Abstract

We have recently developed a novel dual window scheme for processing spectroscopic OCT images to provide spatially resolved true color imaging of chromophores in scattering samples. Here we apply this method to measure the extinction spectra of plasmonic nanoparticles at various concentrations for potential in vivo applications. We experimentally demonstrate sub-nanomolar sensitivity in the measurement of nanoparticle concentrations, and show that colorimetric imaging with multiple species of nanoparticles produces enhanced contrast for spectroscopic OCT in both tissue phantom and cell studies.

© 2012 OSA

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  1. M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
    [CrossRef] [PubMed]
  2. A. L. Oldenburg, M. N. Hansen, D. A. Zweifel, A. Wei, and S. A. Boppart, “Plasmon-resonant gold nanorods as low backscattering albedo contrast agents for optical coherence tomography,” Opt. Express14(15), 6724–6738 (2006).
    [CrossRef] [PubMed]
  3. A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
    [CrossRef] [PubMed]
  4. F. E. Robles, S. Chowdhury, and A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Biomed. Opt. Express1(1), 310–317 (2010).
    [CrossRef] [PubMed]
  5. F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
    [CrossRef]
  6. R. N. Graf, W. J. Brown, and A. Wax, “Parallel frequency-domain optical coherence tomography scatter-mode imaging of the hamster cheek pouch using a thermal light source,” Opt. Lett.33(12), 1285–1287 (2008).
    [CrossRef] [PubMed]
  7. A. Wax, C. Yang, R. R. Dasari, and M. S. Feld, “Measurement of angular distributions by use of low-coherence interferometry for light-scattering spectroscopy,” Opt. Lett.26(6), 322–324 (2001).
    [CrossRef] [PubMed]
  8. F. Robles, R. N. Graf, and A. Wax, “Dual window method for processing spectroscopic optical coherence tomography signals with simultaneously high spectral and temporal resolution,” Opt. Express17(8), 6799–6812 (2009).
    [CrossRef] [PubMed]
  9. B. Duncan, C. Kim, and V. M. Rotello, “Gold nanoparticle platforms as drug and biomacromolecule delivery systems,” J. Control. Release148(1), 122–127 (2010).
    [CrossRef] [PubMed]
  10. A. K. Salem, P. C. Searson, and K. W. Leong, “Multifunctional nanorods for gene delivery,” Nat. Mater.2(10), 668–671 (2003).
    [CrossRef] [PubMed]
  11. A. P. Leonov, J. Zheng, J. D. Clogston, S. T. Stern, A. K. Patri, and A. Wei, “Detoxification of gold nanorods by treatment with polystyrenesulfonate,” ACS Nano2(12), 2481–2488 (2008).
    [CrossRef] [PubMed]
  12. K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
    [CrossRef] [PubMed]
  13. A. Curatolo, B. F. Kennedy, and D. D. Sampson, “Structured three-dimensional optical phantom for optical coherence tomography,” Opt. Express19(20), 19480–19485 (2011).
    [CrossRef] [PubMed]
  14. M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
    [CrossRef] [PubMed]
  15. H. Yuan, A. M. Fales, and T. Vo-Dinh, “TAT peptide-functionalized gold nanostars: enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance,” J. Am. Chem. Soc.134(28), 11358–11361 (2012).
    [PubMed]
  16. A. C. Curry, M. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).
    [CrossRef] [PubMed]
  17. K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
    [CrossRef] [PubMed]

2012

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

H. Yuan, A. M. Fales, and T. Vo-Dinh, “TAT peptide-functionalized gold nanostars: enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance,” J. Am. Chem. Soc.134(28), 11358–11361 (2012).
[PubMed]

2011

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
[CrossRef]

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

A. Curatolo, B. F. Kennedy, and D. D. Sampson, “Structured three-dimensional optical phantom for optical coherence tomography,” Opt. Express19(20), 19480–19485 (2011).
[CrossRef] [PubMed]

