In this work, efficient SERS substrates containing dense hot spots were fabricated by assembling AuNS@Ag on SMCSL superhydrophobic platforms, based on an evaporation assembly technique. Scanning electron microscopy images and Raman images revealed that star-shaped nanoparticles were closely packed on to the SMCSL surfaces, giving rise to a high density of hot spots. The as-prepared AuNS@Ag/SMCSL substrates exhibited higher SERS enhancement than AuNPs/SMCSL substrates. Furthermore, the SERS substrates showed low detection limits to Nile Blue A (10−12 M) with a high analytical enhancement factor of 6 × 109, and excellent signal reproducibility (RSD ∼ 6.3%). Moreover, the results of simulated electric field distribution also proved that there was higher SERS enhancement of the SERS substrates based on the star-shaped particles. Additionally, ultrasensitive detection of OPD, 6-TG, and HGB demonstrated that the AuNS@Ag/SMCSL substrates possessed the capability of trace-level detection for realistic molecules.

We report a facile route for the successful synthesis of urchin-like Au nanocages via galvanic displacement reaction, which can be used as excellent SERS-active substrates.

Herein we introduced a Raman technique based on the two-scale interface enrichment for the detection of aromatic compounds. Silver nanoparticles were fabricated, β-cyclodextrins (β-CD) were physically absorbed on the surface of the silver nanoparticles as capturing layers of aromatic compounds for enriching the analytes on the interface of the silver nanoparticles in solution. After the analyte was captured, a mixture of silver nanoparticles and aromatic compounds were dropped on silicon wafer to form the coffee ring, which comprises densely packed silver nanoparticles loaded with analytes on the interface of the silicon wafer. In light of this, analytes were able to enrich twice in one process. Furthermore, densely-packed substrate produced a large number of “hot-spots” to improve the SERS effect. The combination of pre-concentration of β-CD and the SERS effect of the coffee-ring enhanced the detection ability of SERS to aromatic compounds. Due to the special structure of β-CD, this strategy can also be utilized in the SERS detection of other analytes.

Epithelial–mesenchymal transition (EMT), a process by which epithelial cells undergo a phenotypic conversion that gives rise to fibroblasts and myofibroblasts, plays an important role in tissue repair and fibrosis, chronic inflammation, cancer invasion and metastasis. Therefore, increasing attention has focused on the study of EMT. However, it is still a challenge to distinguish the undifferentiated and differentiated epithelial cells, which are closely related and morphologically similar. In this study, we employed the transactivator of transcription (TAT)-functionalized AuNSs as intracellular surface-enhanced Raman scattering (SERS) probes for characterizing the EMT process in alveolar epithelial type II (ATII) cells, induced by bleomycin (BLM). CCK8 assay and reliable aggregation tests indicated a low cytotoxicity and high stability of the intracellular SERS probes. The internalization of the TAT-functionalized AuNSs acting on the ATII cells was verified by transmission electron microscopy (TEM), fluorescence images, and energy-dispersed spectroscopy (EDS). SERS spectra were analyzed by principal component analysis (PCA), which was able to distinguish between ATII cells at different stages of EMT and monitor the cellular biochemical composition changes in this process. In addition, the expression of epithelial and fibroblastic markers on ATII cells suggested that incubation with BLM could induce ATII cells to differentiate into fibroblasts. The SERS detection of the internalized TAT-functionalized AuNSs provides a continuous, non-invasive, and label-free characterization for the EMT process.

The developed method for monitoring GST, an important drug metabolic enzyme, could greatly facilitate researches on relative biological fields. In this work, we have developed a SERS technique to monitor the absorbance behaviour of 6-mercaptopurine (6-MP) and its glutathione-S-transferase (GST)-accelerated glutathione (GSH)-triggered release behaviour on the surface of gold nanoflowers (GNFs), using the GNFs as excellent SERS substrates. The SERS signal was used as an indicator of absorbance or release of 6-MP on the gold surface. We found that GST can accelerate GSH-triggered release behaviour of 6-MP from the gold surface. We speculated that GST catalyzes nucleophilic GSH to competitively bind with the electrophilic substance 6-MP. Experimental results have proved that the presented SERS protocol can be utilized as an effective tool for accessing the release of anticancer drugs.

For developing a free radical-quenched surface-enhanced Raman scattering (SERS) probe, starch, a linear molecule, was used as a protective layer to coat gold nanoshells (GNSs) as enhancement substrates and then, methylene blue (MB) was absorbed on the starch-coated GNSs as a free radical-responsive element. By detecting the change of the SERS intensity of MB on GNSs, the free radical-quenched SERS probes were used to detect H2O2, a less active reactive oxygen species (ROS), which was first converted to free radicals, a highly active ROS, to react with MB absorbed on GNSs to quench its SERS. The free radical-quenched SERS probe was also used to detect glucose in the presence of glucose oxidase which converted glucose to H2O2. The free radical-quenched SERS probe would be a versatile platform for detection of biochemical processes. The integration of optically changed molecules and optical enhancement of nanomaterials provided a way for advanced materials and analytical science.

