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Early diagnosis and treatment of gastric cancer (GC) play a vital role in improving efficacy, reducing mortality and prolonging patients' lives. Given the importance of early detection of gastric cancer, an electrochemical biosensor was developed for the ultrasensitive detection of miR-19b-3p by integrating MoS 2 -based nanozymes, hybridization chain reaction (HCR) with enzyme catalyzed reaction. The as-prepared MoS 2 -based nanocomposites were used as substrate materials to construct nanoprobes, which can simultaneously load probe DNA and HCR initiator for signal amplification. Moreover, the MoS 2 -based nanocomposites are also employed as nanozymes to amplify electrochemical response. The presence of miR-19b-3p induced the assembly of MoS 2 -based nanoprobes on the electrode surface, which can activate in-situ HCR reaction to load a large number of horseradish peroxidase (HRP) for signal amplification. Coupling with the co-catalytic ability of HRP and MoS 2 -based nanozymes, the designed electrochemical biosensor can detect as low as 0.7 aM miR-19b-3p. More importantly, this biosensor can efficiently analyze miR-19b-3p in clinical samples from healthy people and gastric cancer patients due to its excellent sensitivity and selectivity, suggesting that this biosensor has a potential application in early diagnosis of disease., (© 2024. The Author(s).)

A convenient and ultrasensitive fluorometric method is described for the determination of HIV DNA. It exploits the strong difference in the affinities of MoS 2 nanosheets for long ssDNA versus short oligonucleotide fragments. In addition, efficient signal amplification is accomplished by exonuclease III-assisted target recycling. When absorbed on the MoS 2 nanosheets, the fluorescence of the FAM-labeled ssDNA probe (FP) is quenched. However, in the presence of HIV DNA, the FP hybridizes with target to form a duplex. As a result, the FP in the duplex will be stepwise hydrolyzed into short fragments by Exo III, and the fluorescence signal thus is retained because short fragments have low affinity for the MoS 2 nanosheets. By using the Exo III-assisted target recycling amplification, the detection sensitivity is strongly improved. The sensor can detect DNA in a concentration as low as 5.3 pM (at an S/N ratio of 3), and the analytical range extends from 0.01 nM to 10 nM. The assay is simple, sensitive and specific, and conceivably represents a valuable tool in clinical studies related to the HIV. Graphical abstract Schematic presentation of fluorometric determination of HIV DNA based on molybdenum disulfide nanosheets and Exo III. When the fluorescence-tagged ssDNA probe hybridized with target to form a duplex, the Exo III-assisted target recycling amplification is generated. The method can detect as low as 5.3 pM HIV DNA.

DNA-functionalized layered two-dimensional transition-metal dichalcogenides have attracted tremendous interest for constructing biosensors in recent years. In this work, we report diblock molecular beacons with poly-cytosine (polyC) tails anchored on molybdenum disulfide (MoS 2 ) nanosheets as probes for microRNA detection. The polyC block is adsorbed on MoS 2 and the molecular beacon block is available for hybridization to the target; duplex-specific nuclease provides signal amplification by target recycling. By changing the length of polyC, we regulate the density of probes on MoS 2 and inhibit the adsorption of enzyme-cleaved oligonucleotides, thereby leading to higher quenching efficiency. PolyC-mediated molecular beacons on MoS 2 have very low background signal, ultrahigh sensitivity (limit of detection ∼3.4 fM), specificity to detect a single nucleotide mismatch, and selectivity to detect target microRNA from serum samples. This detection platform holds great potential for quantitative analysis of miRNAs in clinical diagnosis and biomedical research.

MicroRNAs (miRNAs) play significant regulatory roles in physiologic and pathologic processes and are considered as important biomarkers for disease diagnostics and therapeutics. Simple, fast, sensitive, and selective detection of miRNAs, however, is challenged by their short length, low abundance, susceptibility to degradation, and homogenous sequence. Here, we report a novel design of nanoprobes for highly sensitive and selective detection of miRNAs based on MoS 2 -loaded molecular beacons (MBs) and duplex-specific nuclease (DSN)-mediated signal amplification (DSNMSA). We show that MoS 2 nanosheets not only exhibit high affinity toward MBs but also act as an efficient quencher for absorbed MBs. The strong fluorescence-quenching ability of MoS 2 in combination with cyclic DSNMSA contributes to the superior sensitivity of our method, with a limit of detection 4 orders of magnitude lower than that of traditional hybridization methods. Moreover, the nanoprobes also show high selectivity for discriminating homogenous miRNA sequences with one-base differences because of the discrimination ability of MBs and DSN. Furthermore, we demonstrate that the MoS 2 -loaded MB nanoprobes can be utilized for multiplexed detection of miRNAs. Given its high sensitivity and specificity, as well as the multiplexed function; this novel method as an effective tool shows a great promise for simultaneous quantitative analysis of multiple miRNAs in biomedical research and clinical diagnosis.

A single-layer MoS2 nanosheet exhibits high fluorescence quenching ability and different affinity toward ssDNA versus dsDNA. As a proof of concept, the MoS2 nanosheet has been successfully used as a sensing platform for the detection of DNA and small molecules.