2010

2009

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
[CrossRef] [PubMed]

F. Robles, R. N. Graf, and A. Wax, “Dual window method for processing spectroscopic optical coherence tomography signals with simultaneously high spectral and temporal resolution,” Opt. Express17(8), 6799–6812 (2009).
[CrossRef] [PubMed]

2008

R. N. Graf, W. J. Brown, and A. Wax, “Parallel frequency-domain optical coherence tomography scatter-mode imaging of the hamster cheek pouch using a thermal light source,” Opt. Lett.33(12), 1285–1287 (2008).
[CrossRef] [PubMed]

A. P. Leonov, J. Zheng, J. D. Clogston, S. T. Stern, A. K. Patri, and A. Wei, “Detoxification of gold nanorods by treatment with polystyrenesulfonate,” ACS Nano2(12), 2481–2488 (2008).
[CrossRef] [PubMed]

A. C. Curry, M. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).
[CrossRef] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

2006

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

A. L. Oldenburg, M. N. Hansen, D. A. Zweifel, A. Wei, and S. A. Boppart, “Plasmon-resonant gold nanorods as low backscattering albedo contrast agents for optical coherence tomography,” Opt. Express14(15), 6724–6738 (2006).
[CrossRef] [PubMed]

2003

A. K. Salem, P. C. Searson, and K. W. Leong, “Multifunctional nanorods for gene delivery,” Nat. Mater.2(10), 668–671 (2003).
[CrossRef] [PubMed]

2001

Au, L.

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

Boppart, S. A.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
[CrossRef] [PubMed]

A. L. Oldenburg, M. N. Hansen, D. A. Zweifel, A. Wei, and S. A. Boppart, “Plasmon-resonant gold nanorods as low backscattering albedo contrast agents for optical coherence tomography,” Opt. Express14(15), 6724–6738 (2006).
[CrossRef] [PubMed]

Brown, W. J.

Chen, J.

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

Chilkoti, A.

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

Chowdhury, S.

Clogston, J. D.

A. P. Leonov, J. Zheng, J. D. Clogston, S. T. Stern, A. K. Patri, and A. Wei, “Detoxification of gold nanorods by treatment with polystyrenesulfonate,” ACS Nano2(12), 2481–2488 (2008).
[CrossRef] [PubMed]

Crow, M.

A. C. Curry, M. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).
[CrossRef] [PubMed]

Crow, M. J.

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Curatolo, A.

Curry, A. C.

A. C. Curry, M. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).
[CrossRef] [PubMed]

Dasari, R. R.

Duncan, B.

B. Duncan, C. Kim, and V. M. Rotello, “Gold nanoparticle platforms as drug and biomacromolecule delivery systems,” J. Control. Release148(1), 122–127 (2010).
[CrossRef] [PubMed]

Fales, A. M.

H. Yuan, A. M. Fales, and T. Vo-Dinh, “TAT peptide-functionalized gold nanostars: enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance,” J. Am. Chem. Soc.134(28), 11358–11361 (2012).
[PubMed]

Feld, M. S.

Graf, R. N.

Grant, G.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
[CrossRef]

Hansen, M. N.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
[CrossRef] [PubMed]

A. L. Oldenburg, M. N. Hansen, D. A. Zweifel, A. Wei, and S. A. Boppart, “Plasmon-resonant gold nanorods as low backscattering albedo contrast agents for optical coherence tomography,” Opt. Express14(15), 6724–6738 (2006).
[CrossRef] [PubMed]

Hartland, G. V.

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

Hu, M.

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

Izatt, J. A.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Kennedy, B. F.

Kim, C.

B. Duncan, C. Kim, and V. M. Rotello, “Gold nanoparticle platforms as drug and biomacromolecule delivery systems,” J. Control. Release148(1), 122–127 (2010).
[CrossRef] [PubMed]

Leong, K. W.

