Surface-enhanced Raman Scattering Signatures Research Articles

Rapid Identification of Drug Mechanisms with Deep Learning-Based Multichannel Surface-Enhanced Raman Spectroscopy.

Rapid identification of drug mechanisms is vital to the development and effective use of chemotherapeutics. Herein, we develop a multichannel surface-enhanced Raman scattering (SERS) sensor array and apply deep learning approaches to realize the rapid identification of the mechanisms of various chemotherapeutic drugs. By implementing a series of self-assembled monolayers (SAMs) with varied molecular characteristics to promote heterogeneous physicochemical interactions at the interfaces, the sensor can generate diversified SERS signatures for directly high-dimensionality fingerprinting drug-induced molecular changes in cells. We further train the convolutional neural network model on the multidimensional SAM-modulated SERS data set and achieve a discriminatory accuracy toward 99%. We expect that such a platform will contribute to expanding the toolbox for drug screening and characterization and facilitate the drug development process.

Exploring Sensitive Label-Free Multiplex Analysis with Raman-Coded Microbeads and SERS-Coded Reporters.

Suspension microsphere immunoassays are rapidly gaining attention in multiplex bioassays. Accurate detection of multiple analytes from a single measurement is critical in modern bioanalysis, which always requires complex encoding systems. In this study, a novel bioassay with Raman-coded antibody supports (polymer microbeads with different Raman signatures) and surface-enhanced Raman scattering (SERS)-coded nanotags (organic thiols on a gold nanoparticle surface with different SERS signatures) was developed as a model fluorescent, label-free, bead-based multiplex immunoassay system. The developed homogeneous immunoassays included two surface-functionalized monodisperse Raman-coded microbeads of polystyrene and poly(4-tert-butylstyrene) as the immune solid supports, and two epitope modified nanotags (self-assembled 4-mercaptobenzoic acid or 3-mercaptopropionic acid on gold nanoparticles) as the SERS-coded reporters. Such multiplex Raman/SERS-based microsphere immunoassays could selectively identify specific paratope–epitope interactions from one mixture sample solution under a single laser illumination, and thus hold great promise in future suspension multiplex analysis for diverse biomedical applications.

Single Molecule Surface Enhanced Raman Scattering in a Single Gold Nanoparticle-Driven Thermoplasmonic Tweezer.

Surface enhanced Raman scattering (SERS) is optically sensitive and chemically specific to detect single-molecule spectroscopic signatures. Facilitating this capability in optically trapped nanoparticles at low laser power remains a significant challenge. In this letter, we show single molecule SERS signatures in reversible assemblies of trapped plasmonic nanoparticles using a single laser excitation (633 nm). Importantly, this trap is facilitated by the thermoplasmonic field of a single gold nanoparticle dropcasted on a glass surface. We employ the bianalyte SERS technique to ascertain the single molecule statistical signatures and identify the critical parameters of the thermoplasmonic tweezer that provide this sensitivity. Furthermore, we show the utility of this low power (≈ 0.1 mW/μm2) tweezer platform to trap a single gold nanoparticle and transport assembly of nanoparticles. Given that our configuration is based on a dropcasted gold nanoparticle, we envisage its utility to create reconfigurable plasmonic metafluids in physiological and catalytic environments and to be potentially adapted as an in vivo plasmonic tweezer.

Gold-coated silicon nanoripples achieved via picosecond laser ablation for surface enhanced Raman scattering studies

We report the results from ablation studies of polished single crystalline Si targets (of resistivity 1–10 Ohm-cm) submerged in acetone by employing the focused Airy pattern of the p-polarized laser pulses of duration ∼ 2 ps. The Airy pattern was obtained by inserting a circular aperture with hard edge before the focusing convex lens. The ablation was performed on the Si substrate at diverse scanning speeds of the motorized stage (25–600 μm/sec) with a fixed pulse energy (∼50 μJ) resulting in high/low spatial frequency laser induced periodic surface structures (HSFLIPSS/ LSFLIPSS). These are believed to be the outcome of varied electric fields and the varied pulse numbers at different scan speeds. The effective number of pulses estimated on the Si target demonstrated the surface structures with different grating periods. At lower and higher number of pulses HSFLIPSS were obtained. At an intermediate number of pulses, LSFLIPSS were observed. Further, the obtained HSFLIPSS (with grating periods ∼111 nm, 114 nm) were gold coated (25 nm) with magnetron dc sputtering technique and subsequently employed them for surface enhanced Raman scattering (SERS) studies of explosive molecules 5-amino, 3-nitro, 1,3,5-nitrozole (ANTA) at a very low concentration of 100 nM. SERS imaging of ANTA from the mentioned HSFLIPSS illustrated the uniformity in SERS signatures with an intensity variation below 10% at different locations of the SERS active platform.

