DNA nanostructure-based logic circuits with reset-free and real-time input processing

Abstract

DNA logic circuits represent a promising platform for biocompatible and programmable computation. However, conventional systems depend on external reset steps, such as pH changes, temperature cycling, or strand removal, to enable repeated operation. These reset processes interrupt continuous computation and fundamentally limit real-time signal processing and circuit reusability. In this thesis, we propose a reset-free and reusable DNA logic circuit architecture based on a Toehold chain reaction (TCR) implemented on a DNA origami nanostructure. By reconfiguring conventional toehold-mediated strand displacement, TCR enables reversible and bidirectional strand exchange between domains with comparable binding affinities. This DNA-only mechanism allows logic operations to proceed without external reset steps, thereby supporting continuous input processing. To further ensure reaction fidelity, the circuit components are spatially organized on a 2D DNA origami nanostructure. This spatial confinement effectively minimizes nonspecific interactions and suppresses crosstalk between distinct circuit units. Based on this origami-localized TCR architecture, we implemented fundamental combinational DNA logic gates, including AND and OR gates. These logic gates were observed to operate reliably for more than ten computational cycles without loss of function. Together, this work establishes TCR as a reset-free framework for reusable DNA logic circuits and provides a robust foundation for constructing complex, spatially organized molecular computing systems.