In this article, for the first time, we report a facile method for the synthesis and immobilization of AuNPs on m-aminophenol based resin (MAPR) microspheres via a simple reduction route. The AuNP-decorated MAPR (AuNPs/MAPR) microspheres, with a large number of active groups (amino and hydroxy groups), can not only act as suitable immobilization carriers for antibodies (EGFR antibody), but also play an important role in facilitating electron transfer. Moreover, the AuNPs/MAPR microspheres possess a high surface-enhanced Raman scattering (SERS) activity and have great potential as a SERS-active substrate. A novel electrochemical cytosensor which can sensitively differentiate lung cancer cells (A549 cells) from normal ones (AT II cells) by making use of the advantages of EGFR antibodies and AuNPs/MAPR microspheres has been designed. EGFR antibodies are immobilized on the outmost layer of the electrode surface to selectively recognize EGFR receptors that are over-expressed on lung cancer cells. The confocal microscopy images and cytotoxicity assays of the AuNPs/MAPR microspheres confirm that the prepared cytosensors exhibit good biocompatibility, high sensitivity and selectivity for the detection of A549 cells. To the best of our knowledge, this is the first cytosensor using AuNPs/MAPR microspheres as a carrier. It exhibits a broad linear range with a detection limit as low as 5 cells per mL, even in the presence of a large number of normal cells. Our study demonstrates that the proposed cytosensors can also be used to successfully determine A549 cells in diluted blood samples.

A simple multiplexed electrochemical and surface-enhanced Raman spectroscopic (SERS) immunosensor is developed for simultaneous detection of carcinoembryonic antigen (CEA) and cytokeratin-19 (CK-19). We find a kind of Raman dye (thionine and Nile blue A)-decorated resin microspheres by π–π stacking interaction, which show both strong SERS signals and electrochemical redox characteristic peaks. Aminosalicylic acid-based resin (AAR) microspheres are synthesized by a template-free method for the first time. The Au nanoparticle (AuNP) coated AAR microspheres (AuNPs/AAR) are prepared by a convenient reduction approach. A sandwich structure contains Raman dye-labeled AuNPs/AAR with the first antibody, the second antibody immobilized on the electrode modified chitosan stabilized AuNPs, and target antigens. Thus, in the presence of the target antigens, the Raman dye-labeled AuNPs/AAR could be bonded to the modified electrode surface by antibody–antigen–antibody interactions. Compared with thionine, Nile blue A has different Raman signals and electrochemical characteristic peaks. As a result, a simultaneous immunoassay for CEA and CK-19 based on multiple labels is developed by using electrochemical and SERS immunoassays. The prepared immunoassay for detection of CEA and CK-19 shows high sensitivity, selectivity, low detection limit and long term stability. The lowest detectable concentration is 0.01 ng mL−1 and 0.04 ng mL−1 for CEA and CK-19 at a signal to noise rate of 3, respectively. The proposed immunosensor can be applied to determine CEA and CK-19 in human blood serum with favorable results. In addition, the electrochemical and SERS immunosensor has potential application in the diagnosis and treatment of lung cancer in the field of clinical research.

Here, a highly specific, sensitive, and reliable immunoassay has been developed based on surface-enhanced Raman scattering for quantitative detection of carcinoembryonic antigen (CEA). A novel hollow gold nanospheres (HGNs) was firstly fabricated by seed-mediated methods instead of the one-step methods with high homogeneity and then, the monodispersed HGNs were embedded with 4-mercaptobenzonic acid to form surface-enhanced Raman scattering (SERS) tags and magnetic microspheres were synthesized as enrichment substrates. Based on this sandwich immunoassay strategy, CEA monoclonal antibody -conjugated HGNs-based SERS tags and CEA polyclonal antibodies -conjugated magnetic microspheres were used to detect CEA up to 100 ng/mL with a detection limit of 10 pg/mL, which were two orders of magnitudes lower than that of GNSs-based SERS tags. The monodispersed HGNs were desirable SERS tags for quantitative sandwich immunoassay assay, showing strong potential for the clinical diagnosis of cancer biomarkers.

