Narrow Results

Ultrasensitive detection of alpha-fetoprotein (AFP) is critical for the early diagnosis of liver cancer. In this work, a novel surface-enhanced Raman scattering (SERS)-based immunoassay complex has been successfully developed for the detection of AFP by using the Au-Ag alloy nanoparticals and the Ag/AgBr hybrid nanostructure. As the typical bimetal or metal/semiconductor plasmonic materials, besides the strong SERS enhancement characteristics, the Au-Ag alloy nanoparticals exhibit excellent monodispersity and the Ag/AgBr hybrid nanostructure demonstrates good stability. The experimental results show that the SERS-based immunoassay of AFP presents a low limit of detection of 1.86fg/mL and a broad dynamic range from 2fg/mL to 0.8$\mu$g/mL. Furthermore, the clinical applicability of the proposed SERS-based immunoassay has been assessed by the detection of AFP in the human serum samples of cancer patient and healthy person. The test data are consistent well with that of chemiluminescence immunoassay (CLIA) in the relative errors of $-$8.82–8.06% and show better detection sensitivity. It reveals that the proposed immunoassay protocol is significant for giving insight into the design of ultrasensitive biosensor and the point-of-care testing of cancers.

Cervical cancer is a common cause of cancer-related death in women worldwide, and quantitative detection of serum tumor markers has practical implications for diagnosing cervical cancer. In this study, a novel surface-enhanced Raman scattering (SERS)-based immunosensor for the hypersensitive simultaneous detection of survivin and osteopontin (OPN) in cervical cancer serum was proposed, which was composed of the AuNPs@SiO₂ microspheres (Au@SiO₂) array immunosubstrate and Au-Ag nanoshells (Au-AgNSs) immunoprobes. The experimental results demonstrated that the constructed SERS immunosensor exhibited satisfactory selectivity and reproducibility while possessing detection limits as low as 0.908pg/mL and 0.813pg/mL for survivin and OPN in human serum. Finally, its usefulness in real serum samples (from healthy subjects, cervical intraepithelial neoplasia 1 (CIN 1), CIN 2, CIN 3 and cervical cancer patients) was verified, and the detection data were in good agreement with the enzyme-linked immunosorbent assay results. This immunosensor has excellent performance, which is promising for the early screening of cancer.

Branched metal nanoparticles present a promising new class of materials, which have great potential as sensors, catalysts, drug carriers, and imaging agents, owing to their unique nanostructures, physicochemical properties, optical properties, and other characteristics. Many efforts have recently been devoted to the wet-chemical synthesis of branched metal nanoparticles. Seed-mediated growth and seedless growth are two main routes for producing branched metal nanoparticles. Most particle synthesis methods can be modified for different metal systems. In this review, various synthesis methods for the fabrication of branched monometallic, bimetallic, and multimetallic nanoparticles and also branched polymer core-metal nanoshell composite nanoparticles are summarized, catagorized, and discussed. The relevance and performance of such nanostructured materials with regard to their optical properties which arise from localized surface plasmon resonances are summarized, and their potential as excellent substrates for surface enhanced Raman scattering (SERS) is reviewed. Other applications of branched nanoparticles such as drug delivery vehicle, medical imaging agent, catalysis, and magnetism are briefly introduced.

In this paper, we investigate the impact of rice-starch stabilization of gold nanoparticles (AuNPs) on their catalytic and surface-enhanced Raman spectroscopy (SERS) activities. A typical green synthesis protocol was used to prepare AuNPs with rice-starch functioning as the reductant and the stabilizer. The localized surface plasmon resonance (LSPR) of the starch-stabilized AuNPs is pH-sensitive and got red-shifted with the medium’s pH. The average size of the AuNPs formed decreased with the amount of rice-starch up to a certain level. TEM result shows that the polymeric behavior of starch extract may help synthesize the Au nanorod morphologies. AuNPs stabilized by different amounts of rice-starch were applied as the catalysts for the model $p$-nitrophenol reduction reaction. For all AuNP catalysts used, the reaction followed pseudo-first-order kinetics. The catalyst turnover frequencies increased up to a certain level of starch functionalization. Further increase in starch led to a fall in the activity of AuNPs catalyst. The evidence on rate kinetics, induction times, activation energies, and turnover frequencies is combined to explain this phenomenon in terms of starch content. The SERS response of these AuNPs as substrates has also been investigated for methylene blue as the target molecules. AuNP substrates with an excess amount of starch weaken the SERS response and it can be ascribed to decreased light scattering efficiency of NPs as well as reduced interactions of methylene blue molecules with the NP surface.

