Programmable DNA Nanoswitch Sensing with Solid-State Nanopores

Sensing performance of solid-state nanopores is limited by the fast kinetics of small molecular targets. To address this challenge, we translate the presence of a small target to a large conformational change of a long polymer. In this work, we explore the performance of solid-state nanopores for sensing the conformational states of molecular nanoswitches assembled using the principles of DNA origami. These programmable single-molecule switches show great potential in molecular diagnostics and long-term information storage. We investigate the translocation properties of linear and looped nanoswitch topologies using nanopores fabricated in thin membranes, ultimately comparing the performance of our nanopore platform for detecting the presence of a DNA analogue to a sequence found in a Zika virus biomarker gene with that of conventional gel electrophoresis. We found that our system provides a high-throughput method for quantifying several target concentrations within an order of magnitude by sensing only several hundred molecules using electronics of moderate bandwidth that are conventionally used in nanopore sensing systems.