Abstract

A simple fabrication technique to create all silicon/glass microfluidic devices is demonstrated using femtosecond laser ablation and anodic bonding. In a first application, we constructed a cell counting device based on small angle light scattering. The counter featured embedded optical fibers for multiangle excitation and detection of scattered light and/or fluorescence. The performance of the microfluidic cell counter was benchmarked against a commercial fluorescence-activated cell sorter.

© 2009 Optical Society of America

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  1. E. Altendorf, D. Zebert, M. Holl, and P. Yager, "Differential blood cell counts obtained using a microchannel based flow cytometer," in IEEE International Conference on Solid-State Sensors and Actuators (IEEE, 1997) pp. 531-534.
    [CrossRef]
  2. M. Brown and C. Wittwer, "Flow cytometry: principles and clinical applications in hematology," Clin. Chem. 46, 1221-1229 (2000).
    [PubMed]
  3. N. Pamme, R. Koyama, and A. Manz, "Counting and sizing of particles and particle agglomerates in a microfluidic device using laser light scattering: application to a particle-enhanced immunoassay," Lab Chip 3, 187-192 (2003).
    [CrossRef]
  4. H. Chen and Y. Wang, "Optical microflow cytometer for particle counting, sizing and fluorescence detection," Microfluid. Nanofluid. (2008), DOI 10.1007/s10404-008-0335-z.
  5. M. L. Chabinyc, D. T. Chiu, J. Cooper 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, 4491-4498 (2001).
    [CrossRef] [PubMed]
  6. A. Llobera, R. Wilke, and S. Büttgenbach, "Poly(dimethylsiloxane) hollow Abbe Prism with microlenses for detection based on absorption and refractive index shift," Lab Chip 4, 24-27 (2004).
    [CrossRef] [PubMed]
  7. Q1. Y. Tung, M. Zhang, C. Lin, K. Kurabayashi, and S. J. Skerlos, "PDMS-based opto-fluidic micro flow cytometer with two-color multi-angle fluorescence detection capability using PIN photodiodes," Sens. Actuators B 98, 356-367 (2004).
    [CrossRef]
  8. J. B. Ashcom, R. R. Gattass, C. B. Schaffer, and E. Mazur, "Numerical aperture dependence of damage and supercontinuum generation from femtosecond laser pulses in bulk fused silica," J. Opt. Soc. Am. B 23, 2317-2322 (2006).
    [CrossRef]
  9. M. S. Giridhar, K. Seong, A. Schülzgen, P. Khulbe, N. Peyghambarian, and M. Mansuripur, "Femtosecond pulsed laser micromachining of glass substrates with application to microfluidic devices," Appl. Opt. 43, 4584-4589 (2004).
    [CrossRef] [PubMed]
  10. A. A. Said, M. Dugan, P. Bado, Y. Bellouard, A. Scott, and J. R. Mabesa, Jr., "Manufacturing by laser direct-write of three-dimensional devices containing optical and microfluidic networks," Proc. SPIE 5339, 194-204 (2004).
    [CrossRef]
  11. Y. Bellouard, A. Said, and P. Bado, "Integrating optics and micro-mechanics in a single substrate: a step toward monolithic integration in fused silica," Opt. Express 13, 6635-6644 (2005).
    [CrossRef] [PubMed]
  12. K. Ke, E. F. Hasselbrink, Jr., and A. J. Hunt, "Rapidly prototyped three-dimensional nanofluidic channel networks in glass substrates," Anal. Chem. 77, 5083-5088 (2005).
    [CrossRef] [PubMed]
  13. R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, "Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation," Appl. Phys. Lett. 90, 231118 (2007).
    [CrossRef]
  14. Q2. Y. Hanada, K. Sugioka, H. Kawano, I. Ishikawa, A. Miyawaki, and K. Midorikawa, "Nano-aquarium fabrication by femtosecond laser direct writing for microscopic observation of aquatic microorganisms," Rev. Laser Engin. 36, 1222-1225 (2008).
    [CrossRef]
  15. Q3. M. Kim, D. J. Hwang, H. Jeon, K. Hiromatsu and C. P. Grigoropoulos, "Single cell detection using a glass-based optofluidic device fabricated by femtosecond laser pulses," Lab Chip, 2009, DOI: 10.1039/b808366e.
  16. L. Cui, T. Zhang and H. Morgan, "Optical particle detection integrated in a dielectrophoretic lab-on-a-chip," J. Micromech. Microeng. 12, 7-12 (2002).
    [CrossRef]
  17. J. Krüger, K. Singh, A. O'Neill, C. Jackson, A. Morrison, and P. O'Brien, "Development of a microfluidic device for fluorescence activated cell sorting," J. Micromech. Microeng. 12, 486-494 (2002).
    [CrossRef]
  18. K. B. Mogensen, J. El-Ali, A. Wolff, and J. P. Kutter, "Integration of polymer waveguides for optical detection in microfabricated chemical analysis systems," Appl. Opt. 42, 4072-4079 (2003).
    [CrossRef] [PubMed]
  19. C. Lin and G. Lee, "Micromachined flow cytometers with embedded etched optic fibers for optical detection," J. Micromech. Microeng. 13, 447-453 (2003).
    [CrossRef]
  20. L. Fu, R. Yang, C. Lin, Y. Pan, and G. Lee, "Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection," Analytica Chimica Acta 507, 163-169 (2004).
    [CrossRef]
  21. Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
    [CrossRef] [PubMed]
  22. Q4. R. Mazurczyk, J. Vieillard, A. Bouchard, B. Hannes, and S. Krawczyk, "A novel concept of the integrated fluorescence detection system and its application to a lab-on-a-chip microdevice," Sens. Act. B 118, 11-19 (2006).
    [CrossRef]
  23. R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
    [CrossRef] [PubMed]
  24. G. D. Wallis and D. I. Pomerantz. "Field assisted glass-metal sealing," J. Appl. Phys. 40, 3946 (1969).
    [CrossRef]