An enzymatic glucose biosensor was developed that is making use of microspheres consisting of an m-aminophenol based resin decorated with silver nanoparticles (AgNP/MAPR). It was applied to the detection of H2O2 and, if loaded with glucose oxidase (GOx), to the determination of glucose. The AgNPs were thermally immobilized on the MAPR microspheres. The AgNP/MAPR microspheres were deposited on a glassy carbon electrode (GCE) by surface casting. The resultant electrode exhibits remarkable catalytic performance in terms of H2O2 reduction. The sensor gives an amperometric response to H2O2 within <3 s and has a linear response in the 0.1 mM to 0.18 M concentration range (r = 0.997). The detection limit is 2.7 μM at an SNR of 3. The glucose biosensor has a linear response in the 2 to 12 mM range and a detection limit of ~0.1 mM. The biosensor was applied to the determination of glucose in human blood serum.

In this paper, a non-invasive, simple and efficient approach is constructed to make clean gold nanostar substrates with higher enhancement effect, homogeneous surface-enhanced Raman scattering (SERS) activity and high reproducibility, which are the assembly of gold nanostars based on the electrostatically assisted APTES-functionalized surface-assembly method. The obtained substrates enable us to successfully compare and distinguish two lung cancer cell lines [human lung adenocarcinoma epithelial cell line (A549), human non-small cell lung cancer cell line (H1229)] and one normal lung cell line [human type II alveolar epithelial cell line (AT II)] through SERS spectra. The difference spectra (A549 – H1229, A549 – AT II and H1229 – AT II) among the three cell lines are studied to better interpret the spectral differences and gain insight into the biochemical variation. Furthermore, principal component analysis (PCA) score plots of the SERS spectra are also used to better view the differences among these three cell lines. This sensitive, efficient and non-invasive detection method, based on gold nanostar substrates, will have great potential for the differentiation of living cells and play an important role in the early diagnosis and treatment of cancers.

In this study, an ultrasensitive surface-enhanced Raman scattering (SERS) detection of alkaline phosphatase (ALP) has been developed, in which nile blue A (NBA) was chosen to replace nitro blue tetrazolium chloride (NBT) in a reactive system of 5-bromo-4-chloro-3-indolyl phosphate (BCIP), NBT, and ALP. In the reactive process, NBA was converted to a low SERS-active molecule, and its SERS intensity at 592 cm−1 decreased when NBA was reduced by 5-bromo-4-chloro-3-indolyl, which converted from BCIP by ALP. The SERS signal of NBA was inversely proportional to the amount of ALP in the reactive system. Based on convenient SERS materials of gold nanoshells absorbed on acupuncture needles, the detectable concentration range of ALP was 1–104 mU L−1 in a reactive system of BCIP, NBA, and ALP.

•AgNPs/thionine/infinite coordination polymer fibres are prepared for the first time.•The AgNP/THI/ICP fibres can favor the immobilization of antibody.•It is the first CEA biosensor with the use of AgNP/THI/ICP fibres.In this article, for the first time, a novel, high-yield and template-free method for the synthesis of Ag nanoparticle decorated thionine/infinite coordination polymer (AgNP/THI/ICP) fibres is proposed. The thionine can be adsorbed to the AgNP/THI/ICP fibres by π-conjugation and act as the redox probe. The AgNP/THI/ICP fibres not only favor the immobilization of antibody but also facilitate the electron transfer. It is found that the AgNP/THI/ICP fibres can be designed to act as a sensitive label-free electrochemical immunosensor for carcinoembryonic antigen (CEA) determination. Under the optimized conditions, the linear range of the proposed immunosensor is estimated to be from 50 fg/mL to 100 ng/mL and the detection limit is estimated to be 0.5 fg/mL at a signal-to-noise ratio of 3, respectively. The prepared immunosensor for detection of CEA shows high sensitivity, reproducibility and stability. Our study demonstrates that the proposed immunosensor has also been used to determine CEA successfully in diluted blood samples.

•High-yield synthesis of biomolecule (serotonin)-based formaldehyde resin (BFR) microspheres is proposed for the first time.•The BFR microspheres loaded with Au nanoparticles provide a conductive multi-pathway of electron transfer.•A sensitive label-free electrochemical immunosensor based on AuNPs/BFR microspheres is used for carcinoembryonic antigen (CEA) determination.•It is the first CEA biosensor with the use of AuNP/BFR microspheres.•This immunosensor can be used for CEA detection in human serum.A surfactant-free and template-free method for the high-yield synthesis of biomolecule (serotonin)-based formaldehyde resin (BFR) microspheres is proposed for the first time. The colloidal microspheres loaded with Au nanoparticles (AuNPs) prepared by a convenient in-situ synthesis of AuNPs on BFR (AuNPs/BFR) microsphere surface show good stability. AuNPs/BFR microspheres not only favor the immobilization of antibody but also facilitate the electron transfer. It is found that the resultant AuNPs/BFR microspheres can be designed to act as a sensitive label-free electrochemical immunosensor for carcinoembryonic antigen (CEA) determination. The immunosensor is prepared by immobilizing capture anti-CEA on AuNPs/BFR microspheres assembled on thionine (TH) modified glassy carbon electrode (GCE). TH acts as the redox probe. Under the optimized conditions, the linear range of the proposed immunosensor is estimated to be from 25 pg/mL to 2000 pg/mL (R=0.998) and the detection limit is estimated to be 3.5 pg/mL at a signal-to-noise ratio of 3. The prepared immunosensor for detection of CEA shows high sensitivity, reproducibility and stability. Our study demonstrates that the immunosensor can be used for the CEA detection in humans serum.

