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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 3, Iss. 8 — Aug. 1, 2012
  • pp: 1914–1923
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Multispectral nanoparticle contrast agents for true-color spectroscopic optical coherence tomography

You Leo Li, Kevin Seekell, Hsiangkuo Yuan, Francisco E. Robles, and Adam Wax  »View Author Affiliations


Biomedical Optics Express, Vol. 3, Issue 8, pp. 1914-1923 (2012)
http://dx.doi.org/10.1364/BOE.3.001914


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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

1. Introduction

2. Instrumentation and materials

Our device setup is based on a parallel Fourier-domain OCT (pfdOCT) system, which uses an imaging spectrograph that allows simultaneous detection of multiple spectrograms in parallel [6

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]

]. In this particular system, a super-continuum laser source (Fianium, SC450) is used, where light from the laser source is filtered to produce a center wavelength of 575 nm and a bandwidth of 240 nm. The filtered light is input to the pfdOCT system, which is based on a Michelson interferometer with the addition of a 4-f imaging system (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.
) [7

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]

]. Here, light from the source is collimated by lens, L1, and then focused on one axis by a cylindrical lens, L2. L3 and L4 are used to form a line of illumination on the sample and reference arm, respectively. The scattered light returned from the sample is combined with the reflected light from the reference arm at the beam-splitter and imaged onto the entrance slit of the spectrograph. With this setup, up to 400 interferograms, limited by the CCD and beam size, are sampled in parallel. An axial resolution of 1.2 µm and a transverse resolution of 6.9 µm were determined experimentally.

Data collected by the CCD are processed with the DW method, which is a bilinear processing approach that produces spatially resolved spectroscopic information with high resolution in both the spatial and spectral domains [8

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. Express 17(8), 6799–6812 (2009). [CrossRef] [PubMed]

]. In this method, two short-time Fourier transforms (STFTs) are computed, one using a wide spectral window (Δkw = 0.907 µm) and another using a narrow spectral window (Δkw = 0.016 µm). The two resulting time-frequency distributions (TFDs) are then multiplied on a point-by-point basis, forming a TFD with high resolutions in both domains. Thus, the DW method avoids the trade-off between spatial and spectral resolutions that is associated with the use of a single STFT and approaches the high resolution seen for Cohen’s bilinear distributions (e.g., the Wigner distribution) as representations of time frequency distributions. We have shown that this method is equivalent to probing the Wigner distribution of the scattered sample field with two orthogonal windows that independently adjust the spatial and spectral resolutions [8

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. Express 17(8), 6799–6812 (2009). [CrossRef] [PubMed]

]. METRiCs OCT, which utilizes the DW method, has been applied to produce true-color, quantitative, tomographic images of an in vivo rat dorsal skin fold window chamber model [5

5. F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics 5(12), 744–747 (2011). [CrossRef]

]. Quantification of hemoglobin oxygen saturation levels of the vasculature was also demonstrated [4

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

].

The nanoparticles used in this study are gold nanospheres (GNS, BBInternational, 60 ± 3 nm) and gold nanorods (GNR). These nanoparticles have been extensively studied in drug delivery [9

9. B. Duncan, C. Kim, and V. M. Rotello, “Gold nanoparticle platforms as drug and biomacromolecule delivery systems,” J. Control. Release 148(1), 122–127 (2010). [CrossRef] [PubMed]

] or gene delivery [10

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]

], and do not exhibit cytotoxicity with proper polymer coating [11

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 Nano 2(12), 2481–2488 (2008). [CrossRef] [PubMed]

]. The GNS has an extinction peak at 535 nm in deionized water. The synthesis of nanorods follows the standard seed-mediated method [12

12. K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods 56(2), 310–316 (2012). [CrossRef] [PubMed]

]. Two batches of GNR were used. The aspect ratio of the first batch of rods is manually measured from TEM images of 110 nanorods to be 1.55 ± 0.26, with the longitudinal axes having the size of 55.5 ± 10.2 nm, and the transverse axes 36.2 ± 7.2 nm; the aspect ratio of the second batch is 1.48 ± 0.27, with the longitudinal axes being 57.6 ± 11.4 nm and the transverse axes being 39.6 ± 8.2 nm. Both batches of GNR have an extinction peak at 603 nm in deionized water.

3. Experimental methods and results

3.1. Concentration measurement

To demonstrate the limits of detection of these nanoparticles using METRiCS OCT, various concentrations of the nanoparticles are prepared in a solvent of deionized water (DI)/glycerol (vol/vol = 1:9, and refractive index n = 1.461). Glycerol is use here to increase the viscosity of solvent and hence minimize the potential of fringe washout effects induced by the Brownian motion of the nanoparticles.