A. K. Salem, P. C. Searson, and K. W. Leong, “Multifunctional nanorods for gene delivery,” Nat. Mater.2(10), 668–671 (2003).
[CrossRef] [PubMed]

Leonov, A. P.

A. P. Leonov, J. Zheng, J. D. Clogston, S. T. Stern, A. K. Patri, and A. Wei, “Detoxification of gold nanorods by treatment with polystyrenesulfonate,” ACS Nano2(12), 2481–2488 (2008).
[CrossRef] [PubMed]

Li, X.

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

Li, Z.-Y.

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

Marinakos, S.

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

Marquez, M.

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

Oldenburg, A. L.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
[CrossRef] [PubMed]

A. L. Oldenburg, M. N. Hansen, D. A. Zweifel, A. Wei, and S. A. Boppart, “Plasmon-resonant gold nanorods as low backscattering albedo contrast agents for optical coherence tomography,” Opt. Express14(15), 6724–6738 (2006).
[CrossRef] [PubMed]

Ostrander, J.

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

Patri, A. K.

A. P. Leonov, J. Zheng, J. D. Clogston, S. T. Stern, A. K. Patri, and A. Wei, “Detoxification of gold nanorods by treatment with polystyrenesulfonate,” ACS Nano2(12), 2481–2488 (2008).
[CrossRef] [PubMed]

Price, H.

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

Ralston, T. S.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
[CrossRef] [PubMed]

Robles, F.

Robles, F. E.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
[CrossRef]

F. E. Robles, S. Chowdhury, and A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Biomed. Opt. Express1(1), 310–317 (2010).
[CrossRef] [PubMed]

Rotello, V. M.

B. Duncan, C. Kim, and V. M. Rotello, “Gold nanoparticle platforms as drug and biomacromolecule delivery systems,” J. Control. Release148(1), 122–127 (2010).
[CrossRef] [PubMed]

Salem, A. K.

A. K. Salem, P. C. Searson, and K. W. Leong, “Multifunctional nanorods for gene delivery,” Nat. Mater.2(10), 668–671 (2003).
[CrossRef] [PubMed]

Sampson, D. D.

Searson, P. C.

A. K. Salem, P. C. Searson, and K. W. Leong, “Multifunctional nanorods for gene delivery,” Nat. Mater.2(10), 668–671 (2003).
[CrossRef] [PubMed]

Seekell, K.

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

Skala, M. C.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Stern, S. T.

A. P. Leonov, J. Zheng, J. D. Clogston, S. T. Stern, A. K. Patri, and A. Wei, “Detoxification of gold nanorods by treatment with polystyrenesulfonate,” ACS Nano2(12), 2481–2488 (2008).
[CrossRef] [PubMed]

Vo-Dinh, T.

H. Yuan, A. M. Fales, and T. Vo-Dinh, “TAT peptide-functionalized gold nanostars: enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance,” J. Am. Chem. Soc.134(28), 11358–11361 (2012).
[PubMed]

Wax, A.

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
[CrossRef]

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

F. E. Robles, S. Chowdhury, and A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Biomed. Opt. Express1(1), 310–317 (2010).
[CrossRef] [PubMed]

F. Robles, R. N. Graf, and A. Wax, “Dual window method for processing spectroscopic optical coherence tomography signals with simultaneously high spectral and temporal resolution,” Opt. Express17(8), 6799–6812 (2009).
[CrossRef] [PubMed]

R. N. Graf, W. J. Brown, and A. Wax, “Parallel frequency-domain optical coherence tomography scatter-mode imaging of the hamster cheek pouch using a thermal light source,” Opt. Lett.33(12), 1285–1287 (2008).
[CrossRef] [PubMed]

A. C. Curry, M. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).
[CrossRef] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

A. Wax, C. Yang, R. R. Dasari, and M. S. Feld, “Measurement of angular distributions by use of low-coherence interferometry for light-scattering spectroscopy,” Opt. Lett.26(6), 322–324 (2001).
[CrossRef] [PubMed]

