Thermal cycling of DNA devices via associative strand displacement

DNA-based devices often operate through a series of toehold-mediated strand-displacement reactions. To achieve cycling, fluidic mixing can be used to introduce 'recovery' strands to reset the system. However, such mixing can be cumbersome, non-robust, and wasteful of materials. Here we demonstrate mixing-free thermal cycling of DNA devices that operate through associative strand-displacement cascades. These cascades are favored at low temperatures due to the primacy of a net increase in base pairing, whereas rebinding of 'recovery' strands is favored at higher temperatures due to the primacy of a net release of strands. The temperature responses of the devices could be modulated by adjustment of design parameters such as the net increase of base pairs and the concentrations of strands. Degradation of function was not observable even after 500 thermal cycles. We experimentally demonstrated simple digital-logic circuits that evaluate at 35°C and reset after transient heating to 65°C. Thus associative strand displacement enables robust thermal cycling of DNA-based devices in a closed system.