Surface Of Gold Nanoparticles Research Articles

Mechanistic Insights Behind the Self-Assembly of Human Insulin under the Influence of Surface-Engineered Gold Nanoparticles.

Elucidating the underlying principles of amyloid protein self-assembly at nanobio interfaces is extremely challenging due to the diversity in physicochemical properties of nanomaterials and their physical interactions with biological systems. It is, therefore, important to develop nanoscale materials with dynamic features and heterogeneities. In this work, through engineering of hierarchical polyethylene glycol (PEG) structures on gold nanoparticle (GNP) surfaces, tailored nanomaterials with different surface properties and conformations (GNPs-PEG) are created for modulating the self-assembly of a widely studied protein, insulin, under amyloidogenic conditions. Important biophysical studies including thioflavin T (ThT) binding, circular dichroism (CD), surface plasmon resonance (SPR), and atomic force microscopy (AFM) showed that higher-molecular weight GNPs-PEG triggered the formation of amyloid fibrils by promoting adsorption of proteins at nanoparticle surfaces and favoring primary nucleation rate. Moreover, the modulation of fibrillation kinetics reduces the overall toxicity of insulin oligomers and fibrils. In addition, the interaction between the PEG polymer and amyloidogenic insulin examined using MD simulations revealed major changes in the secondary structural elements of the B chain of insulin. The experimental findings provide molecular-level descriptions of how the PEGylated nanoparticle surface modulates protein adsorption and drives the self-assembly of insulin. This facile approach provides a new avenue for systematically altering the binding affinities on nanoscale surfaces by tailoring their topologies for examining adsorption-induced fibrillogenesis phenomena of amyloid proteins. Together, this study suggests the role of nanobio interfaces during surface-induced heterogeneous nucleation as a primary target for designing therapeutic interventions for amyloid-related neurodegenerative disorders.

In situ three-roll mill exfoliation approach for fabricating asphalt/graphite nanoplatelet composites as thermal interface materials

Thermal interface materials (TIMs) are vital to dissipate excess heat generated by electronic components with ever-growing power density to ensure their reliability and performance. However, the limited dispersibility of nano-sized thermal conductive fillers hinders further enhancement of thermal conductivity in TIMs. It remains challenging to manufacture high-performance TIMs with simultaneous high thermal conductivity, low cost, and capability of large-scale production. Herein, a solvent-free and scalable approach was adopted to fabricate asphalt/graphite nanoplatelets (GNPs) composites by in situ exfoliating graphite in asphalt melt using a three-roll mill. During exfoliation, asphalt was adsorbed onto the surface of GNPs via π-π interaction and improved their dispersibility. Hence, GNPs formed integrated thermal conductive pathways with reduced interfacial thermal resistance, which significantly improved the thermal conductivity of asphalt/GNP composites. At 25 vol% loading, the asphalt/GNP composite displayed a thermal conductivity of 1.95 W m−1 K−1, showing a 114 % increase compared to the asphalt/commercial GNP (c-GNP) composite prepared by conventional mechanical mixing. Moreover, the heat-resistant and mechanical properties of the asphalt/GNP composites were also enhanced due to the improved filler dispersion and filler-matrix interactions. Thus, the asphalt/GNP composites fabricated by in situ three-roll milling possessed remarkable advantages as TIMs compared with asphalt/c-GNP composites and commercial silicone rubber thermal pads.

Target-induced DNA nanomachine operation for the detection of proteins

Accurate and sensitive detection of disease-associated proteins in early stage of patients plays an important role in timely treatment and successfully extending patients' lives. To meet this demand, we herein rationally designed a flexible target-induced DNA nanomachine operation (TIDNMO) sensor for the detection of proteins. The TIDNMO system was composed of DNA nanoswitch and DNA walker. Triplex DNA nanoswitch was triggered by specific target, followed by the release of the walking strand, which initiated the DNA walker amplification as signal output. In addition, the Exo III could drive walking strand autonomously move on gold nanoparticle surface to realize 2 orders of magnitude signal amplification. What's more, this sensor could transform its suitable functional recognition element of DNA nanoswitch to recognize other specific molecule and realize different targets sensing based on identical walking tracks. Considering the facile reporter elements and efficient amplification performance, the present DNA nanomachine as a sensor could achieve a detection limit of 68 pM for anti-Dig antibody, 0.95 pM for mucin-1 respectively, along with a superb specificity. Furthermore, the method reported here opened a new chapter in disease-related protein sensing for the development of clinical early diagnosis.

