Engineering Nanostructures for Single-Molecule Surface-Enhanced Raman Spectroscopy

Surface-enhanced Raman spectroscopy (SERS), an effect discovered in the 1970s and studied systematically in the 1980s, received a significant “second wind” with the report (primarily by Nie and by Kneipp) of enhancements large enough to allow the Raman spectrum of single molecules to be obtained. It is now understood that this occurs as a result of the extremely high electromagnetic fields that can exist at appropriately configured gaps and interstices between nanoparticles and other nanostructures composed of suitable materials (such as silver). With this insight one is now in a position to fabricate structures that will dependably and repeatably produce single-molecule SERS. We describe three such strategies: using molecular linkers to self-assemble silver clusters possessing the correct geometry; fabricating nanowire rafts in which the gaps between nanowires are “hot”; and structuring the interior of nanopores so as to produce finely-architectured nanostructured arrays.     

Nanostructured Tin Oxide as a Surface‐Enhanced Raman Scattering Substrate for the Detection of Nitroaromatic Compounds

Sensing of low concentrations of two nitroaromatic compounds, 1,2‐dinitrotoluene and 2‐nitrophenol, is presented. The sensing mechanism is based on surface‐enhanced Raman scattering (SERS) using nanostructured tin oxide as the SERS‐active substrate. The SnO_x nanostructures are synthesized by a simple solgel method and doped with Ag and Au. The Raman signal of a low concentration of the analyte, otherwise extremely weak, becomes significant when the analytes are attached to these substrates. Doping of SnO_x nanopowders with Ag and Au leads to a further increase in the Raman intensities. This study demonstrates the scope of ceramic–metal nanocomposites as convenient solid‐state SERS sensors for low‐level detection.     

Recent advances in molecularly imprinted polymers in food analysis

Food security as a world issue has received increasing concern, and therefore, effective analytical methods and technologies have been continuously developed. However, the matrix complexity of food samples and the trace/ultratrace presence of targeted analytes require highly efficient cleanup and enrichment materials and procedures. Molecularly imprinted polymers (MIPs) with specific recognition abilities as versatile materials are being increasingly developed for diverse species in various fields, especially in food analysis. In this review, we mainly summarize the recent advances in MIPs used for food matrices over the last 5 years. We focus on toxic and harmful substances, such as pesticide/drug residues, heavy metals, microbial toxins, and additives. Some relatively new preparation methods involving surface imprinting, composites, and stimuli responsiveness are reviewed. Different MIPs as solid‐phase adsorbents in solid‐phase extraction, solid‐phase microextraction, matrix solid‐phase dispersion, stirring bar sorptive extraction, and magnetic material extraction and as stationary phases in chromatographic separation for foodstuff have been comprehensively summarized. MIP‐based biomimetic sensing and enzymelike catalysis receive special attention. Moreover, some limitations and comparisons related to MIPs performances are also discussed. Finally, some significant attempts to further promote MIP properties and applications to ensure food safety are discussed. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40766.     

Current and Future Advancements of Raman Spectroscopy Techniques in Cancer Nanomedicine

Raman scattering is one of the most used spectroscopy and imaging techniques in cancer nanomedicine due to its high spatial resolution, high chemical specificity, and multiplexity modalities. The flexibility of Raman techniques has led, in the past few years, to the rapid development of Raman spectroscopy and imaging for nanodiagnostics, nanotherapy, and nanotheranostics. This review focuses on the applications of spontaneous Raman spectroscopy and bioimaging to cancer nanotheranostics and their coupling to a variety of diagnostic/therapy methods to create nanoparticle-free theranostic systems for cancer diagnostics and therapy. Recent implementations of confocal Raman spectroscopy that led to the development of platforms for monitoring the therapeutic effects of anticancer drugs in vitro and in vivo are also reviewed. Another Raman technique that is largely employed in cancer nanomedicine, due to its ability to enhance the Raman signal, is surface-enhanced Raman spectroscopy (SERS). This review also explores the applications of the different types of SERS, such as SERRS and SORS, to cancer diagnosis through SERS nanoprobes and the detection of small-size biomarkers, such as exosomes. SERS cancer immunotherapy and immuno-SERS (iSERS) microscopy are reviewed.     

Impact on the photothermal emission from single wall nanotubes by some alkali halide salts

We demonstrate that alkali-halide salts, particularly potassium bromide, can reduce the photothermal emission (PTE) from single walled carbon nanotubes (SWNT). PTE is a prominent spectral feature in Raman spectroscopy when a near infrared laser is used to analyze a dark colored sample. We subsequently show that trapping salts inside SWNT and coating SWNT with the salt has a more pronounced impact on not only reducing PTE, but also enhancing the intensity of the Raman spectral features. The effect, which we have called nanotube enhanced Raman spectroscopy (NERS), has differences and similarities to the widely studied surface enhanced Raman spectroscopy (SERS).     