•The bimetallic gold–silver nanoplate arrays were fabricated by coating silver nanoparticles uniformly on the gold nanoplate arrays.•The SERS intensity increased with the silver nanoparticle coating, due to a large number of hot spots and nanoparticle interfaces.•The SERS substrate was used for testing against the supramolecular interaction between streptavidin and biotin.The silver-modified gold nanoplate arrays as bimetallic surface-enhanced Raman scattering (SERS) substrates were optimized for the surface-enhanced Raman detection of streptavidin/biotin monolayer assemblies. The bimetallic gold–silver nanoplate arrays were fabricated by coating silver nanoparticles uniformly on the gold nanoplate arrays. Depending on silver nanoparticle coating, the localized surface plasmon resonance (LSPR) peak of the bimetallic gold–silver nanoplate arrays blue-shifted and broadened significantly. The common probe molecule, Niel Blue A sulfate (NBA) was used for testing the SERS activity of the bimetallic gold–silver nanoplate arrays. The SERS intensity increased with the silver nanoparticle coating, due to a large number of hot spots and nanoparticle interfaces. The platforms were tested against a monolayer of streptavidin functionalized over the bimetallic gold–silver nanoplate arrays showing that good quality spectra could be acquired with a short acquisition time. The supramolecular interaction between streptavidin (strep) and biotin showed subsequent modification of Raman spectra that implied a change of the secondary structure of the host biomolecule. And the detection concentration for biotin by this method was as low as 1.0 nM. The enhanced SERS performance of such bimetallic gold–silver nanoplate arrays could spur further interest in the integration of highly sensitive biosensors for rapid, nondestructive, and quantitative bioanalysis, particularly in microfluidics.

We introduce a simple but robust label-free method to detect DNA based on large-scale gold nanoplate (GNP) films with tunable localized surface plasmon resonance (LSPR) and highly surface-enhanced Raman scattering (SERS) activity. The common probe molecule, Neil Blue A sulfate (NBA) is used for testing the SERS activity of the GNP films at very low concentrations. It is found that the SERS properties are highly dependent on the edge lengths of gold nanoplate and gold nanoplate density in the films. Multiple-layer GNP films which are constructed by gold nanoplate with an edge length of 134±6 nm have the density of 916±40 GNPsGNPs/spot. It shows the highest signal intensity with SERS enhancement factor (EF) as high as 5.4×107 and also has excellent stability, reproducibility and repeatability. The optimized SERS-active substrate with the largest enhancement ability could be used to detect double-strand DNA without a dye label, and the detection limit is down to 10−6 mg/mL.Highlights► We developed a simple, fast, and low-cost method to fabricate large-scale gold nanoplate films with tunable localized surface plasmon resonance (LSPR) and surface-enhanced Raman scattering (SERS) activity. ► Controlling the edge lengths of gold nanoplate and gold nanoplate density in the films could result in an optimized substrate with the greatest Raman enhancement. ► The multiple-layer GNP film constructed by gold nanoplates with edge length of 134 ± 6 nm show the highest signal intensity with SERS enhancement factor (EF) as high as 5.4×107. ► The optimized SERS-active substrate with the largest enhancement ability could be used to detect double-strand DNA without a dye label, and the detection limit is down to 10-6 mg/mL.

To detect glucose in vivo with minimal invasion, a glucose-responsive multifunctional acupuncture needle was developed by integrating glucose oxidase (GOx, signal convertor), 4-mercaptobenzoic acid (4-MBA, signal reporter), and a microporous polystyrene (PS)-coated SERS-active acupuncture needle (signal amplifier) which was also used as an integration carrier and sampling device. On the needle, the integrated GOx converted glucose to gluconic acid which changed pH value of the microenvironment and then, the integrated 4-MBA reported the changed pH which indirectly reported the glucose concentration. The integrated SERS-active materials enhanced Raman signal of 4-MBA to provide an optical readout of the glucose concentration. The SERS detection did not depend on the affinity to SERS substrates and intrinsic Raman activity of glucose. Integrating suitable enzymes and corresponding reporters on microporous PS-coated SERS-active needles, the method can become a universal strategy to SERS detection of small biomolecules in vivo.