2009 (1)

Q3. M. Kim, D. J. Hwang, H. Jeon, K. Hiromatsu and C. P. Grigoropoulos, "Single cell detection using a glass-based optofluidic device fabricated by femtosecond laser pulses," Lab Chip, 2009, DOI: 10.1039/b808366e.

2008 (1)

Q2. Y. Hanada, K. Sugioka, H. Kawano, I. Ishikawa, A. Miyawaki, and K. Midorikawa, "Nano-aquarium fabrication by femtosecond laser direct writing for microscopic observation of aquatic microorganisms," Rev. Laser Engin. 36, 1222-1225 (2008).
[CrossRef]

2007 (1)

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, "Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation," Appl. Phys. Lett. 90, 231118 (2007).
[CrossRef]

2006 (3)

J. B. Ashcom, R. R. Gattass, C. B. Schaffer, and E. Mazur, "Numerical aperture dependence of damage and supercontinuum generation from femtosecond laser pulses in bulk fused silica," J. Opt. Soc. Am. B 23, 2317-2322 (2006).
[CrossRef]

Q4. R. Mazurczyk, J. Vieillard, A. Bouchard, B. Hannes, and S. Krawczyk, "A novel concept of the integrated fluorescence detection system and its application to a lab-on-a-chip microdevice," Sens. Act. B 118, 11-19 (2006).
[CrossRef]

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

2005 (2)

Y. Bellouard, A. Said, and P. Bado, "Integrating optics and micro-mechanics in a single substrate: a step toward monolithic integration in fused silica," Opt. Express 13, 6635-6644 (2005).
[CrossRef] [PubMed]

K. Ke, E. F. Hasselbrink, Jr., and A. J. Hunt, "Rapidly prototyped three-dimensional nanofluidic channel networks in glass substrates," Anal. Chem. 77, 5083-5088 (2005).
[CrossRef] [PubMed]

2004 (6)

M. S. Giridhar, K. Seong, A. Schülzgen, P. Khulbe, N. Peyghambarian, and M. Mansuripur, "Femtosecond pulsed laser micromachining of glass substrates with application to microfluidic devices," Appl. Opt. 43, 4584-4589 (2004).
[CrossRef] [PubMed]

A. A. Said, M. Dugan, P. Bado, Y. Bellouard, A. Scott, and J. R. Mabesa, Jr., "Manufacturing by laser direct-write of three-dimensional devices containing optical and microfluidic networks," Proc. SPIE 5339, 194-204 (2004).
[CrossRef]

A. Llobera, R. Wilke, and S. Büttgenbach, "Poly(dimethylsiloxane) hollow Abbe Prism with microlenses for detection based on absorption and refractive index shift," Lab Chip 4, 24-27 (2004).
[CrossRef] [PubMed]

Q1. Y. Tung, M. Zhang, C. Lin, K. Kurabayashi, and S. J. Skerlos, "PDMS-based opto-fluidic micro flow cytometer with two-color multi-angle fluorescence detection capability using PIN photodiodes," Sens. Actuators B 98, 356-367 (2004).
[CrossRef]

