Maximum Surface-enhanced Raman Scattering Research Articles

Assembly of Gold Nanostar Cores Within Silica Shells and Its Impact on Solid-State SERS and Nonenzymatic Catalytic Sensing.

Metal core and dielectric shell nanoparticles (NPs) have garnered considerable attention for their multifaceted properties and extensive applications across diverse fields of nanoscience and nanotechnology. However, a literature gap exists regarding the impact of assembled metallic nanostar cores within a single shell, particularly concerning surface-enhanced Raman scattering (SERS) and electrochemical sensing. In this study, we have demonstrated the better performance of assemblies of gold nanostars (AuNSs) enclosed in single silica shell for SERS enhancement and electrocatalytic activity, particularly in the fields of ascorbic acid (AA) and glucose sensing. We have devised a method to isolate and passivate nanostar assemblies, ranging from 2 to 30 nanostars per assembly, with a functionalized silica (SiO2) shell, facilitating their preservation. The engineered thickness of the silica shell ensures unhindered optical measurements while elucidating the influence of multiple AuNS cores. Due to the formation of nanogaps and nanojunctions between AuNSs within assembly, we have achieved a maximum SERS enhancement factor (EF) of 1.416 × 1010 for the rhodamine 6G analyte. Utilizing assembled AuNS cores within a single silica shell, we have demonstrated AA (sensitivity of 5.278 × 10-5 μA μM-1 cm-2) and glucose (sensitivity of 7.519 × 10-4 μA μM-1 cm-2) sensing via a nonenzymatic electrochemical pathway.

Sensitivity-improved SERS detection of SARS-CoV-2 spike protein by Au NPs/COFs integrated with catalytic-hairpin-assembly amplification technology

BackgroundThe COVID-19 pandemic, caused by the novel coronavirus, has had a profound impact on global health and economies worldwide. This unprecedented crisis has affected individuals, communities, and nations in diverse manners. Developing simple and accurate diagnostic methods is an imperative task for frequent testing to mitigate the spread of the virus. Among these methods, SARS-CoV-2 antigen tests in clinical specimens have emerged as a promising diagnostic method for COVID-19 due to their sensitive and accurate detection of spike (S) protein, which plays a crucial role in viral infection initiation. ResultsIn this work, a dual-signal amplification surface enhanced Raman scattering (SERS)-based S protein biosensor was constructed based on Au NPs/COFs and enzyme-free catalytic hairpin assembly (CHA) amplification method. The approach relies on a released free DNA sequence (T), which is generated from the competition reaction between Aptamer/T and Aptamer/S protein, to trigger a CHA reaction. Due to the high binding affinity and selectivity between the S protein and its aptamer, CHA process was triggered with the maximum SERS tags (H2-conjugated Au@4-mercaptobenzonitrile@Ag) anchored onto Au NPs/COFs substrate surface. This SERS platform could detect the S protein at concentrations with high sensitivity (limit of detection = 3.0 × 10−16 g/mL), wide detection range (1 × 10−16 to 1 × 10−11 g/mL), acceptable reproducibility (relative standard deviation = 7.01 %) and excellent specificity. The biosensor was also employed to detect S protein in artificial human salivas. SignificanceThus, this study not only developed a novel Au NPs/COFs substrate exhibiting strong SERS enhancement ability and high reproducibility, but also proposed a promising dual-signal amplification SERS-based diagnostic method for COVID-19, holding immense potential for the detection of a wide range of antigens and infectious diseases in future applications.

Purines recognition and quantitative analysis by surface-enhanced Raman spectroscopy

The common quantification methods of purines, including high-performance liquid chromatography, micellar electrokinetic chromatography, reverse phase ion pair chromatography, and capillary zone electrophoresis, have been used for the analysis of purines. These conventional techniques are limited by long operation times, large sample volumes, requirements for pretreatment and separation processes, or sophisticated, bulky and expensive equipment. Here, we have developed a simple method to prepare a probe for the quantitative analysis of purines using the surface-enhanced Raman scattering (SERS) method. The SERS probe is a rough Ag wire obtained with simple electrochemical treatment, which is optimized to reach the maximum SERS signal enhancement. The Raman enhancement factor (EF) of Ag wire after roughening can reach ∼106. Under optimized conditions, the rough Ag wire is capable of recognizing four purine bases (namely, guanine, adenine, hypoxanthine, and xanthine) in the range of 10−5 to 10−1 mg/mL with a linear relationship between SERS intensity of signature peak and purine concentration. The recovery rate of each purine base is higher than 80% in the mixture of four purines. The overall method was successfully applied to the monitoring of the level of purines in marketplace beer beverages. The novel wire-based SERS sensor used with portable Raman spectroscopy is prospective in diet safety and personalized point-of-care medical detection.