Silver nanoparticles (NPs) films with different nominal thicknesses were deposited on the anodic aluminum oxide (AAO) templates with pore diameter about 200 nm by thermal evaporation. These NPs films were used as the surface enhanced Raman scattering (SERS) active substrates. The microstructure and surface morphology of the films were studied by X-ray diffraction and scanning electron microscopy, respectively. The SERS activity of the films was investigated by Raman scattering of adsorbed rhodamine 6G (R6G) at different concentrations. The results revealed that the average diameter of Ag NPs in different samples is 58 nm, 75 nm, 93 nm and 108 nm, respectively. Ag NPs film on AAO template is very suitable as a SERS active substrate and can detect R6G molecules with a concentration of 10^-8 M. The intensity of the SERS spectra is related to both the Ag NPs size and interparticle distance. The sample with an average particle diameter of 93 nm has the highest SERS enhancement factor (1.3 × 10⁶).

In this work, Ag nanoparticles were deposited in the TiO${}_{2-X}$ nanotube films through magnetron sputtering to form Ag-TiO${}_{2-X}$ nanocomposite. Scanning electron microscopy (SEM) was used to study microstructure and surface morphology. Rhodamine B (RhB) was deposited on the surface of Ag-TiO${}_{2-X}$ substrate for Raman spectroscopy test. The size of Ag nanoparticles can be controlled by changing the magnetron sputtering time. The result indicated that sputtering for 30 s obtained the highest Raman enhancement.

A simple method for improving surface-enhanced Raman scattering (SERS) performance of aligned silver nanorod (Ag NR) array was investigated. This method was to construct a kind of hybrid substrate by grafting Au@Ag core–shell nanoparticles (NPs) into Ag NR array using poly(2-vinylphridine) (P2VPy) as a bridging agent. The hybrid substrate yielded excellent SERS performance as its detection limit improved from 10${}^{-6}$ M to 10${}^{-8}$ M using trans-1,2-bis(4-pyridyl)ethylene (BPE) as probe molecule, which was increased by two orders of magnitude compared with Ag NR array substrate. The significant improvement of SERS performance of Ag NR arrays was attributed to the addition of Au@Ag core–shell NPs. As a result of surface plasmon resonance generated by the interaction of electromagnetic (EM) (IAEM) filed between NP and NR structures, increasing hotspots were found at the connections of NPs and NRs, the gaps of adjacent rods, and the gaps of two particles consequently. These results were validated by the finite difference time domain (FDTD) calculation. Besides, hybrid substrate shows good performance in stability and reproducibility. The proposed method was simple and robust, which promoted SERS performance of Ag NR array effectively, showing great potential in the application of SERS substrate fabrication and SERS-based bio-chemical sensing.

Imatinib is the standard first line treatment for chronic myeloid leukemia (CML). Owing to dose-related toxicities of Imatinib such as neutropenia, there is scope for treatment optimization through therapeutic drug monitoring (TDM). Trough concentration of 1 μg/mL is considered the therapeutic threshhold. Existing methods for the detection of Imatinib in plasma are limited by long read out time and expensive instrumentation. Hence, Raman spectroscopy was explored as a rapid and objective tool for monitoring Imatinib concentration. Three approaches: conventional Raman spectroscopy (CRS), Drop coating deposition Raman (DCDR) spectroscopy and surface-enhanced Raman spectroscopy (SERS) were employed to detect the required trough concentration of 1 μg/mL and above. Detection of therapeutically relevant concentrations (1 μg/mL) using SERS and suitable nanoparticle substrates has been demonstrated. Prospectively, rigorous validation using clinical samples is necessary to confirm the utility of this approach in routine clinical usage.

