Surface-enhanced Raman Scattering Spectroscopy Research Articles

Establishment of real-time viral pathogen detection method-surface-enhanced Raman scattering system for porcine circovirus type II

The transition towards large-scale intensive pig farming methods has resulted in an increase in cases of complex, mixed infections, and secondary infections. Porcine circovirus (PCV), the causative agent of PCV disease (PCVD), is a small nonenveloped DNA virus containing a single-stranded circular genome. Previously, PCV was even considered nonpathogenic to pigs. However, a novel strain of PCV, designated PCV-2, has been associated with various disease syndromes in pigs over the last 5 years. PCV-2 primarily induces post-weaning multisystemic wasting syndrome, characterized by clinical signs such as debility, dyspnea, palpable lymphadenopathy, diarrhea, and pallor or icterus. PCV-2 is now recognized as an important emerging pathogen. Early diagnosis and disease prevention have become crucial for effective pig farm management. However, clinical diagnosis may be complicated by antibiotic treatment and atypical disease symptoms. To ensure accurate pathology diagnosis, it is essential to integrate robust laboratory diagnostics with traditional methods. Surface-enhanced Raman Scattering (SERS) spectroscopy has emerged as a potentially powerful technique for whole-organism fingerprinting, enabling rapid identification of bacteria. Biosensors utilizing SERS offer promising capabilities for sensitive and quick detection of bacterial pathogens, thereby reducing diagnosis time. In this study, our aim was to characterize and evaluate a SERS-based diagnostic system for detecting and identifying PCV-2 present in pooled swine sera and feces. We compared the spectra of PCV-2 recovered from the specimens to those of pure PCV-2 to determine the PCV-2 molecular fingerprint. Our results demonstrated successful detection, identification, and classification of PCV-2 in swine sera and feces using SERS. SERS provided reproducible molecular spectroscopic signatures suitable for analytical applications. This approach presents a new and potent tool for real-time surveillance of animal viral pathogens in clinical settings.

Interfacial Bonding Induced Charge Transfer in Two-Dimensional Amorphous MoO3-x/Graphdiyne Oxide Non-Van der Waals Heterostructures for Dominant SERS Enhancement.

Two-dimensional semiconductor-based nanomaterials have shown to be an effective substrate for Surface-enhanced Raman Scattering (SERS) spectroscopy. However, the enhancement factor (EF) tends to be relatively weak compared to that of noble metals and does not allow for trace detection of molecules. In this work, we report the successful preparation of two-dimensional (2D) amorphous non-van der Waals heterostructures MoO3-x/GDYO nanomaterials using supercritical CO2. Due to the synergistic effect of the localized surface plasmon resonance (LSPR) effect and the charge transfer effect, it exhibits excellent SERS performance in the detection of methylene blue (MB) molecules, with a detection limit as low as 10-14 M while the enhancement factor (EF) can reach an impressive 2.55×1011. More importantly, the chemical bond bridging at the MoO3-x/GDYO heterostructures interface can accelerate the electron transfer between the interfaces, and the large number of defective surface structures on the heterostructures surface facilitates the chemisorption of MB molecules. And the charge recombination lifetime can be proved by a ~1.7-fold increase during their interfacial electron-transfer process for MoO3-x/GDYO@MB mixture, achieving highly sensitive SERS detection.

One-dimensional SERS nanoprobes based on cellulose nanocrystals and their biomaging performance

Surface enhanced Raman scattering spectroscopy (SERS) technology has received increasing attention in the bioimaging field. Herein, based on the support of cellulose nanocrystal (CNC) with thiol groups, one-dimensional (1D) "hot spot" structure was constructed by the self-assembly of gold nanoparticles (AuNPs) via Au-S bonding. Silica shell was subsequently coated on the CNC loaded with AuNPs to fabricate core-shell SERS nanoprobe, which was further successfully applied for the SERS imaging of Hela cells. Owing to the presence of silica shell, the nanoprobe exhibited excellent water-dispersible stability in phosphate buffer salt solution (PBS). Moreover, the silica shell effectively protected both the "hot spot" structure and the adsorbed Raman reporter of 4-mercaptobenzoic acid from external interference, thereby improving the signal stability of SERS nanoprobe. In addition, the plasma coupling of electromagnetic field between AuNPs and silica significantly enhanced the Raman signal of "hot spots". The SERS nanoprobe possessed good biocompatibility even at relatively high concentrations, and successfully achieved bioimaging of Hela cell using the Raman signal at 1580 cm−1 channel.