L. Fu, R. Yang, C. Lin, Y. Pan, and G. Lee, "Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection," Analytica Chimica Acta 507, 163-169 (2004).
[CrossRef]

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

2003 (3)

K. B. Mogensen, J. El-Ali, A. Wolff, and J. P. Kutter, "Integration of polymer waveguides for optical detection in microfabricated chemical analysis systems," Appl. Opt. 42, 4072-4079 (2003).
[CrossRef] [PubMed]

C. Lin and G. Lee, "Micromachined flow cytometers with embedded etched optic fibers for optical detection," J. Micromech. Microeng. 13, 447-453 (2003).
[CrossRef]

N. Pamme, R. Koyama, and A. Manz, "Counting and sizing of particles and particle agglomerates in a microfluidic device using laser light scattering: application to a particle-enhanced immunoassay," Lab Chip 3, 187-192 (2003).
[CrossRef]

2002 (2)

L. Cui, T. Zhang and H. Morgan, "Optical particle detection integrated in a dielectrophoretic lab-on-a-chip," J. Micromech. Microeng. 12, 7-12 (2002).
[CrossRef]

J. Krüger, K. Singh, A. O'Neill, C. Jackson, A. Morrison, and P. O'Brien, "Development of a microfluidic device for fluorescence activated cell sorting," J. Micromech. Microeng. 12, 486-494 (2002).
[CrossRef]

2001 (1)

M. L. Chabinyc, D. T. Chiu, J. Cooper 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, 4491-4498 (2001).
[CrossRef] [PubMed]

2000 (1)

M. Brown and C. Wittwer, "Flow cytometry: principles and clinical applications in hematology," Clin. Chem. 46, 1221-1229 (2000).
[PubMed]

1969 (1)

G. D. Wallis and D. I. Pomerantz. "Field assisted glass-metal sealing," J. Appl. Phys. 40, 3946 (1969).
[CrossRef]

Applegate, R. W.

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

Ashcom, J. B.

Bado, P.

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

Y. Bellouard, A. Said, and P. Bado, "Integrating optics and micro-mechanics in a single substrate: a step toward monolithic integration in fused silica," Opt. Express 13, 6635-6644 (2005).
[CrossRef] [PubMed]

A. A. Said, M. Dugan, P. Bado, Y. Bellouard, A. Scott, and J. R. Mabesa, Jr., "Manufacturing by laser direct-write of three-dimensional devices containing optical and microfluidic networks," Proc. SPIE 5339, 194-204 (2004).
[CrossRef]

Bellouard, Y.

Y. Bellouard, A. Said, and P. Bado, "Integrating optics and micro-mechanics in a single substrate: a step toward monolithic integration in fused silica," Opt. Express 13, 6635-6644 (2005).
[CrossRef] [PubMed]

A. A. Said, M. Dugan, P. Bado, Y. Bellouard, A. Scott, and J. R. Mabesa, Jr., "Manufacturing by laser direct-write of three-dimensional devices containing optical and microfluidic networks," Proc. SPIE 5339, 194-204 (2004).
[CrossRef]

Bouchard, A.

Q4. R. Mazurczyk, J. Vieillard, A. Bouchard, B. Hannes, and S. Krawczyk, "A novel concept of the integrated fluorescence detection system and its application to a lab-on-a-chip microdevice," Sens. Act. B 118, 11-19 (2006).
[CrossRef]

Brown, M.

M. Brown and C. Wittwer, "Flow cytometry: principles and clinical applications in hematology," Clin. Chem. 46, 1221-1229 (2000).
[PubMed]

Büttgenbach, S.

A. Llobera, R. Wilke, and S. Büttgenbach, "Poly(dimethylsiloxane) hollow Abbe Prism with microlenses for detection based on absorption and refractive index shift," Lab Chip 4, 24-27 (2004).
[CrossRef] [PubMed]

Cerullo, G.

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, "Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation," Appl. Phys. Lett. 90, 231118 (2007).
[CrossRef]

Chabinyc, M. L.

M. L. Chabinyc, D. T. Chiu, J. Cooper 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, 4491-4498 (2001).
[CrossRef] [PubMed]

Chiu, D. T.

M. L. Chabinyc, D. T. Chiu, J. Cooper 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, 4491-4498 (2001).
[CrossRef] [PubMed]

Cui, L.

L. Cui, T. Zhang and H. Morgan, "Optical particle detection integrated in a dielectrophoretic lab-on-a-chip," J. Micromech. Microeng. 12, 7-12 (2002).
[CrossRef]

Dugan, M.

