, H. Blom, J. Holm, T. Heino, and R. Rigler, “Hydrodynamic flow profiling in microchannel structures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72(14), 3260–3265 (2000).
[CrossRef] [PubMed]

Howell, P. B.

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem. 391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Jacobsen, S.

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

Jacobson, S. C.

D. P. Schrum, C. T. Culbertson, S. C. Jacobson, and J. M. Ramsey, “Microchip flow cytometry using electrokinetic focusing,” Anal. Chem. 73, 5334–5338 (2001).

Karger, A. M.

M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, and G. M. Whitesides, “An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications,” Anal. Chem. 73(18), 4491–4498 (2001).
[CrossRef] [PubMed]

Kennedy, R. T.

J. F. Dishinger and R. T. Kennedy, “Multiplexed detection and applications for separations on parallel microchips,” Electrophoresis 29(16), 3296–3305 (2008).
[CrossRef] [PubMed]

Kim, J. S.

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

Kramer, R. N.

H. J. Tiziani, R. Achi, R. N. Kramer, and L. Wiegers, “Theoretical analysis of confocal microscopy with microlenses,” Appl. Opt. 35(1), 120–125 (1996).
[CrossRef] [PubMed]

Kristensen, A.

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

Kurabayashi, K.

Y. C. Tung, M. Zhang, C. T. Lin, K. Kurabayashi, and S. J. Skerlos, “PDMS-based optofluidic micro flow cytometer with two-color, multi-angle fluorescence detection capability using PIN photodiodes,” Sens. Act. B 98(2–3), 356–367 (2004).
[CrossRef]

Lee, L. P.

J. Seo and L. P. Lee, “Disposable integrated microfluidics with self-aligned planar microlenses,” Sens. Act. B 99, 615–622 (2004).
[CrossRef]

Lee, S. H.

H. Farhoosh, M. R. Feldman, S. H. Lee, C. C. Guest, Y. Fainman, and R. Eschbach, “Comparison of binary encoding schemes for electron-beam fabrication of computer generated holograms,” Appl. Opt. 26(20), 4361–4372 (1987).
[CrossRef] [PubMed]

Ligler, F. S.

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem. 391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Lin, C. T.

Y. C. Tung, M. Zhang, C. T. Lin, K. Kurabayashi, and S. J. Skerlos, “PDMS-based optofluidic micro flow cytometer with two-color, multi-angle fluorescence detection capability using PIN photodiodes,” Sens. Act. B 98(2–3), 356–367 (2004).
[CrossRef]

Liu, K. J.

K. J. Liu and T. H. Wang, “Cylindrical illumination confocal spectroscopy: rectifying the limitations of confocal single molecule spectroscopy through one-dimensional beam shaping,” Biophys. J. 95(6), 2964–2975 (2008).
[CrossRef] [PubMed]

McDonald, J. C.

M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, and G. M. Whitesides, “An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications,” Anal. Chem. 73(18), 4491–4498 (2001).
[CrossRef] [PubMed]

Meinhart, C. D.

J. G. Santiago, S. T. Wereley, C. D. Meinhart, D. J. Beebe, and R. J. Adrian, “A particle imaging velocimetry system for microfludics,” Exp. Fluids 25(4), 316–319 (1998).
[CrossRef]

Nasir, M.

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

Paek, E. G.

D. Psaltis, E. G. Paek, and S. S. Venkatesh, “Optical image correlation with a binary spatial light modulator,” Opt. Eng. 23, 698 (1984).

Psaltis, D.

D. Psaltis, E. G. Paek, and S. S. Venkatesh, “Optical image correlation with a binary spatial light modulator,” Opt. Eng. 23, 698 (1984).

Ramsey, J. M.

D. P. Schrum, C. T. Culbertson, S. C. Jacobson, and J. M. Ramsey, “Microchip flow cytometry using electrokinetic focusing,” Anal. Chem. 73, 5334–5338 (2001).

Rigler, R.

M. Gösch, H. Blom, J. Holm, T. Heino, and R. Rigler, “Hydrodynamic flow profiling in microchannel structures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72(14), 3260–3265 (2000).
[CrossRef] [PubMed]

Santiago, J. G.