Preface to the special issue dedicated to Professor Richard P. Van Duyne (1945–2019)

Preface to the special issue dedicated to Professor Richard P. Van Duyne (1945–2019)

SERS characterization of aggregated and isolated bacteria deposited on silver-based substrates.

Surface-enhanced Raman scattering (SERS), based on the enhancement of the Raman signal of molecules positioned within a few nanometres from a structured metal surface, is ideally suited to provide bacterial-specific molecular fingerprints which can be used for analytical purposes. However, for some complex structures such as bacteria, the generation of reproducible SERS spectra is still a challenging task. Among the various factors influencing the SERS variability (such as the nature of SERS-active substrate, Raman parameters and bacterial specificity), we demonstrate in this study that the environment of Gram-positive and Gram-negative bacteria deposited on ultra-thin silver films also impacts the origin of the SERS spectra. In the case of densely packed bacteria, the obtained SERS signatures were either characteristic of the secretion of adenosine triphosphate for Staphylococcus aureus (S. aureus) or the cell wall and the pili/flagella for Escherichia coli (E. coli), allowing for an easy discrimination between the various strains. In the case of isolated bacteria, SERS mapping together with principal component analysis revealed some variabilities of the spectra as a function of the bacteria environment and the bactericidal effect of the silver. However, the variability does not preclude the SERS signatures of various E. coli strains to be discriminated.

Dynamics of deterministically positioned single‐bond surface‐enhanced Raman scattering from DNA origami assembled in plasmonic nanogaps

AbstractWe study the dynamics of single bonds through the surface‐enhanced Raman scattering (SERS) from single SERS‐marker molecules containing a distinctive single alkyl bond. Assembly of the nanogaps and positioning of single molecules inside the electromagnetic hotspot are precisely controlled using DNA origami constructs. The observed SERS intensities and their spectral wandering, together with electromagnetic simulations, all confirm the role of picocavities in this nanogap geometry in allowing observation of SERS signatures from individual vibrating bonds. The strong electromagnetic field around each picocavity and the transient binding of the SERS‐marker molecule reveal significant modifications to bond vibrations and selection rules over time.

Plasmonic and Electrostatic Interactions Enable Uniformly Enhanced Liquid Bacterial Surface-Enhanced Raman Scattering (SERS).

Surface-enhanced Raman spectroscopy (SERS) is a promising cellular identification and drug susceptibility testing platform, provided it can be performed in a controlled liquid environment that maintains cell viability. We investigate bacterial liquid-SERS, studying plasmonic and electrostatic interactions between gold nanorods and bacteria that enable uniformly enhanced SERS. We synthesize five nanorod sizes with longitudinal plasmon resonances ranging from 670 to 860 nm and characterize SERS signatures of Gram-negative Escherichia coli and Serratia marcescens and Gram-positive Staphylococcus aureus and Staphylococcus epidermidis bacteria in water. Varying the concentration of bacteria and nanorods, we achieve large-area SERS enhancement that is independent of nanorod resonance and bacteria type; however, bacteria with higher surface charge density exhibit significantly higher SERS signal. Using cryo-electron microscopy and zeta potential measurements, we show that the higher signal results from attraction between positively charged nanorods and negatively charged bacteria. Our robust liquid-SERS measurements provide a foundation for bacterial identification and drug testing in biological fluids.