A SERS active gold nanostar layer on the surface of ITO glass slip has been prepared by a low-cost electrostatically assisted APTES-functionalized surface-assembly method for SERS analysis. The two-dimensional morphology of the SERS substrate was examined by scanning electron microscopy. Comparative analysis revealed that the optical characteristics and SERS efficiency of these substrates varied as a function of nanostar morphology. It was found that the substrate assembled with the longest branches of nanostars generated the best SERS efficiency, whether the excitation source is 785 or 633 nm. The potential use of these substrates in detection applications was also investigated by using Nile blue A and Rhodamine 6G. The detection limits are 5 × 10–11 M and 1 × 10–9 M, respectively, when using the 785 nm excitation source. Apart from this high enhancement effect, the substrate here also shows extremely good reproducibility at the same time. All of these indicate that gold nanostars are a very good structure for SERS substrate assembly.Keywords: electrostatically assisted APTES-functionalized surface-assembly; gold nanostar; low-cost; reproducible substrate; SERS

A novel method based on surface-enhanced Raman scattering (SERS) was developed to estimate the antioxidant activity of antioxidants by using self-assembled three-dimensionally (3D) ordered gold nanoparticles (GNPs) precursor composite (SiO2/GNPs) arrays as nanoprobes. H2O2 could reduce AuCl4− to Au0 which deposited onto the surface of the SiO2/GNPs arrays and enlarged the GNPs. As the concentration of H2O2 increased, the surface coverage of the resultant gold on the silica cores increased accordingly until continuous gold nanoshells (GNSs) were formed. The change of the intensities of the SERS spectra correlated well with H2O2 concentration which indicated that this SiO2/GNPs array was a potential SERS nanoprobe for H2O2. The presence of antioxidant will prevent the growth of GNPs on the surface of the silica arrays from forming the structure which has strongest SERS-activity and the corresponding change in SERS intensity correlated well with the H2O2 scavenging activity of the antioxidants. The H2O2 scavenging activities of four plant-based antioxidants, tannic acid, citric acid, ferulic acid, and tartaric acid were studied. Our results showed the H2O2 scavenging activities (SAHP values) of these four compounds were: tannic acid > ferulic acid > citric acid > tartaric acid.

A series of phenolic acids were tested for their ability to scavenge hydrogen peroxide (H2O2) by using a novel enzyme-free, spectrophotometry assay. Gold nanoshells (GNSs) precursor composites were selected as the optical nanoprobes. The approach was based on the H2O2-induced growth of GNSs, which combines nanoscience with food/health research as an innovative detection scheme. The addition of phenolic acids inhibits the formation of complete GNSs and the corresponding peak wavelength changes rationally, which could be used as an optical signature. Among the tested samples, caffeic acid is found to be the most efficient H2O2-scavenger with its H2O2-scavenging activity being 125 × 10−3 μM−1, whereas trans-cinnamic acid exhibits the weakest activity (0.73 × 10−3 μM−1). Results obtained were considered on the basis of structure–activity relationships. Additionally, several tea and herb extracts were also evaluated. The presented wavelength-based detection method shows superiority in evaluating coloured samples, which avoids background interference compared with the conventional absorbance-based optical methods.Research highlights► We have tested the antioxidant capacity of a series of phenolic acids and natural antioxidants successfully by utilizing the gold nanoshells precursor composites. ► The wavelength-based detection optical method shows superiority in evaluating colour samples which will avoid background interference. ► The assay provides an alternative perspective for the innovative detection scheme in combination with nanoscience and food/health industry.

Here we report a novel method for detecting 3,4-dihydroxyphenylalanine (L-DOPA) and tyrosinase (TR) activity based on surface-enhance Raman scattering (SERS) by employing a large-scale versatile three-dimensionally (3D) ordered nanocomposite (SiO2/GNPs) array as a nanosensor. L-DOPA could reduce AuCl4− to Au0 and enlarge the gold nanoparticles (GNPs) that attach on the surface of the SiO2/GNPs array, the preadsorbed GNPs serve as nucleation sites for Au0 to deposit. As the concentration of L-DOPA increases, the surface coverage of resultant Au0 on silica cores increases accordingly until complete gold nanoshells (GNSs) are formed. During the growth procedure, the SERS-activity of the GNSs arrays correlate well with the concentration of L-DOPA, which indicates that this SiO2/GNPs array is a potential nanosensor for detecting L-DOPA. As TR can catalyze the hydroxylation of L-tyrosine to form L-DOPA, this approach can also be employed to analyze the activity of TR, which possesses vast clinical and food industrial importance. Compounds such as cinnamic acid and p-hydroxybenzoic acid can inhibit the TR activity. Thus, the TR-triggered growth of the GNSs array system can also be used to detect the TR inhibited activity of inhibitors.

