Optical detection of single non-absorbing molecules using the surface   plasmon of a gold nanorod
  Current optical detection schemes for single molecules require light absorption, either to produce fluorescence or direct absorption signals. This severely limits the range of molecules that can be detected, because most molecules are purely refractive. Metal nanoparticles or dielectric resonators detect non-absorbing molecules by a resonance shift in response to a local perturbation of the refractive index, but neither has reached single-protein sensitivity. The most sensitive plasmon sensors to date detect single molecules only when the plasmon shift is amplified by a highly polarizable label or by a localized precipitation reaction on the particle's surface. Without amplification, the sensitivity only allows for the statistical detection of single molecules. Here we demonstrate plasmonic detection of single molecules in realtime, without the need for labeling or amplification. We monitor the plasmon resonance of a single gold nanorod with a sensitive photothermal assay and achieve a ~ 700-fold increase in sensitivity compared to state-of-the-art plasmon sensors. We find that the sensitivity of the sensor is intrinsically limited due to spectral diffusion of the SPR. We believe this is the first optical technique that detects single molecules purely by their refractive index, without any need for photon absorption by the molecule. The small size, bio-compatibility and straightforward surface chemistry of gold nanorods may open the way to the selective and local detection of purely refractive proteins in live cells. 
Peter Zijlstra, Pedro M.R. Paulo, and Michel Orrit
physics.chem-ph physics.bio-ph physics.optics