DNA-functionalized gold nanoparticle assemblies for Surface Enhanced Raman Scattering

The programmable assembly of DNA strands is a promising tool for building tailored bottom-up nanostructures. Here, we present a plasmonic nanosystem obtained by the base-pairing mediated aggregation of gold nanoparticles (NPs) which are separately functionalized with two different single-stranded DNA chains. Their controlled assembly is mediated by a complementary DNA “bridge” sequence. We monitor the formation of DNA assembled NP aggregates in solution, and we study their Surface Enhanced Raman Scattering (SERS) response by comparison with the single NP constituents. We interpret the revealed SERS signatures in terms of the molecular and NP organization at the nanoscale, demonstrating that the action of the DNA bridge molecule yields regular NP aggregates with controlled interparticle distance and reproducible SERS response. In perspective, this demonstrates the potential of the present system as a stable, biocompatible, and recyclable SERS sensor.

Graphical and SERS dual-modal identifier for encoding OBOC library

‘Split-and-mix’ synthetic methods are widely utilized to prepare extensively large numbers of combinatorial libraries. For this, a simple and reliable encoding/decoding method is required to identify a lead compound, especially when it comes to combinatorial peptide/peptoid libraries. Here, we report a simple, efficient, and reliable on-bead peptoid ligand identification method using dual-modal identifiers (DM-IDs), which have a graphical pattern and a Raman signal. The DM-ID was designed to encode the sequence and the type of peptoid side chain by the number of holes and the surface-enhanced Raman scattering (SERS) signals, respectively. Using this dual encoding strategy, 5832 (183)-individual peptides/peptoids can be encoded with 3 holes and 18 Raman label compounds. In addition, the method can be easily extended to encode more than one hundred billion ligands by expanding to 9 patterns with 3 holes in binary code. After pentapeptoids were encoded with DM-IDs during solid phase synthesis, the peptoid’s affinity towards streptavidin is successfully evaluated, and the on-bead peptoid sequence is determined by the graphical patterns and the SERS signatures of the DM-IDs. We believe that this encoding method using DM-IDs is a promising tool to construct one-bead-one-compound (OBOC) combinatorial libraries for drug discovery.

Gauging Molecular Orientation through Time Domain Simulations of Surface-Enhanced Raman Scattering.

Molecular reorientation dynamics modulate the physical and chemical properties of molecules at interfaces. This is particularly the case for organic molecules interacting with metallic surfaces-structural motifs of current interest to ultrasensitive chemical/biological detection/imaging. In this context, surface-enhanced Raman scattering (SERS) can be used to gauge the orientation of molecules in the immediate vicinity of plasmonic metals. Herein, we analyze SERS spectra of two aromatic thiols (4-mercaptobenzonitrile and thiophenol) chemisorbed onto silver substrates using ab initio molecular dynamics-based Raman spectral simulations that account for the optical response of molecules in the bulk and oriented molecules at the surface. Through a comparison with prior works aimed at gauging the orientation of our two model systems on metallic substrates, we describe the advantages and discuss the limitations of our described models and approach to gauging the orientation of molecules on metals through time domain simulations of their SERS signatures.

A Novel Surface Enhanced Raman Catheter for Rapid Detection, Classification, and Grading of Oral Cancer.

Fabrication and testing of a novel nanostructured surface-enhanced Raman catheter device is reported for rapid detection, classification, and grading of normal, premalignant, and malignant tissues with high sensitivity and accuracy. The sensor part of catheter is formed by a surface-enhanced Raman scattering (SERS) substrate made up of leaf-like TiO2 nanostructures decorated with 30 nm sized Ag nanoparticles. The device is tested using a total of 37 patient samples wherein SERS signatures of oral tissues consisting of malignant oral squamous cell carcinoma (OSCC), verrucous carcinoma, premalignant leukoplakia, and disease-free conditions are detected and classified with an accuracy of 97.24% within a short detection-cum-processing time of nearly 25-30 min per patient. Neoplastic grade changes detected using this device correlate strongly with conventional pathological data, enabling correct classification of tumors into three grades with an accuracy of 97.84% in OSCC. Thus, the potential of a SERS catheter device as a point-of-care pathological tool is shown for the rapid and accurate detection, classification, and grading of solid tumors.

