Raman Signal Enhancement Research Articles

Rapid uropathogen identification using surface enhanced Raman spectroscopy active filters

Urinary tract infection is one of the most common bacterial infections leading to increased morbidity, mortality and societal costs. Current diagnostics exacerbate this problem due to an inability to provide timely pathogen identification. Surface enhanced Raman spectroscopy (SERS) has the potential to overcome these issues by providing immediate bacterial classification. To date, achieving accurate classification has required technically complicated processes to capture pathogens, which has precluded the integration of SERS into rapid diagnostics. This work demonstrates that gold-coated membrane filters capture and aggregate bacteria, separating them from urine, while also providing Raman signal enhancement. An optimal gold coating thickness of 50 nm was demonstrated, and the diagnostic performance of the SERS-active filters was assessed using phantom urine infection samples at clinically relevant concentrations (105 CFU/ml). Infected and uninfected (control) samples were identified with an accuracy of 91.1%. Amongst infected samples only, classification of three bacteria (Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae) was achieved at a rate of 91.6%.

Study on the effect of Ag nanoparticles density on ZnO/Ag nanostructure to enhance raman signals of SERS substrate on abamectin

This study investigated the effect of changing the density of Ag nanoparticles on the ZnO/Ag nanorod structure on the SERS substrate signal amplification ability. First, ZnO nanorods were fabricated by the sol - gel method combining with the chemical bath deposition method. Next, the Ag nanoparticles were decorated on ZnO nanorods by the DC magnetron sputtering method. The density and size of the modified Ag nanoparticles on the ZnO nanorods were changed by adjusting the sputtering times to 5, 10, 15 and 20s respectively. The optical properties of the material are characterized by UV - Vis and PL measurements. The surface morphology of ZnO nanorods and Ag nanoparticles were investigated by scanning electron microscope (SEM). X-ray diffraction measurement (XRD) is used to examine the crystal structures of materials. The composition and distribution of the chemical elements inside the material were investigated by Energy-dispersive X-ray spectroscopy (EDX). The ability of SERS substrates to amplify Raman signals was evaluated by measuring the R6G solution and investigating application for abamectin with a laser excitation wavelength of 532 nm. The results showed that SERS ZnO/Ag substrates with sputtering time of 15s gave the best ability to amplify SERS with the detection of R6G solution at 10􀀀9 M and abamectin at 50 ppm.

A new and facile route to prepare gold nanoparticle clusters on anodic aluminium oxide as a SERS substrate

In the present study, a new SERS-active gold nanoparticle clusters having a flower-shape have been prepared easily on nano porous anodic aluminium oxide (AAO) by immersing it in auric chloride solution without any need for complex production steps. In this process, presented for the first time, the metallic aluminum which were released under the influence of chloride ions due to pitting corrosion act as a reducing agent, while gold ions were reduced onto the AAO layer based on the difference in standard reduction potentials between aluminum and gold. Gold nanoparticle clusters on AAO layer formed “hot spots” providing enhanced Raman signal. Optical microscope, SEM, EDX, AFM, and UV–vis spectrophotometer have been used to characterize the substrate. In order to demonstrate applicability of the method, label free SERS measurements of nitrate ion was performed on the proposed sensing platform. A high sensitivity with 1.03 ppm of limit of detection level and the enhancement factor of 2.9 × 105 were obtained for nitrate ion. In addition, remarkable recoveries ranging from 98.4% to 106.8% were obtained for nitrate spiked into drinking water samples. The inter-day and intra-day precisions of the method as relative standard deviation (RSD) were determined as 3.3% and 5.2%, respectively. The sensor platform, developed using a facile method and a low-cost base material (aluminum), can be a good alternative for SERS based sensing applications.

Au/Ag composite-based SERS nanoprobe of Cr3.

