Surface-enhanced Raman nanoparticle beacons based on bioconjugated gold nanocrystals and long range plasmonic coupling.

We have developed a new class of surface-enhanced Raman scattering beacons (SERS beacons) that can be turned on and off by long-range plasmonic coupling, induced by biomolecular recognition and binding events. The beacons are based on colloidal gold nanocrystals in two sizes (40 and 60 nm) and are prepared by spectral encoding with a Raman reporter molecule, functionalized with thiolated DNA probes, and stabilized and protected by low molecular weight poly(ethylene glycol)s (PEGs). The results show the SERS signal intensities increase by 40-200-fold when the nanoparticle beacons are activated by plasmonic coupling, much higher than the bright-to-dark intensity ratios reported for traditional molecular beacons. Multivalent gold nanoparticles also have exquisite specificity and are able to recognize single-base mismatches or mutations. This class of SERS nanoparticle beacons has novel mechanisms for molecular detection and signal amplification, and its long-range coupling nature raises new opportunities in developing plasmonic probes to detect proteins, cells, and intact viruses.