Magnetic-Plasmonic Nanocomposites as Versatile Substrates for Surface-enhanced Raman Scattering (SERS) Spectroscopy.

Surface-enhanced Raman scattering (SERS) spectroscopy, a highly sensitive technique for detecting trace-level analytes, relies on plasmonic substrates. The choice of substrate, its morphology, and the excitation wavelength are crucial in SERS applications. To address advanced SERS requirements, the design and use of efficient nanocomposite substrates have become increasingly important. Notably, magnetic-plasmonic (MP) nanocomposites, which combine magnetic and plasmonic properties within a single particle system, stand out as promising nanoarchitectures with versatile applications in nanomedicine and SERS spectroscopy. In this review, we present an overview of MP nanocomposite fabrication methods, explore surface functionalization strategies, and evaluate their use in SERS. Our focus is on how different nanocomposite designs, magnetic and plasmonic properties, and surface modifications can significantly influence their SERS-related characteristics, thereby affecting their performance in specific applications such as separation, environmental monitoring, and biological applications. Reviewing recent studies highlights the multifaceted nature of these materials, which have great potential to transform SERS applications across a range of fields, from medical diagnostics to environmental monitoring. Finally, we discuss the prospects of MP nanocomposites, anticipating favorable developments that will make substantial contributions to various scientific and technological areas.

Dual detection and quantification of hypochlorite and sulfite ions via SERS spectroscopy by utilizing the redox reaction of tetramethylbenzidine

We developed a highly efficient, ultra-sensitive, and selective dual detection sensor for hypochlorite (ClO–) and sulfite (SO32–) ions based on surface-enhanced Raman scattering (SERS) spectroscopy. 3,3′,5,5′-Tetramethylbenzidine (TMB) is oxidized by ClO– under acidic conditions to diazotized oxTMB that, when electrostatically adsorbed onto Au nanoparticles (NPs), produces a strong Raman signal at 1605 cm−1. Meanwhile, oxTMB is reduced to TMB by SO32–, which significantly reduces the Raman signal. The linear detection range of the proposed sensor is 10–10 to 10–6 M with a detection limit of 59 pM for ClO– and 10–9 to 10–5 M with a detection limit of 5.4 nM for SO32–. In addition, the sensor was successfully applied to detect ClO– and SO32– in water samples.

Developing highly reliable Ag@NaYF4 hybrid structures for efficiently improving optical property

Here, we report a rational method for constructing a composite functional surface-enhanced Raman scattering (SERS) substrate, which is prepared by modifying the surfaces of β-NaYF4:Yb3+/Er3+ microtubes (MTs) with Ag nanoparticles (NPs). A single Ag@NaYF4 MT hybrid structure (Ag@NaYF4 MTHS) improves SERS activity compared to a typical substrate consisting of pure Ag NPs deposited on glass slide and exhibits excellent Raman signal response to various probe molecules (4-nitrothiophenol (4-NTP), crystal violet (CV), and Rhodamine 6G (Rh6G)). Furthermore, the Ag@NaYF4 MTHS substrate presents good catalytic performance and the plasmon-driven catalytic kinetics process is successfully monitored by using in situ SERS spectroscopy technique. This study provides valuable insights for designing multifunctional hybrid structures that incorporate containing noble metallic and lanthanide-based materials. These composite structures hold significant potential for advancing applications in photocatalysis, sensor, and in situ bio/chemical-analysis.