Combinatorial Approach to Find Nanoparticle Assemblies with Maximum Surface-Enhanced Raman Scattering.

Plasmonic nanoparticles exhibit unique properties that distinguish them from other nanomaterials, including vibrant visible colors, the generation of local electric fields, the production of hot charge carriers, and localized heat emission. These properties are particularly enhanced in the narrow nanogaps formed between nanostructures. Therefore, creating nanogaps in a controlled fashion is the key to achieving a fundamental understanding of plasmonic phenomena originating from the nanogaps and developing advanced nanomaterials with enhanced performance for diverse applications. One of the most effective approaches to creating nanogaps is to assemble individual nanoparticles into a clustered structure. In this study, we present a fast, facile, and highly efficient method for preparing core@satellite (CS) nanoassembly structures using gold nanoparticles of various shapes and sizes, including nanospheres, nanocubes (AuNCs), nanorods, and nanotriangular prisms. The sequential assembly of these building blocks on glass substrates allows us to obtain CS nanostructures with a 100% yield within 4 h. Using 9 different building blocks, we successfully produce 16 distinct CS nanoassemblies and systematically investigate the combinations to search for the highest Raman enhancement. We find that the surface-enhanced Raman scattering (SERS) intensity of AuNC@AuNC CS nanoassemblies is 2 orders of magnitude larger than that of other CS nanoassemblies. Theoretical analyses reveal that the intensity and distribution of the electric field induced in the nanogaps by plasmon excitation, as well as the number of molecules in the interfacial region, collectively contribute to the unprecedentedly large SERS enhancement observed for AuNC@AuNC. This study not only presents a novel assembly method that can be extended to produce many other nanoassemblies but also identifies a highly promising SERS material for sensing and diagnostics through a systematic search process.

Layer-by-layer coating of natural diatomite with silver nanoparticles for identification of circulating cancer protein biomarkers using SERS.

Surface-enhanced Raman scattering (SERS) is an emerging spectroscopy technique for detecting and characterizing chemical or biological structures in the vicinity of plasmonic nanostructures. Colloidal, solid, and flexible nanostructures are widely used in SERS experiments to enhance the Raman intensity. The nanostructure used in SERS is one of the main influencing parameters and a growing research area. Fabrication of simple and cheap SERS substrates with a high enhancement factor is desired. In this study, we fabricated a reproducible, cheap, and flexible SERS active strip by coating natural diatomite (biosilica) with silver nanoparticles (AgNPs) using the layer-by-layer assembly method and the fabricated strip is used for the label-free identification of circulating cancer protein biomarkers. SERS active strips were fabricated having different numbers of AgNP layers on natural diatomite and comprehensive characterization techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV/vis absorption spectrophotometry were used. SERS activities of the strips depending on the number of layers were evaluated using 4-aminothiophenol (4-ATP) and rhodamine 6G (Rh6G) molecules. We found that the SERS intensity is strongly dependent on the number of AgNP layers, with the maximum SERS intensity obtained from the strip with 5 layers of AgNPs, having a 2.0 × 105 enhancement factor. The strip with the highest SERS activity was used for the label-free identification of circulating cancer protein biomarkers (HER2, CA15-3, PSA, MUC4, and CA27-29). The results demonstrate that the fabricated strip can help in the effective label-free identification of circulating protein biomarkers and open new directions for SERS-based label-free biosensing applications.

TiO2 Thickness-dependent charge transfer effect in p-aminothiophenol molecules chemisorbed on TiO2/Ni substrates

Semiconductors have been modulated in thickness to optimize their surface-enhanced Raman scattering (SERS) activity in noble metal/semiconductor SERS substrates. However, the charge transfer (CT) resonance mechanism caused by the change of the semiconductor thickness has not been fully clarified yet, due to the influence of the strong surface plasmon resonance (SPR) effect from the noble metals. Here, systems of p-aminothiophenol (PATP) molecules chemisorbed on TiO2/Ni nanopillar array films with precisely controlled TiO2 thicknesses (PATP/TiO2/Ni) were developed to systematically evaluate the TiO2 thickness-dependent CT mechanism on the premise of minimizing the SPR influence. Ultraviolet–visible, photoluminescence and X-ray photoelectron spectroscopy results demonstrated that four parts that ascribed to the SERS enhancement, photo-induced CT from Ni to TiO2, resonance excitation of TiO2, CT from TiO2 surface states to PATP molecules, and the molecular resonance of PATP molecules, are highly TiO2-thickness dependent. Hence the whole system exhibits a strong TiO2-thickness-dependent CT effect (at the two interfaces of Ni-TiO2 and TiO2-PATP) and SERS activity with a maximum SERS intensity at a TiO2 thickness of 40 nm. This work shall be valuable for future developing an optimal metal/semiconductor SERS substrates and obtaining an in-depth understanding of the semiconductor-thickness-dependent charge transfer mechanism for SERS applications.