Surface-enhanced Raman scattering (SERS) has been widely studied and applied for over three decades. However, reliable SERS detection of molecules with low polarizability is still suffering from poor sensitivity and reproducibility. In this paper, we have reported a new strategy for performing quantitative SERS detection of Raman insensitive Glutathione (GSH), based on GSH-induced replacement of a highly Raman sensitive four-mercaptopyridine (MP) adsorbed on the surface of four-aminothiophenol (ATP) embedded Au-core/Ag-shell particles. This replacement led to a strong decrease of the MP SERS signal, which was used to determine the concentration of GSH. The adoption of GSH-induced Raman probe replacement leads to high sensitivity, while the use of internal reference method provides an improved accuracy of the GSH quantification.

The study of interaction and adsorption of drug molecules on the active surface of noble metal nanocluster is of particular interest due to effective change in the properties of the drug molecules. Surface-enhanced Raman scattering (SERS) theoretical calculations were performed to investigate the adsorption properties of pretomanid (PTD) on pyramidal ${\text{Ag}}_{20}$/${\text{Au}}_{20}$/${\text{Cu}}_{20}$ metal clusters. The charge transfer process from the $M_{20}$ pyramids is revealed by MEP and electronic analysis. The frequencies of PTD are enhanced in the PTD–metal complexes due to the noticeable SERS effect, and the binding energies were calculated to be −36.2 kcal/mol, −46.3 kcal/mol and −43.6 kcal/mol with Ag, Au and Cu structures, respectively. For the PTD–metal clusters, there is an entire potential rearrangement due to adsorption process which is due to charge transfer and adsorptions as chemisorption. The polarizability variations are predicted in the order PTD–Au > PTD–Cu > PTD–Ag which contribute the SERS enhancement due to adsorption. Changes in thermodynamic parameters reveal that adsorption is exothermic and at the same time spontaneous with ordered interactions due to the negative values. There is a redshift for the ultraviolet–visible (UV–vis) absorption of PTD–metal complexes with a lowering intensity in comparison with that of PTD, more likely indicating a chemisorption process. SERS enhancement factors are remarkable due to adsorption of conformationally flexible PTD on metal clusters. The noncovalent interactions between PTD and the metal pyramids were also determined. The study provided key information on designing a molecular structure with a good pharmacological profile by calculating bioactivity and drug similarity parameters for bioactive drug molecules.

We present a theoretical mechanism for electric field enhancement with SERS of InAs particles of subwavelength apertures under THz excitation. The distribution of electric field confirms that there is a strong enhancement in the InAs particles at THz frequencies. The InAs with a Drude-like behavior in THz range, which is similar to metals at optical frequencies, leads to different SERS when the parameters of these two particles change. The SERS enhancement factor can reach $10^{11}$ under the certain conditions.

Flexible surface enhanced Raman scattering (SERS) substrate was prepared by modification of sandpaper with silver nanoparticles. Under 633 nm excitation wavelength, the SERS enhancement effect of sandpapers which were treated with silver nanoparticles were evaluated by collecting Raman signals of probed molecules. The results demonstrate that the SERS enhancement effect of white (12,000 meshes) is better than that of pink (8000 meshes) sandpaper under the same condition; when the concentration of probe molecules is $10^{-4}$ mol/L, white sandpaper has the best SERS enhancement; the Raman scattering spectrum has better signal when the silver sol is 15 $\mu \mathrm{\text{L}}$.

Gold nanostructures were fabricated in porous SiO₂/Si ion-track templates by the wet chemical deposition from a solution of Au(I) sulfite complex. Their morphological features were analyzed, and features of the deposition processes were determined. A mechanism describing the selective formation of gold nanostructures in the pores of SiO₂ was proposed. The present approach allows us to control shape and size of Au nanostructures those which can be used as plasmonic active surfaces for SERS detecting of small amounts of biological and chemical substances.