A particle-based microfluidic molecular separation integrating surface-enhanced Raman scattering sensing for purine derivatives analysis

Based on its highly specific and non-invasive features, surface-enhanced Raman scattering (SERS) has been applied for analytical chemistry or biological applications, such as identification of chemical compositions, cells or bacteria. However, if the targeted sample consists of multiple compounds, the corresponded SERS spectra would be quite difficult to analyze. To address above problems, we developed a particle-based microfluidic molecular separation (PMMS) integrating SERS substrate to separate complicate molecule mixture followed by in situ SERS detection. The platform consists of an automatic microfluidic control system to precisely control the sample and reagent flow in the PMMS–SERS device, composed of a 5-µm particle-packed separation column followed by a two-dimensional Ag nanostructural substrate. To proof-of-concept, we first tested the molecule separation functionality using the mixture of fluorescent FITC and R6G dyes. Later, we introduced the hypoxanthine and adenine mixture—main purine metabolites of E. coli—into the system for on-chip separation, identification, and quantification based on acquired SERS signatures. Overall, the miniaturized PMMS–SERS system enables an easy-to-use and sensitive analyte detection, which could be beneficial in applications requiring bacteria identification and quantification, such as environmental monitoring, AST, and drug development.

Adsorbate enrichment on a zeolite surface and assembly of a SERS sensor: a case study with silver nanoparticles and the flavonoid catechin.

We have studied the adsorption of silver nanoparticles (AgNPs) and catechin on readily available commercial zeolite beads. Both adsorbates became available on the zeolite and were several fold more concentrated after a simple adsorption process, contributing to a 10-times overall increase in the collision probability between the two adsorbates. We were further able to detect AgNP-induced Surface Enhanced Raman Scattering (SERS) of catechin on the zeolite after sequential depositions of AgNPs and catechin on the zeolite using this process. To demonstrate high reproducibility, 93% of the zeolite sensors assembled this way were tested and proved satisfactory, and gave a distinctive catechin SERS signature. Preparation of the zeolite sensor was extremely easy with a nearly 90% yield.

Biosynthesized silver nanoparticles performing as biogenic SERS-nanotags for investigation of C26 colon carcinoma cells

In this work, two classes of silver nanoparticles (AgNPs) were biosynthesized with the goal to assess their reliability in vitro as surface-enhanced Raman scattering (SERS) nanotags. Mycosynthesized silver nanoparticles (MAgNPs) and phytosynthesized silver nanoparticles (PAgNPs) were produced through environmentally friendly procedures by reduction of silver nitrate with Fusarium oxysporum cell filtrate and Azadirachta indica extract, respectively. Two cell lines, namely C26 murine colon carcinoma cells as example of cancer cells and human immortalized keratinocyte cells (HaCaT) as representative of healthy cell line, were selected for in vitro investigation. The in vitro toxicity studies show that M(P)AgNPs present lower cytotoxic effect on both cell lines as compared with standard citrate coated AgNPs. The internalization of M(P)AgNPs by colon carcinoma cells and structural alterations induced in the morphology of treated cells were analyzed by dark-field (DF) and differential interference contrast (DIC) microscopy, respectively. The most informative data about the cellular uptake and tracking potential of M(P)AgNPs were provided by scanning Confocal Raman Microscopy (CRM) and multivariate K-means cluster analysis of collected Raman spectra. The analysis reveals the subcellular components and the localization of AgNPs inside the cell via the intrinsic SERS signature of biogenic coating material. The use of unique biological material to perform synthesis, stability, biocompatibility and SERS tagging is relevant both from the point of view of encoding nanoparticles with Raman reporters and further applications in cell investigation via Raman/SERS imaging.

Intracellular SERS hybrid probes using BSA–reporter conjugates

Surface-enhanced Raman scattering (SERS) hybrid probes are characterized by the typical spectrum of a reporter molecule. In addition, they deliver information from their biological environment. Here, we report SERS hybrid probes generated by conjugating different reporter molecules to bovine serum albumin (BSA) and using gold nanoparticles as plasmonic core. Advantages of the BSA-conjugate hybrid nanoprobes over other SERS nanoprobes are a high biocompatibility, stabilization of the gold nanoparticles in the biological environment, stable reporter signals, and easy preparation. The coupling efficiencies of the BSA-reporter conjugates were determined by MALDI-TOF-MS. The conjugates' characteristic SERS spectra differ from the spectra of unbound reporter molecules. This is a consequence of the covalent coupling, which leads to altered SERS enhancement and changes in the chemical structures of the reporter and of BSA. The application of the BSA-reporter conjugate hybrid probes in 3T3 cells, including duplex imaging, is demonstrated. Hierarchical cluster analysis and principal components analysis were applied for multivariate imaging using the SERS signatures of the incorporated SERS hybrid nanoprobes along with the spectral information from biomolecules in endosomal structures of cells. The results suggest more successful applications of the SERS hybrid probes in cellular imaging and other unordered high-density bioanalytical sensing.

