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

• Published in: Biosensors & bioelectronics 2020-10, Vol.165, p.112401-112401, Article 112401
• Main Authors: Kim, Hye-In, Yim, DaBin, Jeon, Su-Ji, Kang, Tae Woog, Hwang, In-Jun, Lee, Sin, Yang, Jin-Kyoung, Ju, Jong-Min, So, Yoonhee, Kim, Jong-Ho
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; And WS2 nanosheet; Interface engineering; microRNA detection; Optical biosensor
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2020.112401

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. [Display omitted] •The interface of WS2 nanosheets was modulated by polymeric phases to design FRET-based biosensors.•DNA adsorption kinetics and thermodynamics were controlled by different polymeric phases on WS2.•TMA-dex-WS2 exhibited suitable adsorption and desorption properties for a probe DNA and miRNA.•A WS2 nanosheet FRET sensor selectively detected miRNA specific for Alzheimer's disease in serum.