The Molecular Footprint of Peptides on the Surface of Ultrasmall Gold Nanoparticles (2 nm) Is Governed by Steric Demand.

Ultrasmall gold nanoparticles were functionalized with peptides of two to seven amino acids that contained one cysteine molecule as anchor via a thiol-gold bond and a number of alanine residues as nonbinding amino acid. The cysteine was located either in the center of the molecule or at the end (C-terminus). For comparison, gold nanoparticles were also functionalized with cysteine alone. The particles were characterized by UV spectroscopy, differential centrifugal sedimentation (DCS), high-resolution transmission electron microscopy (HRTEM), and small-angle X-ray scattering (SAXS). This confirmed the uniform metal core (2 nm diameter). The hydrodynamic diameter was probed by 1H-DOSY NMR spectroscopy and showed an increase in thickness of the hydrated peptide layer with increasing peptide size (up to 1.4 nm for heptapeptides; 0.20 nm per amino acid in the peptide). 1H NMR spectroscopy of water-dispersed nanoparticles showed the integrity of the peptides and the effect of the metal core on the peptide. Notably, the NMR signals were very broad near the metal surface and became increasingly narrow in a distance. In particular, the methyl groups of alanine can be used as probe for the resolution of the NMR spectra. The number of peptide ligands on each nanoparticle was determined using quantitative 1H NMR spectroscopy. It decreased with increasing peptide length from about 100 for a dipeptide to about 12 for a heptapeptide, resulting in an increase of the molecular footprint from about 0.1 to 1.1 nm2.

Surface-Enhanced Raman Scattering Sensors Employing a Nanoparticle-On-Liquid-Mirror (NPoLM) Architecture.

Surface-enhanced Raman scattering (SERS) sensors typically employ nanophotonic structures that support high-field confinement and enhancement in hotspots to increase the Raman scattering from target molecules by orders of magnitude. In general, high field and SERS enhancement can be achieved by reducing the critical dimensions and mode volumes of the hotspots to nanoscale. To this end, a multitude of SERS sensors employing photonic structures with nanometric hotspots have been demonstrated. However, delivering analyte molecules into nanometric hotspots is challenging, and the trade-off between field confinement/enhancement and analyte delivery efficiency is a critical limiting factor for the performance of many nanophotonic SERS sensors. Here, a new type of SERS sensor employing solid-metal nanoparticles and bulk liquid metal is demonstrated to form nanophotonic resonators with a nanoparticle-on-liquid-mirror (NPoLM) architecture, which effectively resolves this trade-off. In particular, this unconventional sensor architecture allows for the convenient formation of nanometric hotspots by introducing liquid metal after analyte molecules are efficiently delivered to the surface of gold nanoparticles. In addition, a cost-effective and reliable process is developed to produce gold nanoparticles on a substrate suitable for forming NPoLM structures. These NPoLM structures achieve two orders of magnitude higher SERS signals than the gold nanoparticles alone.

Fluorescent immunoassay for chloramphenicol based on the label-free polyadenine-mediated spherical nucleic acids triggered signal amplification.

A fluorescent immunosorbent assay incorporating signal amplification away from the surface of spherical nucleic acid (SNA) was developed for the detection of chloramphenicol (CAP). Through the conjugation of antibodies and poly-adenine (polyA) DNA onto the surface of gold nanoparticles (AuNPs), the fabrication of the nano-immunoprobe was achieved in a more straightforward and cost-effective manner. Moreover, a strategy utilizing the hybridization chain reaction (HCR) in the amplification step was devised, with particular attention given to the enzyme inhibition associated with SNA. The results demonstrated good performance on CAP detection with a linear range of 0.01-5ng/L with a detection limit of 0.005ng/L. The significance of this work mainly lies in the polyA-SNA-based immunoprobe and the thoughtful design to prevent enzyme inhibition.

Pesticide Identification Using Surface-Enhanced Raman Spectroscopy and Density Functional Theory Calculations: From Structural Insights to On-Site Detection.