In this work, we have developed a novel SERS-based approach to detect hydrogen peroxide (H2O2) scavenging activity by using gold nanoshell precursor nanocomposites (SiO2/GNPs) as nanoprobes. H2O2 can reduce AuCl4− to Au0 and enlarge the gold nanoparticles (GNPs) that attached on the surface of SiO2. As the concentration of H2O2 increases, the surface coverage of resultant gold on silica cores increases accordingly until continuous gold nanoshells (GNSs) are formed. During the growth process, there is a strong correlation between the SERS-activity of the GNSs and the amount of H2O2 that is used as reductant. When H2O2 reaches 250 μM, the resultant GNSs show the highest SERS-activity. H2O2 can be scavenged by antioxidants such as tannic acid and L-apple acid. Their H2O2 scavenging activities were determined by restraining the H2O2-mediated (250 μM) growth of SiO2/GNPs. The decrease of the SERS-activity was proportional to the H2O2 scavenging activity of the antioxidant. The results showed that tannic acid had a much higher H2O2 scavenging activity than that of L-apple acid.

In this study, we present a new method to fabricate large-area two-dimensionally (2D) ordered gold nanobowl arrays based on 3D colloidal crystals by wet chemosynthesis, which combines the advantages of a very simple preparation and an applicability to “real” nanomaterials. By combination of in situ growth of gold nanoshell (GNSs) arrays based on three-dimensional (3D) colloidal silica crystals, a monolayer ordered reversed GNS array (2D ordered GNS array) was conveniently manufactured by an acrylic ester modified biaxial oriented polypropylene (BOPP). 2D ordered gold nanobowl array with adjustable periodic holes, good stability, reproducibility, and repeatability could be obtained when the silica core was etched by HF solution. The surface-enhanced Raman scattering (SERS) enhancement factor (EF) of this 2D ordered gold nanobowl array could reach 1.27 × 107, which shows high SERS enhancing activity and can be used as a universal SERS substrate.

Gold nanoshells (GNSs), consisting of a dielectric core coated with gold, have gained extensive attention as they show readily tunable optical properties and good biocompatibility. As highly sensitive and label-free optical biosensors with wide applications, GNSs have been investigated in many fields including drug delivery, immunoassay, cancer treatment, biological sensing and imaging. Taking advantage of the adjustability of the local surface plasmon resonance (LSPR) and the sensitivity of the surface-enhanced Raman scattering (SERS) signal of GNSs, we have developed diverse applications including plasmonic biosensors and nanoprobes based on GNSs. In this review we introduce plasmonic and electromagnetic properties and fabrication methods of GNSs. We describe research progress in recent years, and highlight several applications of GNSs developed by our group. Finally we provide a brief assessment of future development of GNSs as plasmonic materials that can be integrated with complementary analytical techniques.

In the present work, we have developed a novel method for in situ controllable preparation of gold nanorods (GNRs) within the thermo-responsive P(NIPAM-NVP) hydrogel networks by regulating the rates of the reduction and the mass transfer. When the pH value of the medium is gradually decreased, the reduction rate of gold ions is significantly decreased and the morphologies of the gold nanostructures in hydrogel networks are changed from gold nanoparticles to GNRs with different aspect ratios. Besides, lower cross-linking density results in the increased diffusion coefficient and reduced diffusion resistance of the solute in the hydrogels. It is an advantage for maintaining an appropriate balance between the reduction rate and the diffusion rate, in turn, improving the yield of GNRs. The resulting composites combine the thermo-responsive behavior of P(NIPAM-NVP) hydrogels with the optical properties of GNRs. Their localized surface plasmon resonance and the surface enhanced Raman scattering effects can be changed by adjusting the temperature of the hydrogels. The composites are utilized as SERS substrates and demonstrate an excellent thermo-responsive enhancement effect.