Accessible hotspots for single-protein SERS in DNA-origami assembled gold nanorod dimers with tip-to-tip alignment

The label-free identification of individual proteins from liquid samples by surface-enhanced Raman scattering (SERS) spectroscopy is a highly desirable goal in biomedical diagnostics. However, the small Raman scattering cross-section of most (bio-)molecules requires a means to strongly amplify their Raman signal for successful measurement, especially for single molecules. This amplification can be achieved in a plasmonic hotspot that forms between two adjacent gold nanospheres. However, the small (≈1−2 nm) gaps typically required for single-molecule measurements are not accessible for most proteins. A useful strategy would thus involve dimer structures with gaps large enough to accommodate single proteins, whilst providing sufficient field enhancement for single-molecule SERS. Here, we report on using a DNA origami scaffold for tip-to-tip alignment of gold nanorods with an average gap size of 8 nm. The gaps are accessible to streptavidin and thrombin, which are captured at the plasmonic hotspot by specific anchoring sites on the origami template. The field enhancement achieved for the nanorod dimers is sufficient for single-protein SERS spectroscopy with sub-second integration times. This design for SERS probes composed of DNA origami with accessible hotspots promotes future use for single-molecule biodiagnostics in the near-infrared range.

SERS spectroscopy as a tool for the study of thiopurine drug pharmacokinetics in a model of human B leukemia cells

Thiopurine drugs are immunomodulatory antimetabolites relevant for pediatric patients characterized by dose-dependent adverse effects such as myelosuppression and hepatotoxicity, often related to inter-individual differences, involving the activity of important enzymes at the basis of their biotransformation, such as thiopurine S-methyltransferase (TPMT).Surface Enhanced Raman Scattering (SERS) spectroscopy is emerging as a bioanalytical tool and represents a valid alternative in terms of affordable costs, shorter analysis time and easier sample preparation in comparison to the most employed methods for pharmacokinetic analysis of drugs.The aim of this study is to investigate mercaptopurine and thioguanine pharmacokinetics by SERS in cell lysates of a B-lymphoblastoid cell line (NALM-6), that did (TPMT*1) or did not (MOCK) overexpress the wild-type form of TPMT as an in vitro cellular lymphocyte model to discriminate between cells with different levels of TPMT activity on the base of the amount of thioguanosine nucleotides (TGN) metabolites formed.SERS analysis of the cell lysates was carried out using SERS substrates constituted by Ag nanoparticles deposited on paper and parallel samples were used for quantification of thiopurine nucleotides with liquid chromatography-tandem mass spectrometry (LC-MS/MS).A direct SERS detection method has been set up that could be a tool to study thiopurine drug pharmacokinetics in in vitro cellular models to qualitatively discriminate between cells that do and do not overexpress the TPMT enzyme, as an alternative to other more laborious techniques.Results underlined decreased levels of TGN and increased levels of methylated metabolites when TPMT was overexpressed, both after mercaptopurine and thioguanine treatments.A strong positive correlation (Spearman's rank correlation coefficient rho = 0.96) exists between absolute quantification of TGMP (pmol/1 x 106 cells), obtained by LC-MS/MS, and SERS signal (intensity of TGN at 915 cm−1).In future studies, we aim to apply this method to investigate TPMT activity in pediatric patients’ leukocytes.

Rapid SERS detection of diverse filamentous fungi by superparamagnetic particles and flexible silver nanowires

In clinical practice, infections caused by Aspergillus species are common and associated with high mortality rates. However, isolating Aspergillus from clinical samples and cultures is challenging, and serological tests cannot differentiate between strains. Furthermore, the complex cell wall structure in Aspergillus species hinders DNA extraction and subsequent nucleic acid detection. Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger are common and frequently encountered pathogenic species. This study aimed to establish an efficient and rapid method for detecting Aspergillus species in clinical samples. Fe3O4@PEI.NH2 nanoparticles with large particle sizes were employed to capture Aspergillus from the samples. Flexible silver nanowires (AgNWs) were prepared and used as the surface-enhanced Raman scattering (SERS) substrate for Aspergillus detection. Through SERS spectroscopy, the identification of captured Aspergillus species was confirmed. Furthermore, the SERS spectrum underwent principal component analysis employing orthogonal partial least-squares discrimination analysis (OPLS-DA) as a multivariate analysis technique to distinguish between the various Aspergillus species effectively. After 10-fold cross-validation, the trained model achieved a testing accuracy of 99.15%, indicating excellent classification performance. By utilizing pre-prepared Fe3O4@PEI.NH2 and AgNWs, the detection process was completed within 60 min without disrupting the cell wall of Aspergillus.