Tailored FTO/Ag/ZIF-8 structure as SERS substrate for ultrasensitive detection

In this work, a series of F-doped SnO2/Ag/zeolite imidazole framework (FTO/Ag/ZIF-8) sandwich structure have been successfully fabricated via a magnetic sputtering method and serve as surface-enhanced Raman scattering (SERS) substrate. The magnetic sputtering time of Ag was adjusted to obtain the optimal SERS substrate. The commonly used 4-mercaptobenzoic acid (4-MBA) molecules was selected for the SERS experiment. When the sputtering time of Ag nanoparticles (NPs) was 120 s, the FTO/Ag/ZIF-8 substrate showed the maximum SERS performance. In the system, the electromagnetic mechanism (EM) and charge-transfer (CT) enhancement mechanism have synergistic effect on the SERS phenomenon. Ag NPs was used to generate electromagnetic hot spots, which was beneficial to the EM mechanism. ZIF-8 could adsorb and capture more 4-MBA probe molecules to the hotspots. At the same time, CT happened between Ag, ZIF-8, and 4-MBA probe molecules, which was attribute to the CM mechanism. The enhancement factor (EF) of the composite SERS substrate was as high as 7.67 × 106. The detection limit of the substrate can reach 10-9 M of 4-MBA probe molecules. Moreover, the SERS templates showed good stability, the SERS signals almost unchanged after naturally kept for 6 months. Besides, due to the high sensitivity and good stability of the substrates, this work might broaden the potential practical application of SERS.

Gold-Trisoctahedra-Coated Capillary-Based SERS Platform for Microsampling and Sensitive Detection of Trace Fentanyl.

A cost-effective and highly reproducible capillary-based surface-enhanced Raman scattering (SERS) platform for sensitive, portable detection and identification of fentanyl is presented. Through encapsulating gold trisoctahedra (Au TOH) in the capillary tube for the first time, the SERS platform was constructed by combining the superior SERS properties of Au TOH and the advantages of capillaries in SERS signal amplification, facile sample extraction, and portable trace analysis. The effects of the size and density of Au TOH on the SERS performance were investigated by experiments and simulations, which showed that the maximum SERS enhancement was obtained for Au TOH with the size of 75 nm when particle density reached 74.54 counts/μm2. The proposed SERS platform possesses good reproducibility with a relative standard deviation (RSD) of less than 5%. As a demonstration, the platform was applied to detect fentanyl spiked in aqueous solution and serum samples with a limit of detection (LOD) as low as 1.86 and 40.63 ng/mL, respectively. We also validated the feasibility of the designed platform for accurate identification of trace fentanyl adulterated in heroin at mass concentration down to 0.1% (10 ng in 10 μg total). Overall, this work advances more explorations on capillary-based SERS platform to benefit portable trace analysis.

Surface-enhanced Raman scattering of CoTiO3@Ag nanofibers for high-performance sensing applications

Surface-enhanced Raman scattering (SERS) has proven to be a powerful fingerprinting technique for the ultra-sensitive detection of a variety of biological and chemical analytes. Hence, the development of facile, low-cost, and reliable SERS-active substrates is essential for practical applications. In this study, electrospun CoTiO3@Ag nanofibers annealed at different temperatures were developed and explored for SERS detection using R6G as a probe. The results showed that with increasing annealing temperature, more Ag nanoparticles grew on the surface of the CoTiO3 nanofibers, leading to a maximum SERS effect achieved at 700 °C. The substrate showed good reusability during repeated SERS detection of R6G and RhB without appreciable loss of activity. High sensitivity over a range of R6G concentrations (10-9–10-3 M) and good uniformity (RSD = 12.3%) were also observed for the prepared substrate. Moreover, when the individual nanofibers were assembled into helically bundled CoTiO3@Ag nanofibers, the SERS effect was increased by a factor of 9.27. This further enhancement was attributed to the interparticle plasmonic couplings and consequently increased number of hot spots, as demonstrated by FEM simulations of bundled CoTiO3@Ag nanofibers with different spacings. These findings demonstrate that elegant manipulation of the nanofibers can effectively boost the resulting SERS performance.

