Single-Molecule Resettable DNA Computing via Magnetic Tweezers

DNA-based Boolean logic computing has emerged as a leading technique in biosensing, diagnosis, and therapeutics. Due to the development of the biological and chemical methods, especially the toehold-mediated DNA strand displacement (TMSD) reaction, different logic gates as well as circuits can be performed. However, most of these methods have been conducted at the bulk level, which may lead to missing information and be less controllable. Herein, we engineered single-molecule DNA computing controlled by stretching forces using magnetic tweezers. By tracking the real-time signals of the DNA extension, the output can be determined at a single base-pair resolution. A kinetics-controllable TMSD reaction was realized in the range of a ∼19-fold change of the reaction rate by different stretching forces. OR, AND, and NOT gates were also achieved. In addition, resettable DNA computing using force stretching cycles has been further exemplified. Overall, such a real-time, label-free, and force-controlled single-molecule DNA computing system provided new insight into molecular computing.