Effect of a Ag-rGO structure on the SERS activity of PEDOT:PSS films.

π-Conjugated organic semiconductors with tunable electronic structures are new prospective active substrate materials for surface-enhanced Raman scattering (SERS). However, observing higher SERS activity when using organic semiconductors as substrates could be difficult because there is no plasmonic effect of hot electrons. Here, we designed a Ag-reduced graphene oxide (rGO) structure, introduced it into a poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS) solution, and spin-coated the solution to obtain a Ag-rGO/PEDOT:PSS (ARPP) film. Our analyses demonstrate that the introduction of this Ag-rGO structure can not only enhance the electromagnetic field effect based on plasmon resonance but also improve the interaction between the target molecule and the substrate in the ARPP film. This innovative approach not only improves the SERS activity of π-conjugated organic polymers but also provides novel ideas for the preparation of other organic semiconductor-based SERS substrates.

Noble metal-free SERS: mechanisms and applications.

Surface-enhanced Raman scattering (SERS) is a very important tool in vibrational spectroscopy. The coupling of nanomaterials induces local surface plasmon resonance (LSPR), which contributes greatly to SERS. Due to its remarkable sensitivity in trace detection, SERS has gained prominence in the fields of catalysis, biosensors, drug tracking, and optoelectronic devices. SERS activity is believed to be closely related to the LSPR and charge transfer (CT) of the material. Noble metal nanostructures have been commonly used as SERS-active substrates due to their strong local electric fields and relatively mature preparation, application, and enhancement mechanisms. In recent years, SERS research based on semiconductor materials has attracted significant attention because semiconductor materials have advantages such as repeatable preparation, simple pretreatment, stable SERS spectra and superior biocompatibility, stability, and reproducibility. Semiconductor-based SERS has the potential to enrich SERS theory and applications. Thus, the development of semiconductor materials will introduce a new epoch for SERS-based research. In this review, we outline the two main kinds of semiconductor SERS-active substrates: inorganic and organic semiconductor SERS-active substrates. We also provide an overview of the SERS mechanism for different kinds of materials and SERS-based applications.

Molecular-Orbital Delocalization Enhances Charge Transfer in π-Conjugated Organic Semiconductors.

π-Conjugated organic semiconductors are promising materials for surface-enhanced Raman scattering (SERS)-active substrates based on the tunability of electronic structures and molecular orbitals. Herein, we investigate the effect of the temperature-mediated resonance-structure transitions of poly(3,4-ethylenedioxythiophene) (PEDOT) in poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT : PSS) films on the interactions between substrate and probe molecules, thereby affecting the SERS activity. Absorption spectroscopy and density functional theory calculations show that this effect occurs mainly due to delocalization of the electron distribution in molecular orbitals, effectively promoting the charge transfer between the semiconductor and probe molecules. In this work, we investigate for the first time the effect of electron delocalization in molecular orbitals on SERS activity, which will provide new design ideas for the development of highly sensitive SERS substrates.

Highly selective and quantitative in situ monitoring of cell surface proteins by SERS immunoassay system.

Due to their pivotal roles in many biological functions, cell surface proteins (CSPs) are often used for cancer prognosis, as evidenced by a number of studies that have reported significant changes in the expression levels of specific surface proteins depending on the stage of tumorigenesis and selection/variety of reprogrammed cells during cell fate conversion. Current CSP detection strategies suffer from poor selectivity and lack the ability for in situ analysis but maintain the spatial information between cells. Here, we have fabricated nanoprobes for surface-enhanced Raman scattering (SERS) immunoassays by conjugating a specific antibody onto silica-coated gold nanoparticles incorporating an individual Raman reporter (Au-tag@SiO2-Ab NPs) for highly sensitive and selective in situ detection in different types of cells. When multiple HEK293 cell lines stably expressing different levels of the CSP, ACE2, were investigated by the SERS immunoassay, we demonstrated that the level of ACE2 expression in each cell line could be statistically distinguished from that in the other cell lines, indicating the quantitative feature of this biosensing system. When detecting living cells without cell lysis or fixation, as well as fixed cells, the levels of the epithelial CSPs, EpCAM (epithelial cell adhesion molecule) and E-cadherin, were successfully determined using our Au-tag@SiO2-Ab NPs and SERS immunoassay system in a highly selective and quantitative manner without significant cytotoxicity. Hence, our work provides technical insight into the development of a biosensing platform for a variety of biomedical applications, such as cancer metastasis prognosis and the in situ monitoring of stem cell reprogramming and differentiation.

