Abstract

We present a simple approach in electrophoretic DNA separation and fluorescent monitoring that allows to identify the insertion or deletion of base-pairs in DNA probe molecules from genetic samples, and to perform intrinsic calibration/referencing for highly accurate DNA analysis. The principle is based on dual-point, dual-wavelength laser-induced fluorescence excitation using one or two excitation windows at the intersection of integrated waveguides and microfluidic channels in an optofluidic chip and a single, color-blind photodetector, resulting in a limit of detection of ~200 pM for single-end-labeled DNA molecules. The approach using a single excitation window is demonstrated experimentally, while the option exploiting two excitation windows is proposed theoretically.

©2010 Optical Society of America

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References

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  1. A. Manz, N. Graber, and H. M. Widmer, “Miniaturized total chemical analysis systems: A novel concept for chemical sensing,” Sens. Actuators B Chem. 1, 244–248 (1990).
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    [Crossref] [PubMed]
  3. B. Kuswandi, J. Nuriman, J. Huskens, and W. Verboom, “Optical sensing systems for microfluidic devices: a review,” Anal. Chim. Acta 601(2), 141–155 (2007).
    [Crossref] [PubMed]
  4. M. E. Johnson and J. P. Landers, “Fundamentals and practice for ultrasensitive laser-induced fluorescence detection in microanalytical systems,” Electrophoresis 25(21-22), 3513–3527 (2004).
    [Crossref] [PubMed]
  5. D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
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    [Crossref] [PubMed]
  8. S. Götz and U. Karst, “Wavelength-resolved fluorescence detector for microchip capillary electrophoresis separations,” Sens. Actuators B Chem. 123(1), 622–627 (2007).
    [Crossref]
  9. A. E. Karger, J. M. Harris, and R. F. Gesteland, “Multiwavelength fluorescence detection for DNA sequencing using capillary electrophoresis,” Nucleic Acids Res. 19(18), 4955–4962 (1991).
    [Crossref] [PubMed]
  10. H. Sugino, K. Ozaki, Y. Shirasaki, T. Arakawa, S. Shoji, and T. Funatsu, “On-chip microfluidic sorting with fluorescence spectrum detection and multiway separation,” Lab Chip 9(9), 1254–1260 (2009).
    [Crossref] [PubMed]
  11. R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
    [PubMed]
  12. C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
    [Crossref] [PubMed]
  13. R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
    [Crossref] [PubMed]
  14. J. C. Sanders, M. C. Breadmore, Y. C. Kwok, K. M. Horsman, and J. P. Landers, “Hydroxypropyl cellulose as an adsorptive coating sieving matrix for DNA separations: artificial neural network optimization for microchip analysis,” Anal. Chem. 75(4), 986–994 (2003).
    [Crossref] [PubMed]
  15. C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
    [Crossref] [PubMed]
  16. A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
    [Crossref] [PubMed]

2010 (2)

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

2009 (3)

H. Sugino, K. Ozaki, Y. Shirasaki, T. Arakawa, S. Shoji, and T. Funatsu, “On-chip microfluidic sorting with fluorescence spectrum detection and multiway separation,” Lab Chip 9(9), 1254–1260 (2009).
[Crossref] [PubMed]

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

2008 (1)

2007 (2)

B. Kuswandi, J. Nuriman, J. Huskens, and W. Verboom, “Optical sensing systems for microfluidic devices: a review,” Anal. Chim. Acta 601(2), 141–155 (2007).
[Crossref] [PubMed]

S. Götz and U. Karst, “Wavelength-resolved fluorescence detector for microchip capillary electrophoresis separations,” Sens. Actuators B Chem. 123(1), 622–627 (2007).
[Crossref]

2006 (1)

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
[Crossref] [PubMed]

2004 (2)

L. Zhu, W. J. Stryjewski, and S. A. Soper, “Multiplexed fluorescence detection in microfabricated devices with both time-resolved and spectral-discrimination capabilities using near-infrared fluorescence,” Anal. Biochem. 330(2), 206–218 (2004).
[Crossref] [PubMed]

