A method for analyzing combinatorial DNA arrays using oligonucleotide-modif
ied gold nanoparticle probes and a conventional flatbed scanner is describe
d here. Labeling oligonucleotide targets with nanoparticle rather than fluo
rophore probes substantially alters the melting profiles of the target; fro
m an array substrate. This difference permits the discrimination of an olig
onucleotide sequence from targets with single nucleotide mismatches with a
selectivity that is over three times that observed for fluorophore-labeled
targets. In addition, when coupled with a signal amplification method based
on nanoparticle-promoted reduction of silver(I), the sensitivity of this s
canometric array detection system exceeds that of the analogous fluorophore
system by two orders of magnitude.