Pesticides play an important role in conventional agriculture. Yet, their harmful effects on the environment are becoming increasingly apparent. The occurrence of pesticides is hence being monitored worldwide. For fast, easy, yet sensitive identification, surface-enhanced Raman spectroscopy (SERS) is a powerful tool. In this study, a method is introduced that may be amended to in-field detection of pesticides. Gold and silver nanoparticles were synthesized, size-tailored, and characterized. The herbicide paraquat and the fungicide thiram served as model compounds. The preparation yielded reproducible SERS spectra. Using quantum chemical computation, Raman and SERS spectra were calculated and analyzed. The interpretation of vibrational modes in combination with SERS enhancement and attenuation allowed us to identify compound-specific bands. The assignment was interpreted in terms of the orientation of paraquat and thiram on the gold and silver nanoparticle surfaces. Paraquat preferred a co-planar arrangement parallel to the gold nanoparticle surface and a head-on orientation on the silver nanoparticle. For thiram, breaking of the disulfide bond was recognized, such that interaction with the surface occurred via the sulfur atoms. Successful detection of the pesticides after recollection from vegetable leaves demonstrated the method's applicability for pesticide identification.

Composite membrane of graphene oxide and gold nanoparticles functionalized S fiber taper aptasensor for highly sensitive bisphenol A detection.

The S fiber taper (SFT) aptasensor with a composite sensitive membrane of graphene oxide and gold nanoparticles was proposed for the rapid and highly sensitive detection of bisphenol A (BPA). The SFT was obtained using a fusion splicer; subsequently, the composite film was deposited on its surface, and the specific aptamer was covalently bonded to the surface of gold nanoparticles. The detection mechanism relies on monitoring changes in the external refractive index induced by the specific binding of BPA to the aptamer. The developed SFT aptasensor exhibited a remarkable sensitivity of 15.5 nm/nM and a limit of detection as low as 0.01 nM for BPA. These findings highlight the aptasensor's potential for diverse monitoring applications.

Enhancement of flexural modulus and strength of epoxy nanocomposites with the inclusion of functionalized GNPs using Tween 80

In this work, epoxy nanocomposite was prepared with the inclusion of unfunctionalized as-received GNPs (ARGNPs) and functionalized GNPs using surfactant Tween 80 (T80GNPs) in the epoxy resin using a mechanical stirrer. ARGNPs were used as it is, while T80GNPs were prepared through the adsorption of surfactant onto GNPs’ surface using a sonication procedure in an ultrasonic bath. Characterization of nanoparticles using SEM shows that ARGNPs indicated a softer image representing a thinner layer of graphene stacks compared to T80GNP which has a tangible solid-looking image resulting from the sedimentation during the process of filtration. Elementally, both ARGNPs and T80GNPs were found to contain carbon, oxygen, and sulfur, as indicated by the EDX spectrum, with the C/O ratio for T80GNPs being 34.7% higher than that for ARGNPs, suggesting the adsorption of Tween 80 molecules on the GNPs after functionalization. FTIR spectroscopy confirms the attachment of Tween 80 molecules on GNPs surface with T80GNPs spectrum indicated higher peak intensity than ARGNPs. Flexural testing demonstrated that the addition of 0.9 wt.% ARGNPs and 0.9 wt.% T80GNPs to the epoxy increased the modulus of the nanocomposites to 72.1% and 82.6%, respectively, relative to neat epoxy. With the same amount of particle content, both nanocomposites showed increased strength, with ARGNPs and T80GNPs exhibiting strengths of 70.5% and 87.8%, respectively, relative to neat epoxy.

Dual-responsive 3D DNA nanomachines cascaded hybridization chain reactions for novel self-powered flexible microRNA-detecting platform

The microRNA-21 is closely related to chromatin remodeling and epigenetic regulation. In this work, an efficient double-response 3D DNA nanomachine (DRDN) was assembled by co-immobilizing two different lengths of hairpin DNA on the surface of gold nanoparticles (AuNPs) to capture microRNA-21 (miRNA-21), recycle miRNA-21, and trigger hybridization chain reactions (HCR). This work reports the fabrication of a laser-scribed graphene (LSG) electrode with excellent flexibility and electrical conductivity by laser-scribing commercial polyimide films (PI). The as-proposed self-powered biosensing platform presents significantly increased instantaneous current to in real-time monitor miRNA-21 by a capacitor. The biosensing platform exhibited highly sensitive detection of miRNA-21 with a detection limit of 0.142 fM in the range of 0.5 fM to 1 × 104 fM, and demonstrated high efficiency in the analysis of the tumor markers.