M. E. Johnson and J. P. Landers, “Fundamentals and practice for ultrasensitive laser-induced fluorescence detection in microanalytical systems,” Electrophoresis 25(21-22), 3513–3527 (2004).
[Crossref] [PubMed]

2003 (2)

J. P. Landers, “Molecular diagnostics on electrophoretic microchips,” Anal. Chem. 75(12), 2919–2927 (2003).
[Crossref] [PubMed]

J. C. Sanders, M. C. Breadmore, Y. C. Kwok, K. M. Horsman, and J. P. Landers, “Hydroxypropyl cellulose as an adsorptive coating sieving matrix for DNA separations: artificial neural network optimization for microchip analysis,” Anal. Chem. 75(4), 986–994 (2003).
[Crossref] [PubMed]

1991 (1)

A. E. Karger, J. M. Harris, and R. F. Gesteland, “Multiwavelength fluorescence detection for DNA sequencing using capillary electrophoresis,” Nucleic Acids Res. 19(18), 4955–4962 (1991).
[Crossref] [PubMed]

1990 (1)

A. Manz, N. Graber, and H. M. Widmer, “Miniaturized total chemical analysis systems: A novel concept for chemical sensing,” Sens. Actuators B Chem. 1, 244–248 (1990).

Arakawa, T.

H. Sugino, K. Ozaki, Y. Shirasaki, T. Arakawa, S. Shoji, and T. Funatsu, “On-chip microfluidic sorting with fluorescence spectrum detection and multiway separation,” Lab Chip 9(9), 1254–1260 (2009).
[Crossref] [PubMed]

Besselink, G. A. J.

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
[Crossref] [PubMed]

Breadmore, M. C.

J. C. Sanders, M. C. Breadmore, Y. C. Kwok, K. M. Horsman, and J. P. Landers, “Hydroxypropyl cellulose as an adsorptive coating sieving matrix for DNA separations: artificial neural network optimization for microchip analysis,” Anal. Chem. 75(4), 986–994 (2003).
[Crossref] [PubMed]

Cerullo, G.

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
[Crossref] [PubMed]

Chiari, M.

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

Crespi, A.

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

Cretich, M.

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

Dekker, R.

Dongre, C.

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
[Crossref] [PubMed]

Funatsu, T.

H. Sugino, K. Ozaki, Y. Shirasaki, T. Arakawa, S. Shoji, and T. Funatsu, “On-chip microfluidic sorting with fluorescence spectrum detection and multiway separation,” Lab Chip 9(9), 1254–1260 (2009).
[Crossref] [PubMed]

Gesteland, R. F.

A. E. Karger, J. M. Harris, and R. F. Gesteland, “Multiwavelength fluorescence detection for DNA sequencing using capillary electrophoresis,” Nucleic Acids Res. 19(18), 4955–4962 (1991).
[Crossref] [PubMed]

Götz, S.

S. Götz and U. Karst, “Wavelength-resolved fluorescence detector for microchip capillary electrophoresis separations,” Sens. Actuators B Chem. 123(1), 622–627 (2007).
[Crossref]

Graber, N.

A. Manz, N. Graber, and H. M. Widmer, “Miniaturized total chemical analysis systems: A novel concept for chemical sensing,” Sens. Actuators B Chem. 1, 244–248 (1990).

Gu, Y.

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

Harris, J. M.

A. E. Karger, J. M. Harris, and R. F. Gesteland, “Multiwavelength fluorescence detection for DNA sequencing using capillary electrophoresis,” Nucleic Acids Res. 19(18), 4955–4962 (1991).
[Crossref] [PubMed]

Hoekstra, H. J. W. M.

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
[Crossref] [PubMed]

Horsman, K. M.

J. C. Sanders, M. C. Breadmore, Y. C. Kwok, K. M. Horsman, and J. P. Landers, “Hydroxypropyl cellulose as an adsorptive coating sieving matrix for DNA separations: artificial neural network optimization for microchip analysis,” Anal. Chem. 75(4), 986–994 (2003).
[Crossref] [PubMed]

Huskens, J.

B. Kuswandi, J. Nuriman, J. Huskens, and W. Verboom, “Optical sensing systems for microfluidic devices: a review,” Anal. Chim. Acta 601(2), 141–155 (2007).
[Crossref] [PubMed]

Johnson, M. E.

