SERS Platform Research Articles

Highly ordered TiO2 nanotube films photo-decorated with Ag nanoparticles as SERS platforms: Relationship between morphology and enhancement

In this work, we synthesized TiO2 nanotube films (TiO2-NTFs) photo-decorated with Ag nanoparticles for their application in Surface-Enhanced Raman Scattering. In situ growth of Ag nanoparticles was performed through the exposure of anodic TiO2-NTFs to UVC radiation following their pretreatment in an AgNO3 aqueous solution. High nanoparticle surface densities, with uniform coverage on the film surface, and controllable size, were prepared by regulating the UVC exposure time and AgNO3 concentration. Ag nanoparticles nucleation and growth also take place along the tubes, including at the bottoms. The evidence obtained also indicates that a high enough AgNO3 concentration inhibits the well-known water-assisted crystallization mechanism, typically promoted when TiO2-NTFs are exposed for prolonged times in aqueous media. The performance of the photo-decorated films in Surface-Enhanced Raman Scattering shows that the presence of Ag nanoparticles plays a key role, and both the nanoparticle surface density and size must be regulated to promote a large number of hot-spots.

Determination of H2O2 and its antioxidant activity by BCM@Au NPs ratiometric SERS sensor

As a reactive oxygen species (ROS), excessive production of H2O2 contributes to the development of several diseases such as, inflammation, cancer, and respiratory diseases. Supplementation with endogenous or exogenous antioxidants can scavenge ROS and reduce the oxidation of cellular molecules, thus alleviating the generation of diseases. Therefore, the determination of H2O2 content and its antioxidant activity is of great importance in disease diagnosis and treatment. In this paper, a ratiometric SERS sensor with a flexible cellulose membrane was designed for quantitative detection of H2O2 and assessment of antioxidant activity. First, gold seeds were reduced on bacterial cellulose membrane (BCM) and Au NPs were smoothly deposited on the bacterial cellulose membrane (BCM) using halides to reduce the reduction potential in the growth solution to form a flexible BCM@Au NPs SERS substrate. Afterwards, the oxidation of H2O2 was used to convert 3-mercaptophenylboronic acid (3-MPBA) to the corresponding phenol form 3-hydroxyphenylethanol (3-HTP). The change of substance resulted in a good linear relationship between the intensity ratio corresponding to the two Raman shifts of 881 cm−1 and 995 cm−1 and the H2O2 concentration with a detection limit of 0.0186 μM. This opens up a new method for the detection of H2O2 with high sensitivity and accuracy. In addition, this SERS platform was successfully used for the determination of antioxidant activity. It is promising to be applied to disease diagnosis and efficacy evaluation.

Morphology tuned plasmonic TiN nanostructures formed by angle-dependent sputtering process for SERS measurements

Nowadays, most SERS platforms are based on plasmonic metals like silver and gold. The current scientific achievement is to construct SERS non-metallic platform with SERS activity not worse than in case of standard metallic platforms. The prominent combination of opto-electronic properties of TiN (titanium nitride) makes it a promising alternative plasmonic material for noble metals. So far, the TiN nanostructures are widely tested in catalysis, especially in photocatalysis. Despite the TiN potential in SERS sensing applications, there are still several fundamental issues preventing its wide practical application. In this work, the surface morphology of TiN layers was tuned from planar 2D to a high aspect ratio 1D nanorod-like structures by industrially scalable normal and glancing angle deposition (GLAD) pulsed DC reactive sputtering. The morphology of formed samples was studied by SEM microscopy, while the crystallographic properties were examined by Raman and XRD method. The opto-electrical parameters measured by spectroscopic ellipsometry, and DRS spectroscopy revealed substantial changes in optical properties of the TiN films with the variation of glancing angle. This in turn opened the way for tailoring the surface plasmon resonance and hence for SERS activity.

