Abstract

A novel method for detection of noble-metal nanoparticles by their nonlinear optical properties is presented and applied for specific labeling of cellular organelles. When illuminated by laser light in resonance with their plasmon frequency these nanoparticles generate an enhanced multiphoton signal. This enhanced signal is measured to obtain a depth-resolved image in a laser scanning microscope setup. Plasmon-resonance images of both live and fixed cells, showing specific labeling of cellular organelles and membranes, either by two-photon autofluorescence or by third-harmonic generation, are presented.

© 2003 Optical Society of America

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Appl. Phys. B (1)

D. Yelin, D. Oron, E. Korkotian, M. Segal, Y. Silberberg, ???Third-harmonic microscopy with a Ti:Sapphire laser,??? Appl. Phys. B 74, s97 (2002).
[CrossRef]

Appl. Phys. B (1)

M. Quinten, ???Local fields close to the surface of nanoparticles and aggregates of nanoparticles,??? Appl. Phys. B 73, 245 (2001).
[CrossRef]

Appl. Spec. (1)

K. Kneipp et al., ???Surface-enhanced Raman spectroscopy in single living cells using gold nanoparticles,??? Appl. Spec. 56, 150 (2002).
[CrossRef]

Bioimaging (1)

G. Peleg, A. Lewis, O. Bouevitch, L. Loew, D. Parnas, M. Linial, ???Gigantic optical non-linearities from nanopartical-enhanced molecular probes with potential for selectively imaging the structure and physiology of nanometric regions in cellular systems,??? Bioimaging 4, 215 (1996).
[CrossRef]

Brain Res. (1)

M.S. Bush, G. Allt, ???Blood nerve barrier: distribution of anionic sites on the endothelial plasma membrane and basal lamina,??? Brain Res. 535, 181 (1990).
[CrossRef] [PubMed]

Cytometry (1)

R.M. Guasch, C. Guerri, J.-E. O???Connor, ???Study of surface carbohydrates on isolated golgi subfractions by fluorescent-lectin binding and flow cytometry,??? Cytometry 19, 112 (1995); R.M. Guasch, C. Guerri, J.-E. O???Connor, ???Flow cytometric analysis of concanavalin A binding to isolate Golgi fractions from rat liver,??? Exp. Cell Res. 207, 136 (1993).
[CrossRef] [PubMed]

J. Cell Biol. (1)

I. Virtanen, P. Ekblom, P. Laurila, ???Subcellular compartmentalization of saccharide moieties in cultured normal and malignant cells,??? J. Cell Biol. 85, 429 (1980).
[CrossRef] [PubMed]

J. Chem. Phys. (2)

J.T. Golab, J.R. Sprague, K.T. Carron, G.C. Schatz, R.P. Van Duyne,???A Surface enhanced hyper-Raman scattering study of pyridine adsorbed onto silver: experiment and theory,??? J. Chem. Phys. 888, 7942 (1988).
[CrossRef]

S.J. Oldenburg, S.L. Westcott, R.D. Averitt, N.J. Halas, ???Infrared extinction properties of gold nanoshells,??? J. Chem. Phys. 111, 4729 (1999).
[CrossRef]

J. Histochemistry (1)

E. Skutelsky, J. Roth, ???Cationic colloidal gold - a new probe for the detection of anionic cell surface sites by electron microscopy,??? J. Histochemistry 34, 693 (1986).

J. Microsc (1)

M. Muller, J. Squier, K.R. Wilson, G.J. Brakenhoff,???3D-microscopy of transparent objects using third-harmonic generation,??? J. Microsc. 191, 266 (1998).
[CrossRef] [PubMed]

J. Raman Spec. (1)

E.J. Liang, C. Engert,W. Kiefer, ???Surface-enhanced Raman scattering of pyridine in silver colloids excited in the near-infrared region,??? J. Raman Spec. 24, 775 (1993).
[CrossRef]

Opt. Express (1)

Opt. Lett. (1)

Phys. Rev. B (1)

B. J. Messinger, K. Ulrich von Raben, R.K. Chang, P.W. Barber, ???Local fields at the surface of noble metal microspheres,??? Phys. Rev. B 24, 649 (1981).
[CrossRef]

