Identifying Structure in Short DNA Scaffolds Using Solid-State Nanopores.

The identification of molecular tags along nucleic acid sequences has many potential applications in bionanotechnology, disease biomarker detection, and DNA sequencing. An attractive approach to this end is the use of solid-state nanopores, which can electrically detect molecular substructure and can be integrated into portable lab-on-a-chip sensors. We present here a DNA origami-based approach of molecular assembly in which solid-state nanopores are capable of differentiating 165 bp scaffolds containing zero, one, and two dsDNA protrusions. This highly scalable technique requires minimal sample preparation and is customizable for a wide range of targets and applications. As a proof-of-concept, an aptamer-based DNA displacement reaction is performed in which a dsDNA protrusion is formed along a 255 bp scaffold in the presence of ATP. While ATP is too small to be directly sensed using conventional nanopore methods, our approach allows us to detect ATP by identifying molecular substructure along the DNA scaffold.