Surface‐enhanced Raman scattering spectroscopy for potential noninvasive nasopharyngeal cancer detection

Combining membrane electrophoresis with surface-enhanced Raman scattering (SERS) spectroscopy, the serum proteins were first purified and then mixed with silver nanoparticles to perform SERS spectral analysis. Therefore, the spectral signatures were enhanced to high-fidelity SERS signatures because of the purification procedure of the first step. We used the method to analyze blood plasma samples from nasopharyngeal cancer patients (n = 43) and healthy volunteers (n = 33) for cancer detection. Principle component analysis of the SERS spectra revealed that the data points for the cancer group and the normal group form distinct, completely separated clusters with no overlap. Therefore, the nasopharyngeal cancer group can be unambiguously discriminated from the normal group, i.e., with both diagnostic sensitivity and specificity of 100%. These results are very promising for developing a label-free, noninvasive, and reliable clinical tool for rapid cancer detection and screening. Copyright © 2011 John Wiley & Sons, Ltd.

TLC–surface enhanced Raman scattering of apomorphine in human plasma

Apomorphine is a well-known short-acting dopamine agonist typically used in the treatment of patients with advanced Parkinson's disease. In this work we propose a method for detection of apomorphine in blood plasma through Surface Enhanced Raman Scattering (SERS) technique. Detection can be achieved in a few minutes by simply depositing a drop of the blood plasma containing Apofin® on silica Thin Layer Chromatography (TLC) substrates and dropping the silver colloid on it. The Raman measurements carried out on the edges of the stain reveal the presence of the drug through its SERS signal which is found to significantly differ from the normal Raman spectrum. We propose a Density Functional Theory (DFT) model for the interpretation of the major SERS signatures of apomorphine in terms of the interaction of the drug molecule with silver.

Surface‐enhanced Raman scattering spectroscopy for potential noninvasive nasopharyngeal cancer detection

Combining membrane electrophoresis with surface‐enhanced Raman scattering (SERS) spectroscopy, the serum proteins were first purified and then mixed with silver nanoparticles to perform SERS spectral analysis. Therefore, the spectral signatures were enhanced to high‐fidelity SERS signatures because of the purification procedure of the first step. We used the method to analyze blood plasma samples from nasopharyngeal cancer patients (n = 43) and healthy volunteers (n = 33) for cancer detection. Principle component analysis of the SERS spectra revealed that the data points for the cancer group and the normal group form distinct, completely separated clusters with no overlap. Therefore, the nasopharyngeal cancer group can be unambiguously discriminated from the normal group, i.e., with both diagnostic sensitivity and specificity of 100%. These results are very promising for developing a label‐free, noninvasive, and reliable clinical tool for rapid cancer detection and screening. Copyright © 2011 John Wiley & Sons, Ltd.

Ultrasensitive detection of genomic DNA from apple leaf tissues, using surface-enhanced Raman scattering

Ultrasensitive detection of nucleic acids is demonstrated through exploiting the effect of surface-enhanced Raman scattering (SERS). In this work the SERS spectra of eight genomic DNAs from leaves of apple trees grown in the field (Malus domesticaBorkh., Fam.Rosaceae, cultivars. Florina, Idared, Rebra, Goldrush, Romus 3, Romus 4 and the rootstocks M9 and M26) have been analyzed in the wavenumber range 200–1800 cm–1. SERS signatures, spectroscopic band assignments and structural interpretations of these plant genomic DNAs are reported. SERS spectra of nucleic acids are compared here with caution, because these signals are time-dependent and are strongly influenced by DNA amount in the measured sample volume. Similarities of the SERS spectra of genomic DNAs extracted from apple leaves of Goldrush, Rebra and Florina cultivars, respectively, have been detected. Besides, the SERS spectra, corresponding to DNA from M9, Romus 4 and M26, leaves, respectively, show similar features and well resolved bands. Based on this work, specific plant DNA-ligand interactions or DNA structural changes induced by plant stress conditions associated with their natural environment, might be further investigated using surface-enhanced Raman spectroscopy.