Single-Molecule Resettable DNA Computing via Magnetic Tweezers

Abstract

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.

Construction of DNA-based molecular circuits using normally open and normally closed switches driven by lambda exonuclease

“…DNA nanotechnology-related research has made significant progress in many fields, such as biosensors, 1,2 molecular computing, 3,4 DNA storage, 5,6 and molecular machines. [7][8][9] In the field of molecular computing, since Adleman's pioneering work, 10 programmed nucleic acid reaction systems such as those for molecular detection, [11][12][13] logical operation, [14][15][16] and molecular automata [17][18][19] have been developed and realized based on the biochemical characteristics of DNA.…”

Reconfigurable DNA triplex structure for pH responsive logic gates

“…In recent years, DNA nanotechnology 1 has developed rapidly and become the most dynamic frontier discipline in molecular biology. It has been widely used in fields of DNA computing, 2–4 nanomachines, 5–7 biosensing 8,9 and so on. Among them, DNA computing is a new computing model based on the principle of biochemical reaction, which has the characteristics of high parallelism, mass storage capacity, and extremely low energy consumption etc.…”

Highly Efficient Quadruped DNA Walker Guided by Ordered DNA Tracks for Rapid and Ultrasensitive Electrochemical Detection of miRNA-21

“…In the past few decades, researchers have designed many highly complicated and powerful DNA molecular machines that could implement specific functions on a nanoscale, for example, DNA robots, − DNA tweezers, − DNA walkers, − etc. Among the various kinds of molecular machines, the DNA walker, a novel dynamic nanomachine, − which could walk along designed DNA tracks to guarantee transport of cargoes with the help of driving forces (the driving forces including strand displacement reaction (SDR), protein enzyme/DNAzyme reaction, and environmental stimuli), has attracted more and more eyes to explore in sensing systems, , bioimaging, − molecular computing, cargo delivery, programmed synthesis, logic gates devices, and so on.…”