Chongwen Wang

Fe₃O₄@Ag magnetic nanoparticles for microRNA capture and duplex-specific nuclease signal amplification based SERS detection in cancer cells.

A functionalized Fe3O4@Ag magnetic nanoparticle (NP) biosensor for microRNA (miRNA) capture and ultrasensitive detection in total RNA extract from cancer cells was reported in this paper. Herein, Raman tags-DNA probes modified Fe3O4@Ag NPs were designed both as surface-enhanced Raman scattering (SERS) SERS and duplex-specific nuclease signal amplification (DSNSA) platform. Firstly, target miRNAs were captured to the surface of Fe3O4@Ag NPs through DNA/RNA hybridization. In the presence of endonuclease duplex specific nuclease (DSN), one target miRNA molecule could rehybrid thousands of DNA probes to trigger the signal-amplifying recycling. Base on the superparamagnetic of Fe3O4@Ag NPs, target miRNA let-7b can be captured, concentrated and direct quantified within a PE tube without any PCR preamplification treatment. The detection limit was 0.3fM (15 zeptomole, 50μL), nearly 3 orders of magnitude lower than conventional fluorescence based DSN biosensors for miRNA(∼100fM), even single-base difference between the let-7 family members can be discriminated. The result provides a novel proposal to combine the perfect single-base recognition and signal-amplifying ability of the endonuclease DSN with cost-effective SERS strategy for miRNA point-of-care (POC) clinical diagnostics.

Magnetically Assisted Surface-Enhanced Raman Spectroscopy for the Detection of Staphylococcus aureus Based on Aptamer Recognition

A magnetically assisted surface-enhanced Raman scattering (SERS) biosensor for single-cell detection of S. aureus on the basis of aptamer recognition is reported for the first time. The biosensor consists of two basic elements including a SERS substrate (Ag-coated magnetic nanoparticles, AgMNPs) and a novel SERS tag (AuNR-DTNB@Ag-DTNB core-shell plasmonic NPs or DTNB-labeled inside-and-outside plasmonic NPs, DioPNPs). Uniform, monodisperse, and superparamagnetic AgMNPs with favorable SERS activity and magnetic responsiveness are synthesized by using polymer polyethylenimine. AgMNPs use magnetic enrichment instead of repeated centrifugation to prevent sample sedimentation. DioPNPs are designed and synthesized as a novel SERS tag. The Raman signal of DioPNPs is 10 times stronger than that of the commonly used SERS tag AuNR-DTNB because of the double-layer DTNB and the LSPR position adjustment to match the given laser excitation wavelength. Consequently, a strong SERS enhancement is achieved. Under the optimized aptamer density and linker length, capture by aptamer-modified AgMNPs can achieve favorable bacteria arrest (up to 75%). With the conventional Raman spectroscopy, the limit of detection (LOD) is 10 cells/mL for S. aureus detection, and a good linear relationship is also observed between the SERS intensity at Raman peak 1331 cm(-1) and the logarithm of bacteria concentrations ranging from 10(1) to 10(5) cells/mL. With the help of the newly developed SERS mapping technique, single-cell detection of S. aureus is easily achieved.

Facile Synthesis of Au-Coated Magnetic Nanoparticles and Their Application in Bacteria Detection via a SERS Method

This study proposes a facile method for synthesis of Au-coated magnetic nanoparticles (AuMNPs) core/shell nanocomposites with nanoscale rough surfaces. MnFe2O4 nanoparticles (NPs) were first modified with a uniform polyethylenimine layer (2 nm) through self-assembly under sonication. The negatively charged Au seeds were then adsorbed on the surface of the MnFe2O4 NPs through electrostatic interaction for Au shell formation. Our newly developed sonochemically assisted hydroxylamine seeding growth method was used to grow the adsorbed gold seeds into large Au nanoparticles (AuNPs) to form a nanoscale rough Au shell. Au-coated magnetic nanoparticles (AuMNPs) were obtained from the intermediate product (Au seeds decorated magnetic core) under sonication within 5 min. The AuMNPs were highly uniform in size and shape and exhibited satisfactory surface-enhanced Raman scattering (SERS) activity and strong magnetic responsivity. PATP was used as a probe molecule to evaluate the SERS performance of the synthesized AuMNPs with a detection limit of 10(-9) M. The synthesized AuMNPs were conjugated with Staphylococcus aureus (S. aureus) antibody for bacteria capture and separation. The synthesized plasmonic AuNR-DTNB NPs, whose LSPR wavelength was adjusted to the given laser excitation wavelength (785 nm), were conjugated with S. aureus antibody to form a SERS tag for specific recognition and report of the target bacteria. S. aureus was indirectly detected through SERS based on sandwich-structured immunoassay, with a detection limit of 10 cells/mL. Moreover, the SERS intensity at Raman peak of 1331 cm(-1) exhibited a linear relationship to the logarithm of bacteria concentrations ranging from 10(1) cells/mL to 10(5) cells/mL.

