We demonstrate the implementation of fluorescence correlation spectroscopy (FCS) on a chip. Full planar integration is achieved by lithographic definition of sub-picoliter excitation volumes using intersecting solid and liquid-core optical waveguides. Concentration dependent measurements on dye molecules with single molecule resolution are demonstrated. Theoretical modeling of the FCS autocorrelation function in microstructured geometries shows that the FCS behavior can be controlled over a wide range by tailoring the micro-photonic environment. The ability to perform correlation spectroscopy using silicon photonics without the need for free-space microscopy permits implementation of numerous diagnostic applications on compact planar optofluidic devices.

© 2007 Optical Society of America

1. C. Zander, J. Enderlein, and R.A. Keller, "Single-molecule detection in solution: methods and applications," 1st ed., Wiley (2002).
2. E. B. Shera, N. K. Seitzinger, L. M. Davis, R. A. Keller and S. A. Soper, "Detection of single fluorescent molecules," Chem. Phys. Lett. 174, 553 (1990). [CrossRef]
3. W.E. Moerner and D.P. Fromm, "Methods of single-molecule fluorescence spectroscopy and microscopy," Rev. Sci. Instrum. 74, 3597 (2003). [CrossRef]
4. S. Kuhn, U. Hakanson, L. Rogobete, and V. Sandoghdar, "Enhancement of single-molecule fluorescence using a gold nanoparticle as an optical nanoantenna," Phys. Rev. Lett.,  97, 017402 (2006). [CrossRef]
5. D. Magde, E. Elson, and W.W. Webb, "Thermodynamic Fluctuations in a Reacting System—Measurement by Fluorescence Correlation Spectroscopy," Phys. Rev. Lett.,  29, 705 (1972). [CrossRef]
6. M. Brinkmeier, K. Dorre, K. Riebeseel, and R. Rigler, "Confocal spectroscopy in microstructures," Biophys. Chem. 66, 229 (1997). [CrossRef] [PubMed]
7. M. Foquet, J. Korlach, W. R. Zipfel, W.W. Webb and H. G. Craighead, "DNA Fragment Sizing by Single Molecule Detection in Submicrometer-Sized Closed Fluidic Channels," Anal. Chem. 74, 1415-1422 (2002). [CrossRef] [PubMed]
8. M. Foquet, J. Korlach, W. R. Zipfel, W.W. Webb and H. G. Craighead, "Focal Volume Confinement by Submicrometer-Sized Fluidic Channels," Anal. Chem. 76, 1618-1626 (2004). [CrossRef] [PubMed]
9. L. Kastrup, H. Blom, C. Eggeling, S.W. Hell, "Fluorescence fluctuation spectroscopy in subdiffraction focal volumes," Phys. Rev. Lett.,  94, 178104 (2005). [CrossRef]
10. C. Monat, P. Domachuk and B.J. Eggleton, "Integrated optofluidics: A new river of light," Nat. Photonics,  1, 106 (2007). [CrossRef]
11. D. Yin, J.P. Barber, A.R. Hawkins, D.W. Deamer, H. Schmidt, "Integrated optical waveguides with liquid cores," Appl. Phys. Lett.,  85, 3477 (2004). [CrossRef]
12. D. Yin, J.P. Barber, D.W. Deamer, A.R. Hawkins, H. Schmidt, "Single-molecule detection sensitivity using planar integrated optics on a chip," Opt. Lett. 31, 2136 (2006). [CrossRef] [PubMed]
13. H. Schmidt, D. Yin, J.P. Barber, and A.R. Hawkins, "Hollow-core waveguides and 2D waveguide arrays for integrated optics of gases and liquids," IEEE J. Sel. Top. in Quantum.Electron. 11, 519 (2005). [CrossRef]
14. J.P. Barber, E.J. Lunt, Z. George, D. Yin, H. Schmidt, and A.R. Hawkins, "Integrated Hollow Waveguides with Arch-shaped Cores," IEEE Photon. Technol. Lett.,  18, 28 (2006). [CrossRef]
15. D. Yin, J.P. Barber, A.R. Hawkins, and H. Schmidt, "Highly efficient fluorescence detection in picoliter volume liquid-core waveguides," Applied Physics Letters,  87, 211111 (2005). [CrossRef]
16. P.F. Lenne, E. Etienne, and H. Rigneault, "Subwavelength patterns and high detection efficiency in fluorescence correlation spectroscopy using photonic structures," Appl. Phys. Lett. 80, 4106 (2002). [CrossRef]
17. P. Schwille, U. Haupts, S. Maiti, W.W. Webb, "Molecular Dynamics in Living Cells Observed by Fluorescence Correlation Spectroscopy with 1- and 2-Photon Excitation," Biophys. J.,  77, 2251 (1999). [CrossRef]
18. M. Eigen and R. Rigler, "Sorting Single Molecules: Application to Diagnostics and Evolutionary Biotechnology," PNAS 91, 5740 (1994). [CrossRef] [PubMed]

Anal. Chem.

