Abstract

We have performed two-photon fluorescence detection in a new scheme in which femtosecond laser pulses were delivered thorugh an optical fiber for nonlinear excitation and the emitted fluorescence was collected through the same fiber. Single-mode fibers were determined to give higher detection efficiency than multimode fibers, consistent with theoretical considerations. The utility of fiber-optic sensing based on two-photon fluorescence detection was proved by an experiment that measured the uptake of a targeted drug delivery agent into cultured cancer cells.

© 2002 Optical Society of America

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  1. A. Lago, A. T. Obeidat, A. E. Kaplan, J. B. Khurgin, and P. L. Shkolnikov, Opt. Lett. 20, 2054 (1995).
    [CrossRef] [PubMed]
  2. J. S. Sanghera, L. B. Shaw, L. E. Busse, D. Talley, and I. D. Aggarwal, Proc. SPIE 3596, 178 (1999).
    [CrossRef]
  3. A. Mulchandani, S. Pan, and W. Chen, Biotechnol. Prog. 15, 130 (1999).
    [CrossRef] [PubMed]
  4. S. L. R. Baker, Y. Zhao, M. A. Marletta, and R. Kopelman, Anal. Chem. 71, 2071 (1999).
    [CrossRef]
  5. A. P. Abel, M. G. Weller, G. L. Duveneck, M. Ehrat, and H. M. Widmer, Anal. Chem. 68, 2905 (1996).
    [CrossRef] [PubMed]
  6. G. Keiser, Optical Fiber Communications (McGraw-Hill, New York, 1999).
  7. A. W. Bosman, H. M. Janssen, and E. W. Meijer, Chem. Rev. 99, 1665 (1999).
    [CrossRef]
  8. C. Wu, M. W. Brechbiel, R. W. Kozak, and O. A. Gansow, Bioorg. Med. Chem. Lett. 4, 449 (1994).
    [CrossRef]
  9. N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
    [CrossRef]
  10. J. Y. Ye, L. Balogh, and T. B. Norris, Appl. Phys. Lett. 80, 1713 (2002).
    [CrossRef]
  11. L. Balogh, D. A. Tomalia, and G. L. Hagnauer, Chem. Innovation 30, 19 (2000).
  12. J. D. Eichman, A. U. Bielinska, J. F. Kukowska-Latallo, and J. R. Baker, Pharmaceut. Sci. Technol. Today 3, 232 (2000).
    [CrossRef]
  13. A. Quintana, J. Moyer, L. Piehler, E. Raczka, I. Lee, A. Myc, A. Patri, D. Tomalia, D. Swanson, T. Thomas, J. Mulé, and J. Baker, eds., “Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor,” Pharmaceut. Res. (to be published).

2002 (1)

J. Y. Ye, L. Balogh, and T. B. Norris, Appl. Phys. Lett. 80, 1713 (2002).
[CrossRef]

2000 (3)

L. Balogh, D. A. Tomalia, and G. L. Hagnauer, Chem. Innovation 30, 19 (2000).

J. D. Eichman, A. U. Bielinska, J. F. Kukowska-Latallo, and J. R. Baker, Pharmaceut. Sci. Technol. Today 3, 232 (2000).
[CrossRef]

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

1999 (4)

A. W. Bosman, H. M. Janssen, and E. W. Meijer, Chem. Rev. 99, 1665 (1999).
[CrossRef]

J. S. Sanghera, L. B. Shaw, L. E. Busse, D. Talley, and I. D. Aggarwal, Proc. SPIE 3596, 178 (1999).
[CrossRef]

A. Mulchandani, S. Pan, and W. Chen, Biotechnol. Prog. 15, 130 (1999).
[CrossRef] [PubMed]

S. L. R. Baker, Y. Zhao, M. A. Marletta, and R. Kopelman, Anal. Chem. 71, 2071 (1999).
[CrossRef]

1996 (1)

A. P. Abel, M. G. Weller, G. L. Duveneck, M. Ehrat, and H. M. Widmer, Anal. Chem. 68, 2905 (1996).
[CrossRef] [PubMed]

1995 (1)

1994 (1)

C. Wu, M. W. Brechbiel, R. W. Kozak, and O. A. Gansow, Bioorg. Med. Chem. Lett. 4, 449 (1994).
[CrossRef]

Abel, A. P.

