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.