Performance enhancement of paper-based SERS chips by shell-isolated nanoparticle-enhanced Raman spectroscopy

Paper-based flexible surface-enhanced Raman scattering (SERS) chips have been demonstrated to have great potential for future practical applications in point-of-care testing (POCT) due to the potentials of massive fabrication, low cost, efficient sample collection and short signal acquisition time. In this work, common filter paper and Ag@SiO₂core-shell nanoparticles (NP) have been utilized to fabricate SERS chips based on shell‐isolated nanoparticle‐enhanced Raman spectroscopy (SHINERS). The SERS performance of the chips for POCT applications was systematically investigated. We used crystal violet as the model molecule to study the influence of the size of the Ag core and the thickness of the SiO₂coating layer on the SERS activity and then the morphology optimized Ag@SiO₂core-shell NPs was employed to detect thiram. By utilizing the smartphone as a miniaturized Raman spectral analyzer, high SERS sensitivity of thiram with a detection limit of 10⁻⁹M was obtained. The study on the stability of the SERS chips shows that a SiO₂shell of 3 nm can effectively protect the as-prepared SERS chips against oxidation in ambient atmosphere without seriously weakening the SERS sensitivity. Our results indicated that the SERS chips by SHINERS had great potential of practical application, such as pesticide residues detection in POCT.     

Surface-enhanced Raman spectroscopy studies of orderly arranged silica nanospheres-synthesis,characterization and dye detection

Silica nanospheres have been explored much for drug delivery, photocatalysis, sensors and energy storage applications. It also acts as a template for Surface-Enhanced Raman Spectroscopy (SERS) substrates. Uniform nanostructures at low cost with high reproducibility are the major challenges in SERS substrate fabrication. In the present work, silica nanospheres were synthesized using stober method and deposited on to glass slides using Vertical deposition techniques. Different size/thickness of Silver (Ag) nanoparticles were deposited onto silica thin films using sputter deposition technique. The monodispersity of silica nanospheres and size of silver nanoparticles (10 nm, 20 nm and 30 nm) were confirmed by FESEM analysis. The structural properties were confirmed through XRD. UV–Vis analysis revealed that the plasmonic properties of Ag@SiO₂ give high surface plasmons for 30 nm thickness of silver. The binding energy of Ag@SiO₂ confirmed through XPS spectrum. The fabricated SERS substrates were used to detect Rhodamine 6G (R6G), Methylene blue (MB), Methylene violet (MV) and Methyl orange dyes as an analyte molecule with a limit of detection at about 10^?11 mol/L. The addition of SiO₂ nanospheres decreases the Ag oxidation rate and increases their stability. The maximum enhancement factor (1.5?×?10⁷) achieved for 30nm thickness of Ag@SiO₂. The results and technique establish the potential applications and reproducible SERS substrate.

     

Ultrasensitive Surface‐Enhanced Raman Spectroscopy Detection Based on Amorphous Molybdenum Oxide Quantum Dots

Surface‐enhanced Raman spectroscopy (SERS) based on plasmonic semiconductive material has been proved to be an efficient tool to detect trace of substances, while the relatively weak plasmon resonance compared with noble metal materials restricts its practical application. Herein, for the first time a facile method to fabricate amorphous H_xMoO₃ quantum dots with tunable plasmon resonance is developed by a controlled oxidization route. The as‐prepared amorphous H_xMoO₃ quantum dots show tunable plasmon resonance in the region of visible and near‐infrared light. Moreover, the tunability induced by SC CO₂ is analyzed by a molecule kinetic theory combined with a molecular thermodynamic model. More importantly, the ultrahigh enhancement factor of amorphous H_xMoO₃ quantum dots detecting on methyl blue can be up to 9.5 × 10⁵ with expending the limit of detection to 10^?9 m . Such a remarkable porperty can also be found in this H_xMoO₃‐based sensor with Rh6G and RhB as probe molecules, suggesting that the amorphous H_xMoO₃ quantum dot is an efficient candidate for SERS on molecule detection in high precision.     