Achieving Molecular Recognition of Structural Analogues in Surface-Enhanced Raman Scattering Spectroscopy: Inducing Charge and Geometry Complementarity to Mimic Molecular Docking.

Molecular recognition of complex isomeric biomolecules remains challenging in surface-enhanced Raman scattering (SERS) spectroscopy due to their small Raman cross-sections and/or poor surface affinities. To date, the use of molecular probes has achieved excellent molecular sensitivities but still suffers from poor spectral specificity. Here, we induce 'charge and geometry complementarity' between probe and analyte as a key strategy to achieve high spectral specificity for effective SERS molecular recognition of structural analogues. We employ 4-mercaptopyridine (MPY) as the probe, and chondroitin sulfate (CS) disaccharides with isomeric sulfation patterns as our proof-of-concept study. Our experimental and in silico studies reveal that 'charge and geometry complementarity' between MPY's binding pocket and the CS sulfation patterns drives the formation of site-specific, multidentate interactions at the respective CS isomerism sites, which 'locks' each CS in its analogue-specific complex geometry, akin to molecular docking events. Leveraging the resultant spectral fingerprints, we achieve > 97% classification accuracy for 4 CSs and 5 potential structural interferences, as well as attain multiplex CS quantification with < 3 % prediction error. These insights could enable practical SERS differentiation of biologically important isomers to meet the burgeoning demand for fast-responding applications across various fields such as biodiagnostics, food and environmental surveillance.

Cladosporium cladosporioides (strain Clc/1): a candidate for low-density polyethylene degradation

BackgroundPlastic is one of the most widely used materials worldwide in various fields, including packaging and agriculture. Its large quantities require proper disposal and for this reason more and more attention is paid to the issue of degrading plastic. Thanks to the production of non-specific enzymes, fungi are able to attack complex and recalcitrant xenobiotics such as plastics. In recent years, several spectroscopic methods were used to study the plastic degradation ability of different fungal species. Among these, Fourier transform infrared (FT-IR) and FT-Raman spectroscopy techniques are the most used. Surface-enhanced Raman scattering (SERS) spectroscopy is a powerful technique which uses metal nanoparticles (NPs) to enhance the Raman signal of molecules adsorbed on the NPs surface. In this work, the isolation of different fungi from field-collected plastic debris and the ability of these isolates to growth and colonizing the low-density polyethylene (LDPE) were explored by using scanning electron microscope (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and SERS spectroscopies.ResultsForty-seven fungal isolates belonging to 10 genera were obtained; among them only 11 were able to grow and colonize the LDPE film. However, after 90 days trial, only one isolate of Cladosporium cladosporioides (Clc/1) was able to carry out the initial degradation of the LDPE film. In particular, based on SEM observations, small cavities and depressed areas of circular shape were visible in the treated samples. Additionally, ATR-FTIR, normal Raman and SERS analyses supported the structural changes observed via SEM. Notably, ATR-FTIR and normal Raman spectra showed a significant decrease in the relative intensity of the methylene group bands. Similarly, the SERS spectra of LDPE after the fungal attack, confirmed the decrease of methylene groups bands and the appearance of other bands referring to LDPE polyphenolic admixtures.ConclusionsThese results suggest that Cladosporium cladosporioides Clc/1 is able to carry out an initial degradation of LDPE. Moreover, combining ATR-FTIR, Raman and SERS spectroscopies with SEM observations, the early stages of LDPE degradation can be explored without any sample pretreatment.Graphical

Tracking Electrochemistry on Single Nanoparticles with Surface-Enhanced Raman Scattering Spectroscopy and Microscopy.