A. A. Said, M. Dugan, P. Bado, Y. Bellouard, A. Scott, and J. R. Mabesa, Jr., "Manufacturing by laser direct-write of three-dimensional devices containing optical and microfluidic networks," Proc. SPIE 5339, 194-204 (2004).
[CrossRef]

Dugan, M. A.

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

El-Ali, J.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

K. B. Mogensen, J. El-Ali, A. Wolff, and J. P. Kutter, "Integration of polymer waveguides for optical detection in microfabricated chemical analysis systems," Appl. Opt. 42, 4072-4079 (2003).
[CrossRef] [PubMed]

Engelund, M.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

Fu, L.

L. Fu, R. Yang, C. Lin, Y. Pan, and G. Lee, "Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection," Analytica Chimica Acta 507, 163-169 (2004).
[CrossRef]

Gattass, R. R.

Giridhar, M. S.

Gotsæd, T.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

Grigoropoulos, C. P.

Q3. M. Kim, D. J. Hwang, H. Jeon, K. Hiromatsu and C. P. Grigoropoulos, "Single cell detection using a glass-based optofluidic device fabricated by femtosecond laser pulses," Lab Chip, 2009, DOI: 10.1039/b808366e.

Hanada, Y.

Q2. Y. Hanada, K. Sugioka, H. Kawano, I. Ishikawa, A. Miyawaki, and K. Midorikawa, "Nano-aquarium fabrication by femtosecond laser direct writing for microscopic observation of aquatic microorganisms," Rev. Laser Engin. 36, 1222-1225 (2008).
[CrossRef]

Hannes, B.

Q4. R. Mazurczyk, J. Vieillard, A. Bouchard, B. Hannes, and S. Krawczyk, "A novel concept of the integrated fluorescence detection system and its application to a lab-on-a-chip microdevice," Sens. Act. B 118, 11-19 (2006).
[CrossRef]

Hasselbrink, E. F.

K. Ke, E. F. Hasselbrink, Jr., and A. J. Hunt, "Rapidly prototyped three-dimensional nanofluidic channel networks in glass substrates," Anal. Chem. 77, 5083-5088 (2005).
[CrossRef] [PubMed]

Hiromatsu, K.

Q3. M. Kim, D. J. Hwang, H. Jeon, K. Hiromatsu and C. P. Grigoropoulos, "Single cell detection using a glass-based optofluidic device fabricated by femtosecond laser pulses," Lab Chip, 2009, DOI: 10.1039/b808366e.

Hunt, A. J.

K. Ke, E. F. Hasselbrink, Jr., and A. J. Hunt, "Rapidly prototyped three-dimensional nanofluidic channel networks in glass substrates," Anal. Chem. 77, 5083-5088 (2005).
[CrossRef] [PubMed]

Hwang, D. J.

Q3. M. Kim, D. J. Hwang, H. Jeon, K. Hiromatsu and C. P. Grigoropoulos, "Single cell detection using a glass-based optofluidic device fabricated by femtosecond laser pulses," Lab Chip, 2009, DOI: 10.1039/b808366e.

Ishikawa, I.

Q2. Y. Hanada, K. Sugioka, H. Kawano, I. Ishikawa, A. Miyawaki, and K. Midorikawa, "Nano-aquarium fabrication by femtosecond laser direct writing for microscopic observation of aquatic microorganisms," Rev. Laser Engin. 36, 1222-1225 (2008).
[CrossRef]

Jackson, C.

J. Krüger, K. Singh, A. O'Neill, C. Jackson, A. Morrison, and P. O'Brien, "Development of a microfluidic device for fluorescence activated cell sorting," J. Micromech. Microeng. 12, 486-494 (2002).
[CrossRef]

Jeon, H.

Q3. M. Kim, D. J. Hwang, H. Jeon, K. Hiromatsu and C. P. Grigoropoulos, "Single cell detection using a glass-based optofluidic device fabricated by femtosecond laser pulses," Lab Chip, 2009, DOI: 10.1039/b808366e.

Kawano, H.

Q2. Y. Hanada, K. Sugioka, H. Kawano, I. Ishikawa, A. Miyawaki, and K. Midorikawa, "Nano-aquarium fabrication by femtosecond laser direct writing for microscopic observation of aquatic microorganisms," Rev. Laser Engin. 36, 1222-1225 (2008).
[CrossRef]

Ke, K.