Construction of aptamer sensor based on Au nanozymes for ultrasensitive SERS detection of tobramycin

Tobramycin aptamer was adsorbed on the surface of gold nanoparticles (Au NPs) by van der Waals forces, hydrogen bonds, and other factors, limiting nanozyme peroxidase activity. Because tobramycin has a higher affinity for the tobramycin aptamer, including tobramycin in Au@Apts nanozymes was able to dislodge the aptamer from the surface of Au NPs and restore the catalytic activity of nanozymes. Raman spectroscopy of the enzyme-catalyzed product TMBox can detect this shift in enzyme activity. The restored value of nanozyme activity increased with tobramycin concentration and had a good linear correlation in the concentration range of 10−10∼10−1 M with a detection limit of 2.04 × 10−11 M. Aptamer biosensors are built using the SERS platform, which has the advantages of high sensitivity, high precision, and a wide detection range. It is prospectively employed in food safety and the detection of antibiotic residues.

The battle for the future of SERS – TiN vs Au thin films with the same morphology

This work compares for the first time the SERS activity of TiN and Au nano/micro-structures having the same morphology. Si pyramids formed by alkaline etching were coated with Au and TiN layers of three different thicknesses (20, 57 and 80 nm). The morphology of both platforms was investigated using SEM microscopy. The optical properties were examined by spectroscopic ellipsometry and diffuse reflectance spectroscopy.The results prove that both the Si/TiN and Si/Au microstructures exhibit plasmonic properties in the visible range, and can be effectively applied as SERS platforms.Two dyes were chosen as the Raman reporter molecules. Data analysis showed the highest EF for the thickest layer of the deposited Au and TiN layers. It was found that, for the 80 nm layer on both Au and TiN, even as low as 10-9M concentrations of tartrazine could be detected. In both cases, the SERS platform could be cleaned by rinsing in distilled water, and then re-used. It was found that for the Si-Au pyramids the reversibility was equal to 13, while the Si-TiN could be washed even after 20 cycles.

Stimuli-responsive SERS biosensor for ultrasensitive tetracycline sensing using EDTA-driven PEI@CaCO3 microcapsule and CS@FeMMs

In this work, a stimuli-responsive SERS biosensor was fabricated for tetracycline (TTC) by “signal-on” strategy using (EDTA)-driven polyethyleneimine grafted calcium carbonate (PEI@CaCO3) microcapsule and chitosan-Fe magnetic microbeads (CS@FeMMs). Initially, aptamer conjugated magnetic-bead CS@FeMMs@Apt with superparamagnetism and excellent biocompatibility was employed as capture probe, which facilitated the rapid and easy magnetic separation. Subsequently, the PEI cross-linked layer and aptamer network layer were constructed onto the outer layer of CaCO3@4-ATP microcapsule to form sensing probes (PEI@CaCO3@4-ATP@Apt) via the layer-by-layer assembly method. In the presence of TTC, a sandwich SERS-assay was exploited by aptamer recognition induced target-bridged strategy. When the solution of EDTA was added, the core layer of CaCO3 would be dissolved quickly, destroying the microcapsule to release 4-ATP. The released 4-ATP could be quantitatively monitored by dripping the supernatant onto the AuNTs@PDMS SERS platform, resulting in a strong Raman “signal-on”. Under the optimal conditions, a good linear relationship was established with a correlation coefficient (R2) of 0.9938 and a LOD of 0.03 ng/mL. Additionally, the application capacity of the biosensor to detect TTC was also affirmed in food matrixes, and the results were consistent with the standard ELISA method (P > 0.05). Hence, this SERS biosensor affords extensive application prospects for TTC detection with multiple merits such as high sensitivity, environment friendliness, and high stability.

Plasmonic Properties of the Metal Nanoparticles (NPs) on a Metal Mirror Separated by an Ultrathin Oxide Layer

The plasmonic resonance frequency of metal nanoparticles (NPs) strongly depend on the geometry, size, and separation between NPs. Here, a plasmonic structure is designed based on a film-coupled nanoparticle phenomenon and analytically investigated by a finite element method via COMSOL Multiphysics software tool. The optical behavior of the designed structure is studied and compared for two noble metals (gold and silver as a case study). Simulation results confirmed that structural elements such as dielectric layer thickness, metal film thickness, and metal nanoparticle separation distance significantly affect the plasmonic properties. Consequently, optimizing the dimensions of the mentioned structural elements results in a strong field enhancement in the dielectric gap layer. The simplicity of this structure, easy controlling of the dielectric gap layer thickness, strong field confinement in a limited area, and lack of incident light angle tunning are characteristic features of the proposed structure. Strong field enhancement in a limited volume makes this structure promising as plasmonic nanoantennas, SERS platforms, and sensing applications.

