Abstract

We demonstrate that second-harmonic radiation imaging probes are efficient biomarkers for imaging in living tissue. We show that 100 nm and 300 nm BaTiO3 nanoparticles used as contrast markers could be detected through 50 μm and 120 μm of mouse tail tissue in vitro or in vivo. Experimental results and Monte-Carlo simulations are in good agreement.

© 2011 OSA

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  1. I. M. Vellekoop and A. P. Mosk, “Focusing coherent light through opaque strongly scattering media,” Opt. Lett. 32(16), 2309–2311 (2007).
    [CrossRef] [PubMed]
  2. E. Gratton, “Applied physics. Deeper tissue imaging with total detection,” Science 331(6020), 1016–1017 (2011).
    [CrossRef] [PubMed]
  3. C.-L. Hsieh, Y. Pu, R. Grange, G. Laporte, and D. Psaltis, “Imaging through turbid layers by scanning the phase conjugated second harmonic radiation from a nanoparticle,” Opt. Express 18(20), 20723–20731 (2010).
    [CrossRef] [PubMed]
  4. W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
    [CrossRef] [PubMed]
  5. F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
    [CrossRef] [PubMed]
  6. B. N. G. Giepmans, S. R. Adams, M. H. Ellisman, and R. Y. Tsien, “The fluorescent toolbox for assessing protein location and function,” Science 312(5771), 217–224 (2006).
    [CrossRef] [PubMed]
  7. R. M. Dickson, A. B. Cubitt, R. Y. Tsien, and W. E. Moerner, “On/off blinking and switching behaviour of single molecules of green fluorescent protein,” Nature 388(6640), 355–358 (1997).
    [CrossRef] [PubMed]
  8. L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
    [CrossRef]
  9. L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
    [CrossRef]
  10. A. V. Kachynski, A. N. Kuzmin, M. Nyk, I. Roy, and P. N. Prasad, “Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine,” J. Phys. Chem. C 112(29), 10721–10724 (2008).
    [CrossRef]
  11. Y. Pu, M. Centurion, and D. Psaltis, “Harmonic holography: a new holographic principle,” Appl. Opt. 47(4), A103–A110 (2008).
    [CrossRef] [PubMed]
  12. E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
    [CrossRef]
  13. C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Three-dimensional harmonic holographic microcopy using nanoparticles as probes for cell imaging,” Opt. Express 17(4), 2880–2891 (2009).
    [CrossRef] [PubMed]
  14. C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Characterization of the cytotoxicity and imaging properties of second-harmonic nanoparticles,” Proc. SPIE 7759, 77590T, 77590T-6 (2010).
    [CrossRef]
  15. G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
    [CrossRef] [PubMed]
  16. Y. Pu, R. Grange, C.-L. Hsieh, and D. Psaltis, “Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation,” Phys. Rev. Lett. 104(20), 207402 (2010).
    [CrossRef] [PubMed]
  17. C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes,” Biomaterials 31(8), 2272–2277 (2010).
    [CrossRef] [PubMed]
  18. J. Extermann, L. Bonacina, E. Cuña, C. Kasparian, Y. Mugnier, T. Feurer, and J.-P. Wolf, “Nanodoublers as deep imaging markers for multi-photon microscopy,” Opt. Express 17(17), 15342–15349 (2009).
    [CrossRef] [PubMed]
  19. P. Pantazis, J. Maloney, D. Wu, and S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
    [CrossRef] [PubMed]
  20. P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
    [CrossRef] [PubMed]
  21. M. T. Buscaglia, V. Buscaglia, and R. Alessio, “Coating of BaCO3 Crystals with TiO2:Versatile Approach to the Synthesis of BaTiO3 Tetragonal Nanoparticles,” Chem. Mater. 19(4), 711–718 (2007).
    [CrossRef]
  22. K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, “Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes,” Opt. Lett. 22(2), 135–136 (1997).
    [CrossRef] [PubMed]
  23. P. Stoller, B.-M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, “Polarization-dependent optical second-harmonic imaging of a rat-tail tendon,” J. Biomed. Opt. 7(2), 205–214 (2002).
    [CrossRef] [PubMed]
  24. C.-L. Hsieh, Y. Pu, R. Grange, and D. Psaltis, “Second harmonic generation from nanocrystals under linearly and circularly polarized excitations,” Opt. Express 18(11), 11917–11932 (2010).
    [CrossRef] [PubMed]
  25. L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47(2), 131–146 (1995).
    [CrossRef] [PubMed]
  26. W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
    [CrossRef]
  27. B. B. Das, F. Liu, and R. R. Alfano, “Time-resolved fluorescence and photon migration studies in biomedical and model random media,” Rep. Prog. Phys. 60(2), 227–292 (1997).
    [CrossRef]