Quantitative characterization of Cr3+, an important element revealing human metabolism and biological environmental variation, is still difficult to achieve by conventional biochemical methods due to the lack of high-sensitivity, real-time techniques with rapid response detection. Using surface-enhanced Raman scattering (SERS), we construct an Au/Ag composite-based SERS nanoprobe for the quantitative characterization of Cr3+ content in solution, in which DL-mercaptosuccinic acid (DL-MSA) is employed for Raman signal enhancement, and 4-mercaptobenzoic acid (4-MBA) is chosen as the Raman reporter. The achieved result demonstrates obvious advantages of the synthesized Au/Ag composite-based SERS nanoprobe in sensitivity and response speed. Importantly, this Au/Ag composite-based SERS nanoprobe might provide a new strategy for dynamic monitoring of Cr3+ content in human metabolism.

Surface-enhanced shifted excitation Raman difference spectroscopy for trace detection of fentanyl in beverages.

In recognition of the misuse risks of fentanyl, there is an urgent need to develop a useful and rapid analytical method to detect and monitor the opioid drug. The surface-enhanced shifted excitation Raman difference spectroscopy (SE-SERDS) method has been demonstrated to suppress background interference and enhance Raman signals. In this study, the SE-SERDS method was used for trace detection of fentanyl in beverages. To prepare the simulated illegal drug-beverages, fentanyls were dissolved into distilled water or Mizone as a series of test samples. Based on our previous work, the surface-enhanced Raman spectroscopy detection was performed on the beverages containing fentanyl by the prepared AgNPs and the SE-SERDS spectra of test samples were collected by the dual-wavelength rapid excitation Raman difference spectroscopy system. In addition, the quantitative relationship between fentanyl concentrations and the Raman peaks was constructed by the Langmuir equation. The experimental results show that the limits of quantitation for fentanyl in distilled water and Mizone were 10 ng/mL and 200 ng/mL, respectively; the correlation coefficients for the nonlinear regression were as high as 0.9802 and 0.9794, respectively; and the relative standard deviation was less than 15%. Hence, the SE-SERDS method will be a promising method for the trace analyses of food safety and forensics.

Au Films Composed of Nanoparticles Fabricated on Liquid Surfaces for SERS

A series of Au films with different nominal deposition thickness d were fabricated on ionic liquid surfaces by thermal evaporation at room temperature, taken as surface-enhanced Raman scattering (SERS) substrates. Au atoms deposited on the liquid surfaces can diffuse and aggregate randomly and eventually form films with ramified structure, which consist of nanoparticles (NPs). There are amounts of ultrasmall (∼ 1 nm or smaller) nanogaps among the Au NPs, which can dramatically enhance Raman signal. Raman spectra of R6G were investigated with the assistance of the Au films. The results indicate that the Au films with higher thickness possess better SERS performance when 5.0 ≤ d ≤ 30.0 nm. A random distribution model of Au NPs was used in the finite-difference time-domain method and the simulation results are in good agreement with the experimental findings.

In-fiber optofluidic online SERS detection of trace uremia toxin.

In this Letter, we propose a microstructured in-fiber optofluidic surface-enhanced Raman spectroscopy (SERS) sensor for the initial inspection of uremia through the detection of unlabeled urea and creatinine. As a natural microfluidic device, microstructured hollow fiber has a special structure inside. Through chemical bonds, the SERS substrate can be modified and grown on the surface of the suspended core. Here, the silver nanoparticles (Ag NPs) are embedded on the poly diallyl dimethyl ammonium chloride-modified graphene oxide sheet to achieve the self-assembled SERS substrate. The reduced distance between Ag NPs can increase the strong hot spots that generate enhanced Raman signals. Therefore, it can effectively detect the Raman signal of unlabeled trace uremic toxin analytes (urea, creatinine) inside the optical fiber. The results show that under simulated biophysical conditions, the limit detection (LOD) for urea is 10-4M and the linearity is good, especially at the clinical conventional concentration range (2.5-6.5×10-3M). In addition, the online Raman detection of creatinine aqueous solution LOD is 10-6M, which also has good linearity. Significantly, this Letter provides a microstructured optofluidic in-fiber Raman sensor for the preliminary detection of uremia, which will have good development prospects in the field of clinical biomedicine.