M. E. Johnson and J. P. Landers, “Fundamentals and practice for ultrasensitive laser-induced fluorescence detection in microanalytical systems,” Electrophoresis 25(21-22), 3513–3527 (2004).
[Crossref] [PubMed]

Karger, A. E.

A. E. Karger, J. M. Harris, and R. F. Gesteland, “Multiwavelength fluorescence detection for DNA sequencing using capillary electrophoresis,” Nucleic Acids Res. 19(18), 4955–4962 (1991).
[Crossref] [PubMed]

Karst, U.

S. Götz and U. Karst, “Wavelength-resolved fluorescence detector for microchip capillary electrophoresis separations,” Sens. Actuators B Chem. 123(1), 622–627 (2007).
[Crossref]

Kuswandi, B.

B. Kuswandi, J. Nuriman, J. Huskens, and W. Verboom, “Optical sensing systems for microfluidic devices: a review,” Anal. Chim. Acta 601(2), 141–155 (2007).
[Crossref] [PubMed]

Kwok, Y. C.

J. C. Sanders, M. C. Breadmore, Y. C. Kwok, K. M. Horsman, and J. P. Landers, “Hydroxypropyl cellulose as an adsorptive coating sieving matrix for DNA separations: artificial neural network optimization for microchip analysis,” Anal. Chem. 75(4), 986–994 (2003).
[Crossref] [PubMed]

Landers, J. P.

M. E. Johnson and J. P. Landers, “Fundamentals and practice for ultrasensitive laser-induced fluorescence detection in microanalytical systems,” Electrophoresis 25(21-22), 3513–3527 (2004).
[Crossref] [PubMed]

J. P. Landers, “Molecular diagnostics on electrophoretic microchips,” Anal. Chem. 75(12), 2919–2927 (2003).
[Crossref] [PubMed]

J. C. Sanders, M. C. Breadmore, Y. C. Kwok, K. M. Horsman, and J. P. Landers, “Hydroxypropyl cellulose as an adsorptive coating sieving matrix for DNA separations: artificial neural network optimization for microchip analysis,” Anal. Chem. 75(4), 986–994 (2003).
[Crossref] [PubMed]

Manz, A.

A. Manz, N. Graber, and H. M. Widmer, “Miniaturized total chemical analysis systems: A novel concept for chemical sensing,” Sens. Actuators B Chem. 1, 244–248 (1990).

Martinez Vazquez, R.

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

Martinez-Vazquez, R.

Ngamsom, B.

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

Nolli, D.

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

Nuriman, J.

B. Kuswandi, J. Nuriman, J. Huskens, and W. Verboom, “Optical sensing systems for microfluidic devices: a review,” Anal. Chim. Acta 601(2), 141–155 (2007).
[Crossref] [PubMed]

Osellame, R.

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
[Crossref] [PubMed]

Ozaki, K.

H. Sugino, K. Ozaki, Y. Shirasaki, T. Arakawa, S. Shoji, and T. Funatsu, “On-chip microfluidic sorting with fluorescence spectrum detection and multiway separation,” Lab Chip 9(9), 1254–1260 (2009).
[Crossref] [PubMed]

Pollnau, M.

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
[Crossref] [PubMed]

Psaltis, D.

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
[Crossref] [PubMed]

Quake, S. R.

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
[Crossref] [PubMed]

Ramponi, R.

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
[Crossref] [PubMed]

Sanders, J. C.

J. C. Sanders, M. C. Breadmore, Y. C. Kwok, K. M. Horsman, and J. P. Landers, “Hydroxypropyl cellulose as an adsorptive coating sieving matrix for DNA separations: artificial neural network optimization for microchip analysis,” Anal. Chem. 75(4), 986–994 (2003).
[Crossref] [PubMed]

Shirasaki, Y.

H. Sugino, K. Ozaki, Y. Shirasaki, T. Arakawa, S. Shoji, and T. Funatsu, “On-chip microfluidic sorting with fluorescence spectrum detection and multiway separation,” Lab Chip 9(9), 1254–1260 (2009).
[Crossref] [PubMed]

Shoji, S.