2011

E. Gratton, “Applied physics. Deeper tissue imaging with total detection,” Science 331(6020), 1016–1017 (2011).
[CrossRef] [PubMed]

2010

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Characterization of the cytotoxicity and imaging properties of second-harmonic nanoparticles,” Proc. SPIE 7759, 77590T, 77590T-6 (2010).
[CrossRef]

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Y. Pu, R. Grange, C.-L. Hsieh, and D. Psaltis, “Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation,” Phys. Rev. Lett. 104(20), 207402 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes,” Biomaterials 31(8), 2272–2277 (2010).
[CrossRef] [PubMed]

P. Pantazis, J. Maloney, D. Wu, and S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, Y. Pu, R. Grange, and D. Psaltis, “Second harmonic generation from nanocrystals under linearly and circularly polarized excitations,” Opt. Express 18(11), 11917–11932 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, Y. Pu, R. Grange, G. Laporte, and D. Psaltis, “Imaging through turbid layers by scanning the phase conjugated second harmonic radiation from a nanoparticle,” Opt. Express 18(20), 20723–20731 (2010).
[CrossRef] [PubMed]

2009

2008

A. V. Kachynski, A. N. Kuzmin, M. Nyk, I. Roy, and P. N. Prasad, “Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine,” J. Phys. Chem. C 112(29), 10721–10724 (2008).
[CrossRef]

Y. Pu, M. Centurion, and D. Psaltis, “Harmonic holography: a new holographic principle,” Appl. Opt. 47(4), A103–A110 (2008).
[CrossRef] [PubMed]

2007

I. M. Vellekoop and A. P. Mosk, “Focusing coherent light through opaque strongly scattering media,” Opt. Lett. 32(16), 2309–2311 (2007).
[CrossRef] [PubMed]

M. T. Buscaglia, V. Buscaglia, and R. Alessio, “Coating of BaCO3 Crystals with TiO2:Versatile Approach to the Synthesis of BaTiO3 Tetragonal Nanoparticles,” Chem. Mater. 19(4), 711–718 (2007).
[CrossRef]

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

2006

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
[CrossRef]

B. N. G. Giepmans, S. R. Adams, M. H. Ellisman, and R. Y. Tsien, “The fluorescent toolbox for assessing protein location and function,” Science 312(5771), 217–224 (2006).
[CrossRef] [PubMed]

2005

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[CrossRef] [PubMed]

2003

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

2002

P. Stoller, B.-M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, “Polarization-dependent optical second-harmonic imaging of a rat-tail tendon,” J. Biomed. Opt. 7(2), 205–214 (2002).
[CrossRef] [PubMed]

1997

R. M. Dickson, A. B. Cubitt, R. Y. Tsien, and W. E. Moerner, “On/off blinking and switching behaviour of single molecules of green fluorescent protein,” Nature 388(6640), 355–358 (1997).
[CrossRef] [PubMed]

B. B. Das, F. Liu, and R. R. Alfano, “Time-resolved fluorescence and photon migration studies in biomedical and model random media,” Rep. Prog. Phys. 60(2), 227–292 (1997).
[CrossRef]

K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, “Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes,” Opt. Lett. 22(2), 135–136 (1997).
[CrossRef] [PubMed]

1995

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47(2), 131–146 (1995).
[CrossRef] [PubMed]

1990

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[CrossRef]

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Adams, S. R.

