Utilizing Hydrogel-Isolated Dual-Carboxyl Surface-Enhanced Raman Scattering Probe for Accurate Online pH Monitoring.

Surface-enhanced Raman scattering (SERS) is highly promising for ultra-sensitive detection in a series of applications. Although extensive advances have been achieved in SERS technologies, the preparation of highly efficient SERS substrates still suffers from several limitations, including complex preparation procedures, high cost, and instability for long time storage. To address these problems, we report a novel, to the best of our knowledge, SERS platform that combines graphene oxide (GO) and cellulose composite paper with colloidal silver nanoparticle (Ag NP) ink. As an efficient substrate, the GO and cellulose composite paper that features hierarchical micro-nanostructures and improved interaction with target molecules can be fabricated on a large scale, and the Ag NP ink can be well stored, avoiding being oxidized in ambient conditions. In this way, our SERS platform not only reduces the cost, but also improved the stability. The sensitivity, reproducibility, and tunable SERS detection performance were evaluated using rhodamine 6G as probing molecules. To demonstrate the capability of our SERS platform in practical analysis, the SERS spectra of two monosodium salt solutions of different concentrations have been collected. The SERS platform has revealed great potential for practical application of SERS technologies.

Silver nanocubes/graphene oxide hybrid film on a hydrophobic surface for effective molecule concentration and sensitive SERS detection

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

Adenosine plays a crucial role in the regulation of physiological activity in various tissues and organs. As adenosine is a possible biomarker for cancer, the determination of its level presents a demanding task for deeply monitoring progress of diseases. Through the synthesis of Fe3O4/Au/Ag nanocomposites weaved and stabilized by phytic acid and its salt, we develop a magnetically assisted surface-enhanced Raman scattering (SERS) protocol to determine trace level adenosine in urine samples from both lung cancer patients and health human. The magnetic properties of the nanocomposites enable to realize the simple separation of targeted molecules from a complex matrix and the Au/Ag nanoparticles moieties act as the SERS platform. This label-free Fe3O4/Au/Ag-nanocomposites-based SERS protocol shows a good stability, reproducibility, time efficiency (less than 20 min for one sample test), and huge sensitivity down to 1 × 10(-10) M. The protocol also has high selectivity because SERS signal of adenosine provides the molecular fingerprint information as well as an azo coupling pretreatment is performed to remove the interference of urea. Furthermore, a SERS array is designed for on-site screening adenosine in urine samples in a massive way using a portable Raman. Such a magnetically assisted SERS method as a powerful alternative can be expected as a smart and promising tool for effective assessment of healthcare.

With advances in the design, synthesis and analysis of various metallic nanoparticles and substrates, surface‐enhanced Raman scattering (SERS) with plasmonic nanostructures has been extensively studied, and numerous SERS applications have been demonstrated in various applications including biomedical applications; however, the mechanism of SERS is not completely understood yet, and many challenges, including structural and spectral reproducibility, exist to achieve quantitative SERS analysis for practical and reliable use of SERS. Since SERS signal reproducibility mainly stems from structural reproducibility of targeted nanostructures, single‐particle SERS analysis is highly beneficial in understanding SERS signals generated from different plasmonic nanostructures and provides analytical insights that cannot be obtained with ensemble‐average spectrum‐based analysis. Single‐particle analysis is typically composed of single‐particle images and spectra, and the statistical results show the single‐particle SERS enhancement factor distribution of SERS signals and precise structure‐spectrum relationship. In particular, studying and evaluating single‐molecule SERS results require single‐particle analysis to fully understand how single‐particle images and spectra are correlated with how the position, orientation and resonance of a Raman dye affect single‐molecule SERS signals from individual nanoparticles, and this is often correlated with computational simulation results. In this mini‐review, we introduce key issues for quantitative SERS and present the fundamental SERS features obtained by single‐particle analysis, focused on plasmonic nanogap structures since these structures offer the very strong electromagnetic field‐based SERS signals with high controllability in structure and signal. We categorized the nanogap particle‐based SERS platforms into two different classes – plasmonic nanogap strctures with an intergap (the gap between two structures; intergap nanoparticles) and plasmonic nanogap structures with an intragap (the gap formed inside a single particle; intragap nanoparticles). Finally, we discuss the challenges and perspectives in designing and synthesizing nanogap structures that deliver strong, reproducible, and reliable SERS signals for the quantitative SERS analysis.

