Modulation of oligonucleotide-binding dynamics on WS₂ nanosheet interfaces for detection of Alzheimer's disease...

Non-covalent adsorption and desorption of oligonucleotides on two-dimensional nanosheets are widely employed to design nanobiosensors for the rapid optical detection of targets. A precise control over the weak interactions between nanosheet interfaces and oligonucleotides is crucial for a high-sensing performance. Herein, the interface of ultrathin WS₂ nanosheets used as a fluorescence quencher was engineered by four different dextran polymers in an aqueous solution to control the adsorption kinetics and thermodynamics of the DNA probe. The WS₂ nanosheets, functionalized by the carboxyl group-bearing dextran (CM-dex-WS₂) or the trimethylammonium-modified dextran (TMA-dex-WS₂), exhibited 3.6-fold faster adsorption rates of the fluorescein-labeled DNA probe (FAM-DNA), which led to the effective fluorescence quenching of FAM, compared to the nanosheets functionalized with pristine dextran (dex-WS₂) or the hydrophobic phenoxy groups-bearing dextran (PhO-dex-WS₂). Isothermal titration calorimetry measurements showed that the adsorption strength of FAM-DNA for CM-dex-WS₂ was one order of magnitude greater than its hybridization energy for a target microRNA (miR-29a) that is well-known as an Alzheimer's disease (AD) biomarker, leading to the unfavorable desorption of the DNA probe from the surface. In contrast, TMA-dex-WS₂ exhibited the proper adsorption strength of FAM-DNA, which was lower than its hybridization energy for miR-29a, leading to its favorable desorption from the nanosheet surface along with the noticeable restoration of the quenched fluorescence after its hybridization with miR-29a. Finally, the interface modulation of WS₂ nanosheets allowed the selective and sensitive recognition of miR-29a against non-complementary RNA and single base-mismatched RNA in human serum via increases in target-specific fluorescence.