B. N. G. Giepmans, S. R. Adams, M. H. Ellisman, and R. Y. Tsien, “The fluorescent toolbox for assessing protein location and function,” Science 312(5771), 217–224 (2006).
[CrossRef] [PubMed]

Albertazzi, L.

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Alessio, R.

M. T. Buscaglia, V. Buscaglia, and R. Alessio, “Coating of BaCO3 Crystals with TiO2:Versatile Approach to the Synthesis of BaTiO3 Tetragonal Nanoparticles,” Chem. Mater. 19(4), 711–718 (2007).
[CrossRef]

Alfano, R. R.

B. B. Das, F. Liu, and R. R. Alfano, “Time-resolved fluorescence and photon migration studies in biomedical and model random media,” Rep. Prog. Phys. 60(2), 227–292 (1997).
[CrossRef]

Bonacina, L.

J. Extermann, L. Bonacina, E. Cuña, C. Kasparian, Y. Mugnier, T. Feurer, and J.-P. Wolf, “Nanodoublers as deep imaging markers for multi-photon microscopy,” Opt. Express 17(17), 15342–15349 (2009).
[CrossRef] [PubMed]

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Boutou, V.

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Brasselet, S.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
[CrossRef]

Buscaglia, M. T.

M. T. Buscaglia, V. Buscaglia, and R. Alessio, “Coating of BaCO3 Crystals with TiO2:Versatile Approach to the Synthesis of BaTiO3 Tetragonal Nanoparticles,” Chem. Mater. 19(4), 711–718 (2007).
[CrossRef]

Buscaglia, V.

M. T. Buscaglia, V. Buscaglia, and R. Alessio, “Coating of BaCO3 Crystals with TiO2:Versatile Approach to the Synthesis of BaTiO3 Tetragonal Nanoparticles,” Chem. Mater. 19(4), 711–718 (2007).
[CrossRef]

Campagnola, P. J.

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

Centurion, M.

Chauvat, D.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

Cheong, W. F.

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[CrossRef]

Chiellini, F.

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Ciofani, G.

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Clement, R.

E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
[CrossRef]

Courvoisier, F.

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Cubitt, A. B.

R. M. Dickson, A. B. Cubitt, R. Y. Tsien, and W. E. Moerner, “On/off blinking and switching behaviour of single molecules of green fluorescent protein,” Nature 388(6640), 355–358 (1997).
[CrossRef] [PubMed]

Cuña, E.

D’Alessandro, D.

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Da Silva, L. B.

P. Stoller, B.-M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, “Polarization-dependent optical second-harmonic imaging of a rat-tail tendon,” J. Biomed. Opt. 7(2), 205–214 (2002).
[CrossRef] [PubMed]

Danti, S.

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Das, B. B.

B. B. Das, F. Liu, and R. R. Alfano, “Time-resolved fluorescence and photon migration studies in biomedical and model random media,” Rep. Prog. Phys. 60(2), 227–292 (1997).
[CrossRef]

Delahaye, E.

E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
[CrossRef]

Denk, W.

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Dickson, R. M.

R. M. Dickson, A. B. Cubitt, R. Y. Tsien, and W. E. Moerner, “On/off blinking and switching behaviour of single molecules of green fluorescent protein,” Nature 388(6640), 355–358 (1997).
[CrossRef] [PubMed]

Dinucci, D.

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Ellisman, M. H.

B. N. G. Giepmans, S. R. Adams, M. H. Ellisman, and R. Y. Tsien, “The fluorescent toolbox for assessing protein location and function,” Science 312(5771), 217–224 (2006).
[CrossRef] [PubMed]

Extermann, J.

J. Extermann, L. Bonacina, E. Cuña, C. Kasparian, Y. Mugnier, T. Feurer, and J.-P. Wolf, “Nanodoublers as deep imaging markers for multi-photon microscopy,” Opt. Express 17(17), 15342–15349 (2009).
[CrossRef] [PubMed]

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Feurer, T.

