Direct imaging of DNA motif sequences with encoded nanoparticles

We present a method for encoded tagging and imaging of short nucleic acid motif chains (oligomotifs) using selective hybridization of heterogeneous Au nanoparticles (Au-NP). The resulting encoded NP string is thus representative of the underlying motif sequence. As the NPs are much more massive than the motifs, the motif chain order can be directly observed using scanning electron microscopy. Using this technique we demonstrate direct sequencing of oligomotifs in single DNA molecules consisting of four 100-nt motif chains tagged with four different types of NPs. The method outlined is a precursor for a high density direct sequencing technology.