Versatile and Programmable DNA Logic Gates on Universal and Label-Free Homogeneous Electrochemical Platform

Herein, a novel universal and label-free homogeneous. electrochemical platform is demonstrated, on which a complete set of DNA-based two-input Boolean logic gates (OR, NAND, AND, NOR, INHIBIT, IMPLICATION; XOR, and XNTOR) is constructed by simply and rationally deploying the designed DNA polymerization/nicking machines without complicated sequence modulation. Single-stranded DNA is employed as the proof-of-concept target/input to initiate or prevent the DNA polymerization/nicking cyclic reactions on these DNA, machines: to synthesize numerous intact G-quadruplex sequences or binary G-quadruplex subunits as the output. The generated output strands then self-assemble into G-quadruplexes that render remarkable decrease to the diffusion current response of methylene blue and, thus; provide the amplified homogeneous electrochemical readout signal net only for the logic gate operations but also for the ultrasensitive detection of:the target/input, This system represents the first example of homogeneous electrochemical logic operation. Importantly, the proposed homogeneous electrochemical logic gates possess the input/output homogeneity and share a constant output threshold value. Moreover, the modular design of DNA polymerization/nicking machines enables the adaptation of these homogeneous electrochemical logic gates to various input and output sequences. The results of this study demonstrate;the versatility and universality of the label free homogeneous: electrochemical platform in the design of biomolecular logic gates and provide a potential platform for :the further development of large-scale DNA-based biocomputing circuits and advanced biosensors for multiple molecular targets.