J. G. Santiago, S. T. Wereley, C. D. Meinhart, D. J. Beebe, and R. J. Adrian, “A particle imaging velocimetry system for microfludics,” Exp. Fluids 25(4), 316–319 (1998).
[CrossRef]

Schmidt, M. S.

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

Schonbrun, E.

E. Schonbrun, A. R. Abate, P. E. Steinvurzel, D. A. Weitz, and K. B. Crozier, “High-throughput fluorescence detection using an integrated zone-plate array,” Lab Chip 10(7), 852–856 (2010).
[CrossRef] [PubMed]

E. Schonbrun, W. N. Ye, and K. B. Crozier, “Scanning microscopy using a short-focal-length Fresnel zone plate,” Opt. Lett. 34(14), 2228–2230 (2009).
[CrossRef] [PubMed]

Schrum, D. P.

D. P. Schrum, C. T. Culbertson, S. C. Jacobson, and J. M. Ramsey, “Microchip flow cytometry using electrokinetic focusing,” Anal. Chem. 73, 5334–5338 (2001).

Seo, J.

J. Seo and L. P. Lee, “Disposable integrated microfluidics with self-aligned planar microlenses,” Sens. Act. B 99, 615–622 (2004).
[CrossRef]

Shi, P.

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

Simonnet, C.

C. Simonnet and A. Groisman, “High-throughput and high-resolution flow cytometry in molded microfluidic devices,” Anal. Chem. 78(16), 5653–5663 (2006).
[CrossRef] [PubMed]

Skerlos, S. J.

Y. C. Tung, M. Zhang, C. T. Lin, K. Kurabayashi, and S. J. Skerlos, “PDMS-based optofluidic micro flow cytometer with two-color, multi-angle fluorescence detection capability using PIN photodiodes,” Sens. Act. B 98(2–3), 356–367 (2004).
[CrossRef]

Skjolding, L. H. D.

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

Steinvurzel, P. E.

E. Schonbrun, A. R. Abate, P. E. Steinvurzel, D. A. Weitz, and K. B. Crozier, “High-throughput fluorescence detection using an integrated zone-plate array,” Lab Chip 10(7), 852–856 (2010).
[CrossRef] [PubMed]

Stephan, J.

M. Brinkmeier, K. Dorre, J. Stephan, and M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71(3), 609–616 (1999).
[CrossRef] [PubMed]

Stroock, A. D.

M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, and G. M. Whitesides, “An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications,” Anal. Chem. 73(18), 4491–4498 (2001).
[CrossRef] [PubMed]

Tegenfeldt, J. O.

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

Tiziani, H. J.

H. J. Tiziani, R. Achi, R. N. Kramer, and L. Wiegers, “Theoretical analysis of confocal microscopy with microlenses,” Appl. Opt. 35(1), 120–125 (1996).
[CrossRef] [PubMed]

Tung, Y. C.

Y. C. Tung, M. Zhang, C. T. Lin, K. Kurabayashi, and S. J. Skerlos, “PDMS-based optofluidic micro flow cytometer with two-color, multi-angle fluorescence detection capability using PIN photodiodes,” Sens. Act. B 98(2–3), 356–367 (2004).
[CrossRef]

Venkatesh, S. S.

D. Psaltis, E. G. Paek, and S. S. Venkatesh, “Optical image correlation with a binary spatial light modulator,” Opt. Eng. 23, 698 (1984).

Wang, T. H.

K. J. Liu and T. H. Wang, “Cylindrical illumination confocal spectroscopy: rectifying the limitations of confocal single molecule spectroscopy through one-dimensional beam shaping,” Biophys. J. 95(6), 2964–2975 (2008).
[CrossRef] [PubMed]

Weitz, D. A.

E. Schonbrun, A. R. Abate, P. E. Steinvurzel, D. A. Weitz, and K. B. Crozier, “High-throughput fluorescence detection using an integrated zone-plate array,” Lab Chip 10(7), 852–856 (2010).
[CrossRef] [PubMed]

Wereley, S. T.

J. G. Santiago, S. T. Wereley, C. D. Meinhart, D. J. Beebe, and R. J. Adrian, “A particle imaging velocimetry system for microfludics,” Exp. Fluids 25(4), 316–319 (1998).
[CrossRef]

Whitesides, G. M.

M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, and G. M. Whitesides, “An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications,” Anal. Chem. 73(18), 4491–4498 (2001).
[CrossRef] [PubMed]

Wiegers, L.

