Improving the optical contrast of backscattering signal in reflectance-based imaging with gold nanoshells

The application of gold nanoparticles as a contrast agent in optical bioimaging is well appreciated, but limited to a narrow excitation range due to its rather invariable optical resonance typically at 520 nm. Compared to gold nanoparticles, the optical response of gold nanoshells can be tuned to match the higher excitation wavelength of many promising clinical reflectance-based imaging modalities such as the optical coherence tomography (OCT). In this study, we demonstrate the tunability of gold nanoshells to improve the optical contrast of backscattering signal under confocal reflectance microscopy and OCT. The gold nanoshells were synthesized and conjugated to antibodies for in vitro demonstration of their selective optical contrast in cancer cells over normal cells under the confocal reflectance microscopy. The OCT signals from these gold nanoshells were compared to that from bare silica cores and intrinsic tissue scattering using 1% Intralipid. We have shown that gold nanoshells are able to elicit an optical contrast to discriminate between cancerous and normal cells under the confocal reflectance microscopy based on differences in molecular markers expression. Compared to bare silica core, the presence of the gold shell is able to effect a higher backscattered OCT signal with an apparent contrast over 1% Intralipid. This contrast can be made to be dependent on the molecular marker expression with antibody specificity.