Well-Aligned Track-Accelerated Tripedal DNA Walker for Photoelectrochemical Recognition of Dual-miRNAs Based on Molecular Logic Gates

Abstract

Post-transcriptional regulators, microRNAs (miRNAs), are involved in the occurrence and progression of various diseases. However, due to the complexity of disease-related miRNA regulatory networks, the typing and identification of miRNAs have remained challenging. Herein, a linear ladder-like DNA nanoarchitecture (LDN) was constructed to promote the movement efficiency of the tripedal DNA walker (T-walker), which was combined with the DNA-based logic gates and the PTCDA@PDA/CdS/WO3 photoelectrode to develop a novel biosensor for the detection of dual-miRNAs. Two miRNAs, miR-122 and miR-21, were used as targets to operate the logic module, while its output, trigger strands (TSs), initiated a catalytic hairpin assembly (CHA) reaction to form a T-walker. By using LDN as the track, the T-walker efficiently unfolded hairpin 4, which further hybridized with the alkaline phosphatase-modified hairpin 5 (AP-H5). The remaining AP can catalyze the ascorbic acid 2-phosphate (AAP) into ascorbic acid (AA), an ideal electron donor, thus resulting in a photocurrent change. The photocurrent signals of both AND and OR gates displayed a linear relationship with the logarithm of dual-miRNA concentrations with detection limits of 10.1 and 13.6 fM, respectively. Moreover, the intelligent and rational design of DNA tracks gives impetus to create a well-organized sensing interface with wide application in clinical diagnosis and cancer monitoring.

Programmable Entropy-Driven Circuit-Cascaded Self-Feedback DNAzyme Network for Ultra-Sensitive Fluorescence and Photoelectrochemical Dual-Mode Biosensing

“…The limits of detection (LOD) for FL and PEC signals are 0.153 and 0.075 amol L –1 at 3S/N, respectively. Such low detection limits are advantageous over the reported electrochemical (97.2 amol L –1 , 53 amol L –1 ), , surface-enhanced Raman scattering (SERS, 8 fmol L –1 , 349 amol L –1 ), , high-performance liquid chromatography (HPLC, 0.39 fmol L –1 ), FL (0.1 pmol L –1 , 72 pmol L –1 ), , PEC (10.1 fmol L –1 , 3.3 amol L –1 , 94.2 amol L –1 ) − approaches. The ultrasensitivity of dual-signal expression is mainly due to the programmable and unique EDC-DNAzyme self-feedback cascade amplification network, the intrinsic properties of FL and PEC signal expression, and the further reduction of background interference after magnetic separation.…”

Multiplex Signal Transduction and Output at Single Recognition Interface of Multiplexed Photoelectrochemical Sensors

“…Recently, Liu et al utilized the DNA logic gate strategy to construct an “AND” and “OR” logic gate detection platform, which was combined with a tripedal DNA walker and a single recognition interface photoelectrode to develop a novel PEC biosensor for dual miRNAs (miRNA-122 and miRNA-21) detection (Figure ). Similarly, Song’s research group reported an “OR” logic gate mediated multiplexed PEC sensor to differentiate and detect biomarkers of the human papillomavirus (HPV) (HPV 16 and HPV 18) based on a “one pot” recombinase polymerase amplification strategy …”

“…Strategies such as enzyme catalytic regulation and external stimulus regulation have been successfully employed to construct multiplexed PEC sensors. Sensors such as wavelength-resolved, heterojunction-regulated, self-cleaning, and logic-gate PEC sensors have been successfully designed and constructed for multiplex target detection. Undoubtedly, rather than expanding the recognition interfaces of PEC sensors, regulating the signal factors corresponding to multiplex targets to act on the same PEC sensing interface can significantly facilitate the sensor construction process.…”

DNA Nanomachine-Driven Heterogeneous Quadratic Amplification for Sensitive and Programmable miRNA Profiling

“…By simulating the surface structure of the cell membrane, it is possible to artificially construct a microcatalytic environment that accelerates molecular movement. To address the limitations of HOQAC, the higher-order nucleic acid structures, such as track structures, spherical nucleic acids, and DNA nanomachines, were used as high-entropy phase interfaces for constructing versatile heterogeneous quadratic amplification circuits (HEQACs). , Through the deliberate design of the nucleic acid structure, a series of biological functions, including signal exchange, amplification, and transduction, can be conferred upon the heterogeneous interface, thereby realizing the biomimetic property. In addition, the establishment of a localized high osmotic pressure difference facilitates rapid and directed movement of signal molecules, ultimately accelerating the efficient signal multiplication at the biomimetic heterogeneous interface .…”