Imparting recognition sites in poly(HEMA) for two compounds through molecular imprinting

So far, molecularly imprinted polymers (MIPs) have been synthesized and evaluated as selective matrices for single components. It may be possible to impart multiple recognition sites in MIPs, which could be used as elements capable of binding more than one component. Such systems could advantageously be used in the design of sensors having the ability to sense more than one compound at a time. This communication discusses such a possibility by imprinting sites for two model compounds, namely, salicylic acid and hydrocortisone in poly(2‐hydroxy ethyl methacrylate). © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 1823–1826, 1999     

High sensitivity surface enhanced Raman spectroscopy of R6G on in situ fabricated Au nanoparticle/graphene plasmonic substrates

Plasmonic gold nanoparticles (AuNP) with controllable dimensions have been fabricated in situ on graphene at moderately elevated temperature for high sensitivity surface enhanced Raman spectroscopy (SERS) of Rhodamine 6G (R6G) dye molecules. Significantly enhanced Raman signature of R6G dyes were observed on AuNP/graphene substrates as compared to the case without graphene with an improvement factor of 400%, which is remarkably greater than previous results obtained in ex situ fabricated SERS substrate. Simulation of localized electromagnetic field around AuNPs with and without the underneath graphene layer reveals an enhanced local electromagnetic field due to the plasmonic effect of AuNPs, while additional Ohmic loss occurs when graphene is present. The enhanced local electromagnetic field by plasmonic AuNPs is unlikely the dominant factor contributing to the observed high SERS sensitivity on R6G/AuNP/graphene substrate. Instead, the p-doped graphene, which is supported by the large positive Dirac point shift away from “zero” observed in AuNP/graphene field effect transistors, promotes SERS signals through enhanced molecule adsorption and non-resonance molecular–substrate chemical interaction.     

Equilibrium and kinetic isotherms and parameters for molecularly imprinted with sclareol poly(acrylonitrile‐co‐acrylic acid) matrix

The present work continues the previous studies concerning the synthesis and characterization of molecularly imprinted polymers (MIPs) with sclareol as template and three poly(acrylonitrile‐co‐acrylic acid) (AN:AA) copolymers with different ratios between monomers as matrices. The previous studies of rheology, elemental analysis, infrared spectroscopy, size exclusion chromatography, thermogravimetry, differential scanning calorimetry, batch rebinding tests, and Scatchard analysis, which confirmed the molecular imprinting, are being completed with the current equilibrium and kinetic adsorption studies. For this purpose, eight adsorption isotherms and three kinetic adsorption models were applied to six sets of experimental data obtained after three sclareol‐imprinted adsorbents (MIPs) and three nonimprinted adsorbents (NIPs) were submitted to batch adsorption experiments. After ordering the adsorption models according to the “minimum sum of normalized errors (SNE)” criteria, it was concluded that the adsorption in sclareol imprinted AN:AA copolymers is characterized by low surface coverage, takes place on heterogeneous binding sites and is reversible, while for NIPs the results suggest a difficult adsorption and/or easiness of template extraction, and that NIPs have homogeneous, but nonimprinted micropores. For the kinetic experiments, the minimum SNE for MIPs points to the first order kinetic model, fact that suggests a physical adsorption of template molecules on the imprinted sites. POLYM. ENG. SCI., 55:1152–1162, 2015. © 2014 Society of Plastics Engineers     

A SERS spectroelectrochemical investigation of the interaction of 2-mercaptobenzothiazole with copper, silver and gold surfaces

The interaction of the sulfide mineral flotation collector, 2-mercaptobenzothiazole, with silver, copper and gold surfaces has been investigated by surface enhanced Raman scattering (SERS) spectroscopy. 2-mercaptobenzothiazole, the copper, silver and gold compounds of this species, and the dithiolate, 2,2-dithiobis(benzothiazole) were characterised by ¹³C NMR and Raman spectroscopy to provide a basis for identifying surface species. SERS investigations showed that, at pH 4.6 where the solution species is in the protonated form, and at 9.2, where it is present as the ion, adsorption on each metal occurs over a wide potential range. Attachment of the organic compound occurs through bonding between the exocyclic sulfur atom and metal atoms in the surface. X-ray photoelectron spectroscopy confirmed that the adsorbed layer was of monolayer thickness. Adsorption of the protonated 2-mercaptobenzothiazole occurs on copper at pH 4.6 at potentials below that at which charge transfer adsorption commences.     