A Novel Approach for Rapid and Sensitive Detection of Zika Virus Utilizing Silver Nanoislands as SERS Platform

A Novel Approach for Rapid and Sensitive Detection of Zika Virus Utilizing Silver Nanoislands as SERS Platform

Mass producible, robust SERS substrates based on metal film on nanosphere (MFON) on an adhesive substrate for detection of surface-adsorbed molecules and their evaluation by helium ion microscopy.

We have developed a SERS stamp that can be pressed directly onto a solid surface for characterization of surface-adsorbed target molecules. The stamp was fabricated by transfer of a dense monolayer of SiO2 nanospheres from a glass surface onto a piece of adhesive tape and subsequent evaporation of silver. The performance of the resulting SERS stamps was evaluated by their exposure to methyl mercaptan vapor, and immersion in rhodamine 6G and ferbam solutions. It was found that beside the nanosphere diameter and metal deposition thickness, the extent of burial of the nanospheres into the adhesive tape, dictated by the pressure during the nanosphere transfer process, had a significant effect. We carried out FDTD calculations of the near field. Models are based on morphological information obtained from helium ion microscopy, which can provide high-resolution images of poor electrical conductors such as our SERS stamp. While one of our main eventual goals is detection of pesticides on agricultural produce, we have begun to take a careful step by testing our SERS stamp on better characterized surfaces such as a porous gel surface, having been immersed in fungicides such as ferbam. We also present our preliminary results with ferbam on oranges. It is expected that our well-characterized SERS stamp will play a role in shedding light on the poorly studied transfer process of target molecules onto a SERS surface as well as serving as a new SERS platform.

SERS-based immunosensor for E. coli contaminants detection in milk using silver-coated nanoporous silicon substrates

The dairy sector is frequently affected by contagious and environmental factors that spread between animals by numerous means and induce the inflammatory disease of bovine mastitis (BM). Herein, silver decorated porous silicon (Ag-pSi) SERS platform was designed for rapid and reliable Escherichia coli (predominant BM pathogen) detection in various milk origins. The inherent surface void and pore morphology were physically optimized to augment the SERS effect using 4-aminothiphenol (4ATP) while achieving an enhancement factor >4.6 × 107. An indirect immunoassay evaluated the residual unreacted antibodies using an optimized 4ATP/Ag-pSi SERS platform modified with secondary antibodies. Under optimized conditions, the porous substrate offered high sensitivity toward target bacteria detection of 3 CFU mL−1 and linear response of 101–105 CFU mL−1. Moreover, the selectivity and specificity of the designed sensing platform were cross-validated against other interfering bacteria without compromising its performance efficiencies. Finally, the applicability of the developed system for real-life conditions was elucidated in different milk samples (bovine, goat, sheep) with recovery values of 78–115% compared to the conventional culture technique. Considering the complex media analysis, the miniaturized SERS platform is highly reliable, rapid and accurate that could be applicable for routine on-site analysis of various emerging pathogens relevant to BM management.

Rapid Quantitative Determination of Multiple Pesticide Residues in Mango Fruits by Surface-Enhanced Raman Spectroscopy