Surface Enhanced Raman Scattering from Single-Walled Carbon Nanotube Decorated on Ag Nanowires

Surface-enhanced Raman spectroscopy (SERS) is a surface sensitive technique which gives enhanced Raman signal intensity of the molecules by roughening metal surfaces. It can be used to detect trace amounts of analysts including heavy metals, pesticides, explosives, proteins and different biological and chemical contaminants. In this paper, we report a facile approach to synthesise highly nano-crystalline and homogeneous plasmonic wave guide of silver nanowires (Ag-NWs) by polyol method. Morphology of the synthesised Ag-NWs has been characterised using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques and suggests the homogenous formation of nanowires with an average diameter of 400–450 nm and 15–25 µm of length. Surface-enhanced Raman spectroscopy (SERS) of single-walled carbon nanotube (SWNT) when it is coupled with Ag-NW suggests that the enhancement factor is as high as ~ 103 and ~ 102 for the characteristic Raman signals (G-peak and radial breathing modes, respectively). Using numerical method of finite difference time domain (FDTD), it is shown that the enhancement depends on the orientation of the SWNTs with respect to the Ag-NWs and is maximum (~ 107) when they are at 45° to each other. The proposed approach provides an effective, reproducible and facile method for preparing high-quality SERS substrates for remote optical excitation in plasmonic devices.

Fabrication and study of Raman signal enhancement of pyramid/nano-Ag structured Silic substrate

The pyramid-structured silicon substrate was successfully fabricated by a chemical corrosion method with an average thickness of about 1 - 3 μm with the optimal parameters such as corrosion temperature of 70oC, corrosion time of 5 min, concentration KOH of 3 M and isopropyl alcohol concentration of 1 M. After that, the silver nanoparticles layer (thickness 20 nm) was coated on the silicon substrate by a sputtering method to enhance the SERS signal. The results proved that the Pyramid/nano Ag structure silicon substrate showed the enhancement effect of Raman signal, and Rhodamine 6G pigment in food at low concentration (10-6 M) was detected and the enhancement factor was 9.7 × 102.

Raman spectroscopy of copper phthalocyanine/graphene and 2,3,5,6‐tetrafluoro‐tetracyano‐quino‐dimethane/graphene interfaces

The copper phthalocyanine and 2,3,5,6‐tetrafluoro‐tetracyano‐quino‐dimethane molecules adsorbed on the copper and single‐layer graphene‐modified copper surfaces have been investigated using Raman and X‐ray photoelectron spectroscopy. The adsorbed amounts for both molecules on the two different substrates are almost comparable as confirmed by the C 1s and N 1s core level X‐ray photoelectron spectra. Raman signal enhancement has been observed for both molecules when they are adsorbed on the graphene surface. The strongest chemical interaction is observed between the 2,3,5,6‐tetrafluoro‐tetracyano‐quino‐dimethane and copper substrate. Based on the Raman and X‐ray photoelectron spectroscopic data, the mechanism of the graphene‐enhanced Raman scattering is discussed, which might greatly rely on the unique electronic properties of graphene.

An antibody-free liver cancer screening approach based on nanoplasmonics biosensing chips via spectrum-based deep learning

The clinical needs of rapidly screening liver cancer in large populations have asked for a facile and low-cost point-of-care testing (POCT) method. We present a nanoplasmonics biosensing chip (NBC) that would empower antibody-free detection with simplified analysis procedures for POCT. The cheaply fabricable NBC consists of multiple silver nanoparticle-decorated ZnO nanorods on cellulose filter paper and would enable one-drop blood tests through surface-enhanced Raman spectroscopy (SERS) detection. In this work, utilizing such an NBC and deep neural network (DNN) modeling, a direct serological detection platform was constructed for automatically identifying liver cancer within minutes. This chip could enhance Raman signals enough to be applied to POCT. A classification DNN model was established by spectrum-based deep learning with 1140 serum SERS spectra in equal proportions from hepatocellular carcinoma (HCC) patients and healthy individuals, achieving an identification accuracy of 91% on an external validation set of 100 spectra (50 HCC versus 50 healthy). The intelligent platform, based on the biosensing chip and DNN, has the potential for clinical applications and generalizable use in quickly screening or detecting other types of cancer.