Interface Design of 3D Flower-like Ag@ZnSe Composites: SERS and Photocatalytic Performance.

In this work, we cosputtered Ag and ZnSe on a polystyrene template to form a three-dimensional (3D) Ag@ZnSe (x) structure. The 3D surface morphology and material composition that provided abundant "hot spots" were controlled by adjusting the sputtering power of the ZnSe, which was confirmed by finite-difference time-domain (FDTD) simulation. The introduction of ZnSe into the noble metal Ag also introduced a charge-transfer (CT) effect into the system, and the CT path was proven with the two-dimensional correlation spectroscopy (2D-COS)-surface-enhanced Raman scattering (SERS) technique. In addition, the substrate exhibited excellent catalytic activity due to the CT effect. The catalyzed degradation of malachite green (MG) was due to the CT effect in the system, and the catalytic process was successfully monitored by in situ SERS. Most importantly, the catalytic degradation by Ag@ZnSe (x) with different parameters was proportional to the degree of CT (ρCT). The SERS and catalytic mechanisms were analyzed in depth with the 2D-COS-SERS technique, which was also useful in verifying the CT process. The catalytic sites for MG were successfully monitored with the 2D-COS-SERS technique. This study provides a reference for studies of the synergistic effects of the electromagnetic mechanism and CT, as well as a new perspective on photocatalysis with dye molecules and monitoring of the catalytic processes.

Controllable hot electron transfer in the Ag/MoO3 layer by layer system: Thickness-dependent MoO3 layer.

The Ag and MoO3 layer-by-layer sputtering method was employed to fabricate Ag/MoO3 coated on a polystyrene (PS) array (Ag/MoO3@PS), which exhibited excellent surface-enhanced Raman scattering (SERS) activity. The thickness of the MoO3 layer was controlled by changing the sputtering power. The SERS intensity of 4-aminothiophenol (PATP) on Ag/MoO3@PS with a 2 nm thickness of the MoO3 layer was comparable to that on pure Ag coated on the PS array (Ag@PS). This is possible because hot electrons were injected from Ag into the MoO3 layer to enhance the photocatalyst reaction; thus, the SERS spectra of coupled PATP were obtained. The transport of hot electrons rapidly decayed and was blocked with increasing thickness of the MoO3 layer from 2 nm to 9 nm. Thus, the SERS intensity decreased, and interestingly, the b2 mode of PATP decreased and nearly disappeared. This study provides new insight into the control of hot electron reduction for catalytic reduction process monitoring.

Continuing progress in the field of two-dimensional correlation spectroscopy (2D-COS): Part III. Versatile applications.

In this review, the comprehensive summary of two-dimensional correlation spectroscopy (2D-COS) for the last two years is covered. The remarkable applications of 2D-COS in diverse fields using many types of probes and perturbations for the last two years are highlighted. IR spectroscopy is still the most popular probe in 2D-COS during the last two years. Applications in fluorescence and Raman spectroscopy are also very popularly used. In the external perturbations applied in 2D-COS, variations in concentration, pH, and relative compositions are dramatically increased during the last two years. Temperature is still the most used effect, but it is slightly decreased compared to two years ago. 2D-COS has been applied to diverse systems, such as environments, natural products, polymers, food, proteins and peptides, solutions, mixtures, nano materials, pharmaceuticals, and others. Especially, biological and environmental applications have significantly emerged. This survey review paper shows that 2D-COS is an actively evolving and expanding field.

Continuing progress in the field of two-dimensional correlation spectroscopy (2D-COS), part II. Recent noteworthy developments.

This comprehensive survey review compiles noteworthy developments and new concepts of two-dimensional correlation spectroscopy (2D-COS) for the last two years. It covers review articles, books, proceedings, and numerous research papers published on 2D-COS, as well as patent and publication trends. 2D-COS continues to evolve and grow with new significant developments and versatile applications in diverse scientific fields. The healthy, vigorous, and diverse progress of 2D-COS studies in many fields strongly confirms that it is well accepted as a powerful analytical technique to provide an in-depth understanding of systems of interest.

Probe-Free Identification of RNA Virus Variants with Point Mutations by Surface-Enhanced Raman Spectroscopy.

