Abstract

We have developed a simple, highly sensitive and specific optical waveguide sensor for the detection of multivalent proteins. The optical biosensor is based on optically tagged glycolipid receptors embedded within a fluid phospholipid bilayer membrane formed upon the surface of a planar optical waveguide. Binding of multivalent cholera toxin triggers a fluorescence resonance energy transfer that results in a two-color optical change that is monitored by measurement of emitted luminescence above the waveguide surface. The sensor approach is highly sensitive and specific and requires no additional reagents and washing steps. Demonstration of protein-receptor recognition by use of planar optical waveguides provides a path forward for the development of fieldable miniaturized biosensor arrays.

© 1999 Optical Society of America

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References

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  1. R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger, and C. A. Mirkin, Science 277, 1078 (1997).
    [CrossRef] [PubMed]
  2. B. D. Hames and S. J. Higgins, eds., Gene Probes (IRL Press, New York, 1995).
  3. J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
    [CrossRef]
  4. P. Wood, in Principles and Practice of Immunoassay, C. P. Price and D. J. Newman, eds. (Stockton, New York, 1991), p. 365.
  5. J. R. Astles and W. G. Miller, Anal. Chem. 66, 167 (1994).
    [CrossRef]
  6. S. P. A. Fodor, J. L. Read, M. C. Pirrung, L. Stryer, A. T. Lu, and D. Solas, Science 251, 767 (1991).
    [CrossRef] [PubMed]
  7. B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
    [CrossRef] [PubMed]
  8. X. Song, J. Nolan, and B. I. Swanson, J. Am. Chem. Soc. 120, 11514 (1998).
    [CrossRef]
  9. J. Dubendorfer, R. E. Kunz, E. Schurmann, G. L. Duveneck, and M. Ehrat, J. Biomed. Opt. 2, 391 (1997).
    [CrossRef]
  10. B. Klee, G. L. Duveneck, P. Oroszlan, M. Ehrat, and H. M. Widmer, Sensors Actuators B 29, 307 (1995).
    [CrossRef]
  11. G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
    [CrossRef]
  12. S. J. Choquette, L. Locascio-Brown, and R. A. Durst, Proc. SPIE 1368, 258 (1990).
    [CrossRef]
  13. The isobestic point for BTMR?GM1 and BTR?GM1 incorporated within a POPC bilayer was determined in Ref. 8.
  14. X. Song and B. I. Swanson, Anal. Chem. 71, 2097 (1999).
    [CrossRef] [PubMed]

1999 (1)

X. Song and B. I. Swanson, Anal. Chem. 71, 2097 (1999).
[CrossRef] [PubMed]

1998 (1)

X. Song, J. Nolan, and B. I. Swanson, J. Am. Chem. Soc. 120, 11514 (1998).
[CrossRef]

1997 (4)

J. Dubendorfer, R. E. Kunz, E. Schurmann, G. L. Duveneck, and M. Ehrat, J. Biomed. Opt. 2, 391 (1997).
[CrossRef]

G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
[CrossRef]

R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger, and C. A. Mirkin, Science 277, 1078 (1997).
[CrossRef] [PubMed]

B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
[CrossRef] [PubMed]

1996 (1)

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

1995 (1)

B. Klee, G. L. Duveneck, P. Oroszlan, M. Ehrat, and H. M. Widmer, Sensors Actuators B 29, 307 (1995).
[CrossRef]

1994 (1)

J. R. Astles and W. G. Miller, Anal. Chem. 66, 167 (1994).
[CrossRef]

1991 (1)

S. P. A. Fodor, J. L. Read, M. C. Pirrung, L. Stryer, A. T. Lu, and D. Solas, Science 251, 767 (1991).
[CrossRef] [PubMed]

1990 (1)

S. J. Choquette, L. Locascio-Brown, and R. A. Durst, Proc. SPIE 1368, 258 (1990).
[CrossRef]

Astles, J. R.

J. R. Astles and W. G. Miller, Anal. Chem. 66, 167 (1994).
[CrossRef]

Bar, E.

G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
[CrossRef]

Braach-Maksvytis, V. L. B.

B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
[CrossRef] [PubMed]

Budach, W.

G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
[CrossRef]

Cai, X. H.

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

Choquette, S. J.

S. J. Choquette, L. Locascio-Brown, and R. A. Durst, Proc. SPIE 1368, 258 (1990).
[CrossRef]

Cornell, B. A.

B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
[CrossRef] [PubMed]

Dontha, N.