For the measurement of nanoparticle extinction, we use a sample container composed of one coverslip (top) and one silver-coated coverslip (bottom), separated with a spacer of thickness L = 120 μm, which is also the thickness of the nanoparticle colloid. Data are collected with our pfdOCT system and then processed with the DW method.

The concentrations of the nanoparticles are calculated by first computing the extinction coefficientsμ(λ), from the Beer-Lambert law:

μ(λ)=1Lln(I(λ)I0(λ))
(1)

where I0(λ) and I(λ) are the reflected spectra from a sample containing solvent only (control sample) and the spectra from the sample containing nanoparticles, respectively. For each of the samples, we analyzed the absorption profiles of 128 distinct spatial locations obtained from two separate acquisitions (i.e. B-scans), each with a 20 ms exposure. Then an average absorption spectrum was computed. The extinction coefficients are expressed in terms of the concentration and the molar extinction coefficients of the nanoparticles:

μ=Cε(λ)/log10(e)
(2)

in which C is the concentration of the nanoparticles and ε(λ) is the extinction spectrum of the particles.

Note that the molar extinction coefficients, ε, are independent of the path length and concentration. Figure 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.
shows the extinction spectra obtained with our method along with the spectra measured with a UV-Vis spectrometer. As the figure shows, the spectra obtained with both methods are in excellent agreement, where the GNS and GNR in DI/glycerol exhibit resonance peaks at 550 nm and 620 nm, respectively. The NPs are mostly absorbing, so GNS should appear red and GNR should appear blue when observed in a transmission mode measurement.

The limits of detection (LODs) are represented by the average standard deviations, which are 60.9 pM for GNS and 0.5 nM for GNR.

3.2. Tissue phantom experiments

The resulting true-color OCT images are shown in Fig. 4(d) and (e). The results indicate that nanoparticles provide color contrast even when no significant intensity contrast can be observed. The blue color is produced by GNR, and the red is produced by GNS. Therefore, different regions are differentiable with a simple visual inspection. In addition, the color of the scattered light from the phantom within and beneath the layer with nanoparticles agrees with the results of spectral measurements in Fig. 2.

Next, we quantify the spatially resolved spectroscopic information. In order to do this, the spectra corresponding to two slices at the same depth of the sample are used. One spectrum (noted as INP) is from the region doped with nanoparticles and the other spectrum (noted asIcontrol) is from the region without nanoparticles. The spectra can be represented as

INP(λ)=I0(λ)exp((μNP(λ)+μphantom(λ))L)S(λ)Icontrol(λ)=I0(λ)exp(μphantom(λ)L)S(λ)
(3)

in which I0 is the source spectrum; μNP and μphantom are the extinction coefficient of the nanoparticles and the phantom (without nanoparticles), respectively; and S(λ) is the wavelength dependent backscattering term. Note that because the backscattering term varies more slowly than the attenuation term, S(λ) may be assumed to be approximately equal for the NPs and the phantom. Still, a more accurate result is obtained if the spectra are obtained from depths corresponding to regions below the nanoparticle layer, where the backscattering due to the phantom accurately accounts for the scattering by agar and TiO2. Thus, the extinction coefficient of the nanoparticles may be expressed as

μNP(λ)=1Llog(INP(λ)Icontrol(λ))
(4)

To demonstration the fidelity of the spectral information, data from slices more than 200 μm deep in the GNS and the GNR samples are presented. A typical slice has the dimension of 55 μm (axial) × 2.6 mm (lateral). The averaged backscattering spectra from several slices (IControl(λ), INP(λ), and μNP(λ)) are shown in 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.
. As shown, the extinction spectra (green curves) obtained with our method are in good agreement with those shown in Fig. 2.

3.3. Cell experiments

Cell experiments have also been conducted as a proof of concept for using nanoparticles as colorimetric contrast agents within cells using the METRiCS OCT system. In order to deliver the nanoparticles into cells, the nanoparticles are first coated with polymers and then functionalized with cell penetrating peptides. After that, the nanoparticles are delivered to cells which are then integrated into three-dimensional constructs [14

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]

] and imaged with the METRiCS OCT system.

For the coating of the particles, thiol-terminated polyethylene glycol (SH-PEG, MW 5000, Sigma Aldrich) is added to the colloid of GNS, and then kept at room temperature for 2 hours prior to centrifuge washing to remove excessive PEG from the solution. Polystyrene sulfonate (PSS, MW 70,000, Sigma Aldrich) is added to GNR colloid and kept for 24 hours prior to centrifuge to remove excess. The zeta-potential of PSS coated GNRs is measured to be −43 mV, indicating high stability. After characterization, cysteine-terminated trans-activating transcriptional activator (cysteine-TAT), a type of cell penetrating peptide, is added to the colloid, and then kept for 24 hours prior to centrifuge wash, in order to functionalize the particles to facilitate cellular uptake [15

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]

].