Ultrasensitive Detection of Prostate‐Specific Antigen and Thrombin Based on Gold‐Upconversion Nanoparticle Assembled Pyramids

Self‐assembled nanostructures have been used for the detection of numerous cancer biomarkers. In this study, a gold‐upconversion‐nanoparticle (Au‐UCNP) pyramid based on aptamers is fabricated to simultaneously detect thrombin and prostate‐specific antigen (PSA) using surface‐enhanced Raman scattering (SERS) and fluorescence, respectively. The higher the concentration of thrombin, the lower the intensity of SERS. PSA connected with the PSA aptamer leads to an increase in fluorescence intensity. The limit of detection of thrombin and PSA reaches 57 × 10^?18 and 0.032 × 10^?18m , respectively. In addition, the pyramid also exhibits great target specificity. The results of human serum target detection demonstrate that the Au‐UCNP pyramid is an excellent choice for the quantitative determination of cancer biomarkers, and is feasible for the early diagnosis of cancer.     

A facile synthesis of silver nanoparticle with SERS and antimicrobial activity using Bacillus subtilis exopolysaccharides

In this study, we report a facile synthesis of silver nanoparticle having SERS and antimicrobial activity using bacterial exopolysaccharide (EPS). Bacillus subtilis (MTCC 2422) was grown in nutrient broth and the extracellular EPS secreted by the organism was extracted and purified. The purified EPS was used for the synthesis of silver nanoparticles. The kinetics of silver nanoparticle synthesis was deduced by varying the exposure time and the concentration of EPS. The rate constant (k) for the synthesis of silver nanoparticle was calculated from the slope of ln(A^∞ ? A^t) versus time plot. The k value was found to be 3.49 × 10^?3, 5.81 × 10^?3 and 5.03 × 10^?3 per min for particle synthesis using 2, 5 and 10 mg/mL EPS, respectively. The nanoparticles synthesised had an average particle size of 5.18 ± 1.49 nm, 1.96 ± 0.77 nm and 2.08 ± 0.88 nm for 2, 5 and 10 mg/mL EPS, respectively. The synthesised particles were characterised using UV-Vis absorbance spectroscopy, high-resolution transmission electron microscopy (HRTEM) attached to EDS (energy dispersive spectroscopy), Fourier transform infrared spectroscopy (FTIR), surface enhanced Raman spectroscopy (SERS) and zeta potential analyser. To our knowledge, this is the first study to report SERS activity of microbial Bacillus subtilis EPS-based synthesis of silver nanoparticle. HRTEM images showed silver nanoparticle entrapped in polysaccharide nanocages. Silver nanoparticle showed higher adherence towards the bacterial surface, with good bactericidal activity against Pseudomonas aeroginosa and Staphylococcus aureus.     

Focusing Plasmons in Nanoslits for Surface‐Enhanced Raman Scattering

The focusing of plasmons to obtain a strong and localized electromagnetic‐field enhancement for surface‐enhanced Raman scattering (SERS) is increasing the interest in using plasmonic devices as molecular sensors. In this Full Paper, we report the successful fabrication and demonstration of a solid‐state plasmonic nanoslit–cavity device equipped with nanoantennas on a freestanding thin silicon membrane as a substrate for SERS. Numerical calculations predict a strong and spatially localized enhancement of the optical field in the nanoslit (6 nm in width) upon irradiation. The predicted enhancement factor of SERS was 5.3 × 10⁵, localized in an area of just 6 × 1.5 nm². Raman spectroscopy and imaging confirm an enhancement factor of ≈10⁶ for SERS from molecules chemisorbed at the nanoslit, and demonstrate the electromagnetic‐field‐enhancing function of the plasmonic nanoantennas. The freestanding membrane is open on both sides of the nanoslit, offering the potential for through‐slit molecular translocation studies, and opening bright new perspectives for SERS applications in real‐time (bio)chemical analysis.     

Synthesis of tin oxide-coated gold nanostars and evaluation of their surface-enhanced Raman scattering activities

Tin oxide-coated gold nanostar hybrid nanostructures are prepared by first synthesizing gold nanostars (ca. 400 nm), then introducing Na₂SnO₃ precursor followed by its hydrolysis and formation of a tin oxide layer on nanoparticle surface. The synthesized hybrid structures have been characterized by combination of UV–Vis spectroscopy, transmission electron microscope (TEM), energy-dispersive X-ray studies, scanning electron microscope (SEM), X-Ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. The TEM and SEM analyses showed that gold nanostars have a coating with an approximate thickness of 15 nm. The tin (IV) oxide coating on the gold nanostars was identified by XRD and XPS analyses and confirmed by FTIR spectroscopy. Surface-enhanced Raman scattering (SERS) spectroscopy was performed on tin oxide-coated and uncoated gold nanostars with crystal violet as a probe molecule. The SERS studies revealed field enhancement properties of Au nanostars, thus their strong SERS activity remained after tin oxide coating.     