Fraser, S. E.

P. Pantazis, J. Maloney, D. Wu, and S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

Gacoin, T.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

Galez, C.

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Giepmans, B. N. G.

B. N. G. Giepmans, S. R. Adams, M. H. Ellisman, and R. Y. Tsien, “The fluorescent toolbox for assessing protein location and function,” Science 312(5771), 217–224 (2006).
[CrossRef] [PubMed]

Grange, R.

Y. Pu, R. Grange, C.-L. Hsieh, and D. Psaltis, “Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation,” Phys. Rev. Lett. 104(20), 207402 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, Y. Pu, R. Grange, G. Laporte, and D. Psaltis, “Imaging through turbid layers by scanning the phase conjugated second harmonic radiation from a nanoparticle,” Opt. Express 18(20), 20723–20731 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes,” Biomaterials 31(8), 2272–2277 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, Y. Pu, R. Grange, and D. Psaltis, “Second harmonic generation from nanocrystals under linearly and circularly polarized excitations,” Opt. Express 18(11), 11917–11932 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Characterization of the cytotoxicity and imaging properties of second-harmonic nanoparticles,” Proc. SPIE 7759, 77590T, 77590T-6 (2010).
[CrossRef]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Three-dimensional harmonic holographic microcopy using nanoparticles as probes for cell imaging,” Opt. Express 17(4), 2880–2891 (2009).
[CrossRef] [PubMed]

Gratton, E.

Helmchen, F.

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[CrossRef] [PubMed]

Hsieh, C.-L.

C.-L. Hsieh, Y. Pu, R. Grange, G. Laporte, and D. Psaltis, “Imaging through turbid layers by scanning the phase conjugated second harmonic radiation from a nanoparticle,” Opt. Express 18(20), 20723–20731 (2010).
[CrossRef] [PubMed]

Y. Pu, R. Grange, C.-L. Hsieh, and D. Psaltis, “Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation,” Phys. Rev. Lett. 104(20), 207402 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Characterization of the cytotoxicity and imaging properties of second-harmonic nanoparticles,” Proc. SPIE 7759, 77590T, 77590T-6 (2010).
[CrossRef]

C.-L. Hsieh, Y. Pu, R. Grange, and D. Psaltis, “Second harmonic generation from nanocrystals under linearly and circularly polarized excitations,” Opt. Express 18(11), 11917–11932 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes,” Biomaterials 31(8), 2272–2277 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Three-dimensional harmonic holographic microcopy using nanoparticles as probes for cell imaging,” Opt. Express 17(4), 2880–2891 (2009).
[CrossRef] [PubMed]

Jacques, S. L.

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47(2), 131–146 (1995).
[CrossRef] [PubMed]

Kachynski, A. V.

A. V. Kachynski, A. N. Kuzmin, M. Nyk, I. Roy, and P. N. Prasad, “Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine,” J. Phys. Chem. C 112(29), 10721–10724 (2008).
[CrossRef]

Kasparian, C.

Kim, B.-M.

P. Stoller, B.-M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, “Polarization-dependent optical second-harmonic imaging of a rat-tail tendon,” J. Biomed. Opt. 7(2), 205–214 (2002).
[CrossRef] [PubMed]

König, K.

Kuzmin, A. N.

A. V. Kachynski, A. N. Kuzmin, M. Nyk, I. Roy, and P. N. Prasad, “Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine,” J. Phys. Chem. C 112(29), 10721–10724 (2008).
[CrossRef]

Lambert, Y.

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Laporte, G.

Le Dantec, R.

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Ledoux, I.

E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
[CrossRef]

Liu, F.

B. B. Das, F. Liu, and R. R. Alfano, “Time-resolved fluorescence and photon migration studies in biomedical and model random media,” Rep. Prog. Phys. 60(2), 227–292 (1997).
[CrossRef]

Loew, L. M.

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

Maloney, J.