Imidacloprid, acephate, and carbaryl are common insecticides that are extensively used in planting mango, a well-known fruit in Vietnam, to ease mango hopper issues. The accurate detection of pesticide residues is critical for mango export to meet quality criteria. This study developed a novel SERS platform by using polydimethylsiloxane (PDMS) to simulate the rose petal structure incorporated with a silver coating layer and silver nanoparticles (AgNPs) to detect imidacloprid, acephate, and carbaryl in mango fruits. In this paper, the rose petal PDMS/Ag-AgNPs replica was considered the most efficient substrate for SERS measurement with an EF of 4.7 × 107. The Raman spectra of the three insecticides obtained from the PDMS/Ag-AgNPs substrate were clearly observed with their characteristic peaks of 1105 cm−1 for imidacloprid, 1083 cm−1, and 1579 cm−1 for acephate, and 727 cm−1 and 1378 cm−1 for carbaryl. The application of PDMS/Ag-AgNPs substrate in quantitative analysis of the three pesticides in mango fruit was evaluated. As a result, the limit of detection was 0.02 mg/kg for imidacloprid, 5 × 10−5 mg/kg for acephate, and 5 × 10−3 mg/kg for carbaryl. The SERS result also revealed that the pesticide residues in the mango sample were within an acceptable limit. This suggested the possibility of the rose petal PDMS/Ag-AgNPs replica for rapid quantification of pesticide residues not only in mango fruit but also in many other agricultural products.

DNA Structure-Stabilized Liquid-Liquid Self-Assembled Ordered Au Nanoparticle Interface for Sensitive Detection of MiRNA 155.

Au nanoparticles (Au NPs) can be self-assembled in a bottom-up orderly manner at the oil-water interface, which is widely used as SERS platforms, but the stability of the Au NP interface needs to be improved due to shaking or shifting and the Brownian motion. The DNA structure with unique sequence specificity, excellent programmability, and flexible end-group modification capability owns good potential to precisely control the plasmonic structure's distance. In this study, a large area of the SERS substrate is obtained from the DNA structure-stabilized self-assembled ordered Au NPs on the cyclohexane-water interface. Combining with the exonuclease III (exo III)-assisted DNA recycling amplification strategy, we construct a liquid-phase SERS biosensor for efficient detection of microRNA 155 (miRNA 155). Compared with the traditional randomly assembled Au NPs on the two-phase interface, the SERS signal is significantly enhanced and more stable. The detection limit of the SERS biosensor for miRNA 155 reached 1.45 fmol/L, which has a very wide linear range (100 fmol/L-5 nmol/L). This work gives an efficient approach to stabilize the self-assembly Au NPs on the liquid-liquid interface, which can broaden the application of SERS analysis.

A novel SERS substrate with high reusability for sensitive detection of miRNA 21

Electrochemistry combining with Surface Enhanced Raman Spectroscopy (EC-SERS) is a hot area which can achieve real-time analysis of the electrochemical product. In this work, a high-performance reusable Raman substrate was fabricated via electrochemical reduction for miRNA 21 assay. In this strategy, 2′-hydroxymethyl-3, 4-thylenedioxythiophene (EDOT-OH) was electropolymerized to form PEDOT-OH (Red), which acted as a part of SERS substrate and a Raman probe at the same time. The Raman intensity of PEDOT-OH was different between the reduction (Red) and oxidation state (Ox). When it is oxidized, the signal of the PEDOT-OH (Ox) on the electrode surface can be restored by applying a reduction voltage. In view of this feature, a Raman enhanced substrate displaying signal changes is constructed and the constructed Raman substrate can be recycled quickly and efficiently. Combining with double-amplification strategy, the SERS platform can detect miRNA 21 from 100 fM to 1 μM. The Raman substrate can be reused at least 15 times and solves the current problems of poor reusability and troublesome restoration of present reusable Raman substrate. As a result, it indicates that the reusable Raman substrate with high performance and non-destructive property will broaden the application of EC-SERS and SERS analysis.

Plasmonic nanobowtiefluidic device for sensitive detection of glioma extracellular vesicles by Raman spectrometry.