A rapid SERS method for label-free bacteria detection using polyethylenimine-modified Au-coated magnetic microspheres and Au@Ag nanoparticles

A rapid, sensitive, and label-free SERS detection method for bacteria pathogens is reported for the first time. The method, which is based on the combination of polyethylenimine (PEI)-modified Au-coated magnetic microspheres (Fe3O4@Au@PEI) and concentrated Au@Ag nanoparticles (NPs), was named the capture-enrichment-enhancement (CEE) three-step method. A novel Fe3O4@Au microsphere with monodispersity and strong magnetic responsiveness was synthesized as a magnetic SERS substrate and amino functionalized by PEI self-assembly. The negatively charged bacteria were quickly captured and enriched by the positively charged Fe3O4@Au@PEI microspheres, and the bacteria SERS signal was synergistically enhanced by using Fe3O4@Au@PEI microspheres and Au@Ag NPs in conjunction. The CEE three-step method proved useful in tap water and milk samples, and the total assay time required was only 10 min. Results further demonstrated that the CEE three-step method could be a common approach for detecting a wide range of bacteria, as verified by its detection of the Gram-positive bacterium E. coli and Gram-positive bacterium S. aureus at a detection limit of as low as 103 cells per mL. Therefore, our CEE three-step method offered the significant advantages of short assay time, simple operating procedure, and higher sensitivity than previously reported methods of SERS-based bacteria detection.

Polyethylenimine-interlayered silver-shell magnetic-core microspheres as multifunctional SERS substrates

The fabrication of an ideal noble metal modified magnetic microsphere as a high performance SERS substrate that possesses good dispersibility, strong magnetic responsiveness, and high sensitivity is still a challenge. Herein, we report a novel route for fabricating Ag-coated magnetic core–shell microspheres (Fe3O4@PEI@Ag) with most of the desired advantages by using polyethyleneimine (PEI) as an interlayer. The size and coverage level of the Ag-NPs shell on Fe3O4@PEI@Ag microspheres were easily controlled by varying the amount of AgNO3. Meanwhile, the magnetic core endowed the Fe3O4@PEI@Ag microspheres with superior magnetic nature, which enabled convenient separation and further enhanced Raman signals due to enrichment of targeted analytes and abundant interparticle hotspots created by magnetism-induced aggregation. Considering these features, Fe3O4@PEI@Ag is expected to be a versatile SERS substrate, which was verified by the detection of adsorbed PATP molecules and human IgG with a detection limit as low as 10−11 M and 10−14 g mL−1, respectively. Therefore, the novel Fe3O4@PEI@Ag microsphere has an enormous potential for practical SERS detection applications, especially in the field of quantitative detection of target proteins.

Magnetic immunoassay for cancer biomarker detection based on surface-enhanced resonance Raman scattering from coupled plasmonic nanostructures.

A surface-enhanced resonance Raman scattering (SERRS) sensor was developed for the ultrasensitive detection of cancer biomarkers. Capture antibody-coated silver shell magnetic nanoparticles (Fe3O4@Ag MNPs) were utilized as the CEA enrichment platform and the SERRS signal amplification substrate. Gold nanorods (AuNRs) were coated with a thin silver shell to be in resonance with the resonant Raman dye diethylthiatricarbocyanine iodide (DTTC) and the excitation wavelength at 785nm. The silver-coated AuNRs (Au@Ag NRs) were then modified with detection antibody as the SERRS tags. Sandwich immune complexes formed in the presence of the target biomarker carcinoembryonic antigen (CEA), and this formation induced the plasmonic coupling between the Au@Ag NRs and Fe3O4@Ag MNPs. The SERRS signal of DTTC molecules located in the coupled plasmonic nanostructures was significantly enhanced. As a result, the proposed SERRS sensor was able to detect CEA with a low limit of detection of 4.75fg/mL and a wide dynamic linear range from 10fg/mL to 100ng/mL. The sensor provides a novel SERRS strategy for trace analyte detection and has a potential for clinical applications.

Plasmonic Ag Core–Satellite Nanostructures with a Tunable Silica-Spaced Nanogap for Surface-Enhanced Raman Scattering

Plasmonic Ag core-satellite nanostructures were synthesized by utilizing the ultrathin silica shell as a spacer to generate a tunable nanogap between the Ag core and satellites. To synthesize the nanoparticles, Ag nanoparticles (Ag NPs) with a diameter of ∼60 nm were synthesized as cores, on which Raman dyes were adsorbed and then tunable ultrathin silica shells from 2.0 to 6.5 nm were coated, followed by the deposition of Ag NPs as satellites onto the silica surface. The relationships between the SERS signal and the important parameters, including the satellite diameter and the nanogap distance, were studied by experimental methods and theoretical calculations. The maximum SERS intensity of the core-satellite nanoparticles was over 14.6 times stronger than that of the isolated Raman-encoded Ag/PATP@SiO2 NP. The theoretical calculations indicated that the local maximum calculated enhancement factor (EF) of the hot spots with a 2.0 nm nanogap was 9.5 × 10(5). The well-defined Ag core-satellite nanostructures have a high structural uniformity and an anomalously strong electromagnetic enhancement for highly quantitative SERS, leading to a better understanding of hot spot formation and providing new insights into the optimal design and synthesis of the hot SERS nanostructures in a controlled manner.