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

Dubendorfer, J.

J. Dubendorfer, R. E. Kunz, E. Schurmann, G. L. Duveneck, and M. Ehrat, J. Biomed. Opt. 2, 391 (1997).
[CrossRef]

Durst, R. A.

S. J. Choquette, L. Locascio-Brown, and R. A. Durst, Proc. SPIE 1368, 258 (1990).
[CrossRef]

Duveneck, G. L.

J. Dubendorfer, R. E. Kunz, E. Schurmann, G. L. Duveneck, and M. Ehrat, J. Biomed. Opt. 2, 391 (1997).
[CrossRef]

G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
[CrossRef]

B. Klee, G. L. Duveneck, P. Oroszlan, M. Ehrat, and H. M. Widmer, Sensors Actuators B 29, 307 (1995).
[CrossRef]

Ehrat, M.

J. Dubendorfer, R. E. Kunz, E. Schurmann, G. L. Duveneck, and M. Ehrat, J. Biomed. Opt. 2, 391 (1997).
[CrossRef]

G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
[CrossRef]

B. Klee, G. L. Duveneck, P. Oroszlan, M. Ehrat, and H. M. Widmer, Sensors Actuators B 29, 307 (1995).
[CrossRef]

Elghanian, R.

R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger, and C. A. Mirkin, Science 277, 1078 (1997).
[CrossRef] [PubMed]

Farias, P. A. M.

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

Fodor, S. P. A.

S. P. A. Fodor, J. L. Read, M. C. Pirrung, L. Stryer, A. T. Lu, and D. Solas, Science 251, 767 (1991).
[CrossRef] [PubMed]

King, L. G.

B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
[CrossRef] [PubMed]

Klee, B.

B. Klee, G. L. Duveneck, P. Oroszlan, M. Ehrat, and H. M. Widmer, Sensors Actuators B 29, 307 (1995).
[CrossRef]

Kunz, R. E.

J. Dubendorfer, R. E. Kunz, E. Schurmann, G. L. Duveneck, and M. Ehrat, J. Biomed. Opt. 2, 391 (1997).
[CrossRef]

Letsinger, R. L.

R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger, and C. A. Mirkin, Science 277, 1078 (1997).
[CrossRef] [PubMed]

Locascio-Brown, L.

S. J. Choquette, L. Locascio-Brown, and R. A. Durst, Proc. SPIE 1368, 258 (1990).
[CrossRef]

Lu, A. T.

S. P. A. Fodor, J. L. Read, M. C. Pirrung, L. Stryer, A. T. Lu, and D. Solas, Science 251, 767 (1991).
[CrossRef] [PubMed]

Luo, D. B.

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

Miller, W. G.

J. R. Astles and W. G. Miller, Anal. Chem. 66, 167 (1994).
[CrossRef]

Mirkin, C. A.

R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger, and C. A. Mirkin, Science 277, 1078 (1997).
[CrossRef] [PubMed]

Mucic, R. C.

R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger, and C. A. Mirkin, Science 277, 1078 (1997).
[CrossRef] [PubMed]

Neuschafer, D.

G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
[CrossRef]

Nielsen, P. E.

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

Nolan, J.

X. Song, J. Nolan, and B. I. Swanson, J. Am. Chem. Soc. 120, 11514 (1998).
[CrossRef]

Oroszlan, P.

B. Klee, G. L. Duveneck, P. Oroszlan, M. Ehrat, and H. M. Widmer, Sensors Actuators B 29, 307 (1995).
[CrossRef]

Osman, P. D.

B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
[CrossRef] [PubMed]

Pace, R. J.

B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
[CrossRef] [PubMed]

Palecek, E.

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

Pawlak, M.

G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
[CrossRef]

Pieles, U.

G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
[CrossRef]

Pirrung, M. C.

S. P. A. Fodor, J. L. Read, M. C. Pirrung, L. Stryer, A. T. Lu, and D. Solas, Science 251, 767 (1991).
[CrossRef] [PubMed]

Raguse, B.

B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
[CrossRef] [PubMed]

Read, J. L.

S. P. A. Fodor, J. L. Read, M. C. Pirrung, L. Stryer, A. T. Lu, and D. Solas, Science 251, 767 (1991).
[CrossRef] [PubMed]

Rivas, G.

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

Schurmann, E.

J. Dubendorfer, R. E. Kunz, E. Schurmann, G. L. Duveneck, and M. Ehrat, J. Biomed. Opt. 2, 391 (1997).
[CrossRef]

Shiraishi, H.