Highly reproducible solid-phase extraction membrane for removal and surface-enhanced Raman scattering detection of antibiotics

A disposable solid-phase extraction (SPE) membrane was developed for rapid removal and sensitive surface-enhanced Raman scattering (SERS) detection of antibiotics in water samples. The membrane was fabricated on commercially available SPE column by filtration of the activated carbon modified with silver nanoparticles (Ag NPs/AC). The prepared SPE membrane exhibited outstanding preconcentration ability due to the high adsorption properties of AC, and excellent ability to enhance Raman signal resulting from “hot spots” between the embedded Ag NPs, improving the sensitivity of SERS detection. A detection limit (LOD) of 5.0?×?10^?11 and 1.6?×?10^?10 M was achieved for rhodamine 6G and p-aminothiophenol. In addition, the membrane exhibited high reproducibility with spot-to-spot variation in SERS spectral intensity less than 15%. Based on the membrane, the qualitative and quantitative analysis of the antibiotics in aqueous solution was accomplished with the LOD at nM level, demonstrating the feasibility of the disposable SPE membrane for in situ rapid preconcentration and detection.     

Plasmonic Nanoassemblies: Tentacles Beat Satellites for Boosting Broadband NIR Plasmon Coupling Providing a Novel Candidate for SERS and Photothermal Therapy

Optical theranostic applications demand near‐infrared (NIR) localized surface plasmon resonance (LSPR) and maximized electric field at nanosurfaces and nanojunctions, aiding diagnosis via Raman or optoacoustic imaging, and photothermal‐based therapies. To this end, multiple permutations and combinations of plasmonic nanostructures and molecular “glues” or linkers are employed to obtain nanoassemblies, such as nanobranches and core–satellite morphologies. An advanced nanoassembly morphology comprising multiple linear tentacles anchored onto a spherical core is reported here. Importantly, this core‐multi‐tentacle‐nanoassembly (CMT) benefits from numerous plasmonic interactions between multiple 5 nm gold nanoparticles (NPs) forming each tentacle as well as tentacle to core (15 nm) coupling. This results in an intense LSPR across the “biological optical window” of 650?1100 nm. It is shown that the combined interactions are responsible for the broadband LSPR and the intense electric field, otherwise not achievable with core–satellite morphologies. Further the sub 80 nm CMTs boosted NIR‐surface‐enhanced Raman scattering (SERS), with detection of SERS labels at 47 × 10^‐9 m , as well as lower toxicity to noncancerous cell lines (human fibroblast Wi38) than observed for cancerous cell lines (human breast cancer MCF7), presents itself as an attractive candidate for use as biomedical theranostics agents.     

High Surface‐Enhanced Raman Scattering Performance of Individual Gold Nanoflowers and Their Application in Live Cell Imaging

Molecular imaging techniques based on surface‐enhanced Raman scattering (SERS) face a lack of reproducibility and reliability, thus hampering its practical application. Flower‐like gold nanoparticles have strong SERS enhancement performance due to having plenty of hot‐spots on their surfaces, and this enhancement is not dependent on the aggregation of the particles. These features make this kind of particle an ideal SERS substrate to improve the reproducibility in SERS imaging. Here, the SERS properties of individual flower‐like gold nanoparticles are systematically investigated. The measurements reveal that the enhancement of a single gold nanoparticle is independent of the polarization of the excitation laser with an enhancement factor as high as 10⁸. After capping with Raman signal molecules and folic acid, the gold nanoflowers show strong Raman signal in the living cells, excellent targeting properties, and a high signal‐to‐noise ratio for SERS imaging.     