K. Ke, E. F. Hasselbrink, Jr., and A. J. Hunt, "Rapidly prototyped three-dimensional nanofluidic channel networks in glass substrates," Anal. Chem. 77, 5083-5088 (2005).
[CrossRef] [PubMed]

Khulbe, P.

Kim, M.

Q3. M. Kim, D. J. Hwang, H. Jeon, K. Hiromatsu and C. P. Grigoropoulos, "Single cell detection using a glass-based optofluidic device fabricated by femtosecond laser pulses," Lab Chip, 2009, DOI: 10.1039/b808366e.

Koyama, R.

N. Pamme, R. Koyama, and A. Manz, "Counting and sizing of particles and particle agglomerates in a microfluidic device using laser light scattering: application to a particle-enhanced immunoassay," Lab Chip 3, 187-192 (2003).
[CrossRef]

Krawczyk, S.

Q4. R. Mazurczyk, J. Vieillard, A. Bouchard, B. Hannes, and S. Krawczyk, "A novel concept of the integrated fluorescence detection system and its application to a lab-on-a-chip microdevice," Sens. Act. B 118, 11-19 (2006).
[CrossRef]

Krüger, J.

J. Krüger, K. Singh, A. O'Neill, C. Jackson, A. Morrison, and P. O'Brien, "Development of a microfluidic device for fluorescence activated cell sorting," J. Micromech. Microeng. 12, 486-494 (2002).
[CrossRef]

Kurabayashi, K.

Q1. Y. Tung, M. Zhang, C. Lin, K. Kurabayashi, and S. J. Skerlos, "PDMS-based opto-fluidic micro flow cytometer with two-color multi-angle fluorescence detection capability using PIN photodiodes," Sens. Actuators B 98, 356-367 (2004).
[CrossRef]

Kutter, J. P.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

K. B. Mogensen, J. El-Ali, A. Wolff, and J. P. Kutter, "Integration of polymer waveguides for optical detection in microfabricated chemical analysis systems," Appl. Opt. 42, 4072-4079 (2003).
[CrossRef] [PubMed]

Lee, G.

L. Fu, R. Yang, C. Lin, Y. Pan, and G. Lee, "Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection," Analytica Chimica Acta 507, 163-169 (2004).
[CrossRef]

C. Lin and G. Lee, "Micromachined flow cytometers with embedded etched optic fibers for optical detection," J. Micromech. Microeng. 13, 447-453 (2003).
[CrossRef]

Lin, C.

Q1. Y. Tung, M. Zhang, C. Lin, K. Kurabayashi, and S. J. Skerlos, "PDMS-based opto-fluidic micro flow cytometer with two-color multi-angle fluorescence detection capability using PIN photodiodes," Sens. Actuators B 98, 356-367 (2004).
[CrossRef]

L. Fu, R. Yang, C. Lin, Y. Pan, and G. Lee, "Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection," Analytica Chimica Acta 507, 163-169 (2004).
[CrossRef]

C. Lin and G. Lee, "Micromachined flow cytometers with embedded etched optic fibers for optical detection," J. Micromech. Microeng. 13, 447-453 (2003).
[CrossRef]

Llobera, A.

A. Llobera, R. Wilke, and S. Büttgenbach, "Poly(dimethylsiloxane) hollow Abbe Prism with microlenses for detection based on absorption and refractive index shift," Lab Chip 4, 24-27 (2004).
[CrossRef] [PubMed]

Mabesa, J. R.

A. A. Said, M. Dugan, P. Bado, Y. Bellouard, A. Scott, and J. R. Mabesa, Jr., "Manufacturing by laser direct-write of three-dimensional devices containing optical and microfluidic networks," Proc. SPIE 5339, 194-204 (2004).
[CrossRef]

Mansuripur, M.

Manz, A.

N. Pamme, R. Koyama, and A. Manz, "Counting and sizing of particles and particle agglomerates in a microfluidic device using laser light scattering: application to a particle-enhanced immunoassay," Lab Chip 3, 187-192 (2003).
[CrossRef]

Marr, D. W. M.

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

Maselli, V.

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, "Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation," Appl. Phys. Lett. 90, 231118 (2007).
[CrossRef]

Mazur, E.

Mazurczyk, R.

Q4. R. Mazurczyk, J. Vieillard, A. Bouchard, B. Hannes, and S. Krawczyk, "A novel concept of the integrated fluorescence detection system and its application to a lab-on-a-chip microdevice," Sens. Act. B 118, 11-19 (2006).
[CrossRef]

Midorikawa, K.

