Single-Molecule Nanomechanical Genotyping with DNA Origami-Based Shape IDs.

ABSTRACT

Atomic force microscopy (AFM)-based nanomechanical imaging provides a sub-10-nm-resolution approach for imaging biomolecules under ambient conditions. Here we describe how to generate a set of DNA origami-based shape IDs (triangular and cross shape, with and without streptavidin) to site-specifically label target genomic DNA sequences containing two single-nucleotide polymorphisms (SNPs). Adjacent labeling sites separated by only 30 nucleobases (~10 nm) can be differentiated under AFM imaging. We can directly genotype single molecules of human genomic DNA.