In the present work, the gold nanoshells (GNSs) precursor composites were preadsorbed onto the surface of ITO substrates. With the treatment of modified electrodes immersed in the gold nanoparticles (GNPs) growth solution containing different phenolic acids, the GNSs precursor composites were enlarged to varying degrees. Phenolic acids with one or more phenolic hydroxyl groups served as reductants for the growth of GNPs. The enlargement conditions varied with the different reducing capacity of phenolic acids, exhibiting specific morphologies differ from the complete GNSs. Consequently, the UV–vis–NIR spectra and cyclic voltammetry curves for the phenolic acid-treated ITO electrode were gradually changed. Results showed that the higher reducing capacity for phenolic acid to reduce AuCl4− to Au0 resulted in the intensified localized surface plasmon resonance features and reduced cathodic currents. The spectral wavelength peaks red shifted hundreds of nanometers across the visible region. Moreover, the antioxidant capacity of phenolic acids correlates well with their reducing activity, both of which reflect their tendency to donate electrons. Thus, the optical and electrochemical results could be used to evaluate the antioxidant capacity of phenolic acids by utilizing GNSs precursor composites as nanoprobes. The method is simple, rapid and could be used in visual analysis to a certain extent.

In the present work, we have developed a novel nanocomposite-based method for estimating antioxidant activity. The assay implements a new enzyme-free optical nanoprobe for assessing hydrogen peroxide (H2O2) scavenging activity based on the formation process of gold nanoshells (GNSs). H2O2 could enlarge the gold nanoparticles (GNPs) on the surface of GNSs precursor nanocomposites (SiO2/GNPs), and the preadsorbed GNPs served as nucleation sites for Au deposition. As the concentration of H2O2 increases, more GNPs on the SiO2 cores are enlarged until continuous GNSs are formed. During the growth procedure, the spectra changes correlate well with H2O2 concentrations which indicate that this nanocomposite is a good nanoprobe for detecting H2O2. H2O2 scavenging activities of several antioxidants were determined by restraining the H2O2-mediated formation of GNSs from SiO2/GNPs, and the changes of the corresponding plasmon absorption bands correlated well with H2O2 scavenging activity of antioxidants. The spectra were monitored by a UV−vis-near-infrared (NIR) spectrophotometer, and the wavelength changes were adopted as detection signal. The results obtained expressed the difference of H2O2 scavenging activity between various tested compounds, and the relationship between function and structure of antioxidants was also discussed in this article. The new method based on the formation process of GNSs is simple, rapid, and sensitive and, additionally, can be used in visual analysis to a certian extent for antioxidant functional evaluation.

A simple biosensor for hydrogen peroxide (H2O2) and glucose was fabricated by incorporating gold nanoparticles (GNPs) onto a cuttlebone-derived matrix substrate (CDMS). Such a three-dimensional chamber-like structure naturally bears abundant amino groups for the direct immobilization of GNPs without a series of modifications. And preferably, the framework endows CDMS with a very high surface area for the attachment of GNPs, resulting in effective optical signal transduction and improved sensitivity of the detection system. The principle behind this biosensor is that the localized surface plasmon resonance (LSPR) of the immobilized GNPs changes with the enlargement of GNPs by H2O2-mediated chemical reduction of chloroauric acid. Using this approach, we demonstrate the proof of an optical biosensor to quantify the concentration of H2O2 as well as glucose. UV–vis absorption spectra were recorded to obtain quantitative information about the H2O2 or glucose concentration. The detection range of our biosensor to H2O2 concentration was from 2 × 10−6 to 1.5 × 10−4 M, while the linear response range of glucose concentration was from 5 × 10−6 to 5 × 10−5 M. Inspiringly and interestingly, the growth of GNPs on CDMS gives rise to color changes, this phenomenon shows that the rapid detection by our sensor has the superiority in visual detection to a certian extent, which has been a potential application in qualitative or semiquantitative analysis for medicine and biotechnology.

Biologically derived materials provide a rich variety of approaches toward new functional materials because of their fascinating structures and environment-friendly features, which is currently a topic of research interest. In this paper, we show that the cuttlebone-derived organic matrix (CDOM) is an excellent scaffold for the one-step synthesis and assembly of silver nanoparticles (AgNPs), which can be further used as substrate for surface-enhanced Raman scattering (SERS). Formation of AgNPs–CDOM composite was accomplished by the reaction of CDOM with AgNO3 and NH3·H2O solution at 80 °C without using any other stabilizer and reducing agents. UV–vis spectra and TEM were utilized to characterize the AgNPs and investigate their formation process. Results demonstrate that the size and distribution of AgNPs can be partly regulated by changing incubation time; the concentration of NH3·H2O is critical to the formation rate of AgNPs. As a proof of principle, we show that the AgNPs–CDOM composite can be employed in trace analysis using SERS.