H. J. Tiziani, R. Achi, R. N. Kramer, and L. Wiegers, “Theoretical analysis of confocal microscopy with microlenses,” Appl. Opt. 35(1), 120–125 (1996).
[CrossRef] [PubMed]

Ye, W. N.

E. Schonbrun, W. N. Ye, and K. B. Crozier, “Scanning microscopy using a short-focal-length Fresnel zone plate,” Opt. Lett. 34(14), 2228–2230 (2009).
[CrossRef] [PubMed]

Zhang, M.

Y. C. Tung, M. Zhang, C. T. Lin, K. Kurabayashi, and S. J. Skerlos, “PDMS-based optofluidic micro flow cytometer with two-color, multi-angle fluorescence detection capability using PIN photodiodes,” Sens. Act. B 98(2–3), 356–367 (2004).
[CrossRef]

Anal. Bioanal. Chem.

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem. 391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Anal. Chem.

D. P. Schrum, C. T. Culbertson, S. C. Jacobson, and J. M. Ramsey, “Microchip flow cytometry using electrokinetic focusing,” Anal. Chem. 73, 5334–5338 (2001).

C. Simonnet and A. Groisman, “High-throughput and high-resolution flow cytometry in molded microfluidic devices,” Anal. Chem. 78(16), 5653–5663 (2006).
[CrossRef] [PubMed]

M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, and G. M. Whitesides, “An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications,” Anal. Chem. 73(18), 4491–4498 (2001).
[CrossRef] [PubMed]

M. Gösch, H. Blom, J. Holm, T. Heino, and R. Rigler, “Hydrodynamic flow profiling in microchannel structures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72(14), 3260–3265 (2000).
[CrossRef] [PubMed]

M. Brinkmeier, K. Dorre, J. Stephan, and M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71(3), 609–616 (1999).
[CrossRef] [PubMed]

Appl. Opt.

H. Farhoosh, M. R. Feldman, S. H. Lee, C. C. Guest, Y. Fainman, and R. Eschbach, “Comparison of binary encoding schemes for electron-beam fabrication of computer generated holograms,” Appl. Opt. 26(20), 4361–4372 (1987).
[CrossRef] [PubMed]

H. J. Tiziani, R. Achi, R. N. Kramer, and L. Wiegers, “Theoretical analysis of confocal microscopy with microlenses,” Appl. Opt. 35(1), 120–125 (1996).
[CrossRef] [PubMed]

Biophys. J.

K. J. Liu and T. H. Wang, “Cylindrical illumination confocal spectroscopy: rectifying the limitations of confocal single molecule spectroscopy through one-dimensional beam shaping,” Biophys. J. 95(6), 2964–2975 (2008).
[CrossRef] [PubMed]

Electrophoresis

J. F. Dishinger and R. T. Kennedy, “Multiplexed detection and applications for separations on parallel microchips,” Electrophoresis 29(16), 3296–3305 (2008).
[CrossRef] [PubMed]

Exp. Fluids

J. G. Santiago, S. T. Wereley, C. D. Meinhart, D. J. Beebe, and R. J. Adrian, “A particle imaging velocimetry system for microfludics,” Exp. Fluids 25(4), 316–319 (1998).
[CrossRef]

Lab Chip

D. Di Carlo, “Inertial microfluidics,” Lab Chip 9(21), 3038–3046 (2009).
[CrossRef] [PubMed]

E. Schonbrun, A. R. Abate, P. E. Steinvurzel, D. A. Weitz, and K. B. Crozier, “High-throughput fluorescence detection using an integrated zone-plate array,” Lab Chip 10(7), 852–856 (2010).
[CrossRef] [PubMed]

J. P. Golden, J. S. Kim, J. S. Erickson, L. R. Hilliard, P. B. Howell, G. P. Anderson, M. Nasir, and F. S. Ligler, “Multi-wavelength microflow cytometer using groove-generated sheath flow,” Lab Chip 9(13), 1942–1950 (2009).
[CrossRef] [PubMed]

S. Camou, H. Fujita, and T. Fujii, “PDMS 2D optical lens integrated with microfluidic channels: principle and characterization,” Lab Chip 3, 40–45 (2003).
[CrossRef]

Micro. Eng.

