Parallel DNA circuits by autocatalytic strand displacement and nanopore readout

DNA nanotechnology provides a unique opportunity for molecular computation, with strand displacement reactions enabling controllable reorganization of nanostructures. Additional DNA strand exchange strategies with high selectivity for input will enable novel complex systems including biosensing applications. Herein, we propose an autocatalytic strand displacement (ACSD) circuit: initiated by DNA breathing and accelerated by a seesaw catalytic reaction, ACSD ensures that only the correct base sequence starts the catalytic cycle. Analogous to an electronic circuit with a variable resistor, two ACSD reactions with different rates are connected in parallel to mimic a parallel circuit containing branches with different resistances. Finally, we introduce a multiplexed nanopore sensing platform to report the output results of a parallel path selection system at the single-molecule level. By combining the ACSD strategy with fast and sensitive single-molecule nanopore readout, a new generation of DNA-based computing tools is established.