Q2. Y. Hanada, K. Sugioka, H. Kawano, I. Ishikawa, A. Miyawaki, and K. Midorikawa, "Nano-aquarium fabrication by femtosecond laser direct writing for microscopic observation of aquatic microorganisms," Rev. Laser Engin. 36, 1222-1225 (2008).
[CrossRef]

Miyawaki, A.

Q2. Y. Hanada, K. Sugioka, H. Kawano, I. Ishikawa, A. Miyawaki, and K. Midorikawa, "Nano-aquarium fabrication by femtosecond laser direct writing for microscopic observation of aquatic microorganisms," Rev. Laser Engin. 36, 1222-1225 (2008).
[CrossRef]

Mogensen, K. B.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

K. B. Mogensen, J. El-Ali, A. Wolff, and J. P. Kutter, "Integration of polymer waveguides for optical detection in microfabricated chemical analysis systems," Appl. Opt. 42, 4072-4079 (2003).
[CrossRef] [PubMed]

Morgan, H.

L. Cui, T. Zhang and H. Morgan, "Optical particle detection integrated in a dielectrophoretic lab-on-a-chip," J. Micromech. Microeng. 12, 7-12 (2002).
[CrossRef]

Morrison, A.

J. Krüger, K. Singh, A. O'Neill, C. Jackson, A. Morrison, and P. O'Brien, "Development of a microfluidic device for fluorescence activated cell sorting," J. Micromech. Microeng. 12, 486-494 (2002).
[CrossRef]

Oakey, J.

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

O'Brien, P.

J. Krüger, K. Singh, A. O'Neill, C. Jackson, A. Morrison, and P. O'Brien, "Development of a microfluidic device for fluorescence activated cell sorting," J. Micromech. Microeng. 12, 486-494 (2002).
[CrossRef]

O'Neill, A.

J. Krüger, K. Singh, A. O'Neill, C. Jackson, A. Morrison, and P. O'Brien, "Development of a microfluidic device for fluorescence activated cell sorting," J. Micromech. Microeng. 12, 486-494 (2002).
[CrossRef]

Osellame, R.

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, "Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation," Appl. Phys. Lett. 90, 231118 (2007).
[CrossRef]

Pamme, N.

N. Pamme, R. Koyama, and A. Manz, "Counting and sizing of particles and particle agglomerates in a microfluidic device using laser light scattering: application to a particle-enhanced immunoassay," Lab Chip 3, 187-192 (2003).
[CrossRef]

Pan, Y.

L. Fu, R. Yang, C. Lin, Y. Pan, and G. Lee, "Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection," Analytica Chimica Acta 507, 163-169 (2004).
[CrossRef]

Perch-Nielsen, I. R.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

Peyghambarian, N.

Pomerantz, D. I.

G. D. Wallis and D. I. Pomerantz. "Field assisted glass-metal sealing," J. Appl. Phys. 40, 3946 (1969).
[CrossRef]

Ramponi, R.

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, "Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation," Appl. Phys. Lett. 90, 231118 (2007).
[CrossRef]

Said, A.

Said, A. A.

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

A. A. Said, M. Dugan, P. Bado, Y. Bellouard, A. Scott, and J. R. Mabesa, Jr., "Manufacturing by laser direct-write of three-dimensional devices containing optical and microfluidic networks," Proc. SPIE 5339, 194-204 (2004).
[CrossRef]

Schaffer, C. B.

Schülzgen, A.

Scott, A.

A. A. Said, M. Dugan, P. Bado, Y. Bellouard, A. Scott, and J. R. Mabesa, Jr., "Manufacturing by laser direct-write of three-dimensional devices containing optical and microfluidic networks," Proc. SPIE 5339, 194-204 (2004).
[CrossRef]

Seong, K.

Singh, K.

J. Krüger, K. Singh, A. O'Neill, C. Jackson, A. Morrison, and P. O'Brien, "Development of a microfluidic device for fluorescence activated cell sorting," J. Micromech. Microeng. 12, 486-494 (2002).
[CrossRef]

Skerlos, S. J.

Q1. Y. Tung, M. Zhang, C. Lin, K. Kurabayashi, and S. J. Skerlos, "PDMS-based opto-fluidic micro flow cytometer with two-color multi-angle fluorescence detection capability using PIN photodiodes," Sens. Actuators B 98, 356-367 (2004).
[CrossRef]

Snakenborg, D.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

Squier, J.

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

Sugioka, K.