A graphene-interlayered magnetic composite as a multifunctional SERS substrate

Investigations in the combination of graphene with noble-metal nanostructures mostly focus on the fabrication of stacked hybrid films or nanoparticle (Au or Ag NPs) decorated graphene sheets, while few are carried out in graphene built-in monodispersed microspheres. Herein, we propose a novel hierarchical composite with a silver-shelled Fe3O4 microsphere as the initial core and graphene oxide (GO) as the multifunctional inserted layer. The flexible GO provides abundant nucleation sites for further in situ growth of Au nanoparticles. Moreover, it introduces considerable chemical enhancement and enhances surface adsorption toward aromatic molecules. Considering the synergistic properties of versatile GO with noble-metal nanostructures, the synthesized Fe3O4@Ag-rGO-Au microspheres were expected to have excellent surface-enhanced Raman scattering (SERS) activity, which was verified by the detection of the sulfhydryl-contained PATP and aromatic DTTC, with respective detection limits of 10−11 M and 10−10 M. The enhancement factor (EF) was calculated to be 2.83 × 106 for totally symmetric (a1) vibrations located at 1077 cm−1 of PATP. Additionally, its fast magnetic response enables rapid separation from solution, which is a key factor for many practical applications. Therefore, the well-dispersed hybrid microspheres have enormous potential in sensing applications as well as in effective immobilization and enrichment of biomolecules and aromatic pollution.

Polyethyleneimine-mediated seed growth approach for synthesis of silver-shell silica-core nanocomposites and their application as a versatile SERS platform

We synthesized silver-shell silica-core nanoparticles (SiO2@PEI@Ag NPs) with complete silver shells through the proposed polyethyleneimine (PEI)-mediated seed growth method. Cationic PEI rapidly self-assembled on the silica spheres through sonication to form a thin multifunctional interlayer, which can adsorb Au seeds densely and uniformly and stabilize the entire structure. Ag shell formation was completed within 2 min, and generated SiO2@PEI@Ag NPs were highly uniform in size and shape with nanoscale roughness. The improved seed growth method can be generally used to coat Ag shells of different thicknesses on the SiO2 cores with any particle size to form a well-dispersed core/shell nanostructure with high SERS activity. SiO2@PEI@Ag NPs of different sizes could be versatile SERS platforms for different applications. The potential of these particles as SERS substrates was verified by detection of the pesticide thiram and potential as SERS tags was verified by detection of human IgG, with detection limits as low as 10−9 M and 10 pg mL−1, respectively. Hence, SiO2@PEI@Ag NPs are powerful tools for practical SERS detection.

Vancomycin-modified Fe 3 O 4 @SiO 2 @Ag microflowers as effective antimicrobial agents

Nanomaterials combined with antibiotics exhibit synergistic effects and have gained increasing interest as promising antimicrobial agents. In this study, vancomycin-modified magnetic-based silver microflowers (Van/Fe3O4@SiO2@Ag microflowers) were rationally designed and prepared to achieve strong bactericidal ability, a wide antimicrobial spectrum, and good recyclability. High-performance Fe3O4@SiO2@Ag microflowers served as a multifunction-supporting matrix and exhibited sufficient magnetic response property due to their 200 nm Fe3O4 core. The microflowers also possessed a highly branched flower-like Ag shell that provided a large surface area for effective Ag ion release and bacterial contact. The modified-vancomycin layer was effectively bound to the cell wall of bacteria to increase the permeability of the cell membrane and facilitate the entry of the Ag ions into the bacterium, resulting in cell death. As such, the fabricated Van/Fe3O4@SiO2@Ag microflowers were predicted to be an effective and environment-friendly antibacterial agent. This hypothesis was verified through sterilization of Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentrations of 10 and 20 μg mL−1, respectively. The microflowers also showed enhanced effect compared with bare Fe3O4@SiO2@Ag microflowers and free-form vancomycin, confirming the synergistic effects of the combination of the two components. Moreover, the antimicrobial effect was maintained at more than 90% after five cycling assays, indicating the high stability of the product. These findings reveal that Van/Fe3O4@SiO2@Ag microflowers exhibit promising applications in the antibacterial fields.