Studying electrochemical reactions on single nanoparticles is important to understand the heterogeneous performance of individual nanoparticles. This nanoscale heterogeneity remains hidden during the ensemble-averaged characterization of nanoparticles. Electrochemical techniques have been developed to measure currents from single nanoparticles but do not provide information about the structure and identity of the molecules that undergo reactions at the electrode surface. Optical techniques such as surface-enhanced Raman scattering (SERS) microscopy and spectroscopy can detect electrochemical events on individual nanoparticles while simultaneously providing information on the vibrational modes of electrode surface species. In this paper, a protocol to track the electrochemical oxidation-reduction of Nile Blue (NB) on single Ag nanoparticles using SERS microscopy and spectroscopy is demonstrated. First, a detailed protocol for fabricating Ag nanoparticles on a smooth and semi-transparent Ag film is described. A dipolar plasmon mode aligned along the optical axis is formed between a single Ag nanoparticle and Ag film. The SERS emission from NB fixed between the nanoparticle and the film is coupled into the plasmon mode, and the high-angle emission is collected by a microscope objective to form a donut-shaped emission pattern. These donut-shaped SERS emission patterns allow for the unambiguous identification of single nanoparticles on the substrate, from which the SERS spectra can be collected. In this work, a method for employing the SERS substrate as a working electrode in an electrochemical cell compatible with an inverted optical microscope is provided. Finally, tracking the electrochemical oxidation-reduction of NB molecules on an individual Ag nanoparticle is shown. The setup and the protocol described here can be modified to study various electrochemical reactions on individual nanoparticles.

High-performance SERS biosensor based on in-situ reduction of silver nanoparticles in an ultra-filtration centrifuge device for label-free detection of colon cancer in serum

Label-free surface-enhanced Raman scattering (SERS) technology is used to screen for colon cancer for its rapid identification, high specificity and non-invasiveness. Here, we have developed a high-performance SERS biosensor that has combined concentration, separation and detection for effective screening of colon cancer. This SERS biosensor is equipped with a centrifuge tube and a filter that consists of two ultrafiltration membranes (UFMs). First, silver nanoparticles (Ag NPs) are uniformly reduced in-situ on the UFM using a controlled “silver mirror reaction”, then the filter and centrifuge tube are assembled into an ultrafiltration centrifuge tube containing Ag NPs (Ag NPs/UFT biosensor). And finally, the Ag NPs/UFT biosensor is applied to concentrate and separate colon cancer serum. The biosensor reduces signal fluctuations in the detection of liquid phase substrates (Ag NPs colloids), which are prone to aggregation and instability, more importantly minimizes the interference of large amounts of small molecule proteins and also concentrates and retains molecular weight proteins of high diagnostic value. Furthermore, we employed SERS spectroscopy by portable Raman, combined with principal component analysis-linear discriminant analysis (PCA-LDA) models, to further assess the screening diagnosis of colon cancer. As a proof of concept, we achieved 100% specificity and 87.5% accuracy with our sensors. This study will contribute to the field of non-invasive, rapid and practical screening for colon cancer together with the ultrafiltration system.

A Charge-Transfer-Induced Strategy for Enantioselective Discrimination by Potential-Regulated Surface-Enhanced Raman Scattering Spectroscopy.

A simple and efficient enantioselective discrimination method, especially the chirality-label-free discrimination method, for the recognition of chiral small molecules with high resolution and wide applicability has been urgently desired. Herein, achiral Au/p-aminothiophenol (PATP) substrates were prepared to link the enantiomers via coupling reactions for constructing the enantioselective discrimination system. The resultant Au/PATP/enantiomer systems displayed charge-transfer (CT)-induced surface-enhanced Raman scattering (SERS) spectra that offered distinguishable information for the systems with different chirality. The differentiated spectral signal can be amplified by regulating the applied electrode potential, leading to great enantioselective discrimination performance. Moreover, the relationship between the discrimination performance and the potential-regulated CT process was revealed by SERS, which enabled an accurate and effective enantiomeric determination for various chiral molecules, including aromatic and aliphatic small molecules. The aliphatic molecule with the shorter chain was discriminated with a higher resolution, since the longer-chain molecule in the discrimination system may cause a change in the molecular electronic structure of the PATP. In addition, the aromatic chiral molecule can be distinguished easier than the aliphatic molecules, which means that the generation of the conjugation of electrons in the aromatic molecule-involved enantiomeric systems facilitates CT-induced SERS discrimination. Our work provides guidance for the design and development of an effective enantioselective discrimination strategy with high discrimination performance in diverse application fields.