A magnetic surface-enhanced Raman scattering platform for performing successive breast cancer exosome isolation and analysis.

The rapid development of exosome research provides new insights into the physiological role of exosomes and their significant correlation with human health. Although the exosomes derived from tumor sources have been proven to be promising biomarkers for cancer detection and disease progression due to their inherited biological contents from the parent cancer cells and unique roles in tumor metastasis and invasion, it is still a challenging task to perform rapid and effective isolation from complex biological samples and conduct high-precision real-time analysis. Herein, we propose a magnetic surface-enhanced Raman scattering (SERS) platform to integrate successive breast cancer exosome isolation and Raman signal enhancement into one system to achieve the goal. In addition, principal component analysis (PCA) was conducted to investigate major patterns of the samples. According to the results, the magnetic SERS platform can be applied to distinguish exosomes derived from MCF-7 and MDA-MB-231 cells with 100% sensitivity and 100% specificity for the 95% confidence interval. More importantly, this platform can fully identify breast cancer patients and healthy people with 91.67% sensitivity and 100% specificity. These studies revealed that our magnetic SERS platform would serve as a great potential system for highly efficient real-time liquid biopsy by using the exosomes as cancerous markers, while exempting from pre-treatment of clinical samples or the extra introduction of elements for SERS signal enhancement.

Gold-iron oxide nanohybrids: insights into colloidal stability and surface-enhanced Raman detection.

Nanoparticles are acquiring an ever increasing role in analytical technologies for enhanced applications such as signalling of hazardous dyes. One challenge for the synthesis of hybrid nanomaterials is to control their shape, size and properties. The colloidal and interfacial properties of initial nanoparticles are decisive for the formation, growth and characteristics of nanohybrids. Our objective is to combine the advantages of iron oxide nanoparticles for magnetic separation with nanoscale gold for a surface enhanced Raman scattering (SERS) effect which could be used e.g. for improved detection of dye molecules. We synthesized iron oxide nanoparticles (∼10 nm) with a high saturation magnetization of around 80 Am2 kg−1 and coupled nanoscale gold to these particles. The focus was set in testing multiple approaches to combine these two materials with the goal of understanding and discussing the effect of the colloidal stability of iron oxide nanoparticles on the properties of the hybrid material. Stability is a seldom addressed issue; however, it plays a critical role for guaranteeing a homogeneous distribution of the gold on the iron oxide surface. We characterized the produced materials with UV/Vis spectroscopy, dynamic light scattering, and transmission electron microscopy, and their capability to enhance Raman signals is investigated. The seed-mediated growth method of oleate and PEG-stabilized magnetic particles yielded the best enhancement of Raman scattering for identification of the dye Rhodamin 6G. This approach can be used to couple gold nanoparticles to other surfaces and microfluidic devices. The presented method might pave the way to further applications in diagnostics or also in environmental approaches and beyond.

A cyclodextrin-decorated plasmonic gold nanosatellite substrate for selective detection of bipyridylium pesticides.