Gold nanoshells (GNSs) were self-assembled on the surface of transparent glasses modified with 3-aminopropyltrimethoxysilane (APTES) to form GNS self-assembled monolayers (SAMs). Because the localized surface plasmon resonance (LSPR) of GNSs can be controlled in the near-infrared (NIR) region of the spectrum, where the optical transmission through tissue and whole blood is optimal, GNSs would be used as an effective signal transduction in whole blood. Accordingly, after modified with cystamine and biotin-NHS (N-hydroxy succinimide), GNS SAMs were used as a novel optical biosensor for real-time detection of streptavidin–biotin interactions in diluted human whole blood within short assay time, without any sample purification/separation. An UV–vis–NIR spectrophotometer was used to monitor the absorbance changes at 730 nm as a function of time for different concentrations of streptavidin in 20% whole blood, and the results showed that the biosensor displayed low detection limit of ∼3 μg/mL and wide dynamic range of ∼3–50 μg/mL. This approach provides an opportunity to construct LSPR biosensor for protein sensing and cellular analysis in diluted whole blood.

Gold nanoshells (GNSs), consisting of a silica core and a thin gold shell, were self-assembled on the surface of 3-aminopropyltrimethoxysilane (APTES) modified indium tin oxide (ITO) electrode. The resulting novel GNSs-coated ITO (GNSs/APTES/ITO) electrode could provide a biocompatible surface for the adsorption of hemoglobin (Hb). The UV-visible (UV–vis) spectra indicated that Hb adsorbed on the GNSs interface retained the native structure. Electrochemical impedance spectra and cyclic voltammetric techniques were employed to evaluate the electrochemical behaviors of Hb, the results demonstrated that GNSs could act as electron tunnels to facilitate electron transfer between Hb and the electrode. Based on the activity of Hb adsorbed on the GNSs/APTES/ITO electrode toward the reduction of hydrogen peroxide, a mediator-free H2O2 biosensor was constructed, which showed a broad linear range from 5 μM to 1 mM with a detection limit of 3.4 μM (S/N = 3). The apparent Michaelis–Menten constant was calculated to be 180 μM, suggesting a high affinity.

In the present work, we have developed a novel method for in situ controllable preparation of gold nanorods (GNRs) within the thermo-responsive P(NIPAM-NVP) hydrogel networks by regulating the rates of the reduction and the mass transfer. When the pH value of the medium is gradually decreased, the reduction rate of gold ions is significantly decreased and the morphologies of the gold nanostructures in hydrogel networks are changed from gold nanoparticles to GNRs with different aspect ratios. Besides, lower cross-linking density results in the increased diffusion coefficient and reduced diffusion resistance of the solute in the hydrogels. It is an advantage for maintaining an appropriate balance between the reduction rate and the diffusion rate, in turn, improving the yield of GNRs. The resulting composites combine the thermo-responsive behavior of P(NIPAM-NVP) hydrogels with the optical properties of GNRs. Their localized surface plasmon resonance and the surface enhanced Raman scattering effects can be changed by adjusting the temperature of the hydrogels. The composites are utilized as SERS substrates and demonstrate an excellent thermo-responsive enhancement effect.

To detect glucose in vivo with minimal invasion, a glucose-responsive multifunctional acupuncture needle was developed by integrating glucose oxidase (GOx, signal convertor), 4-mercaptobenzoic acid (4-MBA, signal reporter), and a microporous polystyrene (PS)-coated SERS-active acupuncture needle (signal amplifier) which was also used as an integration carrier and sampling device. On the needle, the integrated GOx converted glucose to gluconic acid which changed pH value of the microenvironment and then, the integrated 4-MBA reported the changed pH which indirectly reported the glucose concentration. The integrated SERS-active materials enhanced Raman signal of 4-MBA to provide an optical readout of the glucose concentration. The SERS detection did not depend on the affinity to SERS substrates and intrinsic Raman activity of glucose. Integrating suitable enzymes and corresponding reporters on microporous PS-coated SERS-active needles, the method can become a universal strategy to SERS detection of small biomolecules in vivo.

In this study, an ultrasensitive surface-enhanced Raman scattering (SERS) detection of alkaline phosphatase (ALP) has been developed, in which nile blue A (NBA) was chosen to replace nitro blue tetrazolium chloride (NBT) in a reactive system of 5-bromo-4-chloro-3-indolyl phosphate (BCIP), NBT, and ALP. In the reactive process, NBA was converted to a low SERS-active molecule, and its SERS intensity at 592 cm−1 decreased when NBA was reduced by 5-bromo-4-chloro-3-indolyl, which converted from BCIP by ALP. The SERS signal of NBA was inversely proportional to the amount of ALP in the reactive system. Based on convenient SERS materials of gold nanoshells absorbed on acupuncture needles, the detectable concentration range of ALP was 1–104 mU L−1 in a reactive system of BCIP, NBA, and ALP.