Cancer cells shed into biofluids extracellular vesicles (EVs) - nanoscale membrane particles carrying diagnostic information. EVs shed by heterogeneous populations of tumor cells offer a unique opportunity to access biologically important aspects of disease complexity. Glioblastoma (GBM) exemplifies cancers that are incurable, because their temporal dynamics and molecular complexity evade standard diagnostic methods and confound therapeutic efforts. Liquid biopsy based on EVs offers unprecedented real-time access to complex tumour signatures, but it is not used clinically due to inefficient testing methods. We report on a nanostructured microfluidic-device that employs SERS for unambiguous identification of EVs from different GBM cell populations. The device features fabless plasmonic nanobowties for label-free and non-immunological SERS detection of EVs. This nanobowtiefluidic device combines the advanced characteristics of plasmonic nanobowties with a high throughput sample-delivery system for concentration of the analytes in the vicinity of the detection site. We showed theoretically and experimentally that the fluidic device assists the monolayer distribution of the EVs, which dramatically increase the probability of EV's existence in the laser illumination area. In addition, the optimized fabless nanobowtie structures with an average electric field enhancement factor of 9 × 105 achieve distinguishable and high intensity SERS signals. Using the nanobowtiefluidic and micro-Raman equipment, we were able to distinguish a library of peaks expressed in GBM EV subpopulations from two distinct glioblastoma cell lines (U373, U87) and compare them to those of non-cancerous glial EVs (NHA) and artificial homogenous vesicles (e.g. DOPC/Chol). This cost-effective and easy-to-fabricate SERS platform and a portable sample-delivery system for discerning the sub-population of GBM EVs and non-cancerous glial EVs may have broader applications to different types of cancer cells and their molecular/oncogenic signature.

Fabrication of Al/Al2O3/Ag SERS substrate by the corrosion method to detect ketoprofen

In this work, we studied and fabricated SERS substrate (surface-enhanced Raman scattering) substrates based on Al/Al2O3/Ag to detect ketoprofen solution at low concentrations. Silver nanoparticles were decorated on Al2O3/Al substrate due to a displacement reaction. By changing the volume ratios of hexadecyltrimethylammonium bromide (CTAB) to AgNO3 and annealing temperature, the SERS substrates were fabricated with the large effective surface area, high density of ``hot-spots. The structure and surface morphology of these SERS substrates were investigated by measurements such as surface image recorded with scanning electron microscopy (SEM), energy dispersion X-ray spectroscopy at a point (EDS pointing), and X-ray diffraction analysis (XRD). The results showed that in the experimental condition of the ratio volume 1:1 between CTAB 0.01M and AgNO3 0.02M solutions, and the displacement reaction time of 30 minutes, annealed samples at 100oC in 2 hours were formed Al/Al2O3/Ag SERS platforms with nanostructure leaf-shaped. The Ag NPs with sizes of 10 - 50 nm were distributed homogeneously on the surface. The Raman signal of the sample showed that Al/Al2O3/Ag SERS substrates could detect rhodamine 6G (R6G) at a very low concentration at 10-11M, analytical enhancement factor (EF) of ~ 8x108. From that, this SERS substrate could be used to detect a ketoprofen solution at a concentration as low as 10 ppm with the enhancement factor of ~ 1.5x106.

Utilization of doped/undoped graphene quantum dots for ultrasensitive detection of duphaston, a SERS platform.

Recently nanocluster based drug delivery systems have become the most skillful to study. Interaction mechanism of duphaston (DPH) over graphene (G), carboxyl substituted graphene (COG) and doped COG-X (X=O/S/N/B) were investigated. We studied different spectroscopic properties of adsorbed DPH with nanoclusters. To study effect adsorption of DPH with nanoclusters, the adsorption energies were measured. To track DPH, surface enhanced Raman scattering is used since it is an efficient approach to vibrational spectroscopy. The DPH detection was investigated using GQDs SERS property. For the adsorption of DPH with COG-B nanocluster maximum energy interaction is determined. DPH works on the electrophilic site of nanoclusters as donor of electrons and adsorbs. Charge transfer is higher for to COG-B nanocluster than for other nanoclusters. Variations in chemical descriptors are also noted to understand sensing property of DPH molecule-nanoclusters. The analysis of different properties demonstrates enhancement effect which makes it significant in detecting DPH in other products.

