Magnetomotive microscopy techniques are introduced to investigate cell dynamics and biomechanics. These techniques
are based on magnetomotive transducers present in cells and optical coherence imaging techniques. In this study,
magnetomotive transducers include magnetic nanoparticles (MNPs) and fluorescently labeled magnetic microspheres,
while the optical coherence imaging techniques include integrated optical coherence (OCM)and multiphoton (MPM)
microscopy,and diffraction phase microscopy (DPM). Samples used in this study are murine macrophage cells in culture
that were incubated with magnetomotive transducers. MPMis used to visualize multifunctional microspheres based on
their fluorescence, while magnetomotive OCM detects sinusoidal displacements of the sample induced by a magnetic
field. DPM is used to image single cells at a lower frequency magnetic excitation, and with its Fourier transform light
scattering (FTLS) analysis, oscillation amplitude is obtained, indicating the relative biomechanical properties of
macrophage cells. These magnetomotive microscopy method shave potential to be used to image and measure cell
dynamics and biomechanical properties. The ability to measure and understand biomechanical properties of cells and
their microenvironments, especially for tumor cells, is of great importance and may provide insight for diagnostic and
subsequently therapeutic interventions.
Plasmon-resonant gold nanorods have been demonstrated recently as contrast agents for optical coherence
tomography (OCT). To evaluate their ability to produce contrast in a structurally heterogeneous environment,
nanorods were injected at discrete locations into an excised sample of human breast invasive ductal carcinoma. The
distribution of nanorods within the tissue was revealed using spectroscopic OCT imaging techniques, by analyzing
the evolution of the backscattered light spectrum over tissue depth. We compare a variety of signal processing
methods including spatial averaging and least-squares fitting to the a priori extinction spectrum of the nanorods,
with the goal of optimizing the detection sensitivity to the nanorods in these tissues. Because nanorods can be
conjugated with proteins specific to biomolecular targets, they may potentially be used with these imaging methods
to provide molecular contrast in human tissues.
Gold nanorods ~14 × 44nm exhibit a surface-plasmon resonance (SPR) peaked near 800nm which is dominated by
absorption, not scattering. Because biological tissues in the near-infrared wavelength regime are predominantly
scattering (high albedo), the addition of trace amounts of nanorods can be detected by their lowering of the albedo.
Albedo is a preferred measurement parameter because it is insensitive to inhomogeneities in the density of scatterers.
For optical coherence tomography (OCT) imaging applications, a related parameter called the backscattering albedo,
equal to the ratio of the backscattering coefficient to the total extinction, is introduced for detecting gold nanorods. Here
we use this parameter to investigate gold nanorods as contrast agents for optical coherence tomography (OCT).
Measurements in 2% intralipid tissue phantoms reveal a sensitivity to ~30ppm nanorods when the density of the
intralipid is randomized by 0.4% (or a fraction of 0.2). This has application toward molecular imaging using targeted
nanorods within densely scattering, inhomogeneous tissues.
Plasmon-resonant gold nanorods have outstanding potential as multifunctional agents for image-guided therapies.
Nanorods have large absorption cross sections at near-infrared (NIR) frequencies, and produce two-photon
luminescence (TPL) when excited by fs-pulsed laser irradiation. The TPL signals can be detected with single-particle
sensitivity, enabling nanorods to be imaged in vivo while passing through blood vessels at subpicomolar concentrations.
Furthermore, cells labeled with nanorods become highly susceptible to photothermal damage when irradiated at
plasmon resonance, often resulting in a dramatic blebbing of the cell membrane. However, the straightforward
application of gold nanorods for cell-specific labeling is obstructed by the presence of CTAB, a cationic surfactant
carried over from nanorod synthesis which also promotes their nonspecific uptake into cells. Careful exchange and
replacement of CTAB can be achieved by introducing oligoethyleneglycol (OEG) units capable of chemisorption onto
nanorod surfaces by in situ dithiocarbamate formation, a novel method of surface functionalization. Nanorods with a
dense coating of methyl-terminated OEG chains are shielded from nonspecific cell uptake, whereas nanorods
functionalized with folate-terminated OEG chains accumulate on the surface of tumor cells overexpressing their cognate
receptor, with subsequent delivery of photoinduced cell damage at low laser fluence.
The potential for using plasmon-resonant gold nanorods as targeted contrast agents for in vivo coherent optical imaging is investigated. Separation of the relative strengths of light scattering and absorption of plasmon-resonant nanorods are measured with a double-integrating sphere system at 774 and 1304nm. The maximum likelihood ratio is then used to test the statistical significance of optical changes observed after application of contrast agents to tissue phantoms. Gold plasmon-resonant nanorods with a longitudinal resonance near 800nm are imaged within varying concentrations of intralipid using a 101dB sensitivity, 800nm optical coherence tomography (OCT) system. We estimate the minimum OCT detectible concentration of these nanorods (ca. 15 by 45nm) within 1.1% intralipid to be 25microg/mL of gold.
Analytical theory and numerical calculations for periodic arrays of metal nanoparticles indicate resonant-like enhancement of local electromagnetic field, which can be tuned by varying a ratio of particle diameter to interparticle spacing. For Raman scattering, local field enhancements on the order of 1013 and surface-averaged field enhancements on the order of 1011 can be achieved udner optimal conditions. This is several orders of magnitude greater tan that obtaiend in disordered metal-dielectric films, and suggests a new design for engineering plasmonic substrates supporting intense and spatially well-defined field patterns, with direct applications for surface-enhanced Raman scattering (SERS), and surface-enhanced optical nonlinearities.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.