Surface-Enhanced Raman Spectroscopy for DNA Detection by Nanoparticle Assembly onto Smooth Metal Films

A simple, sensitive, and reproducible sensing technique is described for the unambiguous detection of unlabeled single-stranded DNA by surface-enhanced Raman spectroscopy (SERS). By self-assembling probe-tethered Ag nanoparticles to a moderately smooth Ag film using the complementary target species, electromagnetic "hot spots" are created which strongly enhance the Raman signal of the species present in the hot spot. These species can include a Raman label (a molecule with a very large Raman cross-section) that dominates the spectrum and generates highly reproducible signals. The self-assembly process does not take place in the absence of the target species. Consequently, a strong SERS signal is observed only in the presence of the target. The SERS signal was also absent in the presence of noncomplementary species. AFM analysis indicates that strong SERS signal intensity arises from only a few surface-bound nanoparticles which generate an enhancement factor ∼105−106 greater than the metal film alone. Notably, this nanoparticle−film DNA detection method does not require any chemical deposition of silver to read out the SERS spectrum from the surface-bound labels.