Copper nanostructures demonstrating an activity in the surface-enhanced Raman scattering (SERS) spectroscopy were formed via electrochemical deposition of copper on porous aluminum oxide (PAO) and protected from oxidation by surface coverage with polyethylene glycol (PEG) and silver. The SERS measurements of 10${}^{-6}$-M 4-mercaptophenylboronic acid (MPBA) molecules adsorbed on fresh Cu-coated samples, Cu–PEG and Cu–PEG–Ag nanocomposites after 5, 10, 15, 60, 180 and 300min of storage in air indicated the effectiveness of the proposed approach in protection from oxidation.

Four new meso-tetraphenylporphyrin derivatives were prepared, singly and doubly substituted with thiocarbamate and thioacetate groups. These compounds were subsequently attached to gold nanoparticles suspended in chloroform. Very different kinetics of the attachment were revealed; the process was much faster for the thiocarbamate derivatives. Spectral, photophysical, and scanning electron microscopy studies revealed large differences in the morphology of the gold–porphyrin systems. The porphyrins with one linker attach to single nanoparticles, whereas the dual linker derivatives induce formation of aggregates, characterized by readily detectable Raman signals. A "hot-spot" type structure is proposed for the latter, with the porphyrin bridging two gold nanoparticles.

A series of monodisperse Ag nanoparticles (Ag NPs), whose size can be tuned between 2 nm and 34 nm, have been successfully synthesized in one pot by controlling the growth time. The standard deviation of the small-size Ag NPs is 12% while that of the large-size ones is 15%. During the synthesis process, sodium borohydride and sodium dodecyl sulfate were used as reducing agent and surfactant, respectively, and the effect of the synthesis parameters on the size-tuning range and the size distribution of Ag NPs was studied to get the optimum growth condition. Moreover, surface enhanced Raman scattering (SERS) spectra were analyzed to explore the synthesis mechanism of Ag NPs.

The sandwich-type immunoassays have been developed by using electrochemical and surface-enhanced Raman scattering (SERS) techniques for the detection of carcinoembryonic antigen (CEA). Nile blue as a kind of Raman dye has been decorated on nanospheres with polydopamine resin (PDR) via $\pi$-stacking interaction. The Nile blue displays the strong SERS signals as well as a characteristic electrochemical reduction peak at $-$0.33V (versus Ag/AgCl). The implementation of the PDR nanospheres mixing with Au nanoparticles (AuNPs/PDR) exhibits a better electrical conductivity and large SERS enhancement. The immunoassays based on Nile blue-labeled AuNPs/PDR nanospheres have been fabricated by using electrochemical and SERS techniques for the detection of CEA. The proposed immunoassay shows higher sensitivity, high selectivity, lower detection limit and long-term stability. The performances of the electrochemical immunoassay are better than that of SERS immunoassay. For the electrochemical immunoassay, the linear range occurs from 1pg/mL to 100ng/mL ($R=0.995$) with a detection limit of 0.68pg/mL and signal-to-noise ratio of 3 in the detection of CEA. The data for the analysis of human serum samples by using the electrochemical method are acceptably consistent with those obtained from the enzyme-linked immunosorbent assay (ELISA). The proposed immunoassay exhibits a promising potential for application in clinical diagnosis.

We report a surface enhanced Raman spectroscopy (SERS) ratiometry method based on peak intensity coupled in a nano-stress sensing platform to detect and quantify biological molecules. Herein, we employed an antibody-conjugated $p$-aminothiophenol (ATP) functionalized on a bimetallic-film-over-nanosphere (BMFON) substrate as a sensitive SERS platform to detect human haptoglobin (Hp) protein, which is an acute phase protein and a biomarker for various cancers. Correlation between change in the ATP spectral characteristics and concentration of Hp protein was established by examining the peak intensity ratio at 1572cm${}^{-1}$ and 1592cm${}^{-1}$ that reflects the degree of stress experienced by the aromatic ring of ATP during Hp protein–antibody interaction. Development of this platform shows the potential in developing a low-cost and sensitive SERS sensor for the pre-screening of various biomarkers.