The coated and functionalized particles are added to the flasks containing 85% confluent BT549 cells. The particle concentrations are 2 nM for GNS and 0.32 nM for GNR. These concentrations have been carefully chosen so as to produce strong color contrast while keeping the cells alive. After 24 hours of incubation, the cells are washed with phosphate buffered saline (PBS) to remove excessive particles in the medium and then trypsinized and centrifuged. A typical measured survival rate of these cells is 89%. Hyperspectral darkfield images [12

12. K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods 56(2), 310–316 (2012). [CrossRef] [PubMed]

] and phase contrast images (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.
) of the cells incubated with NPs, taken prior to trypsinization, show the co-localization of the cells and particles, indicating the cellular uptake of the particles. 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.

The cells are spun down in a centrifuge to yield a numerical density of 108 cells/mL and then mixed with low gelling point agar according to an established method [14

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]

]. As shown in 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.
, the cells are then made into three-dimensional cell constructs. The cells with GNS are shaped to be a layer of 100 μm thick, embedded into the TiO2 phantom and then imaged. The cells with GNR are made into a construct thicker than the axial field of view of our system, and then imaged. In addition, a control sample made with cells without nanoparticles is also imaged.

As shown in Fig. 7, the nanoparticles provide additional contrast for identifying cellular regions. In addition, as shown in 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.
, extinction spectra can also be extracted from more than 200 μm deep in the GNS and GNR sample in the same manner as described in the tissue experiment section, providing additional specificity. As shown in Fig. 8(a) and (b), the extinction peaks for GNR and GNS within the cells are 606 nm and 537 nm, respectively. As shown in Fig. 8(c), spectra from the sample containing cells without any NPs exhibit decreasing scattering with wavelength, the typical extinction trend seen for cell features.

4. Discussion

As shown, METRiCS OCT system has the capability to extract the extinction spectra of multiple species of gold nanoparticles to produce colorimetric and spectral contrast in three dimensions. The analysis presented here shows that it can discriminate concentrations of nanoparticles down to the sub-nanomolar level. In addition, the high resolution and intuitive true color display of our system makes it a potentially useful functional imaging modality for detecting nanoparticle contrast agents.

The extinction peaks of the GNR and GNS in the tissue phantom and cell experiments, as shown in Fig. 5 and Fig. 8, respectively, are red shifted from the corresponding peak locations with DI water as the solvent. This red shift is expected due to changes in the dielectric environment of the NPs [16

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]

]. In addition, the yellow color seen below the cell layer in Fig. 7(g), as well as the extinction spectra of cells without NPs shown in Fig. 8, agrees with the general optical extinction properties of cells.

5. Conclusion

We applied METRiCS OCT to measure the extinction spectra of plasmonic nanoparticles at various concentrations for potential in vivo applications. As previously mentioned, nanoparticles are of great interest to the biomedical community. Their drug loading capability, potential for active cellular targeting, and high biocompatibility make them an ideal multifunctional platform for simultaneous molecular contrast imaging and drug delivery. As demonstrated in this work, METRiCS OCT provides a unique method to identify different types of nanoparticles based on their optical absorption properties potentially for tumor cell imaging, monitoring treatment therapies (e.g. using photothermal therapies). Our method has high spatial and spectral resolution, high sensitivity, and can also provide real time information, which are important features for in vivo applications.

In order to implement molecular imaging with this approach, this work must be extended to include the bioconjugation of these nanoparticles to active-targeting antibodies, which can target molecules such as cell receptors. The utilization of their distinct absorption spectra makes it possible to achieve multiplexed molecular detection in vivo [17

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]

].

Acknowledgments

The authors acknowledge Hillel Price and Sanghoon Kim for their assistance in the preparation of silvered coverslips, and Jun Wang for her help in cell culture. This work is funded by grants from the National Institutes of Health (NCI 1 R01 CA138594-01).

References and Links

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. Express 14(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. Express 1(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. Photonics 5(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. Express 17(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. Release 148(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 Nano 2(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,” Methods 56(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. Express 19(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]

OCIS Codes
(110.4500) Imaging systems : Optical coherence tomography
(300.1030) Spectroscopy : Absorption
(160.4236) Materials : Nanomaterials

ToC Category:
Optical Coherence Tomography

History
Original Manuscript: June 7, 2012
Revised Manuscript: July 18, 2012
Manuscript Accepted: July 18, 2012
Published: July 20, 2012

Virtual Issues
BIOMED 2012 (2012) Biomedical Optics Express

Citation
You Leo Li, Kevin Seekell, Hsiangkuo Yuan, Francisco E. Robles, and Adam Wax, "Multispectral nanoparticle contrast agents for true-color spectroscopic optical coherence tomography," Biomed. Opt. Express 3, 1914-1923 (2012)
http://www.opticsinfobase.org/boe/abstract.cfm?URI=boe-3-8-1914


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References

  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]

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