As observed in the COVID-19 pandemic, RNA viruses continue to rapidly evolve through mutations. In the absence of effective therapeutics, early detection of new severely pathogenic viruses and quarantine of infected people are critical for reducing the spread of the viral infections. However, conventional detection methods require a substantial amount of time to develop probes specific to new viruses, thereby impeding immediate response to the emergence of viral pathogens. In this study, we identified multiple types of viruses by obtaining the spectral fingerprint of their surface proteins with probe-free surface-enhanced Raman scattering (SERS). In addition, the SERS-based method can remarkably distinguish influenza virus variants with several surface protein point mutations from their parental strain. Principal component analysis (PCA) of the SERS spectra systematically captured the key Raman bands to distinguish the variants. Our results show that the combination of SERS and PCA can be a promising tool for rapid detection of newly emerging mutant viruses without a virus-specific probe.

Continuing progress in the field of two-dimensional correlation spectroscopy (2D-COS), part I. Yesterday and today.

This comprehensive survey review, as the first of three parts, compiles past developments and early concepts of two-dimensional correlation spectroscopy (2D-COS) and subsequent evolution, as well as its early applications in various fields for the last 35 years. It covers past review articles, books, proceedings, and numerous research papers published on 2D-COS. 2D-COS continues to evolve and grow with new significant developments and versatile applications in diverse scientific fields. The healthy, vigorous, and diverse progress of 2D-COS studies in many fields confirms that it is well accepted as a powerful analytical technique to provide the in-depth understanding of systems of interest.

Evaluation of SERS activity for cosputtered Ag-ZnX@PS (X = O, S, Se) composites: Carrier density dependence.

Ag-ZnX (X = O, S, Se) composites coated on polystyrene (PS) arrays (Ag-ZnO@PS, Ag-ZnS@PS, Ag-ZnSe@PS) were successfully fabricated by using cosputtering technology. We found that ZnX doping decreased the carrier densities of these composites compared to that of pure Ag@PS, which was due to redistribution of electrons between Ag and ZnX. Thus, the carrier density of Ag was decreased, and the surface plasmon resonance (SPR) of Ag was redshifted in the Ag-ZnX composites. As the redshift of the SPR of Ag induced a high SPR contribution to the surface-enhanced Raman scattering (SERS), the SPR and charge transfer (CT) contributions were simultaneously increased with increasing carrier density in the Ag-ZnX composites. This study opens a new path to designing metal-semiconductor composites with controllable carrier density. Regulation of the carrier density will be of great help in understanding SPR and CT contributions.

Fluorescence-Shadowing Nanoparticle Clusters for Real-Time Monitoring of Tumor Progression.

Monitoring tumor progression is important for elucidating appropriate therapeutic strategies in response to anticancer therapeutics. To fluorescently monitor the in vivo levels of tumor-specific enzymes, we prepared matrix metalloprotease (MMP)-responsive gold nanoparticle (AuNP) clusters to sense tumor microenvironments. Specifically, AuNPs and quantum dots (QDs) were surface-engineered with two poly(ethylene glycol) [PEG] shells and cyclooctyne moieties, respectively, for the copper-free click reaction. Upon "peeling off" of the secondary shell from the double-PEGylated AuNPs under MMP-rich conditions, shielded azide moieties of the AuNPs were displayed toward the QD, and those two particles were clicked into nanoparticle clusters. This consequently resulted in a dramatic size increase and fluorescence quenching of QDs via fluorescence energy transfer (FRET) due to the molecular proximity of the particles. We observed that FRET efficiency was modulated via changes in MMP levels and exposure time. Cancer cell numbers exhibited a strong correlation with FRET efficiency, and in vivo studies that employed solid tumor models accordingly showed that FRET efficiency was dependent on the tumor size. Thus, we envision that this platform can be tailored and optimized for tumor monitoring based on MMP levels in solid tumors.

Novel insight into charge transfer regulation based on carrier density-dependent Ag/ITO composite films.

Cosputtering technology was utilized to prepare a Ag and indium tin oxide (ITO) composite on a flat polystyrene (PS) microsphere array. The carrier density estimated by Hall effect testing of different Sn concentrations in the cosputtered films can be tuned from 1018 to 1020 cm-3. The bandgap calculated based on ultraviolet photoelectron spectroscopy can be adjusted within the range of 3.95-4.02 eV. We explored the possible mechanism of charge transfer (CT) by varying the bandgap and explained the causes of the surface-enhanced Raman scattering (SERS). Surprisingly, a synchronous change in the CT process with the carrier density was discovered. This observation suggests that the CT process can be precisely regulated by changes in the composition of the metal-semiconductor nanostructures. Our study provides a reference for the application of Ag/ITO films as alternative near-infrared plasmonic materials.