P. Pantazis, J. Maloney, D. Wu, and S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

Mantulin, W. W.

Marquier, F.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

Menciassi, A.

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Moerner, W. E.

R. M. Dickson, A. B. Cubitt, R. Y. Tsien, and W. E. Moerner, “On/off blinking and switching behaviour of single molecules of green fluorescent protein,” Nature 388(6640), 355–358 (1997).
[CrossRef] [PubMed]

Moscato, S.

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Mosk, A. P.

Mugnier, Y.

J. Extermann, L. Bonacina, E. Cuña, C. Kasparian, Y. Mugnier, T. Feurer, and J.-P. Wolf, “Nanodoublers as deep imaging markers for multi-photon microscopy,” Opt. Express 17(17), 15342–15349 (2009).
[CrossRef] [PubMed]

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Nyk, M.

A. V. Kachynski, A. N. Kuzmin, M. Nyk, I. Roy, and P. N. Prasad, “Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine,” J. Phys. Chem. C 112(29), 10721–10724 (2008).
[CrossRef]

Pantazis, P.

P. Pantazis, J. Maloney, D. Wu, and S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

Perruchas, S.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

Petrini, M.

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Prahl, S. A.

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[CrossRef]

Prasad, P. N.

A. V. Kachynski, A. N. Kuzmin, M. Nyk, I. Roy, and P. N. Prasad, “Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine,” J. Phys. Chem. C 112(29), 10721–10724 (2008).
[CrossRef]

Psaltis, D.

C.-L. Hsieh, Y. Pu, R. Grange, and D. Psaltis, “Second harmonic generation from nanocrystals under linearly and circularly polarized excitations,” Opt. Express 18(11), 11917–11932 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes,” Biomaterials 31(8), 2272–2277 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Characterization of the cytotoxicity and imaging properties of second-harmonic nanoparticles,” Proc. SPIE 7759, 77590T, 77590T-6 (2010).
[CrossRef]

Y. Pu, R. Grange, C.-L. Hsieh, and D. Psaltis, “Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation,” Phys. Rev. Lett. 104(20), 207402 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, Y. Pu, R. Grange, G. Laporte, and D. Psaltis, “Imaging through turbid layers by scanning the phase conjugated second harmonic radiation from a nanoparticle,” Opt. Express 18(20), 20723–20731 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Three-dimensional harmonic holographic microcopy using nanoparticles as probes for cell imaging,” Opt. Express 17(4), 2880–2891 (2009).
[CrossRef] [PubMed]

Y. Pu, M. Centurion, and D. Psaltis, “Harmonic holography: a new holographic principle,” Appl. Opt. 47(4), A103–A110 (2008).
[CrossRef] [PubMed]

Pu, Y.

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Characterization of the cytotoxicity and imaging properties of second-harmonic nanoparticles,” Proc. SPIE 7759, 77590T, 77590T-6 (2010).
[CrossRef]

C.-L. Hsieh, Y. Pu, R. Grange, and D. Psaltis, “Second harmonic generation from nanocrystals under linearly and circularly polarized excitations,” Opt. Express 18(11), 11917–11932 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes,” Biomaterials 31(8), 2272–2277 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, Y. Pu, R. Grange, G. Laporte, and D. Psaltis, “Imaging through turbid layers by scanning the phase conjugated second harmonic radiation from a nanoparticle,” Opt. Express 18(20), 20723–20731 (2010).
[CrossRef] [PubMed]

Y. Pu, R. Grange, C.-L. Hsieh, and D. Psaltis, “Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation,” Phys. Rev. Lett. 104(20), 207402 (2010).
[CrossRef] [PubMed]

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Three-dimensional harmonic holographic microcopy using nanoparticles as probes for cell imaging,” Opt. Express 17(4), 2880–2891 (2009).
[CrossRef] [PubMed]

Y. Pu, M. Centurion, and D. Psaltis, “Harmonic holography: a new holographic principle,” Appl. Opt. 47(4), A103–A110 (2008).
[CrossRef] [PubMed]

Reiser, K. M.