A. P. Abel, M. G. Weller, G. L. Duveneck, M. Ehrat, and H. M. Widmer, Anal. Chem. 68, 2905 (1996).
[CrossRef] [PubMed]

Aggarwal, I. D.

J. S. Sanghera, L. B. Shaw, L. E. Busse, D. Talley, and I. D. Aggarwal, Proc. SPIE 3596, 178 (1999).
[CrossRef]

Baker, J. R.

J. D. Eichman, A. U. Bielinska, J. F. Kukowska-Latallo, and J. R. Baker, Pharmaceut. Sci. Technol. Today 3, 232 (2000).
[CrossRef]

Baker, S. L. R.

S. L. R. Baker, Y. Zhao, M. A. Marletta, and R. Kopelman, Anal. Chem. 71, 2071 (1999).
[CrossRef]

Balogh, L.

J. Y. Ye, L. Balogh, and T. B. Norris, Appl. Phys. Lett. 80, 1713 (2002).
[CrossRef]

L. Balogh, D. A. Tomalia, and G. L. Hagnauer, Chem. Innovation 30, 19 (2000).

Bielinska, A. U.

J. D. Eichman, A. U. Bielinska, J. F. Kukowska-Latallo, and J. R. Baker, Pharmaceut. Sci. Technol. Today 3, 232 (2000).
[CrossRef]

Bosman, A. W.

A. W. Bosman, H. M. Janssen, and E. W. Meijer, Chem. Rev. 99, 1665 (1999).
[CrossRef]

Brechbiel, M. W.

C. Wu, M. W. Brechbiel, R. W. Kozak, and O. A. Gansow, Bioorg. Med. Chem. Lett. 4, 449 (1994).
[CrossRef]

Busse, L. E.

J. S. Sanghera, L. B. Shaw, L. E. Busse, D. Talley, and I. D. Aggarwal, Proc. SPIE 3596, 178 (1999).
[CrossRef]

Chen, W.

A. Mulchandani, S. Pan, and W. Chen, Biotechnol. Prog. 15, 130 (1999).
[CrossRef] [PubMed]

Duncan, R.

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

Duveneck, G. L.

A. P. Abel, M. G. Weller, G. L. Duveneck, M. Ehrat, and H. M. Widmer, Anal. Chem. 68, 2905 (1996).
[CrossRef] [PubMed]

Ehrat, M.

A. P. Abel, M. G. Weller, G. L. Duveneck, M. Ehrat, and H. M. Widmer, Anal. Chem. 68, 2905 (1996).
[CrossRef] [PubMed]

Eichman, J. D.

J. D. Eichman, A. U. Bielinska, J. F. Kukowska-Latallo, and J. R. Baker, Pharmaceut. Sci. Technol. Today 3, 232 (2000).
[CrossRef]

Frey, H.

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

Gansow, O. A.

C. Wu, M. W. Brechbiel, R. W. Kozak, and O. A. Gansow, Bioorg. Med. Chem. Lett. 4, 449 (1994).
[CrossRef]

Hagnauer, G. L.

L. Balogh, D. A. Tomalia, and G. L. Hagnauer, Chem. Innovation 30, 19 (2000).

Janssen, H. M.

A. W. Bosman, H. M. Janssen, and E. W. Meijer, Chem. Rev. 99, 1665 (1999).
[CrossRef]

Kaplan, A. E.

Keiser, G.

G. Keiser, Optical Fiber Communications (McGraw-Hill, New York, 1999).

Khurgin, J. B.

