Multilayer resonant light scattering nanoshells as a novel class of nonbleaching labels for multi-marker molecular imaging

Optical molecular imaging of living tissues could potentially allow tissue characterization and disease diagnosis with high resolution, non-invasively and at a low cost. The capability to image multiple molecular targets simultaneously is particularly important. However, currently this task cannot be achieved, due to the broad spectral responses (∼80-200 nm) of current optical contrast agents, which limit the number of markers that can be used simultaneously to, typically, not more than three. Therefore, ideal nanoparticle-labels for multi-color multi-marker detection should exhibit sharp resonances, whose spectral position can be controlled. We hereby describe a new concept that utilizes resonant light-scattering spectroscopy of multi-layered metallic nanospheres to achieve the labeling of multiple targets simultaneously. Our model of light-scattering predicts that multilayered metallic-dielectric nanoshells exhibit tunable ultra-sharp resonance peaks with widths as narrow as 10 nm. By varying the materials and size ratios between different layers, the position of the resonance peaks can be easily controlled, which may enable detection of more than 10 different labels simultaneously by recording the spectra of resonant light scattering in the visible range. Conjugated with molecular probes, such as antibodies, these novel structured nanospheres may enable previously unattainable multi-label optical molecular imaging.