Nanoflower-like Ag/AAO SERS platform with quasi-photonic crystal nanostructure for efficient detection of goat serum

An effective SERS-based detection method has been developed to quantitatively diagnose the goat serum which overcomes the problem of diffusion limitation in traditional heterogeneous immunoassay. In this work, the ultra-sensitive silver/anodic aluminum oxide (Ag/AAO) SERS platform was explored via magnetron sputtering which can precisely control the sample morphology and intergap distances. Results indicated that the localized surface plasmon resonance (LSPR) effect was sharply strengthened as the sub-10 nm nanogaps generated and the enhancement factor (EF) for crystal violet (CV) was calculated to be 3.677 × 107. This novel Ag/AAO substrate with substantial “hot spots” exhibited high SERS sensitivity which could obtain extremely low limits of detection (LOD) of 10−12 M for CV. Importantly, this SERS platform was employed to detect goat serum and reached a LOD at 1 ng/μl. As a nondestructive detection technique, our SERS-based methodology required small sample quantity which expected to achieve more biomolecular detection.

Fabrication of zein-based electrospun nanofiber decorated with gold nanoparticles as a SERS platform

In this study, a new technique was developed to create an eco-friendly and biodegradable SERS sensor platform using electrospun corn zein fibers. First, electrospinning was used in conjunction with glutaraldehyde, a crosslinker for proteins, to create crosslinked zein nanofibers. The surface of the nanofibers was then decorated with 20-nm-diameter gold nanoparticles, and the biosensor platform was tested with the Raman active Rhodamine 6G. The high surface area and the high surface roughness enabled a SERS signal enhancement of 1.06 × 106, which only required 2.8 × 10−7 g of gold nanoparticle deposition on the fibers. This electrospun zein-based gold nanoparticle-decorated sensor platform is not only made with a quicker, simpler and an inexpensive method compared to the other techniques requiring etching procedures and has a very good shelf life stability, but also serves as a green alternative to the plastic-based SERS sensor platforms with an equivalent and sometimes lesser SERS signal enhancement.

Ag@TiO2 nanogranular films by gas phase synthesis as hybrid SERS platforms.

The synthesis of hybrid metallic-dielectric substrates as reliable SERS platforms relies on core-shell nanoparticles, obtained by wet chemistry, with an outer dielectric shell composed of SiO2 or TiO2. Apart from the shell composition, the nanoparticle density and aggregation type strongly affect the surface-enhanced SERS. Going beyond a single layer by building random aggregates of hybrid NPs would result in a step forward in the production of reliable hybrid SERS platforms. Here we achieve the fabrication of a 3D nanogranular film of Ag metallic cores not fully enclosed in a TiO2 capping layer, defined as a Ag@TiO2 quasi-shell-isolated Raman substrate (Ag@TiO2 QuaSIRS) by an environmentally friendly gas phase synthesis technique (SCBD). The Ag core drives the electromagnetic enhancement with plasmonic hotspots while the TiO2 shell passivates it and leads to different possible surface functionalization. The SERS capabilities of the Ag@TiO2 QuaSIRS peak at a film thickness of 60 nm providing a detection limit of 10-9 M concentration for Methylene Blue at 632.81 nm. The importance of the nanogranular 3D morphology is evidenced by the very good detection of analytes dispersed in aqueous solutions, since the liquid can penetrate the pores hence exploiting most of the plasmonic hotspots present in the film. The versatility of SCBD to deposit such reliable hybrid SERS platforms by a single step at room temperature over different substrates provides an opportunity to design a new generation of hybrid SERS-active substrates based on hybrid nanoparticles.

Superhydrophobic Ag–Cu Composite Metal Film as Surface-Enhanced Raman Scattering Substrate

In this paper, a superhydrophobic Ag–Cu composite metal film was fabricated as surface-enhanced Raman scattering substrate. Ag–Cu composite metal film was prepared from galvanic displacement on commercial copper foil. The prepared silver films were modified by PFDT to create a stable superhydrophobic SERS platform. Superhydrophobic substrates were characterized by a variety of characterization methods, including scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-Vis, XPS and Raman spectra. The superhydrophobic substrate could enrich probing molecules with the volatilization of solvent. Mathematical model was presented and applied to investigate concentration factor of hydrophobic substrate. The measurements were in good agreement with the calculation results. The superhydrophobic Ag–Cu composite metal film can reduce the detection limits and provide a new way to prepare efficient SERS substrates for ultra-low concentration detection.