Klopsch, R.

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

Kopelman, R.

S. L. R. Baker, Y. Zhao, M. A. Marletta, and R. Kopelman, Anal. Chem. 71, 2071 (1999).
[CrossRef]

Kozak, R. W.

C. Wu, M. W. Brechbiel, R. W. Kozak, and O. A. Gansow, Bioorg. Med. Chem. Lett. 4, 449 (1994).
[CrossRef]

Kukowska-Latallo, J. F.

J. D. Eichman, A. U. Bielinska, J. F. Kukowska-Latallo, and J. R. Baker, Pharmaceut. Sci. Technol. Today 3, 232 (2000).
[CrossRef]

Lago, A.

Lorenz, K.

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

Malik, N.

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

Marletta, M. A.

S. L. R. Baker, Y. Zhao, M. A. Marletta, and R. Kopelman, Anal. Chem. 71, 2071 (1999).
[CrossRef]

Meijer, E. W.

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

A. W. Bosman, H. M. Janssen, and E. W. Meijer, Chem. Rev. 99, 1665 (1999).
[CrossRef]

Mulchandani, A.

A. Mulchandani, S. Pan, and W. Chen, Biotechnol. Prog. 15, 130 (1999).
[CrossRef] [PubMed]

Norris, T. B.

J. Y. Ye, L. Balogh, and T. B. Norris, Appl. Phys. Lett. 80, 1713 (2002).
[CrossRef]

Obeidat, A. T.

Pan, S.

A. Mulchandani, S. Pan, and W. Chen, Biotechnol. Prog. 15, 130 (1999).
[CrossRef] [PubMed]

Paulus, W.

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

Sanghera, J. S.

J. S. Sanghera, L. B. Shaw, L. E. Busse, D. Talley, and I. D. Aggarwal, Proc. SPIE 3596, 178 (1999).
[CrossRef]

Shaw, L. B.

J. S. Sanghera, L. B. Shaw, L. E. Busse, D. Talley, and I. D. Aggarwal, Proc. SPIE 3596, 178 (1999).
[CrossRef]

Shkolnikov, P. L.

Talley, D.

J. S. Sanghera, L. B. Shaw, L. E. Busse, D. Talley, and I. D. Aggarwal, Proc. SPIE 3596, 178 (1999).
[CrossRef]

Tomalia, D. A.

L. Balogh, D. A. Tomalia, and G. L. Hagnauer, Chem. Innovation 30, 19 (2000).

Weener, J. W.

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

Weller, M. G.

A. P. Abel, M. G. Weller, G. L. Duveneck, M. Ehrat, and H. M. Widmer, Anal. Chem. 68, 2905 (1996).
[CrossRef] [PubMed]

Widmer, H. M.

A. P. Abel, M. G. Weller, G. L. Duveneck, M. Ehrat, and H. M. Widmer, Anal. Chem. 68, 2905 (1996).
[CrossRef] [PubMed]

Wiwattanapatapee, R.

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

Wu, C.

C. Wu, M. W. Brechbiel, R. W. Kozak, and O. A. Gansow, Bioorg. Med. Chem. Lett. 4, 449 (1994).
[CrossRef]

Ye, J. Y.

J. Y. Ye, L. Balogh, and T. B. Norris, Appl. Phys. Lett. 80, 1713 (2002).
[CrossRef]

Zhao, Y.