Direct Thermal Growth of Gold Nanopearls on 3D Interweaved Hydrophobic Fibers as Ultrasensitive Portable SERS Substrates for Clinical Applications

Surface-enhanced Raman spectroscopy (SERS)-based biosensors have attracted much attention for their label-free detection, ultrahigh sensitivity, and unique molecular fingerprinting. In this study, a wafer-scale, ultrasensitive, highly uniform, paper-based, portable SERS detection platform featuring abundant and dense gold nanopearls with narrow gap distances, are prepared and deposited directly onto ultralow-surface-energy fluorosilane-modified cellulose fibers through simple thermal evaporation by delicately manipulating the atom diffusion behavior. The as-designed paper-based SERS substrate exhibits an extremely high Raman enhancement factor (3.9 × 10¹¹), detectability at sub-femtomolar concentrations (single-molecule level) and great signal reproductivity (relative standard deviation: 3.97%), even when operated with a portable 785-nm Raman spectrometer. This system is used for fingerprinting identification of 12 diverse analytes, including clinical medicines (cefazolin, chloramphenicol, levetiracetam, nicotine), pesticides (thiram, paraquat, carbaryl, chlorpyrifos), environmental carcinogens (benzo[a]pyrene, benzo[g,h,i]perylene), and illegal drugs (methamphetamine, mephedrone). The lowest detection concentrations reach the sub-ppb level, highlighted by a low of 16.2 ppq for nicotine. This system appears suitable for clinical applications in, for example, i) therapeutic drug monitoring for individualized medication adjustment and ii) ultra-early diagnosis for pesticide intoxication. Accordingly, such scalable, portable and ultrasensitive fibrous SERS substrates open up new opportunities for practical on-site detection in biofluid analysis, point-of-care diagnostics and precision medicine.     

Electrospun Fe3O4/PVP//Tb(BA)3phen/PVP magnetic–photoluminescent bifunctional bistrand aligned composite nanofibers bundles

Fe₃O₄/PVP//Tb(BA)₃phen/PVP magnetic–photoluminescent bifunctional bistrand aligned composite nanofibers bundles based on Fe₃O₄ nanoparticles (NPs) and terbium complex Tb(BA)₃phen (BA = benzoic acid) were fabricated by employing a parallel axial electrospinning setup and were characterized by X-ray diffraction, field-emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), transmission electron microscopy, fluorescence spectroscopy, and vibrating sample magnetometer. It is found that Fe₃O₄ NPs were only dispersed into one strand of the bistrand aligned composite nanofibers bundles, but no nanoparticles in the other strand. And the average diameter of the individual strand fiber was 200 ± 25 nm. The bistrand aligned composite nanofibers bundles exhibit strong green emissions under the excitation of 275 nm ultraviolet light, and the ⁵ D ₄ → ⁷ F ₅ hypersensitive transition at 545 nm was the predominant emission peak of Tb³⁺ ions. The newly obtained bifunctional nanofibers bundles exhibit excellent magnetism and high fluorescence intensity and are expected to apply in biology cell separation, magnetic resonance imaging, drug deliver, and fluorescence immunoassays/imaging.     

Tunable and highly reproducible surface-enhanced Raman scattering substrates made from large-scale nanoparticle arrays based on periodically poled LiNbO3 templates

Abstract

This work describes novel surface-enhanced Raman scattering (SERS) substrates based on ferroelectric periodically poled LiNbO₃ templates. The templates comprise silver nanoparticles (AgNPs), the size and position of which are tailored by ferroelectric lithography. The substrate has uniform and large sampling areas that show SERS effective with excellent signal reproducibility, for which the fabrication protocol is advantageous in its simplicity. We demonstrate ferroelectric-based SERS substrates with particle sizes ranging from 30 to 70 nm and present tunable SERS effect from Raman active 4-mercaptopyridine molecules attached to AgNPs when excited by a laser source at 514 nm.     

Silver nanoparticles deposited on anodic aluminum oxide template using magnetron sputtering for surface-enhanced Raman scattering substrate

Low-cost and highly sensitive surface-enhanced Raman scattering (SERS) substrates have been fabricated by a simple anodizing process and a magnetron sputtering deposition. The substrates, which consist of silver nanoparticles embedded on anodic aluminum oxide (AAO) templates, are investigated by a scanning electron microscope and a confocal Raman spectroscopy. The SERS activities are demonstrated by Raman scattering from adsorbed solutions of methylene blue and pyridine on the SERS substrate surface. The most optimized SERS substrate contains the silver nanoparticles, with a size distribution of 10-30 nm, deposited on the AAO template. From a calculation, the SERS enhancement factor is as high as 8.5 × 10⁷, which suggests strong potentials for direct applications in the chemical detection and analyses.     