Cancer diagnostics often faces challenges, such as invasiveness, high costs, and limited sensitivity for early detection, emphasizing the need for improved approaches. We present a surface-enhanced Raman scattering (SERS)-based platform leveraging inverted pyramid SU-8 nanostructured substrates fabricated via nanoimprint lithography. These substrates, characterized by sharp apices and edges, are further functionalized with (3-aminopropyl)triethoxysilane (APTES), enabling the uniform self-assembly of AuNPs to create a highly favorable configuration for enhanced SERS analysis. Performance testing of the substrates using malachite green (MG) as a model analyte demonstrated excellent detection capabilities, achieving a limit of detection as low as 10-12 M. Building on these results, the SERS platform was adapted for the sensitive and specific detection of hyaluronic acid (HA), a key biomarker associated with inflammation and cancer progression. The system employs a sandwich immunoassay configuration, with substrates functionalized with antibodies to capture HA molecules and 4-MBA-labeled SERS tags for detection. This setup achieved an ultra-sensitive detection limit of 10-11 g/mL for HA. Comprehensive characterization confirmed the uniformity and reproducibility of the SERS substrates, while validation in complex biological matrices demonstrated their robustness and reliability, highlighting their potential in cancer diagnostics and biomarker detection.

Decoupling the contributions of electromagnetic and chemical enhancements in surface‐enhanced Raman scattering (SERS) would lead to greater reliability and applicability in biological systems that involve large, localized pH gradients. However, suppressing short‐range, chemical enhancement effects in SERS has proved challenging due to unavoidable charge‐transfer interactions between analyte and the SERS platforms. This extends to both lithographically fabricated top‐down and self‐assembled bottom‐up SERS platforms. Here, we employ a Soret effect‐driven monodisperse nanoparticle assembly (Soret colloids [SCs]) with negligible surface charge (ξ < 16 mV) that provides exceptional SERS enhancement (analytical enhancement factor ~106) contributed predominantly by excitation of localized surface plasmon resonance (electromagnetic enhancement) with minimal electrostatic or charge‐transfer–based short‐range interactions. Significantly, the low ξ of SCs is invariant over a wide pH range (pH 4–7) indicating minimal electrostatic surface charge. The interaction of such SCs with ionic analytes such as tyrosine leads to uniform SERS dictated by electromagnetic enhancement mechanism. The absence of contribution from chemical enhancement is clearly established by the vibrational fingerprints of tyrosine that are devoid of any spectral shifts originating from charge transfer between tyrosine and SCs. Accordingly, all features of the tyrosine that are independent of pH such as C―H stretch (2,700–3,000 cm−1) and C―C stretch (1,440 cm−1) and C―C―C bending (1,010 cm−1) are completely preserved without any spectral shifts. Simultaneously, pH‐dependent vibrational features of tyrosine such as N―H stretch (1,545 cm−1), CO stretch (1,700 cm−1), COO− stretch (1,640 cm−1), C―O stretch (1,240 cm−1), and amide III bands (1,246 and 1,260 cm−1) are clearly observed. The intensities of such bands correspond exactly to the ionic state of tyrosine as dictated by the pH of the medium. This is reinforced by the crossover in the intensity of the pH‐dependent vibrational modes (C―O vs. COO‐ stretch, COO− vs. NH3+ stretch) that coincides with the isoelectric pH of tyrosine. Finally, reliable quantification of the charge and concentration of tyrosine using SCs are established, enabling its use for studying intrinsic cellular pathways using SERS.

Rapid and fingerprinted monitoring of pesticide methyl parathion on the surface of fruits/leaves as well as in surface water enabled by gold nanorods based casting-and-sensing SERS platform

Utilization of doped GQDs for ultrasensitive detection of catastrophic melamine: A new SERS platform.