A cyclodextrin-decorated gold nanosatellite (AuNSL) substrate was developed as a surface-enhanced Raman scattering sensor for the selective sensing of bipyridylium pesticides such as paraquat (PQ), diquat (DQ), and difenzoquat (DIF). The AuNSL structure was fabricated via vacuum deposition of gold nanoparticles (AuNPs) on a gold nanopillar substrate, and a large density of hot-spots was formed for Raman signal enhancement. Thiolated β-cyclodextrin (SH-CD) was surface-modified on the AuNSL as a chemical receptor. The detection limit of PQ, DQ, and DIF on the SH-CD-coated AuNSL (CD-AuNSL) was 0.05 ppm for each, and showed linear correlation in a concentration range of 10 ppm-0.05 ppm. Then, selective bipyridylium pesticide detection was performed by comparing the Raman intensity of each pesticide with and without the washing step. After the washing step, 90% of the PQ, DQ, and DIF Raman signals were maintained on the CD-AuNSL substrate with a uniform selectivity in a mapping area of 200 μm × 200 μm. Furthermore, selective pesticide detection was performed using a ground-apple solution without pretreatment. Raman signals were clearly observed after the washing step and they showed a limit of detection down to a concentration of 0.05 ppm for each pesticide. Principal component analysis (PCA) of the binary and ternary mixtures of PQ, DQ, and DIF showed that each component could be easily identified via the typical Raman fingerprint analysis. The developed CD-AuNSL is expected to be applied for various chemical sensors, especially for pyridine-containing toxic substances in the environment and metabolite biomarkers in biofluids.

Functionalized SERS substrate based on silicon nanowires for rapid detection of prostate specific antigen

Abstract Owing to its high sensitivity, surface-enhanced Raman spectroscopy (SERS) is widely used in biosensing as an efficient optical transduction technique. In this work, we report the elaboration of a novel SERS-powered aptasensing substrate for the ultra-sensitive and selective detection of prostate specific antigen (PSA). The transducing SERS substrate is formed by vertically aligned silicon nanowires (SiNWs) decorated with silver nanoparticules (AgNPs). The silver nanoparticles have two purposes : a) aptamer immobilization via thiol chemistry and b) Raman signal enhancement. The presence of PSA induces the appearance of amide bond vibration modes only if the aptamer is present on the surface of SiNWs. The platform is highly sensitive, selective and specific to PSA in a wide range of concentrations from 0.1 to 20 μg.L−1 with a detection limit of 0.1 μg.L−1, which encompasses the blood serum range of healthy subjects and ill patients. This optical biosensor shows a great stability and it is successfully validated in human blood serum samples showing very good results.

Photochemical synthesis of ZnO/Ag heterogeneous nanostructure on chemically patterned ferroelectric crystals for high performance SERS detection

An attractive strategy for effective Raman signal enhancement is to employ the synergistic action of electromagnetic and chemical mechanisms by using semiconductor/noble-metal nanostructures in the SERS substrates. This work presents the utilization of ferroelectric templates to synthesize the ZnO/Ag heterogeneous nanostructures photochemically for the SERS application. Under UVC illumination, the ferroelectric templates with permanent electrostatic field provide the photoelectrons required for silver photoreduction. Various shapes of ZnO nanostructures are grown on the ferroelectric templates by controlling the growth time. The influences of ZnO nanostructures on the size, density, and morphology of photoreduced silver nanomaterials are studied by various analytical techniques. The produced SERS substrate with the optimal ZnO/Ag nanostructures possesses the superior SERS performance, such as the limit of detection< 10−8 M, the enhancement factor 6.99 × 108, the uniformity 9.5% ± 1.0%, and 16-fold Raman intensity enhancement. This study demonstrates a promising green technique to produce semiconductor/noble-metal nanostructures using ferroelectric templates.

Multicolor Activatable Raman Probes for Simultaneous Detection of Plural Enzyme Activities

Raman probes based on alkyne or nitrile tags hold promise for highly multiplexed imaging. However, sensing of enzyme activities with Raman probes is difficult because few mechanisms are available to modulate the vibrational response. Here we present a general strategy to prepare activatable Raman probes that show enhanced Raman signals due to electronic preresonance (EPR) upon reaction with enzymes under physiological conditions. We identified a xanthene derivative bearing a nitrile group at position 9 (9CN-JCP) as a suitable scaffold dye, and synthesized four types of activatable Raman probes, which are targeted to different enzymes (three aminopeptidases and a glycosidase) and tuned to different vibrational frequencies by isotope editing of the nitrile group. We validated the activation of the Raman signals of these probes by the target enzymes and succeeded in simultaneous imaging of the four enzyme activities in live cells. Different cell lines showed different patterns of these enzyme activities.