H. Sugino, K. Ozaki, Y. Shirasaki, T. Arakawa, S. Shoji, and T. Funatsu, “On-chip microfluidic sorting with fluorescence spectrum detection and multiway separation,” Lab Chip 9(9), 1254–1260 (2009).
[Crossref] [PubMed]

Soper, S. A.

L. Zhu, W. J. Stryjewski, and S. A. Soper, “Multiplexed fluorescence detection in microfabricated devices with both time-resolved and spectral-discrimination capabilities using near-infrared fluorescence,” Anal. Biochem. 330(2), 206–218 (2004).
[Crossref] [PubMed]

Stryjewski, W. J.

L. Zhu, W. J. Stryjewski, and S. A. Soper, “Multiplexed fluorescence detection in microfabricated devices with both time-resolved and spectral-discrimination capabilities using near-infrared fluorescence,” Anal. Biochem. 330(2), 206–218 (2004).
[Crossref] [PubMed]

Sugino, H.

H. Sugino, K. Ozaki, Y. Shirasaki, T. Arakawa, S. Shoji, and T. Funatsu, “On-chip microfluidic sorting with fluorescence spectrum detection and multiway separation,” Lab Chip 9(9), 1254–1260 (2009).
[Crossref] [PubMed]

van den Vlekkert, H. H.

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
[Crossref] [PubMed]

van Weeghel, R.

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

C. Dongre, R. Dekker, H. J. W. M. Hoekstra, M. Pollnau, R. Martinez-Vazquez, R. Osellame, G. Cerullo, R. Ramponi, R. van Weeghel, G. A. J. Besselink, and H. H. van den Vlekkert, “Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides,” Opt. Lett. 33(21), 2503–2505 (2008).
[Crossref] [PubMed]

van Weerd, J.

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

Vazquez, R. M.

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

Verboom, W.

B. Kuswandi, J. Nuriman, J. Huskens, and W. Verboom, “Optical sensing systems for microfluidic devices: a review,” Anal. Chim. Acta 601(2), 141–155 (2007).
[Crossref] [PubMed]

Vlekkert, H.

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

Watts, P.

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

Widmer, H. M.

A. Manz, N. Graber, and H. M. Widmer, “Miniaturized total chemical analysis systems: A novel concept for chemical sensing,” Sens. Actuators B Chem. 1, 244–248 (1990).

Yang, C.

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
[Crossref] [PubMed]

Zhu, L.

L. Zhu, W. J. Stryjewski, and S. A. Soper, “Multiplexed fluorescence detection in microfabricated devices with both time-resolved and spectral-discrimination capabilities using near-infrared fluorescence,” Anal. Biochem. 330(2), 206–218 (2004).
[Crossref] [PubMed]

Anal. Bioanal. Chem. (1)

R. Martinez Vazquez, R. Osellame, M. Cretich, M. Chiari, C. Dongre, H. J. W. M. Hoekstra, M. Pollnau, H. Vlekkert, R. Ramponi, and G. Cerullo, “Optical sensing in microfluidic lab-on-a-chip by femtosecond-laser-written waveguides,” Anal. Bioanal. Chem. 393(4), 1209–1216 (2009).
[Crossref] [PubMed]

Anal. Biochem. (1)

L. Zhu, W. J. Stryjewski, and S. A. Soper, “Multiplexed fluorescence detection in microfabricated devices with both time-resolved and spectral-discrimination capabilities using near-infrared fluorescence,” Anal. Biochem. 330(2), 206–218 (2004).
[Crossref] [PubMed]

Anal. Chem. (2)

J. P. Landers, “Molecular diagnostics on electrophoretic microchips,” Anal. Chem. 75(12), 2919–2927 (2003).
[Crossref] [PubMed]

J. C. Sanders, M. C. Breadmore, Y. C. Kwok, K. M. Horsman, and J. P. Landers, “Hydroxypropyl cellulose as an adsorptive coating sieving matrix for DNA separations: artificial neural network optimization for microchip analysis,” Anal. Chem. 75(4), 986–994 (2003).
[Crossref] [PubMed]

Anal. Chim. Acta (1)