Plasmonic properties of individual heterogeneous dimers of Au and In nanospheres

In this paper, a new type of heterogeneous dimer of Au and In nanospheres is proposed, which refractive index (RI) sensing and surface enhanced Raman scattering (SERS) performances are numerically predicted by finite element method. It combines both LSPR advantages of Au and In. Under visible and UV light excitations, the maximum RI sensitivity factor S is revealed to reach 259 nm/RIU and 535 nm/RIU, while the maximum SERS enhancement factor reaches ∼107 and 105, respectively. They are improved significantly than that of monomer counterparts. The near-electric-field coupling effect on the dimer localized surface plasmon resonance (LSPR) peak wavelength, S, and the corresponding fractional shifts are discussed, which provide alternatives to estimate the gap distance in-between dimer components. It holds great promise for future designing Au, In heterogeneous nanostructure based SERS and RI sensing substrates which work efficiently both at visible and UV light regions.

Fast and eco-friendly fabrication of uniform Ag substrates for highly sensitive surface-enhanced Raman scattering

This study proposed a fast, simple, eco-friendly method for obtaining highly sensitive and uniform surface-enhanced Raman scattering (SERS) of silver (Ag) nanotextured substrates decorated with silver nanoparticles in open air. By splitting conventional femtosecond pulses (subpulse delay Δt = 0 ps) into pulse trains (subpulse delay Δt = 3 ps), the mean diameter of Ag nanoparticles was reduced by almost half and the amount of Ag nanoparticles with a diameter ranging from 20 to 60 nm was increased by more than 11 times. The substrate fabricated by femtosecond pulse trains has four main merits as follows: (1) High sensitivity: the maximum SERS enhancement factor is 1.26 × 109; (2) High efficiency: the fabrication rate can be up to 1600 μm2/s, which is 20–40 times faster than femtosecond photochemical reduction; (3) Good reproducibility: the relative standard deviation of the Raman signal intensity is 10.7%, which is one-third of that for conventional femtosecond laser; (4) Eco-friendly fabrication: neither chemical reagents nor vacuum conditions are needed during the fabrication process.

High Surface-Enhanced Raman Scattering (SERS) Amplification Factor Obtained with Silver Printed Circuit Boards and the Influence of Phenolic Resins for the Characterization of the Pesticide Thiram.

In this work, low-cost substrates with rough silver surfaces were prepared from commercial copper foil-covered phenolic board (CPB) and an aqueous solution of AgNO3, and were used for surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS) measurements. A maximum SERS amplification factor of 1.2 × 10(7) was obtained for Rhodamine 6G (R6G), and use of the CPB resulted in a detection limit for Thiram pesticide of 0.5 µmol L(-1) The minimum detection level was limited by residual traces of phenolic groups that originated from the substrate resin, which became solubilized in the aqueous Ag(+) solution. It was found that the bands corresponding to the impurities had less influence in the Thiram analysis, which could be explained by the high affinity of sulfur for Ag surfaces. The influence of impurities in the SERS analyses therefore depended on the linkage between the rough silver surface and the analyte. The findings demonstrated the ease and effectiveness of using CPB to prepare a nanostructured surface for SERS.

Surface-enhanced Raman spectroscopy on single Fe2O3@Au spindle nanoparticle: polarization dependence and FDTD simulation

The surface-enhanced Raman scattering (SERS) effect was critically dependent on the shape of the plasmonic nanostructures. It still remains a significant challenge in exploring the correlation between the SERS effect and the shape of nanostructures. Here, the polarized SERS combined with finite difference time domain (FDTD) calculation was developed to elucidate the origination of the SERS effect on an anisotropic spindle-shaped Fe2O3@Au nanoparticle. The surface enhancement factor for spindle-shaped Fe2O3@Au nanoparticles was estimated to be about six-orders by using pyridine as model molecules. A dramatic variation in SERS effect was observed by changing the excitation polarization direction. The maximum SERS intensity was detected when the excitation polarization was parallel to the long axes of Fe2O3@Au nanoparticles, while the minimum intensity was observed at the perpendicular orientation. The remarkable polarization-dependent SERS effects can be attributed to the local enhanced electric field that strongly depends on the polarization direction. The theoretical simulation based on the FDTD method was performed to evaluate the distribution of a local electromagnetic field on Fe2O3@Au single nanoparticles. It was in good agreement with the experimental results. This strategy provided deeper insight into the distribution of the SERS effect on a single anisotropic nanoparticle.