Structural and optical properties of phosphate-zinc-nickel oxide glasses for narrow band pass absorption filters

Novel two phosphate glass systems with compositions 50P₂O₅–30ZnO–20NiO and 50P₂O₅–30ZnO–20[NiCl_2–6H₂O] were prepared using a conventional melt-quench technique. The absorbance and transmittance were measured using a spectrophotometer in the spectral range between 190 and 1100 nm. The data demonstrates that the system acts as a narrow bandpass optical absorption filter, with a transmission band in the UV region of 311–376 nm, which is centred at 350 nm and has a full width half maximum (FWHM) of almost 34 nm, whereas, the red region is the UV region of 617–684 nm, and centred at 650 nm and has a full width half maximum (FWHM) of nearly 32 nm. However, the refractive index (n), optical band gap (E_opt), non-linear refractive index n₂, third order non-linear susceptibility χ⁽³⁾ and non-linear absorption coefficient β were also calculated. It was apparent that the non-linear refractive index, third order non-linear susceptibility and non-linear absorption coefficient increases by decreasing the optical energy gap. Finally, we investigated the structure of the prepared glasses by using Raman and FTIR spectra. We found that the local network structure based mainly on Q¹ and Q² tetrahedron units connected by P–O–P linkages.     

Novel Mn3[Co(CN)6]2@SiO2@Ag Core–Shell Nanocube: Enhanced Two‐Photon Fluorescence and Magnetic Resonance Dual‐Modal Imaging‐Guided Photothermal and Chemo‐therapy

The versatile Mn₃[Co(CN)₆]₂@SiO₂@Ag core–shell NCs are prepared by a simple coprecipitation method. Ag nanoparticles with an average diameter of 12 nm deposited on the surface of Mn₃[Co(CN)₆]₂@SiO₂ through S–Ag bonding are fabricated in ethanol solution by reducing silver nitrate (AgNO₃) with NaBH₄. The NCs possess T₁–T₂ dual‐modal magnetic resonance imaging ability. The inner Prussian blue analogs (PBAs) Mn₃[Co(CN)₆]₂ exhibit bright two‐photon fluorescence (TPF) imaging when excited at 730 nm. Moreover, the TPF imaging intensity displays 1.85‐fold enhancement after loading of Ag nanoparticles. Besides, the sample also has multicolor fluorescence imaging ability under 403, 488, and 543 nm single photon excitation. The as‐synthesized Mn₃[Co(CN)₆]₂@SiO₂@Ag NCs show a DOX loading capacity of 600 mg g⁻¹ and exhibit an excellent ability of near‐infrared (NIR)‐responsive drug release and photothermal therapy (PTT) which is induced from the relative high absorbance in NIR region. The combined chemotherapy and PTT against cancer cells in vitro test shows high therapeutic efficiency. The multimodal treatment and imaging could lead to this material a potential multifunctional system for biomedical diagnosis and therapy.     

Light-responsive color switching of self-doped TiO2-x/WO3·0.33H2O hetero-nanoparticles for highly efficient rewritable paper

Smart materials that reversibly change color upon light illumination are widely explored for diverse appealing applications.However,light-responsive color switching materials are mainly limited to organic molecules.The synthesis of inorganic counterparts has remained a significant challenge because of their slow light response and poor reversibility.Here,we report a seeded growth strategy for the synthesis of TiO_2-x/WO₃·0.33H₂Ohetero-nanoparticles(HNPs)with networked wire-like structure of?10 nm in diameters that enable the highly reversible light-responsive color switching properties.For the TiO_2-x/WO₃·0.33H₂OHNPs,T P species self-doped in TiO_2-xnanoparticles(NPs)act as efficient sacrificial electron donors(SEDs)and Ti-O-W linkages formed between TiO2-x and WO30.33H2O NPs ensure the nanoscale interfacial contact,endowing the HNPs enhanced photoreductive activity and efficient interfacial charge transfer upon ultraviolet(UV)illumination to achieve highly efficient color switching.The TiO_2-x/WO₃·0.33H₂OHNPs exhibits rapid light response(<15 s)and long reversible color switching cycles(>180 times).We further demonstrate the applications of TiO_2-x/WO₃·0.33H₂O HNPs in ink-free,light-printable rewritable paper that can be written on freehand or printed on through a photomask using UV light.This work opens an avenue for designing inorganic light-responsive color switching nanomaterials and their smart applications.     

