We report on a novel method for detecting DNA hybridization, based on the p
recipitation of silver on gold nanoparticle tags and a subsequent electroch
emical stripping detection of the dissolved silver. Such coupling of a nano
particle-promoted silver precipitation with the remarkable sensitivity of s
tripping metal analysis offers a dramatic enhancement of the hybridization
response. An efficient magnetic isolation of the duplex is used for discrim
inating against nonhybridized DNA, including an excess of mismatched oligon
ucleotides. The new silver-enhanced colloidal gold stripping detection stra
tegy holds great promise for the detection of DNA hybridization and represe
nts an attractive alternative to indirect optical affinity assays of nuclei
c acids and other biomolecules.