Characterization of Gold Nanoparticles Synthesized with Zingiber zerumbet Extracts

Gold nanoparticles have been used as drug carriers and imaging reagents. The plant extract-capped gold nanoparticles provide better properties than chemically synthesized gold nanoparticles. In this study, Zingiber zerumbet extract-mediated green production of gold nanoparticles (Z. zerumbet@Au NPs) was established. Based on the UV-visible spectroscopy and transmission electron microscope (TEM) results, most Z. zerumbet@Au NPs were spherical. When more Z. zerumbet extracts were added, more spherical nanoparticles were formed. The hydrodynamic size changed slightly along with time, and the average size was approximately 170 nm. Capping of Z. zerumbet extract on the surface of gold nanoparticles was confirmed by Fourier transform infrared spectroscopy (FTIR). In general, phenolic compounds or flavonoid compounds were considered to be the reducing agent. However, zerumbone was identified as the reducing agent in this study. The resulting oxidized products were characterized by high-performance liquid chromatography-mass spectrometry (HPLC-MS). As a result, the solvent was proven to be involved in nanoparticle synthesis. Overall, Z zerumbet@Au NPs showed great potential to be used in cosmetic- or biomedicine-related fields.

Green synthesis of anti-cancer drug-loaded gold nanoparticles for low-intensity pulsed ultrasound targeted drug release.

In the present work, we have designed a one-pot green protocol in which anti-cancer drugs (curcumin and doxorubicin) can be directly loaded on the surface of gold nanoparticles during their formation. We have further demonstrated that low-intensity pulsed ultrasound (LIPUS) can be used to effectively induce the release of anti-cancer drugs from the surface of gold nanoparticles in an ex vivo tissue model. With this protocol, gold nanoparticles can be easily loaded with different types of anticancer drugs, irrespective of their affinity towards water, and even hydrophobic molecules, like curcumin, can be attached onto the gold nanoparticles in an aqueous medium. The method is very simple and straightforward and does not require stirring or mechanical shaking. The drug molecules interact with the gold seeds formed during the reduction and growth process and modulate the final morphology into a spherical shape. A black-colored colloidal solution of gold nanowire networks is formed in the absence of these anti-cancer drug molecules in the reaction mixture. We used hyperspectral-enhanced dark field microscopy to examine the uptake of gold nanoparticles by breast cancer cells. Upon exposure to LIPUS, the release of the anti-cancer drug from the particle surface can be quantified by fluorescence measurements. This release of drug molecules along with trisodium citrate from the surface of gold nanoparticles by ultrasound resulted in their destabilization and subsequent aggregation, which could be visually observed through the change in the color of colloidal sol. Cancer cell viability was studied by MTT assay to examine the efficacy of this nanoparticle-based drug delivery system. Ultraviolet-visible spectroscopy, dynamic light scattering (DLS), and transmission electron microscope (TEM) analysis were used to characterize the nanoparticles and quantify anti-cancer drug release.

One-Shot Dual-Detection-Based Single-Molecule Super-Resolution Imaging Method for Real-Time Observation of Spatiotemporal Catalytic Activity Variations on the Plasmonic Gold Nanoparticle Surface.

Understanding the relationship between the surface properties of a single plasmonic nanoparticle and its catalytic performance is critical for developing highly efficient nanocatalysts. In this study, a one-shot dual-detection-based single-molecule super-resolution imaging method in the evanescent field was developed to observe real-time spatiotemporal catalytic activity on a single plasmonic gold nanoparticle (AuNP) surface. The scattering intensity of AuNPs and the fluorescence of resorufin molecules produced on the AuNP surface were obtained simultaneously to investigate the relationship between nanoparticles and catalytic reactions at a single-molecule level. Chemisorbed adsorbates (i.e., catalytic product and resorufin) changed the electron density of individual AuNPs throughout the catalytic cycle, resulting in the fluctuation of the scattering intensity of individual AuNPs, which was attributed to the electron transfer between reactant resazurin molecules and AuNPs. The increase in the electron density of individual AuNPs affected the catalytic reaction rate. Furthermore, sequential mapping of individual catalytic events at the subdiffraction limit resolution was completed for real-time surface dynamics and spatiotemporal activity variations on the single AuNP surface. The developed method can aid in understanding surface-property-dependent catalytic kinetics and facilitate the development of nanoparticle-based heterogeneous catalysts at subdiffraction limit resolution.