Wei, A.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
[CrossRef] [PubMed]

A. P. Leonov, J. Zheng, J. D. Clogston, S. T. Stern, A. K. Patri, and A. Wei, “Detoxification of gold nanorods by treatment with polystyrenesulfonate,” ACS Nano2(12), 2481–2488 (2008).
[CrossRef] [PubMed]

A. L. Oldenburg, M. N. Hansen, D. A. Zweifel, A. Wei, and S. A. Boppart, “Plasmon-resonant gold nanorods as low backscattering albedo contrast agents for optical coherence tomography,” Opt. Express14(15), 6724–6738 (2006).
[CrossRef] [PubMed]

Wilson, C.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
[CrossRef]

Xia, Y.

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

Yang, C.

Yuan, H.

H. Yuan, A. M. Fales, and T. Vo-Dinh, “TAT peptide-functionalized gold nanostars: enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance,” J. Am. Chem. Soc.134(28), 11358–11361 (2012).
[PubMed]

Zheng, J.

A. P. Leonov, J. Zheng, J. D. Clogston, S. T. Stern, A. K. Patri, and A. Wei, “Detoxification of gold nanorods by treatment with polystyrenesulfonate,” ACS Nano2(12), 2481–2488 (2008).
[CrossRef] [PubMed]

Zweifel, D. A.

ACS Nano

A. P. Leonov, J. Zheng, J. D. Clogston, S. T. Stern, A. K. Patri, and A. Wei, “Detoxification of gold nanorods by treatment with polystyrenesulfonate,” ACS Nano2(12), 2481–2488 (2008).
[CrossRef] [PubMed]

Biomed. Opt. Express

Chem. Soc. Rev.

M. Hu, J. Chen, Z.-Y. Li, L. Au, G. V. Hartland, X. Li, M. Marquez, and Y. Xia, “Gold nanostructures: engineering their plasmonic properties for biomedical applications,” Chem. Soc. Rev.35(11), 1084–1094 (2006).
[CrossRef] [PubMed]

J. Am. Chem. Soc.

H. Yuan, A. M. Fales, and T. Vo-Dinh, “TAT peptide-functionalized gold nanostars: enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance,” J. Am. Chem. Soc.134(28), 11358–11361 (2012).
[PubMed]

J. Biomed. Opt.

A. C. Curry, M. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).
[CrossRef] [PubMed]

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

J. Control. Release

B. Duncan, C. Kim, and V. M. Rotello, “Gold nanoparticle platforms as drug and biomacromolecule delivery systems,” J. Control. Release148(1), 122–127 (2010).
[CrossRef] [PubMed]

J. Mater. Chem.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
[CrossRef] [PubMed]

Methods

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

Nano Lett.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Nat. Mater.

A. K. Salem, P. C. Searson, and K. W. Leong, “Multifunctional nanorods for gene delivery,” Nat. Mater.2(10), 668–671 (2003).
[CrossRef] [PubMed]

Nat. Photonics

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
[CrossRef]

Opt. Express

Opt. Lett.

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Figures (8)

Fig. 1
Fig. 1

Parallel frequency domain OCT system and sample. L = 120 µm is the thickness of the sample used in the concentration measurement. Red dashed lines and black lines show the propagation of light in two orthogonal dimensions.

Fig. 2
Fig. 2

Extinction spectra (μ) of the nanospheres and nanorods in DI/glycerol. The solid curve represents the curves obtained with METRiCS OCT (labeled as SOCT) technique, and the dashed curved is obtained from Cary 300 Bio UV-Vis Spectrometer (Agilent Technologies, Santa Clara, US). The GNS shows an extinction peak at 550 nm and the GNR shows an extinction peak at 620 nm in DI/glycerol, both red-shifted compared to the peaks seen in pure DI water. All the curves were normalized for better illustration. Note that the NPs are mostly absorbing, so GNS should appear red and GNR should appear blue when observed in a transmission mode measurement. The discrepancy in the width of the spectra is caused by (1) the lower SNR in the short wavelength and long wavelength portions of the spectra, and (2) the normalization of the signal.