One-Pot Synthesis of Silica-Coated Gold Nanostructures Loaded with Cyanine 5.5 for Cell Imaging by SERS Spectroscopy

Anisotropic gold nanoparticles have been recognized as promising agents for medical diagnostics and cancer therapy due to their wide functionality, photothermal effect, and ability for optical signal amplification in the near-infrared range. In this work, a simple and rapid method for the preparation of bone-shaped gold nanoparticles coated with a dye-impregnated silica shell with an aminated surface is proposed. The possibility of further functionalization the nanostructures with a delivery vector using folic acid as an example is demonstrated. The average size of the resulting tags does not exceed 70 nm, meeting the criteria of cell endocytosis. The prepared tags exhibit surface-enhanced Raman scattering (SERS) spectra at excitation with lasers of 632.8 and 785 nm. Cell imaging is performed on HeLa cells based on the most pronounced SERS bands as a tracking signal. The obtained images, along with scanning electron microscopy of cell samples, revealed the tendency of tags to agglomerate during endocytosis followed by the "hot spots" effect. To evaluate the toxic and proliferative effect of the nanotags, an MTT assay was performed with two HeLa and HEP G2 cell lines. The results revealed higher viability for HEP G2 cells.

Hidden Dynamics of Noble-metal-bound Thiol Monolayers Revealed by SERS-monitored Entropy-driven Exchange of Cysteine Isotopologues

Vibrational spectroscopy coupled with isotopic labeling provides insight into the dynamics of various molecular processes. Here, a newfound approach in surface-enhanced Raman scattering (SERS) spectroscopy to study noble metal-anchored thiol monolayers is demonstrated for a pair of L-cysteine isotopologues competing for binding to silver nanoparticles (AgNPs): Cys-cabn (all 12C/14N) and Cys-CABN (all 13C/15N). As predicted by our DFT calculations, a distinct difference in the Raman shift value (>50 cm−1) of the ν(C = O) band was observed for these two AgNP-anchored isotopologues. SERS intensity ratio of these two peaks allowed for quantitative monitoring of an exclusively entropy-driven exchange of Cys molecules between the surface and the solution, revealing a reversible and rapid activation after a mild temperature increase (50 °C). This behavior is attributed to the collective phase transition within the monolayer. This work highlights unexplored potential of SERS spectroscopy coupled with isotopic exchange to study dynamic phenomena within a metal-anchored layer.

Rapid Prediction of Multidrug-Resistant Klebsiella pneumoniae through Deep Learning Analysis of SERS Spectra.

Klebsiella pneumoniae is listed by the WHO as a priority pathogen of extreme importance that can cause serious consequences in clinical settings. Due to its increasing multidrug resistance all over the world, K. pneumoniae has the potential to cause extremely difficult-to-treat infections. Therefore, rapid and accurate identification of multidrug-resistant K. pneumoniae in clinical diagnosis is important for its prevention and infection control. However, the limitations of conventional and molecular methods significantly hindered the timely diagnosis of the pathogen. As a label-free, noninvasive, and low-cost method, surface-enhanced Raman scattering (SERS) spectroscopy has been extensively studied for its application potentials in the diagnosis of microbial pathogens. In this study, we isolated and cultured 121 K. pneumoniae strains from clinical samples with different drug resistance profiles, which included polymyxin-resistant K. pneumoniae (PRKP; n = 21), carbapenem-resistant K. pneumoniae, (CRKP; n = 50), and carbapenem-sensitive K. pneumoniae (CSKP; n = 50). For each strain, a total of 64 SERS spectra were generated for the enhancement of data reproducibility, which were then computationally analyzed via the convolutional neural network (CNN). According to the results, the deep learning model CNN plus attention mechanism could achieve a prediction accuracy as high as 99.46%, with robustness score of 5-fold cross-validation at 98.87%. Taken together, our results confirmed the accuracy and robustness of SERS spectroscopy in the prediction of drug resistance of K. pneumoniae strains with the assistance of deep learning algorithms, which successfully discriminated and predicted PRKP, CRKP, and CSKP strains. IMPORTANCE This study focuses on the simultaneous discrimination and prediction of Klebsiella pneumoniae strains with carbapenem-sensitive, carbapenem-resistant, and polymyxin-resistant phenotypes. The implementation of CNN plus an attention mechanism makes the highest prediction accuracy at 99.46%, which confirms the diagnostic potential of the combination of SERS spectroscopy with the deep learning algorithm for antibacterial susceptibility testing in clinical settings.