Q2. Y. Hanada, K. Sugioka, H. Kawano, I. Ishikawa, A. Miyawaki, and K. Midorikawa, "Nano-aquarium fabrication by femtosecond laser direct writing for microscopic observation of aquatic microorganisms," Rev. Laser Engin. 36, 1222-1225 (2008).
[CrossRef]

Tung, Y.

Q1. Y. Tung, M. Zhang, C. Lin, K. Kurabayashi, and S. J. Skerlos, "PDMS-based opto-fluidic micro flow cytometer with two-color multi-angle fluorescence detection capability using PIN photodiodes," Sens. Actuators B 98, 356-367 (2004).
[CrossRef]

Vazquez, R. M.

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, "Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation," Appl. Phys. Lett. 90, 231118 (2007).
[CrossRef]

Vestad, T.

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

Vieillard, J.

Q4. R. Mazurczyk, J. Vieillard, A. Bouchard, B. Hannes, and S. Krawczyk, "A novel concept of the integrated fluorescence detection system and its application to a lab-on-a-chip microdevice," Sens. Act. B 118, 11-19 (2006).
[CrossRef]

Wallis, G. D.

G. D. Wallis and D. I. Pomerantz. "Field assisted glass-metal sealing," J. Appl. Phys. 40, 3946 (1969).
[CrossRef]

Wang, Z.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

Wilke, R.

A. Llobera, R. Wilke, and S. Büttgenbach, "Poly(dimethylsiloxane) hollow Abbe Prism with microlenses for detection based on absorption and refractive index shift," Lab Chip 4, 24-27 (2004).
[CrossRef] [PubMed]

Wittwer, C.

M. Brown and C. Wittwer, "Flow cytometry: principles and clinical applications in hematology," Clin. Chem. 46, 1221-1229 (2000).
[PubMed]

Wolff, A.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

K. B. Mogensen, J. El-Ali, A. Wolff, and J. P. Kutter, "Integration of polymer waveguides for optical detection in microfabricated chemical analysis systems," Appl. Opt. 42, 4072-4079 (2003).
[CrossRef] [PubMed]

Yang, R.

L. Fu, R. Yang, C. Lin, Y. Pan, and G. Lee, "Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection," Analytica Chimica Acta 507, 163-169 (2004).
[CrossRef]

Zhang, M.

Q1. Y. Tung, M. Zhang, C. Lin, K. Kurabayashi, and S. J. Skerlos, "PDMS-based opto-fluidic micro flow cytometer with two-color multi-angle fluorescence detection capability using PIN photodiodes," Sens. Actuators B 98, 356-367 (2004).
[CrossRef]

Zhang, T.

L. Cui, T. Zhang and H. Morgan, "Optical particle detection integrated in a dielectrophoretic lab-on-a-chip," J. Micromech. Microeng. 12, 7-12 (2002).
[CrossRef]

Anal. Chem. (2)

M. L. Chabinyc, D. T. Chiu, J. Cooper 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, 4491-4498 (2001).
[CrossRef] [PubMed]

K. Ke, E. F. Hasselbrink, Jr., and A. J. Hunt, "Rapidly prototyped three-dimensional nanofluidic channel networks in glass substrates," Anal. Chem. 77, 5083-5088 (2005).
[CrossRef] [PubMed]

Analytica Chimica Acta (1)

L. Fu, R. Yang, C. Lin, Y. Pan, and G. Lee, "Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection," Analytica Chimica Acta 507, 163-169 (2004).
[CrossRef]

Appl. Opt. (2)

Appl. Phys. Lett. (1)

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, "Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation," Appl. Phys. Lett. 90, 231118 (2007).
[CrossRef]

Clin. Chem. (1)

M. Brown and C. Wittwer, "Flow cytometry: principles and clinical applications in hematology," Clin. Chem. 46, 1221-1229 (2000).
[PubMed]

J. Appl. Phys. (1)

G. D. Wallis and D. I. Pomerantz. "Field assisted glass-metal sealing," J. Appl. Phys. 40, 3946 (1969).
[CrossRef]

J. Micromech. Microeng. (3)

C. Lin and G. Lee, "Micromachined flow cytometers with embedded etched optic fibers for optical detection," J. Micromech. Microeng. 13, 447-453 (2003).
[CrossRef]

L. Cui, T. Zhang and H. Morgan, "Optical particle detection integrated in a dielectrophoretic lab-on-a-chip," J. Micromech. Microeng. 12, 7-12 (2002).
[CrossRef]