Light-Triggered Structural Modulation of Nanofibrous Meshes to Promote Deep Penetration of Cultured Cells.

Although nanofibrous meshes are considered promising cultivation beds for maintaining cell differentiation, 3D cultivation is not possible because their nanoporous structures impede cell infiltration. To facilitate transverse cell migration across nanofibrous meshes, electrospun nanofibers are prepared with structures that vary in response to red laser light. Polyoxalate (POX), composed of oxalate linkers and oligomeric caprolactone, is synthesized and electrospun into fibrous meshes with a photosensitizer (chlorin e6, Ce6). These meshes exhibit morphological and chemical changes upon laser irradiation, and mass erosion rates of the meshes are faster after laser irradiation. Cell cultivation on POX meshes reveals that red laser effectively facilitates traverse migration of the cells without affecting cell viability. The use of light-triggered change of meshes is envisioned to promote the migration of cells during 3D matrix cultivation.

Process monitoring of photocatalytic degradation of 2,4-dinitrotoluene by Au-decorated Fe3O4@TiO2 nanoparticles: surface-enhanced Raman scattering method.

Recently, the degradation and detection of 2,4-dinitrotoluene (2,4-DNT) capable of producing 2,4,6-trinitrotoluene (TNT) for environmental and human health risks have been developed. We prepared photoresponsive Au-decorated Fe3O4@TiO2 nanoparticles (Fe3O4@TiO2-Au NPs) under sunlight simulated Xe lamp irradiation. The photodegradation process of 2,4-DNT by Fe3O4@TiO2-Au NPs was successfully monitored by surface-enhanced Raman scattering (SERS). Since SERS monitoring shows intrinsic information about the molecular structure, it was possible to predict the photodegradation of 2,4-DNT. The 2,4-DNT photodegradation mechanism based on two-dimensional correlation spectroscopy (2D-COS), which provides very beneficial information for a deeper understanding of systems, has been identified. We confirmed that Fe3O4@TiO2-Au NPs can be widely used in organic pollutant degradation under sunlight. Furthermore, the combination of SERS based process monitoring and 2D-COS can be a convincing analytical technique for photodegradation studies of organic pollutants.

Linear and Symmetric Li-Based Composite Memristors for Efficient Supervised Learning.

Emerging energy-efficient neuromorphic circuits are based on hardware implementation of artificial neural networks (ANNs) that employ the biomimetic functions of memristors. Specifically, crossbar array memristive architectures are able to perform ANN vector-matrix multiplication more efficiently than conventional CMOS hardware. Memristors with specific characteristics, such as ohmic behavior in all resistance states in addition to symmetric and linear long-term potentiation/depression (LTP/LTD), are required in order to fully realize these benefits. Here, we demonstrate a Li-based composite memristor (LCM) that achieves these objectives. The LCM consists of three phases: Li-doped TiO2 as a Li reservoir, Li4Ti5O12 as the insulating phase, and Li7Ti5O12 as the metallic phase, where resistive switching correlates with the change in the relative fraction of the metallic and insulating phases. The LCM exhibits a symmetric and gradual resistive switching behavior for both set and reset operations during a full bias sweep cycle. This symmetric and linear weight update is uniquely enabled by the symmetric bidirectional migration of Li ions, which leads to gradual changes in the relative fraction of the metallic phase in the film. The optimized LCM in ANN simulation showed that exceptionally high accuracy in image classification is realized in fewer training steps compared to the nonlinear behavior of conventional memristors.

Ag-decorated polymer chip for the determination of the respective concentrations of TTD and Hg2+ by surface-enhanced raman scattering.