Can DFT Calculations Provide Useful Information for SERS Applications?

Density functional theory (DFT) calculations allow us to reproduce the SERS (surface-enhanced Raman scattering) spectra of molecules adsorbed on nanostructured metal surfaces and extract the most information this spectroscopy is potentially able to provide. The latter point mainly concerns the anchoring mechanism and the bond strength between molecule and metal as well as the structural and electronic modifications of the adsorbed molecule. These findings are of fundamental importance for the application of this spectroscopic technique. This review presents and discusses some SERS-DFT studies carried out in Italy as a collaboration between the universities of Modena and Reggio-Emilia and of Florence, giving an overview of the information that we can extract with a combination of experimental SERS spectra and DFT modeling. In addition, a selection of the most recent studies and advancements on the DFT approach to SERS spectroscopy is reported with commentary.

Remote plasmonic-enhanced Raman spectroscopy with the plasmon-molecule coupling in distance over 100 nm

We propose remote plasmonic-enhanced Raman scattering (RPERS) spectroscopy for molecular sensing and imaging applications. RPERS requires no contact between analyte molecules and metallic nanostructures, which overcomes the limitations of surface-enhanced Raman scattering (SERS). We constructed RPERS substrates consisting of silver nanoislands and columnar silica structures, which demonstrated a 2×107 enhancement in Raman scattering for Rhodamine 6G molecules, even when the metal nanostructures and analyte molecules were over 100 nm apart. The RPERS substrate also exhibited improved reproducibility (&lt;15% RSD), long-term stability (&gt;1 month), and sensitivity (&gt;10 times) compared to conventional SERS substrates. We also confirmed the feasibility of RPERS for biophotonic analysis, i.e., enhancing Raman histological imaging of oesophagus tissues with oesophageal adventitia of a Wistar rat attached atop the columnar silica structure layer. Our demonstration is a promising advancement in the field of enhanced spectroscopy using plasmon and offers a solution to the challenges faced by conventional SERS spectroscopy. It has the potential to pave the way for future developments in remote plasmonic-enhanced spectroscopy.

Characterization of Hyaluronic Acid-Coated PLGA Nanoparticles by Surface-Enhanced Raman Spectroscopy

Nanoparticles (NPs) coated with hyaluronic acid (HA) seem to be increasingly promising for targeted therapy due to HA chemical versatility, which allows them to bind drugs of different natures, and their affinity with the transmembrane receptor CD-44, overexpressed in tumor cells. However, an essential aspect for clinical use of NPs is formulation stability over time. For these reasons, analytical techniques capable of characterizing their physico-chemical properties are needed. In this work, poly(lactide-co-glycolide) (PLGA) NPs with an average diameter of 100-150 nm, coated with a few 10 s of nm of HA, were synthesized. For stability characterization, two complementary investigative techniques were used: Dynamic Light Scattering (DLS) and Surface-Enhanced Raman Scattering (SERS) spectroscopy. The first technique provided information on size, polidispersity index, and zeta-potential, and the second provided a deeper insight on the NP surface chemicals, allowing distinguishing of HA-coated NPs from uncoated ones. Furthermore, in order to estimate formulation stability over time, NPs were measured and monitored for two weeks. SERS results showed a progressive decrease in the signal associated with HA, which, however, is not detectable by the DLS measurements.