Phys. Rev. Lett. (3)

A. Zumbusch, G.R. Holtom, X.S. Xie, ???Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,??? Phys. Rev. Lett. 82, 4142 (1999).
[CrossRef]

B. Lamprecht, J.R. Krenn, A. Leitner, F.R. Aussenegg, ???Resonant and off-resonant light-driven plasmons in metal nanoparticles studied by femtosecond-resolution third-harmonic generation,??? Phys. Rev. Lett. 83, 4421 (1999).
[CrossRef]

J. Aizpurua, P. Hanarp, D. S. Sutherland, M. Kall, G. W. Bryant, F. J. Garcia de Abajo, ???Optical properties of gold nanorings,??? Phys. Rev. Lett. 90, 057401 (2003).
[CrossRef] [PubMed]

Science (6)

D. Boyer, P. Tamarat, A. Maali, B. Lounis, M. Orrit, ???Photothermal imaging of nanometer-sized metal particles among scatterers,??? Science 297, 1160 (2002).
[CrossRef] [PubMed]

W. C. W. Chan, S. Nie, ???Quantum dot bioconjugates for ultrasensitive nonisotopic detection,??? Science 281, 2016 (1998).
[CrossRef] [PubMed]

M. Bruchez Jr., M. Moronne, P. Gin, S. Weiss, A. P. Alivisatos, ???Semiconductor nanocrystals as fluorescent biological labels,??? Science 281, 2013 (1998).
[CrossRef]

W. Denk, J.H. Strickler, W.W. Webb, ???Two-photon laser scanning fluorescence microscopy,??? Science 248, 73 (1990).
[CrossRef] [PubMed]

S. Maiti, J.B. Shear, R.M.Williams, W.R. Zipfel, W.W.Webb, ???Measuring serotonin distribution in live cells with three-photon excitation,??? Science 275, 530 (1997).
[CrossRef] [PubMed]

S. Nie, S.R. Emory, ???Probing single molecules and single nanoparticles by surface-enhanced Raman scattering,??? Science 275, 1102 (1997).
[CrossRef] [PubMed]

Other (3)

G. Peleg, A. Lewis, M. Linial, L.M. Loew, ???Nonlinear optical measurement of membrane potential around single molecules at selected cellular sites,??? Proc. Natl. Acad. Sci. USA 96, 6700 (1999).
[CrossRef] [PubMed]

B. Alberts et al., Molecular Biology of The Cell (Garland Publishing Inc., New York, 1994).

Concanavalin A as a Tool, eds. H. Bittiges, H.P. Schnebli, (London, 1976).

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Figures (4)

Fig. 1.
Fig. 1.

Plasmon-resonance TPAF images of CHO cells incubated with (a) 10nm cationic gold. (b) 40nm Concanavalin A gold. (c) two cells which were submitted to the same treatments performed in the positive experiments (a and b), but no gold was added to the growing medium. The strong TPAF spots in a and b are attributed to plasmon-resonance with the laser frequency where nanoparticles are aggregated.

Fig. 2.
Fig. 2.

Plasmon-resonance TPAF image of a live CHO cell incubated with 10nm cationic gold, superimposed on a simple transmission image of the cell. The transmission image is blue, while the TPAF signal goes from red (weak) to yellow (strong).

Fig. 3.
Fig. 3.

(a) THG image of a fixed NIH3T3 cell. While the nucleus appears dark, numerous bright spots are observed in the cell volume. (b) THG image of a NIH3T3 cell, in which the nucleus membrane was labelled by 10nm gold nanoparticles followed by silver enhancement.

Fig. 4.
Fig. 4.

Four THG sections of a NIH3T3 epithelial cell whose membrane was labelled by 10nm gold nanoparticles, followed by silver enhancement. Bright areas denote strong third-harmonic signal. The top of the cell is shown on the top left corner, while the bottom of the cell is shown on the bottom right corner. The spacing between sections is approximately 3µm. The average illumination power is of the order of 1mW. The cell shape, in the form of a triangular pyramid is clearly evident. The inside of the cell, where there are no nanoparticles, is completely dark.

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