J. Krüger, K. Singh, A. O'Neill, C. Jackson, A. Morrison, and P. O'Brien, "Development of a microfluidic device for fluorescence activated cell sorting," J. Micromech. Microeng. 12, 486-494 (2002).
[CrossRef]

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

Lab Chip (5)

N. Pamme, R. Koyama, and A. Manz, "Counting and sizing of particles and particle agglomerates in a microfluidic device using laser light scattering: application to a particle-enhanced immunoassay," Lab Chip 3, 187-192 (2003).
[CrossRef]

A. Llobera, R. Wilke, and S. Büttgenbach, "Poly(dimethylsiloxane) hollow Abbe Prism with microlenses for detection based on absorption and refractive index shift," Lab Chip 4, 24-27 (2004).
[CrossRef] [PubMed]

Q3. M. Kim, D. J. Hwang, H. Jeon, K. Hiromatsu and C. P. Grigoropoulos, "Single cell detection using a glass-based optofluidic device fabricated by femtosecond laser pulses," Lab Chip, 2009, DOI: 10.1039/b808366e.

R. W. Applegate Jr., J. Squier, T. Vestad, J. Oakey, D. W. M. Marr, P. Bado, M. A. Dugan, and A. A. Said, "Microfluidic sorting based on optical waveguide integration and diode laser bar sensing," Lab Chip 6, 422-426 (2006).
[CrossRef] [PubMed]

Z. Wang, J. El-Ali, M. Engelund, T. Gotsæd, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, "Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements," Lab Chip 4, 372-377 (2004).
[CrossRef] [PubMed]

Opt. Express (1)

Proc. SPIE (1)

A. A. Said, M. Dugan, P. Bado, Y. Bellouard, A. Scott, and J. R. Mabesa, Jr., "Manufacturing by laser direct-write of three-dimensional devices containing optical and microfluidic networks," Proc. SPIE 5339, 194-204 (2004).
[CrossRef]

Rev. Laser Engin. (1)

Q2. Y. Hanada, K. Sugioka, H. Kawano, I. Ishikawa, A. Miyawaki, and K. Midorikawa, "Nano-aquarium fabrication by femtosecond laser direct writing for microscopic observation of aquatic microorganisms," Rev. Laser Engin. 36, 1222-1225 (2008).
[CrossRef]

Sens. Act. B (1)

Q4. R. Mazurczyk, J. Vieillard, A. Bouchard, B. Hannes, and S. Krawczyk, "A novel concept of the integrated fluorescence detection system and its application to a lab-on-a-chip microdevice," Sens. Act. B 118, 11-19 (2006).
[CrossRef]

Sens. Actuators B (1)

Q1. Y. Tung, M. Zhang, C. Lin, K. Kurabayashi, and S. J. Skerlos, "PDMS-based opto-fluidic micro flow cytometer with two-color multi-angle fluorescence detection capability using PIN photodiodes," Sens. Actuators B 98, 356-367 (2004).
[CrossRef]

Other (2)

H. Chen and Y. Wang, "Optical microflow cytometer for particle counting, sizing and fluorescence detection," Microfluid. Nanofluid. (2008), DOI 10.1007/s10404-008-0335-z.

E. Altendorf, D. Zebert, M. Holl, and P. Yager, "Differential blood cell counts obtained using a microchannel based flow cytometer," in IEEE International Conference on Solid-State Sensors and Actuators (IEEE, 1997) pp. 531-534.
[CrossRef]

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Figures (5)

Fig. 1.
Fig. 1.

Fiber placement in a femtosecond laser ablated groove.

Fig. 2.
Fig. 2.

(a) White light image of the fluid channel (horizontal) with four fiber grooves: one above at 14 degrees from normal and three below at -45, 0, and 45 degrees from normal. (b) Nanoport connectors were attached to either end of the fluid channel. In these experiments, light was delivered through the fiber at 0 degrees from normal and collected through the fiber opposite it at 14 degrees from normal.

Fig. 3.
Fig. 3.

An illustration of the experimental setup.

Fig. 4.
Fig. 4.

Overlap of the illumination region with the anticipated detection region was determined by filling the fluid channel with a fluorescent dye and then imaging the fluorescence. Lineouts along the center of the fluid channel (parallel to the x axis) show the overlap of the illumination region (A) with the detection region (B).

Fig. 5.
Fig. 5.

Sample data set showing the peaks from light scattered by passing HeLa cells.

Tables (1)

Tables Icon

Table 1. The conditions for obtaining a cell count on each aliquot are given along with the total cell count obtained with our system and with the FACS system and the percent agreement between these two counts.

Metrics