Fig. 3
Fig. 3

Measured concentrations of the gold nanospheres (GNS) and the gold nanorods (GNR). The error bars reflect the standard deviations obtained from 128 measurements.

Fig. 4
Fig. 4

(a): Schematic of sample structure. The tissue phantom has three layers: Intralipid/agar layer on top, NP/agar layer in the middle, and TiO2 /agar layer in the bottom. The B-scan is taken in the region in the blue rectangle. (b) and (c): Conventional OCT images of the tissue phantoms with GNR (b) and GNS (c). The regions with different species of nanoparticles are not differentiable in conventional OCT images. Yellow lines indicate the approximate position of the interfaces between regions with and without NPs. (d) and (e) True-color OCT images of the same region as shown in (b) and (c), respectively. The color contrast produced with the nanoparticles can help differentiate the regions with different NPs and the region without any NPs. The blue color (white arrow) is produced by GNR, and the red color (white arrow) is produced by GNS. Note that the concentration of GNR (6.3 nM) is higher than the concentration of GNS (2.3 nM). Also, the absorption of GNR is stronger than GNS. Therefore, color contrast starts to be visible at a lower depth in (d) than in (e).

Fig. 5
Fig. 5

Spatially resolved spectroscopic information extracted from the tissue phantom containing different species of NPs. Left: spectra from the sample containing GNR. The peak of the extinction curve (green) has a peak at 609 nm, which is shifted 6 nm from its extinction peak in DI water. Right: spectra from the sample containing GNS. The extinction peak at 545.5 nm which is shifted 10.5 nm shift from its extinction peak in DI water. All the curves are normalized for better illustration.

Fig. 6
Fig. 6

Phase contrast images (top) and hyperspectral darkfield images (bottom) of cells incubated with NPs. Left: images of cells incubated with GNR. Middle: images from cells incubated with GNS. The bright spots in (d) and (e) indicate the positions of the nanoparticles and the color indicates the peak of their scattering spectra. Right: images from the cells without GNR or GNS. Note that dark field microscopy detects scattered light, so the color of NPs in these image are different from those in images obtained with METRiCS OCT, which show the absorption of the NPs.

Fig. 7
Fig. 7

(a): Schematic of the three-dimensional cell construct. The cell construct has two parts: cell/agar construct, and TiO2 /agar as control. The B-scan is taken in the interface region indicated by the blue rectangle. (b), (c) and (d): Conventional OCT images of the B-scan. The images are taken from phantoms with GNR (b), GNS (c), and no NPs (d). (e), (f), and (g): True color OCT images of the corresponding B-scans. The color contrast produced with the nanoparticles can help differentiate the regions with cells filled with different species of NPs, as wells as from the cells without any NPs. The blue color is produced by GNR, and the red is produced by GNS.

Fig. 8
Fig. 8

Spatially resolved spectroscopic information extracted from the tissue phantoms containing different species of NPs. (a): spectra from the sample containing cells incubated with GNR. The peak of the extinction curve (green) is at 606 nm, showing a 3 nm shift from its extinction peak in DI water. (b): spectra from the sample containing cells with GNS. The extinction peak (green) is at 537.1 nm, which has a 2.1 nm shift from its extinction peak in DI water. (c): spectra from the sample containing cells without any NPs, exhibiting decreasing scattering with wavelength, the typical extinction trend seen for cell features. All curves are normalized.

Equations (4)

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μ(λ)= 1 L ln( I(λ) I 0 (λ) )
μ=Cε(λ)/ log 10 (e)
I NP (λ)= I 0 (λ)exp(( μ NP (λ)+ μ phantom (λ))L)S(λ) I control (λ)= I 0 (λ)exp( μ phantom (λ)L)S(λ)
μ NP (λ)= 1 L log( I NP (λ) I control (λ) )

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