Single-mismatch detection using gold-quenched fluorescent oligonucleotides

Here we describe a hybrid material composed of a single-stranded DNA (ssDNA ) molecule, a 1.4 nm diameter gold nanoparticle, and a fluorophore that is highly quenched by the nanoparticle through a distance-dependent process. T he fluorescence of this hybrid molecule increases by a factor of as much as several thousand as it binds to a complementary ssDNA. We show that this c omposite molecule is a different type of molecular beacon with a sensitivit y enhanced up to 100-fold. In competitive hybridization assays, the ability to detect singlemismatch is eightfold greater with this probe than with ot her molecular beacons.