Agcore–Aushell bimetallic nanocomposites: Gold shell thickness dependent study for SERS enhancement

This study reports the synthesized core–shell bimetallic nanocomposites of silver and gold, respectively by varying the thickness of Au shell and studying its role in enhancing the Raman scattering of the molecule. The crystal violet (CV) was chosen as the target analyte molecule and the surface enhanced Raman scattering (SERS) enhancement of this molecule was studied as a function of Au shell thickness. The appropriate thickness of Au nanoshell, deposited on the Ag nanoparticles to obtain the maximum SERS enhancement, was identified and further increase in thickness of Au showed a decrease in intensity of the SERS signals. Among all the fabricated Ag@Au specimens ~30nm of Ag seed with 8nm of Au nanoshell showed the maximum enhancement of the SERS signals of CV. The close proximity of discontinuous Au shell acts as SERS hot spots by creating molecular level gap that accommodates the CV molecules responsible for the SERS enhancement up to the order of 1013 which is highly reproducible.

Gain-assisted U-shaped Au nanostructure for ultrahigh sensitivity single molecule detection by surface-enhanced Raman scattering

We report an efficient gain-assisted U-shaped Au nanostructure for ultrahigh sensitivity single-molecule detection by surface-enhanced Raman scattering (SERS). The localized surface plasmon resonance (LSPR) amplification property and SERS characteristics of the proposed nanosystem are numerically analyzed by the finite-element method (FEM). The calculations show that the LSPR strength and the local electric field intensity of the active nanosystem can be greatly amplified when the nanosystem reaches its spaser threshold (kthre). Furthermore, the maximum SERS enhancement factor of the nanosystem is as high as 4.7 × 1017 on the Au surface areas and 5.8 × 1018 in volume, respectively. Moreover, there is a high SERS enhancement factor of 1014−1017 on the entire surface of the active nanosystem, which is sufficient for single-molecule detection. Finally, the plasmon hybridization theory and effective LC circuit are used to qualitatively illustrate the red-shift of the resonance wavelength by increasing the geometric parameter W2.

Off-Resonant Gold Superstructures as Ultrabright Minimally Invasive Surface-Enhanced Raman Scattering (SERS) Probes

Surface-enhanced Raman scattering (SERS) tags that serve as exogenous contrast agents for SERS-based bioimaging are comprised of size- and shape-controlled plasmonic nanostructures. For maximum SERS activity and image contrast, the localized surface plasmon resonance (LSPR) wavelength of SERS tags based on individual nanostructures must match with the excitation wavelength (typically in the near-infrared (NIR) therapeutic window, i.e., 650–900 nm). However, under the resonant excitation, these SERS tags typically exhibit very high photothermal conversion efficiency, resulting in excessive heat that can perturb or even damage the biological species being imaged. Here, we demonstrate bioenabled synthesis of a novel class of ultrabright SERS probes with built-in and accessible electromagnetic hotspots formed by densely packed satellite nanoparticles grown on a plasmonic core. Through the rational choice of the shape of the core, the LSPR wavelength of Au superstructures can be tuned to be either off- or on-r...

Detection and quantitative analysis of carbendazim herbicide on Ag nanoparticles via surface‐enhanced Raman scattering

Carbendazim (MBC) is a fungicide widely used in agriculture, and there are serious concerns regarding the health risks that could be caused by this fungicide. Here, we explore its ultrasensitive detection by surface‐enhanced Raman scattering (SERS). First, to obtain maximum SERS signal, the adsorption of the target molecule onto metallic surface is essential. Therefore, we study the adsorption of the MBC onto the nanoparticle surface by SERS under different experimental conditions, such as different synthesis methods of nanoparticle, variable excitation wavelength, and fungicide concentration with the aim to detect MBC at low concentrations. Experiments are carried out with three kinds of colloidal nanoparticles: Ag and Au reduced by citrate and Ag reduced by hydroxylamine. However, mainly Ag colloids are highly efficient in the SERS detection of MBC. In addition, theoretical calculations of MBC Raman spectrum and that of the surface complex are used to help with the understanding the mechanisms responsible for the interaction between MBC and Ag. Ultraviolet–visible absorption spectroscopy showed displacement to the red of the plasmon resonance of Ag colloid in the presence of MBC. Copyright © 2015 John Wiley & Sons, Ltd.