Split‐GFP: SERS Enhancers in Plasmonic Nanocluster Probes

The assembly of plasmonic metal nanoparticles into hot spot surface‐enhanced Raman scattering (SERS) nanocluster probes is a powerful, yet challenging approach for ultrasensitive biosensing. Scaffolding strategies based on self‐complementary peptides and proteins are of increasing interest for these assemblies, but the electronic and the photonic properties of such hybrid nanoclusters remain difficult to predict and optimize. Here, split‐green fluorescence protein (sGFP) fragments are used as molecular glue and the GFP chromophore is used as a Raman reporter to assemble a variety of gold nanoparticle (AuNP) clusters and explore their plasmonic properties by numerical modeling. It is shown that GFP seeding of plasmonic nanogaps in AuNP/GFP hybrid nanoclusters increases near‐field dipolar couplings between AuNPs and provides SERS enhancement factors above 10⁸. Among the different nanoclusters studied, AuNP/GFP chains allow near‐infrared SERS detection of the GFP chromophore imidazolinone/exocyclic C?C vibrational mode with theoretical enhancement factors of 10⁸–10⁹. For larger AuNP/GFP assemblies, the presence of non‐GFP seeded nanogaps between tightly packed nanoparticles reduces near‐field enhancements at Raman active hot spots, indicating that excessive clustering can decrease SERS amplifications. This study provides rationales to optimize the controlled assembly of hot spot SERS nanoprobes for remote biosensing using Raman reporters that act as molecular glue between plasmonic nanoparticles.     

Six Birds with One Stone: Versatile Nanoporphyrin for Single-Laser-Triggered Synergistic Phototheranostics and Robust Immune Activation

Simultaneous photodynamic therapy (PDT) and photothermal therapy (PTT) can reduce the risks of drug leakage, body burden, and preparation complexity in traditional combination PDT/PTT. Here, a versatile nanoporphyrin (Pp18-lipos) self-assembled from lipid–purpurin 18 conjugates (Pp18-lipids) and pure lipids is presented. The as-prepared Pp18-lipos with 2 mol% Pp18-lipids can perform effective PDT and fluorescence imaging. The Pp18-lipos with 65 mol% Pp18 can perform potent PTT and photoacoustic imaging. The chelation of Mn²⁺ endows the Pp18-lipids-Mn²⁺ a high T₁-weighted magnetic resonance imaging contrast. Notably, pretreatment of low-dose PDT facilitates the endocytosis and tumor accumulation of Pp18-lipos, thus achieving synergistic PDT/PTT. Upon exposure to a single 705 nm-laser, the combination of PDT/PTT achieves a significantly higher tumor growth inhibition rate than PDT or PTT alone. In addition, it is found that the synergistic PDT/PTT triggers more potent anti-tumor immune response including tumor infiltration of immune cells and release of related cytokines.     

Bright Surface‐Enhanced Raman Scattering with Fluorescence Quenching from Silica Encapsulated J‐Aggregate Coated Gold Nanoparticles

Plexitonic nanoparticles offer variable optical properties through tunable excitations, in addition to electric field enhancements that far exceed molecular resonators. This study demonstrates a way to design an ultrabright surface‐enhanced Raman spectroscopy (SERS) signal while simultaneously quenching the fluorescence background through silica encapsulation of the semiconductor–metal composite nanoparticles. Using a multistep approach, a J‐aggregate‐forming organic dye is assembled on the surface of gold nanoparticles using a cationic linker. Excitonic resonance of the J‐aggregate–metal system shows an enhanced SERS signal at an appropriate excitation wavelength. Further encapsulation of the decorated particles in silica shows a significant reduction in the fluorescence signal of the Raman spectra (5× reduction) and an increase in Raman scattering (7× enhancement) when compared to phospholipid encapsulation. This reduction in fluorescence is important for maximizing the useful SERS enhancement from the particle, which shows a signal increase on the order of 10⁴ times greater than J‐aggregated dye in solution and 24 times greater than Oxonica S421 SERS tag. The silica layer also serves to promote colloidal stability. The combination of reduced fluorescence background, enhanced SERS intensity, and temporal stability makes these particles highly distinguishable with potential to enable high‐throughput applications such as SERS flow cytometry.