Improving the SERS effect of van der Waals material by intercalation strategy

A multifunctional surface-enhanced Raman scattering (SERS) platform integrating sensitive detection and drug resistance analysis was developed for Gram-positive bacteria. The substrate was based on self-assembled Ti3C2Tx@Au NPs films and capture molecule phytic acid (IP6) to achieve specific capture of Gram-positive bacteria and different bacteria were analyzed by fingerprint signal. It had advantages of good stability and homogeneity (RSD = 8.88%). The detection limit (LOD) was 102CFU/mL for Staphylococcus aureus and 103CFU/mL for MRSA, respectively. A sandwich structure was formed on the capture substrate by signal labels prepared by antibiotics (penicillin G and vancomycin) and non-interference SERS probe molecules (4-mercaptobenzonitrile (2223cm-1) and 2-amino-4-cyanopyridine (2240cm-1)) to improve sensitivity. The LOD of Au NPs@4-MBN@PG to S. aureus and Au NPs@AMCP@Van to MRSA and S. aureus were all improved to 10 CFU/mL, with a wide dynamic linear range from 108 to 10CFU/mL (R2 ≥ 0.992). The SERS platform can analyze the drug resistance of drug-resistant bacteria. Au NPs@4-MBN@PG was added to the substrate and captured MRSA to compare the SERS spectra of 4-MBN. The intensity inhomogeneity of 4-MBN at the same concentrations of MRSA and the nonlinearity at the different concentrations of MRSA revealed that MRSA was resistant to PG. Finally, the SERS platform achieved the determination of MRSA in blood. Therefore, this SERS platform has great significance for the determination and analysis of Gram-positive bacteria.

Surface molecular imprinting onto silver microspheres for surface enhanc24 June 2013ed Raman scattering applications

We present an optical fiber device involving metal-dielectric colloidal crystal (MDCC) structures as a platform for surface enhanced Raman-scattering (SERS) sensing applications. The MDCC structures received large interest in last years since they permit to combine localized surface plasmonic resonance (LSPR) of noble metallic nanoparticles and photonic bandgap (PBG) of colloidal type photonic crystals (PhCs). Most of the MDCC structures have been provided onto planar substrates and then investigated as SERS platform. However, the integration and/or combination of the advantages MDCC structures with optical fiber technology represent still open challenges. The present paper reports recent results about MDCCs fabricated directly onto fiber optic tip surface by successive depositions of Au-NPs on PSbased CCs. Our goal is the fabrication of miniaturized fiber optic devices for SERS sensing applications. Numerical and experimental results of different samples are here presented and discussed. For the sensing test, the fiber probes were immersed in a 100μM ethanol solution of 4-Mercaptobenzoic acid (4MBA). Then, preliminary SERS results were retrieved by a Labspec Aramis confocal Raman spectrometer.

Surface-enhanced Raman scattering (SERS) probes offer considerable opportunities in label-based biosensing and analysis. However, achieving specific and reproducible performance, where low detection limits are needed in complex media, remains a challenge. Herein, we present a general strategy employing gold nanorod SERS probes and rationally designed surface chemistry involving protein resistant layers and antibodies to allow for the selective detection of species in complex media. By utilizing the ability of gold nanorods for selective surface modification, Raman reporters (4-mercaptobenzoic acid) were attached to the tips. Importantly, the sides of the nanorods were modified using a mixed layer of two different length stabilizing ligands (carboxyl-terminated oligo ethylene glycols) to ensure colloidal stability, while antibodies were attached to the stabilizing ligands. The nanoparticle interfacial design improves the colloidal stability, unlocks the capability of the probes for targeting biomolecules in complex matrices, and gives the probes the high SERS efficiency. The utility of this probe is demonstrated herein via the detection of Salmonella bacteria at the single bacterium level in complex food matrices using an anti-Salmonella IgG antibody-conjugated probe. The modular nature of the surface chemistry enables the SERS probes to be employed with a molecularly diverse range of biorecognition species (e.g., antibodies and peptides) for many different analytes, thus opening up new opportunities for efficient biosensing applications.

Surface-enhanced Raman scattering (SERS) substrates have shown rapid development in recent years, but the use of transparent conductive oxides (TCOs) in SERS is still limited. Here, a series of In-doped CdO (ICO) NPs with different In3+ doping contents x (x = 0, 0.025, 0.050, 0.075, 0.100, 0.125, 0.150, and 0.200) were synthesized by a hydrothermal method and first employed as a SERS platform. The structures and properties of the ICO NPs influenced by dopant concentration of In3+ ions were characterized by powder X-ray diffraction (XRD), inductively coupled plasma (ICP) analysis, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) spectroscopy. Furthermore, the SERS spectra of ICO-MPY were investigated. Interestingly, the enhancement was dominated by the charge-transfer (CT) contribution through the free electrons in conduction bands (CBs). The changes in electronic distributions in energy levels of ICO NPs at different doping contents were explored, and the corresponding effect on SERS was discussed by employing 633 and 785 nm excitation lines, respectively. The CT route was found to be the excitation of electrons from CBs of semiconductor to the LUMO of molecule, which provides a new perspective in understanding SERS mechanisms. The present work provides a new approach to develop potential semiconductive SERS substrates.