Experimental methods in chemical engineering: Raman spectroscopy

When photons impinge on a substrate, most scatter with the same frequency (elastic scattering or Rayleigh dispersion) and only 10^?7 scatter with a different energy (inelastic scattering). This inelastic interaction (Raman scattering) exchanges energy in the region of molecular vibrational transitions for crystalline and amorphous materials. Raman bands in a spectra represent vibrational transitions, like infrared, however the selection rules are different. Typically, the vibrations that are intense in Raman are weak in infrared and vice versa. A remarkable feature of the Raman effect is that it is highly sensitive to nanocrystals, even below 4 nm, which are too small to generate XRD patterns. Plasmonic enhancement, like surface‐enhanced Raman spectroscopy (SERS) boost the Raman signal by 10⁴, providing single‐molecule detection capability. Glass, quartz, and sapphire are transparent to Raman effect (depending on the energy of the incident excitation radiation), which makes it ideal to examine materials under reaction conditions (in‐situ cells and operando reactors that operate over a broad range of temperature, pressures, and environments). Raman spectroscopy emerged in the 1930s; however, infrared spectrometry displaced it. With the advent of powerful lasers in the 1970s, more researchers began to apply Raman routinely. In 2019, the Web of Science indexed 20 400 articles mentioning Raman against 50 000 articles mentioning infrared. Chemical engineers apply Raman less frequently than in material science, physical chemistry, and applied physics, with 887 articles vs 6250, 3700, and 3510 for the other disciplines. A bibliometric analysis identified four research clusters centred on thin films and optics, graphene and nanocomposites, nanoparticles and SERS, and photocatalyst.     

Gold nanoparticle‐functionalized thread as a substrate for SERS study of analytes both bound and unbound to gold

The potential of thread for use as a substrate for inexpensive, disposable diagnostics for surface‐enhanced Raman scattering (SERS) spectroscopy has been showed in this study. Gold‐nanoparticle coated thread can be embedded into fabrics to detect chemical or biological analytes in military and medical applications through SERS. Using this inexpensive and widely available material enables reduction in the volumes of nanoparticle solution required compared to alternatives. By testing multiple analytes, it was observed that molecular structure played a significant role in SERS signal amplification, and hence, the technique is limited to the detection of a small number of analytes possessing highly polarizable structures. Although direct chemical bonding between analyte molecules and nanoparticles gives the strongest signal enhancement, it remains possible to easily discern signals generated by analytes not directly bound, provided they possess suitable structure. Amplification of SERS signal by controlling the aggregation state of the gold nanoparticles to increase the number of SERS hotspots was observed. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1598–1605, 2014     

Preparation and characterization of polyaniline,multiwall carbon nanotubes,and starch bionanocomposite material for potential bioanalytical applications

In this article, we are reporting the preparation and characterization of a multi‐component integrated nanocomposite material by the combination of a naturally occuring biocompatible biopolymer (Starch—a type of polysaccharide), functional conjugated synthetic polymer (Polyaniline “PANI”—a type of intrinsic conducting polymer) and nanosize tubular conducting template material (multiwalled carbon nanotubes “MWCNTs”—a type of carbonaceous nanotube structure). Comparative studies of the four material systems viz. system‐1: PANI, system‐2: PANI/MWCNTs, system‐3: PANI/Starch, and system‐4: PANI/MWCNTs/Starch have been carried out to understand the physical and chemical characteristics by using following instrumental techniques; UV‐Visible spectroscopy, fourier infrared spectroscopy, Raman, X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, BET‐surface area, conductivity, thermal gravimetric analysis, differential scanning calorimetry, and cyclic voltammetry. Proposed nanocomposite material, PANI/MWCNTs/Starch has nanosized integrated porous morphology (∼200–300 nm) with interconnected architecture, while simultaneously having good conductivity and better electroactivity. Moreover, the presence of hydroxyl functionality empowers it with good dispersion ability which is further supported by good biodegradability and biocompatibility. These properties together attest the proposed system for promising applications in biosensors and screen printed electrode ink formulation. POLYM. COMPOS., 38:496–506, 2017. © 2015 Society of Plastics Engineers     

Surface molecularly imprinted polymer microspheres based on nano‐TiO2 for selective recognition of kaempferol