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

Solas, D.

S. P. A. Fodor, J. L. Read, M. C. Pirrung, L. Stryer, A. T. Lu, and D. Solas, Science 251, 767 (1991).
[CrossRef] [PubMed]

Song, X.

X. Song and B. I. Swanson, Anal. Chem. 71, 2097 (1999).
[CrossRef] [PubMed]

X. Song, J. Nolan, and B. I. Swanson, J. Am. Chem. Soc. 120, 11514 (1998).
[CrossRef]

Storhoff, J. J.

R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger, and C. A. Mirkin, Science 277, 1078 (1997).
[CrossRef] [PubMed]

Stryer, L.

S. P. A. Fodor, J. L. Read, M. C. Pirrung, L. Stryer, A. T. Lu, and D. Solas, Science 251, 767 (1991).
[CrossRef] [PubMed]

Swanson, B. I.

X. Song and B. I. Swanson, Anal. Chem. 71, 2097 (1999).
[CrossRef] [PubMed]

X. Song, J. Nolan, and B. I. Swanson, J. Am. Chem. Soc. 120, 11514 (1998).
[CrossRef]

Wang, J.

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

Widmer, H. M.

B. Klee, G. L. Duveneck, P. Oroszlan, M. Ehrat, and H. M. Widmer, Sensors Actuators B 29, 307 (1995).
[CrossRef]

Wieczorek, L.

B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
[CrossRef] [PubMed]

Wood, P.

P. Wood, in Principles and Practice of Immunoassay, C. P. Price and D. J. Newman, eds. (Stockton, New York, 1991), p. 365.

Anal. Chem. (2)

J. R. Astles and W. G. Miller, Anal. Chem. 66, 167 (1994).
[CrossRef]

X. Song and B. I. Swanson, Anal. Chem. 71, 2097 (1999).
[CrossRef] [PubMed]

J. Am. Chem. Soc. (2)

J. Wang, E. Palecek, P. E. Nielsen, G. Rivas, X. H. Cai, H. Shiraishi, N. Dontha, D. B. Luo, and P. A. M. Farias, J. Am. Chem. Soc. 118, 7667 (1996).
[CrossRef]

X. Song, J. Nolan, and B. I. Swanson, J. Am. Chem. Soc. 120, 11514 (1998).
[CrossRef]

J. Biomed. Opt. (1)

J. Dubendorfer, R. E. Kunz, E. Schurmann, G. L. Duveneck, and M. Ehrat, J. Biomed. Opt. 2, 391 (1997).
[CrossRef]

Nature (1)

B. A. Cornell, V. L. B. Braach-Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace, Nature 387, 580 (1997).
[CrossRef] [PubMed]

Proc. SPIE (1)

S. J. Choquette, L. Locascio-Brown, and R. A. Durst, Proc. SPIE 1368, 258 (1990).
[CrossRef]

Science (2)

S. P. A. Fodor, J. L. Read, M. C. Pirrung, L. Stryer, A. T. Lu, and D. Solas, Science 251, 767 (1991).
[CrossRef] [PubMed]

R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger, and C. A. Mirkin, Science 277, 1078 (1997).
[CrossRef] [PubMed]

Sensors Actuators B (2)

B. Klee, G. L. Duveneck, P. Oroszlan, M. Ehrat, and H. M. Widmer, Sensors Actuators B 29, 307 (1995).
[CrossRef]

G. L. Duveneck, M. Pawlak, D. Neuschafer, E. Bar, W. Budach, U. Pieles, and M. Ehrat, Sensors Actuators B 38–39, 88 (1997).
[CrossRef]

Other (3)

B. D. Hames and S. J. Higgins, eds., Gene Probes (IRL Press, New York, 1995).

P. Wood, in Principles and Practice of Immunoassay, C. P. Price and D. J. Newman, eds. (Stockton, New York, 1991), p. 365.

The isobestic point for BTMR?GM1 and BTR?GM1 incorporated within a POPC bilayer was determined in Ref. 8.

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Figures (2)

Fig. 1
Fig. 1

Overhead schematic view of integrated optical biosensor (see text for explanation).

Fig. 2
Fig. 2

Fluorescence spectra of BTMRGm1 and BTRGm1 within a POPC bilayer attached to the waveguide surface parametric in concentration of cholera toxin (CT). Inset, ratio of fluorescence emission at peak intensity for BTRGm1BTMRGm1 as a function of exposure to CT.

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