B. Kuswandi, J. Nuriman, J. Huskens, and W. Verboom, “Optical sensing systems for microfluidic devices: a review,” Anal. Chim. Acta 601(2), 141–155 (2007).
[Crossref] [PubMed]

Electrophoresis (2)

M. E. Johnson and J. P. Landers, “Fundamentals and practice for ultrasensitive laser-induced fluorescence detection in microanalytical systems,” Electrophoresis 25(21-22), 3513–3527 (2004).
[Crossref] [PubMed]

C. Dongre, J. van Weerd, G. A. J. Besselink, R. van Weeghel, R. M. Vazquez, R. Osellame, G. Cerullo, M. Cretich, M. Chiari, H. J. W. M. Hoekstra, and M. Pollnau, “High-resolution electrophoretic separation and integrated-waveguide excitation of fluorescent DNA molecules in a lab on a chip,” Electrophoresis 31(15), 2584–2588 (2010).
[Crossref] [PubMed]

Lab Chip (3)

A. Crespi, Y. Gu, B. Ngamsom, H. J. W. M. Hoekstra, C. Dongre, M. Pollnau, R. Ramponi, H. H. van den Vlekkert, P. Watts, G. Cerullo, and R. Osellame, “Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection,” Lab Chip 10(9), 1167–1173 (2010).
[Crossref] [PubMed]

H. Sugino, K. Ozaki, Y. Shirasaki, T. Arakawa, S. Shoji, and T. Funatsu, “On-chip microfluidic sorting with fluorescence spectrum detection and multiway separation,” Lab Chip 9(9), 1254–1260 (2009).
[Crossref] [PubMed]

R. M. Vazquez, R. Osellame, D. Nolli, C. Dongre, H. H. van den Vlekkert, R. Ramponi, M. Pollnau, and G. Cerullo, “Integration of femtosecond laser written optical waveguides in a lab-on-chip,” Lab Chip 9(1), 91–96 (2009).
[PubMed]

Nature (1)

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
[Crossref] [PubMed]

Nucleic Acids Res. (1)

A. E. Karger, J. M. Harris, and R. F. Gesteland, “Multiwavelength fluorescence detection for DNA sequencing using capillary electrophoresis,” Nucleic Acids Res. 19(18), 4955–4962 (1991).
[Crossref] [PubMed]

Opt. Lett. (1)

Sens. Actuators B Chem. (2)

A. Manz, N. Graber, and H. M. Widmer, “Miniaturized total chemical analysis systems: A novel concept for chemical sensing,” Sens. Actuators B Chem. 1, 244–248 (1990).

S. Götz and U. Karst, “Wavelength-resolved fluorescence detector for microchip capillary electrophoresis separations,” Sens. Actuators B Chem. 123(1), 622–627 (2007).
[Crossref]

Other (1)

R. Iten, “Apparatus for emitting and detecting light in a nucleic acid amplification reaction,” Eur. Patent 1962084 (2007).

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Figures (3)

Fig. 1
Fig. 1 Layout of the optofluidic chip indicating the MF reservoirs, MF channels, and the two DWs, each comprising two WGs crossing the MCE separation channel perpendicularly in plane
Fig. 2
Fig. 2 Electropherograms depicting the MCE separation of two fluorescently labeled DNA molecules: (a) cumulative signal during simultaneous dual-wavelength excitation of migrating 19-nt-AF647 and 19-nt-Cy3 molecules; (b) individual signals detected during different flow experiments applying single-wavelength excitation with only one of the two lasers switched on, temporally superimposed on each other; (c) and (d) the same for 19-nt-AF647 and 20-nt-Cy3 molecules.
Fig. 3
Fig. 3 Simulated electropherograms as would be detected from the two DWs with swapped excitation wavelengths during an experiment with internal calibration using a green-labeled DNA sample (“S”) consisting of four different molecule sizes (250 bp, 300 bp, 450 bp, and 700 bp) and a red-labeled DNA reference (“R”) consisting of three different molecule sizes (150 bp, 355 bp, and 1000 bp). Fluorescence signals S were excited through WG1, R through WG2, R' through WG3 and S' through WG4.

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