Graphene-coated Si nanowires as substrates for surface-enhanced Raman scattering

Si nanowires always exhibited no Raman enhancement for application in surface-enhanced Raman scattering (SERS). Herein, surface modifications of Si nanowires, without the presence of noble metals, were carried out to develop biocompatible SERS substrates. The treatment of hydrogen plasma on as-prepared Si nanowires leads to no enhanced Raman signals for the absorbed R6G molecules. The coatings of nanocrystalline diamond and multilayer graphene enable Raman signals to be enhanced with a reduced fluorescent background. The graphene-coated sample exhibits a much lower fluorescent background than the diamond-coated sample at a high concentration of the dye molecules. For the sample with graphene-coated Si nanowires, the minimum detection limit is 10-7 mol/L, and the enhancement factor reaches above 104. Such stable Raman enhancement is attributed to the formation of hydrogen-terminated graphene and the presence of the nanowire structure, accelerating charger transfer between graphene and the dye molecules. Importantly, the Raman enhancement is independent of the number of graphene layers. The Raman signal remains stable after exposure to the atmosphere for one month. Therefore, a new nanostructure of Si nanowires with graphene coating is developed, which shows great potential in SERS applications.

Ag-Nanostars for the Sensitive SERS Detection of Dyes in Artistic Cross-Sections—Madonna della Misericordia of the National Gallery of Parma: A Case Study

In historical paintings, the detection of low amounts of pigments and dyes by Raman spectroscopy can sometimes be challenging, in particular for fluorescent dyes. This issue can be overcome by using SERS (surface-enhanced Raman spectroscopy) which takes advantage of the properties of nanostructured metal surfaces to quench fluorescence and enhance Raman signals. In this work, silver nanostars (AgNSs) are applied for the first time to real art samples, in particular to painting cross-sections, exploiting their effective SERS properties for pigment identification. The case study is the Madonna della Misericordia of the National Gallery of Parma (Italy). Cross-sections were analyzed at first by optical microscopy, SEM-EDS, and micro-Raman spectroscopy. Unfortunately, in some cross-sections, the application of conventional Raman spectroscopy was hindered by an intense background fluorescence. Therefore, AgNSs were deposited and used as SERS-active agent. The experimentation was successful, allowing us to identify a modern dye, namely copper phthalocyanine. This result, together with the detection of other modern pigments (titanium white) and expert visual examination, allowed to reconstruct the painting history, postdating its realization from the 15th century (according to the Gallery inventory) to 19th century with a heavy role of recent (middle 20th century) restoration interventions.

Hierarchically ordered microcrater array with plasmonic nanoparticle clusters for highly sensitive surface-enhanced Raman scattering

Surface-enhanced Raman scattering (SERS) with unique molecular vibrational fingerprints for identifying analytes provides an effective spectroscopic approach for the detection of trace molecules in biomedical/analytical fields. Although a great amount of efforts has been devoted to developing various SERS substrates with hierarchical micro/nanostructures, challenges remain in completely concentrating the target molecules within a sensitive area and thereby enhancing detection sensitivity. Here, we report trace molecular detection using superhydrophobic microcrater array as surface-enhanced Raman substrate (SMA-SERS). The hierarchically ordered microcrater array with plasmonic nanoparticle clusters is quickly obtained by the two-step process of femtosecond laser texturing and magnetron sputtering. The resultant substrates with hierarchical micro-/nanostructures show excellent superhydrophobicity with a contact angle above 150° and satisfactory plasmonic nanostructures with the easily attainable Raman signal enhancement factor of ~4.82 × 108. The signals on the SMA-SERS maintain uniformity with a relative standard deviation of <15%. These findings manifest that the SMA-SERS is an extraordinary strong candidate for obtaining high-quality and reliable SERS, facilitating a widespread use of SERS for practical applications.