The molecular imprinting technique is a new method for preparing molecularly imprinted polymers (MIPs) with specific molecular recognition sites for certain target molecules. In this study, a novel, facile preparation method was presented, called “seed precipitation polymerization,” for the synthesis of MIPs via surface imprinting and a support matrix. In the polymerization process, kaempferol was used as the template molecule, methacrylic acid as the functional monomer, nano‐TiO₂ as the support, azodiisobutyronitrile as the initiator, and ethylene glycol dimethacrylate as the crosslinker in acetonitrile solvent. The synthesized T‐MIP and MIP were analyzed by infrared spectroscopy and scanning electron microscopy. In addition, the obtained polymers were evaluated by adsorption isotherms and dynamic curves for their selective recognition properties for kaempferol. The results show that T‐MIP shows regular spherical particles; the adsorption dynamic curves of T‐MIP show that the adsorption capacity increases with time and reaches a maximum value and then finally reaches equilibrium, and the T‐MIP exhibits a higher affinity for kaempferol than does the MIP. The adsorption follows pseudo‐second‐order kinetics, the Freundlich adsorption equation fits the experimental data well, and there is strong evidence for multiple‐layer adsorption. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44888.     

表面增强拉曼散射基底的研究进展

表面增强拉曼光谱(SERS)由于其高的灵敏度、抗干扰能力强等优点,被广泛应用在表面科学、分析化学、物理学等领域,是研究表面和界面过程的重要工具,是定性鉴定化学组成相近化合物的有力手段.因此,高品质、高活性的SERS基底一直是科研工作者们追求和研究的重点.本文对SERS活性基底的发展进行了介绍,从金、银金属纳米粒子作为基底的拉曼效应的科学研究,又进一步总结了非金属纳米粒子ZnO、TiO₂、ZnS、Cu₂O、CdTe、CdS等SERS基底.今后,将贵金属与半导体纳米材料复合将是SERS基底的研究热点.SERS光谱目前可以在液相色谱分析的检测器、医学检测仪器、刑侦分析检测等众多领域得到应用.     

Hydrogel-Assisted 3D Volumetric Hotspot for Sensitive Detection by Surface-Enhanced Raman Spectroscopy

Effective hotspot engineering with facile and cost-effective fabrication procedures is critical for the practical application of surface-enhanced Raman spectroscopy (SERS). We propose a SERS substrate composed of a metal film over polyimide nanopillars (MFPNs) with three-dimensional (3D) volumetric hotspots for this purpose. The 3D MFPNs were fabricated through a two-step process of maskless plasma etching and hydrogel encapsulation. The probe molecules dispersed in solution were highly concentrated in the 3D hydrogel networks, which provided a further enhancement of the SERS signals. SERS performance parameters such as the SERS enhancement factor, limit-of-detection, and signal reproducibility were investigated with Cyanine5 (Cy5) acid Raman dye solutions and were compared with those of hydrogel-free MFPNs with two-dimensional hotspots. The hydrogel-coated MFPNs enabled the reliable detection of Cy5 acid, even when the Cy5 concentration was as low as 100 pM. We believe that the 3D volumetric hotspots created by introducing a hydrogel layer onto plasmonic nanostructures demonstrate excellent potential for the sensitive and reproducible detection of toxic and hazardous molecules.     

SERS-Based Colloidal Aptasensors for Quantitative Determination of Influenza Virus

Development of sensitive techniques for rapid detection of viruses is on a high demand. Surface-enhanced Raman spectroscopy (SERS) is an appropriate tool for new techniques due to its high sensitivity. DNA aptamers are short structured oligonucleotides that can provide specificity for SERS biosensors. Existing SERS-based aptasensors for rapid virus detection had several disadvantages. Some of them lacked possibility of quantitative determination, while others had sophisticated and expensive implementation. In this paper, we provide a new approach that combines rapid specific detection and the possibility of quantitative determination of viruses using the example of influenza A virus.     

Fabrication of ordered microporous styrene‐acrylonitrile copolymer blend imprinted membranes for selective adsorption of phenol from salicylic acid using breath figure method

Highly selective, ordered microporous molecularly imprinted membranes (MIMs) for phenol were synthesized by breath figure (BF) method using styrene‐acrylonitrile copolymer (SAN) as the membrane matrix and molecularly imprinted polymer nanoparticles (nano‐MIPs) as the imprinted nanoparticles. The nano‐MIPs were synthesized by oil‐in‐water emulsion polymerization using 4‐vinyl pyridine (4‐VP), methyl methacrylate (MMA) or cinnamic acid (CA) as the functional monomer, respectively. The prepared nano‐MIPs were characterized by transmission electron microscope (TEM) and Raman, whereas MIMs were characterized by SEM, membrane flux, and selective adsorption experiments. Morphological analysis exhibited that the addition of nano‐MIPs improved the formation of ordered and well‐defined porous membrane morphology. Compared with MMA‐MIM and CA‐MIM, the 4‐VP‐MIM exhibited higher membrane flux, adsorption capacity, and stronger selective binding for phenol as well as excellent permeation selectivity for phenol. Moreover, the selective effect of 4‐VP‐MIM on phenol was strongly affected by the amount of 4‐VP imprinted nanoparticles (nano‐4‐VP‐MIPs). The experimental data revealed that the 4‐VP‐MIM containing 2.0 wt % of nano‐4‐VP‐MIPs exhibited the highest separation selectivity for the template phenol, whose selectivity coefficients for phenol relative to salicylic acid (SA) and p‐hydroxybenzoic acid (p‐HB) were 5.6770 and 5.5433, respectively, which was close to the predicted selectivity coefficient value. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42350.     