B. Bilenberg, S. Jacobsen, M. S. Schmidt, L. H. D. Skjolding, P. Shi, P. Bøggild, J. O. Tegenfeldt, and A. Kristensen, “High resolution 100 kV electron beam lithography in SU8,” Micro. Eng. 83(4–9), 1609–1612 (2006).
[CrossRef]

Opt. Eng.

D. Psaltis, E. G. Paek, and S. S. Venkatesh, “Optical image correlation with a binary spatial light modulator,” Opt. Eng. 23, 698 (1984).

Opt. Lett.

E. Schonbrun, W. N. Ye, and K. B. Crozier, “Scanning microscopy using a short-focal-length Fresnel zone plate,” Opt. Lett. 34(14), 2228–2230 (2009).
[CrossRef] [PubMed]

Sens. Act. B

J. Seo and L. P. Lee, “Disposable integrated microfluidics with self-aligned planar microlenses,” Sens. Act. B 99, 615–622 (2004).
[CrossRef]

Y. C. Tung, M. Zhang, C. T. Lin, K. Kurabayashi, and S. J. Skerlos, “PDMS-based optofluidic micro flow cytometer with two-color, multi-angle fluorescence detection capability using PIN photodiodes,” Sens. Act. B 98(2–3), 356–367 (2004).
[CrossRef]

Other

H. M. Shapiro, Practical Flow Cytometry, 3rd ed. (Wiley-Liss, 1995).

J. W. Goodman, Introduction to Fourier Optics (McGraw-Hill, New York, 1996).

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Figures (7)

Fig. 1
Fig. 1

Schematic of the optofluidic fluorescence measurement system. The microfluidic channel and microlens array are integrated onto the same substrate. The microlens array is illuminated by a broad fluorescence excitation laser beam and imaged onto a high speed CMOS camera by off chip relay optics that have unity magnification. The fast CMOS camera is a Phantom V7.1 from Vision Research. Image stacks are collected by the camera and later analyzed to quantify the fluorescence signal collected from each detection region.

Fig. 2
Fig. 2

Astigmatic diffractive microlens. a) Microscope image of SU8 lens master. b, c) Experimentally-observed focal spot intensity distribution at front and back focal planes, respectively, taken with a 50× objective lens.

Fig. 3
Fig. 3

Optofludic device. a) Brightfield microscope image, taken with a 10× objective lens, of the flow focus microfluidic device aligned to the diffractive microlens array. The diffractive microlenses are separated from the microfluidic channel by the coverslip thickness of 170 μm, so they appear slightly out of focus. b) Fluorescent emission resulting from the diffractive lenses focusing the excitation laser into the dye-filled channel, showing the focal spot distributions of all three detection regions.

Fig. 4
Fig. 4

Bead counting at multiple detection regions. a) Time trace sampled at 4,000 frames per second (fps) of signals produced at each of three detection regions (DR), corresponding to each of three diffractive microlenses. Inset shows a higher resolution time trace of seven beads as they flow by the three detection regions. b) Histograms of the peak heights for each of the three different detection regions.

Fig. 5
Fig. 5

Time resolution characterization. a) Time trace sampled at 40,000 fps of signals produced at two detection regions. Inset shows a higher resolution time trace of the signal from two beads. b) Autocorrelation of each detection region, yielding a half width at half maximum of 23 and 31 μs, respectively. For a velocity of 90 mm/s, beads travel an average of 2.3 μm in between frames.

Fig. 6
Fig. 6

High speed size discrimination. (a) Time trace sampled at 100,000 fps of signals produced at two detection regions for a mixture of 500 nm and 1.1 μm beads. (b) and (c) Histograms of the peak heights at the first and second detection region, respectively, plotted as a function of the cube root of peak intensity.

Fig. 7
Fig. 7

Size resolved velocity dispersion. (a) Cross correlation of the total signal of a heterogeneous sample of 0.5 and 1.1 μm beads from two consecutive detection regions. (b) Cross correlation of the intensity gated signals from the same two detection regions, showing that the 1.1 μm beads have greater velocity dispersion.

Equations (2)

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A D W = exp ( j k x 2 + y 2 + f o 2 ) exp ( j k x 2 + f 1 2 ) ,
w f = ( f b f f ) R / f b ,

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