P. Stoller, B.-M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, “Polarization-dependent optical second-harmonic imaging of a rat-tail tendon,” J. Biomed. Opt. 7(2), 205–214 (2002).
[CrossRef] [PubMed]

Roch, J. F.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

Roy, I.

A. V. Kachynski, A. N. Kuzmin, M. Nyk, I. Roy, and P. N. Prasad, “Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine,” J. Phys. Chem. C 112(29), 10721–10724 (2008).
[CrossRef]

Rubenchik, A. M.

P. Stoller, B.-M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, “Polarization-dependent optical second-harmonic imaging of a rat-tail tendon,” J. Biomed. Opt. 7(2), 205–214 (2002).
[CrossRef] [PubMed]

So, P. T. C.

Stoller, P.

P. Stoller, B.-M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, “Polarization-dependent optical second-harmonic imaging of a rat-tail tendon,” J. Biomed. Opt. 7(2), 205–214 (2002).
[CrossRef] [PubMed]

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Tancrez, N.

E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
[CrossRef]

Tard, C.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

Treussart, F.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

Tsien, R. Y.

B. N. G. Giepmans, S. R. Adams, M. H. Ellisman, and R. Y. Tsien, “The fluorescent toolbox for assessing protein location and function,” Science 312(5771), 217–224 (2006).
[CrossRef] [PubMed]

R. M. Dickson, A. B. Cubitt, R. Y. Tsien, and W. E. Moerner, “On/off blinking and switching behaviour of single molecules of green fluorescent protein,” Nature 388(6640), 355–358 (1997).
[CrossRef] [PubMed]

Vellekoop, I. M.

Wang, L.

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47(2), 131–146 (1995).
[CrossRef] [PubMed]

Webb, W. W.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Welch, A. J.

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[CrossRef]

Wolf, J. P.

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Wolf, J.-P.

Wu, D.

P. Pantazis, J. Maloney, D. Wu, and S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

Xuan, L. L.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

Yi, T.

E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
[CrossRef]

Zheng, L.

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47(2), 131–146 (1995).
[CrossRef] [PubMed]

Zyss, J.

E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
[CrossRef]

Appl. Opt.

Appl. Phys. B

L. Bonacina, Y. Mugnier, F. Courvoisier, R. Le Dantec, J. Extermann, Y. Lambert, V. Boutou, C. Galez, and J. P. Wolf, “Polar Fe(IO3)(3) nanocrystals as local probes for nonlinear microscopy,” Appl. Phys. B 87(3), 399–403 (2007).
[CrossRef]

Appl. Phys. Lett.

L. L. Xuan, S. Brasselet, F. Treussart, J. F. Roch, F. Marquier, D. Chauvat, S. Perruchas, C. Tard, and T. Gacoin, “Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters,” Appl. Phys. Lett. 89(12), 121118 (2006).
[CrossRef]

Biomaterials

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes,” Biomaterials 31(8), 2272–2277 (2010).
[CrossRef] [PubMed]

Chem. Mater.

M. T. Buscaglia, V. Buscaglia, and R. Alessio, “Coating of BaCO3 Crystals with TiO2:Versatile Approach to the Synthesis of BaTiO3 Tetragonal Nanoparticles,” Chem. Mater. 19(4), 711–718 (2007).
[CrossRef]

Chem. Phys. Lett.

E. Delahaye, N. Tancrez, T. Yi, I. Ledoux, J. Zyss, S. Brasselet, and R. Clement, “Second harmonic generation from individual hybrid MnPS3-based nanoparticles investigated by nonlinear microscopy,” Chem. Phys. Lett. 429(4-6), 533–537 (2006).
[CrossRef]

Colloids Surf. B Biointerfaces

G. Ciofani, S. Danti, S. Moscato, L. Albertazzi, D. D’Alessandro, D. Dinucci, F. Chiellini, M. Petrini, and A. Menciassi, “Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine,” Colloids Surf. B Biointerfaces 76(2), 535–543 (2010).
[CrossRef] [PubMed]

Comput. Methods Programs Biomed.