A "hotspot"-rich Ag-nanoparticle-decorated three-dimensional polymer substrate was fabricated, exhibiting an excellent surface-enhanced Raman scattering (SERS) activity. 4-Mercaptobenzoic acid (MBA) was selected as a probe molecule for comparing the SERS activity on selected substrates. The proposed detection chip with the adsorption of tetramethylthiuram disulfide (TTD) shows an excellent sensitivity for the quantitative determination of TTD and mercury ions (Hg2+). This chip exhibited a high sensitivity for the trace detection of the targets. Interestingly, we found that the adsorbed TTD is selectively sensitive to Hg2+. The SERS band had a significant frequency shift of 11 cm-1 as the concentration of Hg2+ increased from 10-10 to 10-3 mol L-1. More importantly, the frequency shift of the SERS band exhibited an excellent linear relationship with the concentration of Hg2+, and the determination limit for Hg2+ was 10-10 mol L-1. Furthermore, the proposed detection chip shows great application potential for the determination of pesticides and Hg2+.

Trapping analytes into dynamic hot spots using Tyramine-medicated crosslinking chemistry for designing versatile sensor.

HYPOTHESIS: Due to the intrinsic nature of the surface-enhanced Raman scattering (SERS), the detection of molecules with weak binding affinities toward metal substrates is critical for development of a universal SERS sensing platform. We hypothesized the physical trapping of small pesticide molecules for active hot spot generation using tyramine-mediated crosslinking chemistry and silver nanoparticles (Ag NPs) enhances SERS detection sensitivity. EXPERIMENTS: Tyramine-mediated crosslinking chemistry for sensor application was validated by ultraviolet-visible absorption spectroscopy, scanning electron microscopy, dynamic light scattering, and Raman spectroscopy. SERS sensing platform using tyramine-mediated crosslinking reaction was systematically studied for detection of 1,4-dyethylnylbenzene as a model analyte. This sensor system was applied to detect two other pesticides, thiabendazole and 1,2,3,5-tetrachlorobenzene, which have different binding affinities toward metal surfaces. FINDINGS: The SERS signal of 1,4-dyethylnylbenzene obtained using this sensor system was 3.6 times stronger than that obtained using the Ag colloidal due to the nanogap of approximately 1.3 nm within the generated hot spots. This sensor system based on tyramine-mediated crosslinked Ag NPs was evaluated as a promising tool to achieve a solution based sensitive detection of various pesticide molecules that cannot be adsorbed on the surfaces of typical SERS substrates such as metal nanoparticles.

Atom transfer radical-polymerized cationic shells on gold nanoparticles for near infrared-triggered photodynamic therapy of tumor-bearing animals.

Gold nanoparticles (AuNPs) were surface-engineered with a cationic corona to enhance the incorporation of photosensitizers for photodynamic therapy (PDT). The cationic corona composed of poly(2-(dimethylamino)ethyl methacrylate) was atom transfer radical-polymerized on the surface of the AuNPs. The cationic corona of the engineered surface was characterized by dynamic light scattering, electron microscopy, Raman spectroscopy, and mass spectroscopy. Chlorin-e6 (Ce6) incorporated onto the surface-engineered AuNPs exhibited higher cell incorporation efficiency than bare AuNPs. Ce6-incorporated AuNPs were confirmed to release singlet oxygen upon NIR irradiation. Compared to Ce6, Ce6-incorporated AuNPs exhibited higher cellular uptake and cytotoxicity against cancer cells in an irradiation time-dependent manner. Near-infrared-irradiated animals administered Ce6-incorporated AuNPs exhibited higher levels of tumor suppression without noticeable body weight loss. This result was attributed to the higher localization of Ce6 at the tumor sites to induce cancer cell apoptosis. Thus, we envision that engineered AuNPs with cationic corona can be tailored to effectively deliver photosensitizers to tumor sites for photodynamic therapy.

Modulating Mechanism of the LSPR and SERS in Ag/ITO Film: Carrier Density Effect.

Herein, we fabricated a uniform and dispersible Ag/indium tin oxide (ITO) cosputtered film on a two-dimensional ordered polystyrene template and observed distinct localized surface plasmon resonance (LSPR) properties that can be tuned by changing the doping level. The increase in the optical band gap is due to the variation in the metallic Ag content, which can effectively change the accumulation of free electrons in the conduction band, in addition to the near-IR absorbance. Surface-enhanced Raman scattering (SERS) was used to monitor the variations in the band gap and transfer of electrons, which causes variations in the SERS intensity. The presented research provides new insights into the relationships between the carrier density and maximum absorption wavelength, band gap distribution, and charge transfer process. This is the first study on the influence of the carrier density on the properties of Ag/ITO cosputtered films and suggests practical applications of these films.