A smartphone-based nanoenzyme-modulated aptasensor using an infrared camera for rapid detection of kanamycin

The detection of antibiotics in water is crucial to ensure the safety of drinking water and prevent the spread of antibiotic resistance in the environment. In this study, we present a novel strategy for the selective and sensitive detection of kanamycin (KAN) in water by combining infrared thermography with aptamer detection technology. The aptamers specific to KAN were immobilized on the surface of gold nanoparticles (AuNPs), thereby enhancing the catalytic activity of AuNPs in the 3,3′,5,5′-tetramethylbenzidine (TMB)-hydrogen peroxide system to produce oxidized TMB with photothermal conversion capability. KAN competitively binds to the aptamer and modulates the catalytic capacity of the AuNPs surface, resulting in different photothermal conversion capacities of the final solution. Under near-infrared laser irradiation, the target KAN concentration is converted into a measurable thermal signal. To fabricate a portable sensing setup, we integrated the device with a smartphone. The aptasensor can selectively detect KAN with a limit of detection of 1.55 ng·mL−1 and a limit of quantification of 13.62 ng·mL−1. The detection time of our sensor is real time with a reaction time of 30 min. It demonstrates excellent stability and recoveries ranging from 96.9 % to 106.1 % for practical water samples. This portable aptasensor offers rapid detection, simplicity, and affordability, enabling real-time analysis of antibiotic residues in water.

In Situ Monitoring of the Polymerization Kinetics of Organic Pollutants during Persulfate-Based Advanced Oxidation Processes Using Plasmonic Colorimetry.

Using sulfate radicals to initiate polymer production in persulfate-based advanced oxidation processes (AOPs) is an emerging strategy for organics removal. However, our understanding of this process remains limited due to a dearth of efficient methods for in situ and real time monitoring of polymerization kinetics. This study leverages plasmonic colorimetry to monitor the polymerization kinetics of an array of aromatic pollutants in the presence of sulfate radicals. We observed that the formation of polymer shells on the surfaces of gold nanoparticles (AuNPs) led to an increase and red shift in their localized surface plasmon resonance (LSPR) band as a result of an increased refractive index surrounding the AuNP surfaces. This observation aligns with Mie theory simulations and transmission electron microscopy-electron energy loss spectroscopy characterizations. Our study demonstrated that the polymerization kinetics exhibits a significant reliance on the electrophilicity and quantity of benzene rings, the concentration of aromatic pollutants, and the dosage of oxidants. In addition, we found that changes in LSPR band wavelength fit well into a pseudo-first-order kinetic model, providing a comprehensive and quantitative insight into the polymerization kinetics involving diverse organic compounds. This technique holds the potential for optimizing AOP-based water treatment by facilitating the polymerization of aromatic pollutants.

Tunable growth of a single high-density ZIF nanoshell on a gold nanoparticle isolated in an optical trap.

Here, we demonstrate an all-optical method using an optical tweezer to controllably grow high quality zeolitic imidazolate framework (ZIF) nanoshells on the surface of gold nanoparticles (AuNPs) and monitor the growth via darkfield spectroscopy. Our single particle approach allows us to localize an individual NP within a microscope slide chamber containing ZIF precursors at the focus of an optical microscope and initiate growth through localized heating without affecting the bulk system. Darkfield spectroscopy is used to characterize changes to the localized surface plasmon resonance (LSPR) of the AuNP resulting from refractive index changes as the ZIF crystal grows on the surface. We show that the procedure can be generalized to grow various types of ZIF crystals, such as ZIF-8, ZIF-11, and a previously undocumented ZIF variety. Utilizing both computational models and experimental methods, we identify the thickness of ZIF layers to be self-limiting to ∼50 nm or less, depending on the trapping laser power. Critically, the refractive index of the shells here was found to be above 1.6, indicating the formation of high-density crystals, previously accessible only through slow atomic layer deposition and not through a bulk heating process. The single particle method developed here opens the door for bottom-up controllable growth of custom nanostructures with tunable optical properties.