Tuning the SERS Response with Ag-Au Nanoparticle-Embedded Polymer Thin Film Substrates.

Development of facile routes to the fabrication of thin film substrates with tunable surface enhanced Raman scattering (SERS) efficiency and identification of the optimal conditions for maximizing the enhancement factor (EF) are significant in terms of both fundamental and application aspects of SERS. In the present work, polymer thin films with embedded bimetallic nanoparticles of Ag-Au are fabricated by a simple two-stage protocol. Ag nanoparticles are formed in the first stage, by the in situ reduction of silver nitrate by the poly(vinyl alcohol) (PVA) film through mild thermal annealing, without any additional reducing agent. In the second stage, aqueous solutions of chloroauric acid spread on the Ag-PVA thin film under ambient conditions, lead to the galvanic displacement of Ag by Au in situ inside the film, and the formation of Ag-Au particles. Evolution of the morphology of the bimetallic nanoparticles into hollow cage structures and the distribution of Au on the nanoparticles are revealed through electron microscopy and energy dispersive X-ray spectroscopy. The localized surface plasmon resonance (LSPR) extinction of the nanocomposite thin film evolves with the Ag-Au composition; theoretical simulation of the extinction spectra provides insight into the observed trends. The Ag-Au-PVA thin films are found to be efficient substrates for SERS. The EF follows the variation of the LSPR extinction vis-à-vis the excitation laser wavelength, but with an offset, and the maximum SERS effect is obtained at very low Au content; experiments with Rhodamine 6G showed EFs on the order of 10(8) and a limit of detection of 0.6 pmol. The present study describes a facile and simple fabrication of a nanocomposite thin film that can be conveniently deployed in SERS investigations, and the utility of the bimetallic system to tune and maximize the EF.

A facile high‐performance SERS substrate based on broadband near‐perfect optical absorption

Plasmonic systems based on metal nanoparticles on a metal film with high optical absorption have generated great interests for surface‐enhanced Raman scattering (SERS). In this study, we prepare a broadband‐visible light absorber consisting Au nanotriangles on the surface of a continuous optically opaque gold film separated with a dielectric SiO2 layer, which is a typical metal‐insulator‐metal (MIM) system, and demonstrate it as an efficient SERS substrate. The MIM nanostructure, prepared using nanosphere lithography with a very large area, shows a broadband with absorption exceeding 90% in the wavelength regime of 630–920 nm. We observe an average SERS enhancement factor (EF) as large as 4.9 × 106 with a 22‐fold increase compared to a single layer of Au nanotriangles directly on a quartz substrate. A maximum SERS EF can be achieved by optimizing the thicknesses of the dielectric layer to control the optical absorption. Owing to the simple, productive, and inexpensive fabrication technique, our MIM nanostructure could be a potential candidate for SERS applications. Copyright © 2015 John Wiley & Sons, Ltd.

Surface-enhanced Raman scattering and gap-mode tip-enhanced Raman scattering investigations of phthalocyanine molecules on gold nanostructured substrates

This study reports the use of surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS), both independent and in combination, to investigate Raman enhancement of films under different confinement geometries. The experiments are performed on ultrathin cobalt phthalocyanine (CoPc) films deposited on specially designed SERS structures. The SERS structures are fabricated by electron-beam lithography and contain nanostructured gold films and gold dimer arrays with controlled size and internanocluster distance. Such structures allow investigation of the effects of nanocluster size and internanocluster distance, excitation wavelength, and polarization of light upon the electromagnetic SERS enhancement. Significant enhancement of the Raman scattering by CoPc is observed under 632.8 nm excitation because of the double resonance originating from the energy match between the laser excitation and the localized surface plasmon and electronic transitions in CoPc. The SERS signal of CoPc is further enhanced by decreasing the internanocluster distance. Maximum SERS enhancement occurs when the polarization of the incident light is perpendicular to the dimer axis. Under 514.5 nm excitation, nanostructured gold films give greater enhancement than any of the nanocluster arrays, with the highest enhancement realized using the so-called “gap-mode TERS” wherein the SERS structures are probed in the TERS condition. The TERS experiment is performed using a customized TERS setup and all-metal atomic force microscopy tips custom fabricated. In terms of obtaining the ultimate sensitivity in Raman spectroscopy, further enhancement is achieved by confining the electromagnetic field in a gap between two metallic nanostructures either by using SERS or by combining SERS and TERS.