Design and Synthesis of Novel Raman Reporters for Bioorthogonal SERS Nanoprobes Engineering

Surface-enhanced Raman spectroscopy (SERS) exploiting Raman reporter-labeled nanoparticles (RR@NPs) represents a powerful tool for the improvement of optical bio-assays due to RRs’ narrow peaks, SERS high sensitivity, and potential for multiplexing. In the present work, starting from low-cost and highly available raw materials such as cysteamine and substituted benzoic acids, novel bioorthogonal RRs, characterized by strong signal (10³ counts with FWHM < 15 cm⁻¹) in the biological Raman-silent region (>2000 cm⁻¹), RRs are synthesized by implementing a versatile, modular, and straightforward method with high yields and requiring three steps lasting 18 h, thus overcoming the limitations of current reported procedures. The resulting RRs’ chemical structure has SH-pendant groups exploited for covalent conjugation to high anisotropic gold-NPs. RR@NPs constructs work as SERS nanoprobes demonstrating high colloidal stability while retaining NPs’ physical and vibrational properties, with a limit of detection down to 60 pM. RR@NPs constructs expose carboxylic moieties for further self-assembling of biomolecules (such as antibodies), conferring tagging capabilities to the SERS nanoprobes even in heterogeneous samples, as demonstrated with in vitro experiments by transmembrane proteins tagging in cell cultures. Finally, thanks to their non-overlapping spectra, we envision and preliminary prove the possibility of exploiting RR@NPs constructs simultaneously, aiming at improving current SERS-based multiplexing bioassays.     

Electrical conductivity of silicon carbonitride‐reduced graphene oxide composites

Silicon carbonitride ceramics–reduced graphene oxide (SiCN–rGO) composites are synthesized using polyvinylsilazne (PVSZ) and GO as precursors and N‐dimethylformamide (DMF) as a solvent. We find that the electrical conductivity of SiCN–rGO composites exhibits nonmonotonic changes as a function of GO concentrations, in which the conductivity increases by six orders of magnitude from 7.41E‐09 (Ω/cm)^?1 to 4.35E‐03 (Ω/cm)^?1 after the integration of 0.2 wt% GO, followed by three orders of magnitude drop to 3.34E‐06 (Ω/cm)^?1 when 0.3 wt% GO is integrated. Based on the energy‐dispersive spectroscopy and Raman spectroscopy analysis, we conclude that the conductive behavior of SiCN–rGO composites is controlled by both the concentration and the distribution of “free‐carbon” in the composites.     

From Structure–Activity to Structure–Selectivity Relationships: Quantitative Assessment,Selectivity Cliffs,and Key Compounds

The exploration of structure–activity relationships (SARs) in chemical lead optimization is mostly focused on activity against single targets. Because many active compounds have the potential to act against multiple targets, achieving a sufficient degree of target selectivity often becomes a major issue during optimization. Herein we report a data analysis approach to explore compound selectivity in a systematic and quantitative manner. Sets of compounds that are active against multiple targets provide a basis for exploring structure–selectivity relationships (SSRs). Compound similarity and selectivity data are analyzed with the aid of network‐like similarity graphs (NSGs), which organize molecular networks on the basis of similarity relationships and SAR index (SARI) values. For this purpose, the SARI framework has been adapted to quantify SSRs. Using sets of compounds with differential activity against four cathepsin thiol proteases, we show that SSRs can be quantitatively described and categorized. Furthermore, local SSR environments are identified, the analysis of which provides insight into compound selectivity determinants at the molecular level. These environments often contain “selectivity cliffs” formed by pairs or groups of similar compounds with significantly different selectivity. Moreover, key compounds are identified that determine characteristic features of single‐target SARs and dual‐target SSRs. The comparison of compounds involved in the formation of selectivity cliffs often reveals chemical modifications that render compounds target selective.