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47(2), 131–146 (1995).
[CrossRef] [PubMed]

IEEE J. Quantum Electron.

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[CrossRef]

J. Biomed. Opt.

P. Stoller, B.-M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, “Polarization-dependent optical second-harmonic imaging of a rat-tail tendon,” J. Biomed. Opt. 7(2), 205–214 (2002).
[CrossRef] [PubMed]

J. Phys. Chem. C

A. V. Kachynski, A. N. Kuzmin, M. Nyk, I. Roy, and P. N. Prasad, “Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine,” J. Phys. Chem. C 112(29), 10721–10724 (2008).
[CrossRef]

Nat. Biotechnol.

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

Nat. Methods

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[CrossRef] [PubMed]

Nature

R. M. Dickson, A. B. Cubitt, R. Y. Tsien, and W. E. Moerner, “On/off blinking and switching behaviour of single molecules of green fluorescent protein,” Nature 388(6640), 355–358 (1997).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Phys. Rev. Lett.

Y. Pu, R. Grange, C.-L. Hsieh, and D. Psaltis, “Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation,” Phys. Rev. Lett. 104(20), 207402 (2010).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

P. Pantazis, J. Maloney, D. Wu, and S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

Proc. SPIE

C.-L. Hsieh, R. Grange, Y. Pu, and D. Psaltis, “Characterization of the cytotoxicity and imaging properties of second-harmonic nanoparticles,” Proc. SPIE 7759, 77590T, 77590T-6 (2010).
[CrossRef]

Rep. Prog. Phys.

B. B. Das, F. Liu, and R. R. Alfano, “Time-resolved fluorescence and photon migration studies in biomedical and model random media,” Rep. Prog. Phys. 60(2), 227–292 (1997).
[CrossRef]

Science

E. Gratton, “Applied physics. Deeper tissue imaging with total detection,” Science 331(6020), 1016–1017 (2011).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

B. N. G. Giepmans, S. R. Adams, M. H. Ellisman, and R. Y. Tsien, “The fluorescent toolbox for assessing protein location and function,” Science 312(5771), 217–224 (2006).
[CrossRef] [PubMed]

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Figures (6)

Fig. 1
Fig. 1

In vitro sample for SHG imaging. (a) Sample diagram (b) Scanning confocal imaging of 300 nm SHRIMPs embedded 120 μm below an in vitro mouse tail tissue. (The pixel sizes are x and y = 1.52 μm, z = 168 nm).

Fig. 2
Fig. 2

SHG confocal section images (x-y plane) of 300 nm SHRIMPs with (a) no tissue, (b) 20 μm (c) 120 μm of in vitro tissue. Scale bar of 2 μm.

Fig. 3
Fig. 3

Lin-log plot of the averaged signal-to-noise ratio from several 300 nm SHRIMPs located under in vitro tissue of different thicknesses.

Fig. 4
Fig. 4

SHG confocal section images (x-y plane) of (a) 100 nm SHRIMPs under 50 μm of in vitro tissue (the pixel sizes are x and y = 138 nm) and (b) 300 nm SHRIMPs under 120 um of tissue (the pixel sizes are x and y = 168 nm).

Fig. 5
Fig. 5

In vivo sample for SHG imaging. (a) Sample diagram (b) Scanning confocal imaging of SHRIMPs embedded 100 μm below a mouse tail tissue. (The pixel sizes are x and y = 379 nm, z = 881 nm). The arrows show the same SHRIMPs on both views.

Fig. 6
Fig. 6

Lin-log plot of the simulation results (data points) of the power detected from SHRIMP versus the thickness of the mouse tail tissue. Both simulated curves are fitted with a single exponential (solid lines). The red and blue vertical lines show the depth for which it is possible to experimentally detect 100 nm and 300 nm SHRIMP respectively.

Tables (1)

Tables Icon

Table 1 Tissue parameters used in the Monte-Carlo simulation.

Metrics