Microstructure evolution and lath martensite precipitation behavior of Co@GNPs/CoCrMo composites fabricated by selective laser melting

Spherical cobalt nanoparticles were reduced and deposited in situ on the graphene (GNP) surface using a novel hydrothermal method, and the prepared Co@GNPs reinforced powder were uniformly dispersed in the alloy matrix. The Co@GNPs/CoCrMo composite fabricated using selective laser melting (SLM) was densely organized with reduced hole defects, and fine equiaxed grains, elongated columnar grains, and duplex ε + γ were observed in the composite organization. Meanwhile, a high density of dislocations and nanoscale stacked layer dislocations were observed at the equiaxed grain boundaries. Further, the GNPs acted as heterogeneous nucleation sites, which promoted the transformation of the γ-Co (FCC) austenite phase to the ε-Co (HCP) martensite phase by means of slip. A unique characteristic structure of nanoscale parallel-arranged lath martensite is formed on the surface of GNPs. Therefore, a co-lattice structure between ε-co and γ-co shows the specific orientation relationship between the crystallographic plane (1 1 1)γ-co//(0 0 0 2)ε-co and the crystallographic zone axis [1 1 0]γ-co//[1 1 2‾ 0]ε-co.

Boosting Photon Emission from the Chemiluminescence of Luminol Based on Host-Guest Recognition for the Determination of Dopamine.

Modulating the photon emission of the luminophore for boosting chemiluminescence (CL) response is very crucial for the construction of highly sensitive sensors via the introduction of functionalized materials. Herein, the integration of the emitter and coreactant accelerator into one entity is realized by simply assembling cucurbit[7]uril (CB[7]) on the surface of gold nanoparticles (AuNPs) through simple assembly via a Au-O bond. The loaded CB[7] on the AuNPs improves their catalytic capacity for the generation of hydroxyl radicals(•OH). Moreover, the host-guest recognition interaction between luminol and CB[7] enables the capture of luminol on AuNPs efficiently. Also, the intramolecular electron-transfer reaction between the luminol and •OH enables the CL response more effectively in the entity, which greatly boosts photon emission ca 100 folds compared with the individual luminol/H2O2. The host-guest recognition between luminol and CB[7] is revealed by Fourier transform infrared spectroscopy, electrochemical, and thermogravimetric characterization. Moreover, the proposed CL system is successfully used for the sensitive and selective determination of dopamine (DA) based on a synergistic quenching mechanism including the competition quenching and radical-scavenging effect from DA. The present amplified strategy by integrating recognized and amplified elements within one entity simplifies the sensing process and holds great potential for sensitive analysis based on the self-enhanced strategies.

Screening of Acetylcholinesterase Inhibitors by Capillary Electrophoresis with Oriented-Immobilized Enzyme Microreactors Based on Gold Nanoparticles.

A facial and efficient method for the screening of acetylcholinesterase (AChE) inhibitors by capillary electrophoresis was developed. Based on the specific affinity of concanavalin A (Con A) for binding to the glycosyl group of AChE, enzyme molecules were oriented-immobilized on the surface of gold nanoparticles (AuNPs@Con A@AChE). Then, these modified nanoparticles were bounded to the capillary inlet (about 1.0 cm) by electrostatic self-assembly to obtain the oriented-immobilized enzyme microreactor (OIMER). Compared to an IMER with a free enzyme, the peak area of the product obtained by the OIMER increased by 52.6%. The Michaelis-Menten constant (Km) was as low as (0.061 ± 0.003) mmol/L. The method exhibits good repeatability with a relative standard deviation (RSD) of 1.3% for 100 consecutive runs. The system was successfully applied to detect the IC50 values of donepezil and four components from Chinese medicinal plants. This work demonstrates the potential of this method as a low cost, simple, and accurate screening method for other enzyme inhibitors.

Confined-Enhanced Raman Spectroscopy.

In 1997, the discovery of single molecule-surface enhanced Raman spectroscopy (SM-SERS) rekindled broad interests owing to its ultrahigh enhancement factor up to the 1014-1015 level. However, regretfully, the advantage of SM-SERS with an ultralow detection limit has not yet been fully utilized in commercialized applications. Here, we report a strategy, which we name confined-enhanced Raman spectroscopy, in which the overall Raman properties can be remarkably improved with in situ-formed active nanoshell on the surface of silver or gold nanoparticles. The nanoshell can confine and anchor molecules onto the surface of plasmonic nanoparticles and avoid desorption from hot spots so that the "on and off" blinking effect can be eliminated. It is the first time the single-molecule detection of analytes with super sensitivity, high stability, and reproducibility based on gold nanoparticles has been realized. In addition, this strategy is suitable for SERS detection in diverse molecule systems, including biomedical diagnosis, catalytic reaction, etc.