S. L. R. Baker, Y. Zhao, M. A. Marletta, and R. Kopelman, Anal. Chem. 71, 2071 (1999).
[CrossRef]

Anal. Chem. (2)

S. L. R. Baker, Y. Zhao, M. A. Marletta, and R. Kopelman, Anal. Chem. 71, 2071 (1999).
[CrossRef]

A. P. Abel, M. G. Weller, G. L. Duveneck, M. Ehrat, and H. M. Widmer, Anal. Chem. 68, 2905 (1996).
[CrossRef] [PubMed]

Appl. Phys. Lett. (1)

J. Y. Ye, L. Balogh, and T. B. Norris, Appl. Phys. Lett. 80, 1713 (2002).
[CrossRef]

Bioorg. Med. Chem. Lett. (1)

C. Wu, M. W. Brechbiel, R. W. Kozak, and O. A. Gansow, Bioorg. Med. Chem. Lett. 4, 449 (1994).
[CrossRef]

Biotechnol. Prog. (1)

A. Mulchandani, S. Pan, and W. Chen, Biotechnol. Prog. 15, 130 (1999).
[CrossRef] [PubMed]

Chem. Innovation (1)

L. Balogh, D. A. Tomalia, and G. L. Hagnauer, Chem. Innovation 30, 19 (2000).

Chem. Rev. (1)

A. W. Bosman, H. M. Janssen, and E. W. Meijer, Chem. Rev. 99, 1665 (1999).
[CrossRef]

J. Controlled Release (1)

N. Malik, R. Wiwattanapatapee, R. Klopsch, K. Lorenz, H. Frey, J. W. Weener, E. W. Meijer, W. Paulus, and R. Duncan, J. Controlled Release 65, 133 (2000).
[CrossRef]

Opt. Lett. (1)

Pharmaceut. Sci. Technol. Today (1)

J. D. Eichman, A. U. Bielinska, J. F. Kukowska-Latallo, and J. R. Baker, Pharmaceut. Sci. Technol. Today 3, 232 (2000).
[CrossRef]

Proc. SPIE (1)

J. S. Sanghera, L. B. Shaw, L. E. Busse, D. Talley, and I. D. Aggarwal, Proc. SPIE 3596, 178 (1999).
[CrossRef]

Other (2)

G. Keiser, Optical Fiber Communications (McGraw-Hill, New York, 1999).

A. Quintana, J. Moyer, L. Piehler, E. Raczka, I. Lee, A. Myc, A. Patri, D. Tomalia, D. Swanson, T. Thomas, J. Mulé, and J. Baker, eds., “Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor,” Pharmaceut. Res. (to be published).

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Figures (4)

Fig. 1
Fig. 1

Experimental setup for TPF detection through an optical fiber. PMT, photomultiplier tube.

Fig. 2
Fig. 2

Quadratic power dependence of TPF. In the lables of the symbols used here, the first number indicates the core diamter in micrometers and the second number represents the numerical aperture. S, single-mode fibers; M50_0.20, graded-index MMF; M200_0.48, M200_0.37, step-index MMFs.

Fig. 3
Fig. 3

(a) Comparison of calculated TPF detection efficiency of a SMF and of a step-index MMF. We assume that τin is 80 fs, β2 is 35,000 fs2/m, and NA is 0.11 and 0.48 for SMFs and MMFs, respectively. (b) Calculated TPF power as a function of incident pulse duration for five lengths of a SMF (assuming no dispersion compensation), showing that there is an optimum incident pulse duration for each length. Our experiment used a pulse duration of 80 fs and a fiber length of 24 cm, which are close to optimal conditions.

Fig. 4
Fig. 4

(a) TPF power as functions of concentrations of G5–FI and G5–FI–FA. The slight difference in the TPF power between G5–FI and G5–FI–FA may be caused by FA reducing the fluorescence quantum yield of FI. (b) Dose-response curve for the binding of G5–FI and G5–FI–FA on KB cells. The G5–FI–FA specific binding is obtained by subtraction of the nonspecific G5–FI signal. At saturation, the level of G5–FI–FA bound was 2 pmol/106 cells.

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

Pf0ηϕzIout2zτoutRπW2zdz,
PfηC2PL2RτoutλarctannλπaNA-1-NA/n21/2arctannλ1-NA/n21/2πaNA,
τout=τin1+L/LD21/2,
τout=ncoreNA2L/cncladncore+nclad.

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