• M. Foquet, J. Korlach, W. R. Zipfel, W.W. Webb and H. G. Craighead, "DNA Fragment Sizing by Single Molecule Detection in Submicrometer-Sized Closed Fluidic Channels," Anal. Chem. 74, 1415-1422 (2002). [CrossRef] [PubMed]
• M. Foquet, J. Korlach, W. R. Zipfel, W.W. Webb and H. G. Craighead, "Focal Volume Confinement by Submicrometer-Sized Fluidic Channels," Anal. Chem. 76, 1618-1626 (2004). [CrossRef] [PubMed]

Appl. Phys. Lett.

• D. Yin, J.P. Barber, A.R. Hawkins, D.W. Deamer, H. Schmidt, "Integrated optical waveguides with liquid cores," Appl. Phys. Lett.,  85, 3477 (2004). [CrossRef]
• P.F. Lenne, E. Etienne, and H. Rigneault, "Subwavelength patterns and high detection efficiency in fluorescence correlation spectroscopy using photonic structures," Appl. Phys. Lett. 80, 4106 (2002). [CrossRef]

Applied Physics Letters

• D. Yin, J.P. Barber, A.R. Hawkins, and H. Schmidt, "Highly efficient fluorescence detection in picoliter volume liquid-core waveguides," Applied Physics Letters,  87, 211111 (2005). [CrossRef]

Biophys. Chem.

• M. Brinkmeier, K. Dorre, K. Riebeseel, and R. Rigler, "Confocal spectroscopy in microstructures," Biophys. Chem. 66, 229 (1997). [CrossRef] [PubMed]

Biophys. J.

• P. Schwille, U. Haupts, S. Maiti, W.W. Webb, "Molecular Dynamics in Living Cells Observed by Fluorescence Correlation Spectroscopy with 1- and 2-Photon Excitation," Biophys. J.,  77, 2251 (1999). [CrossRef]

Chem. Phys. Lett.

• E. B. Shera, N. K. Seitzinger, L. M. Davis, R. A. Keller and S. A. Soper, "Detection of single fluorescent molecules," Chem. Phys. Lett. 174, 553 (1990). [CrossRef]

Electron.

• H. Schmidt, D. Yin, J.P. Barber, and A.R. Hawkins, "Hollow-core waveguides and 2D waveguide arrays for integrated optics of gases and liquids," IEEE J. Sel. Top. in Quantum.Electron. 11, 519 (2005). [CrossRef]

IEEE Photon. Technol. Lett.

• J.P. Barber, E.J. Lunt, Z. George, D. Yin, H. Schmidt, and A.R. Hawkins, "Integrated Hollow Waveguides with Arch-shaped Cores," IEEE Photon. Technol. Lett.,  18, 28 (2006). [CrossRef]

Nat. Photonics

• C. Monat, P. Domachuk and B.J. Eggleton, "Integrated optofluidics: A new river of light," Nat. Photonics,  1, 106 (2007). [CrossRef]

Opt. Lett.

• D. Yin, J.P. Barber, D.W. Deamer, A.R. Hawkins, H. Schmidt, "Single-molecule detection sensitivity using planar integrated optics on a chip," Opt. Lett. 31, 2136 (2006). [CrossRef] [PubMed]

Phys. Rev. Lett.

• S. Kuhn, U. Hakanson, L. Rogobete, and V. Sandoghdar, "Enhancement of single-molecule fluorescence using a gold nanoparticle as an optical nanoantenna," Phys. Rev. Lett.,  97, 017402 (2006). [CrossRef]
• D. Magde, E. Elson, and W.W. Webb, "Thermodynamic Fluctuations in a Reacting System—Measurement by Fluorescence Correlation Spectroscopy," Phys. Rev. Lett.,  29, 705 (1972). [CrossRef]
• L. Kastrup, H. Blom, C. Eggeling, S.W. Hell, "Fluorescence fluctuation spectroscopy in subdiffraction focal volumes," Phys. Rev. Lett.,  94, 178104 (2005). [CrossRef]

PNAS

• M. Eigen and R. Rigler, "Sorting Single Molecules: Application to Diagnostics and Evolutionary Biotechnology," PNAS 91, 5740 (1994). [CrossRef] [PubMed]

Rev. Sci. Instrum.

• W.E. Moerner and D.P. Fromm, "Methods of single-molecule fluorescence spectroscopy and microscopy," Rev. Sci. Instrum. 74, 3597 (2003). [CrossRef]

Other

• C. Zander, J. Enderlein, and R.A. Keller, "Single-molecule detection in solution: methods and applications," 1st ed., Wiley (2002).

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