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A metasurface composed of silver nanoflower arrays, which exhibit asymmetrical absorption and surface‐enhanced Raman scattering (SERS) due to hybrid plasmonic effects, is reported. The silver nanoflowers are fabricated by oblique deposition of silver on a polymer nanohole array on a glass substrate, forming petal‐like semicontinuous thin films on the inner walls of the holes. Depending on the deposition angle, three‐ or five‐petal nanoflowers are obtained. The nanoflower arrays show strong reflection from the air side and broadband and wide‐angle absorption from the glass side, as a result of transmission surface plasmon resonance and localized surface plasmon resonance, respectively. The three‐petal structure, which absorbs most of the incident light from the glass side, induces a localized enhancement of electric field in the center of each nanohole, providing a high‐sensitivity SERS substrate. The SERS performance of the metasurface by direct measurement and near‐field simulation is demonstrated.

Abstract To develop a field applicable hazardous molecular detection system, highly sensitive and multiplex detection capability is required for practical utilization. Here, a paper‐based 3D spiky needle‐clustered gold grown on silver (Ag@Au) plasmonic nanoarchitecture (3D‐SNCP) is fabricated through whole solution process. The developed substrate is investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X‐ray diffraction (XRD) to find out morphological development mechanism. Also, finite‐domain time difference (FDTD) simulation is conducted for the observation of electromagnetic field (E‐field) distribution. After surface‐enhanced Raman scattering (SERS) characterization, the 3D‐SNCP is utilized for ultra‐sensitive and multiplex hazardous molecular detection, such as bipyridine pesticides including paraquat (PQ), diquat (DQ), and difenzoquat (DIF). Then, each of pesticide molecular Raman signals are trained by a machine learning technique of multinomial logistic regression (MLR), followed by multiplex classificationf of blank, PQ, DQ, DIF, and four mixture types of each pesticide, spiked in real agricultural matrix. The developed 3D‐SNCP substrate combined with the machine learning method successfully verifies the multiple pesticides and it is expected to be applied for various hazardous molecular detection in much complicated matrix environments.

Abstract Topological insulators (TIs) exhibit unconventional quantum phases that can be tuned by external quantum confinements. The geometry of the surface of 3D TIs plays a crucial role. For example, the geometrical crossover from 2D surfaces to a 1D cylinder results in a novel state with a Spin‐Berry Phase (SBP). Surface‐Enhanced Raman Scattering (SERS) with a sub‐micron spatial resolution is utilized to study the quantum‐confinement effects of quasi‐relativistic electrons along the perimeter of the circular bismuth selenide (Bi2Se3) nanowires. The presence of diameter‐dependent SERS in nanowires can be attributed to the self‐interference effect of the electronic wave‐function along the circumferential direction of the TI nanowires. Nanoribbons with rectangular cross‐section do not show this effect. Further gold nanoparticles are applied as plasmonic SERS sensors attached to the distinct topological surface states to manipulate quasi‐relativistic surface states of nanoribbons and nanowires. This technique enables to discriminate between different geometries of TI surface states and also opens a novel pathway to probe the quantum properties of topological surface states.

Surface‐enhanced Raman scattering (SERS) is a versatile spectroscopic technique, which plays a crucial role in enhancing analytical sensitivity, investigating interfacial reaction mechanisms, enabling biosensing, and fostering efficient catalysis. Currently, the common SERS substrates are primarily metal nanostructures, which entail high manufacturing costs, complex processes, and the metal surface undergo change over time and with environmental conditions. These issues limit the development of SERS technology. In this work, a nitrogen‐doped graphene (N‐graphene) hydrangea was synthesized on a silicon (Si) substrate using plasma‐assisted chemical vapor deposition (PACVD), forming an N‐graphene hydrangea/Si hybrid structure as a SERS substrate. This substrate offers the advantages of high stability, ultra‐sensitivity, and reusability. The three‐dimensional nano‐cavity structure of graphene can increase the interaction between light and graphene, resulting in an increased localized electric field. Combining theoretical simulation analysis, the introduction of nitrogen (N) elements adjusts the Fermi level of graphene, promoting efficient charge transfer. In practical scenarios, Di(2‐ethylhexyl) phthalate (DEHP), a commonly used plasticizer, has raised concerns due to its potential as an endocrine disruptor and carcinogen. The as‐prepared SERS substrate achieves a remarkable detection limit of as low as 10−8 m for DEHP, providing significant support for environmental conservation and human health.

Abstract The size, distribution, and specific shape of ordered nanophotonic structures are crucial for their biomedical applications. Bottom‐up approaches such as self‐assembly, emulsification, and precipitation are commonly fabricated nanophotonic structures, which often lack control of nanophotonic structures morphologies and monodispersed sizes. On the contrary, top‐down nanofabrication techniques offer the advantages of high fidelity and high controllability and are employed in the fabrication of nanophotonic structures. This review focuses on top‐down nanofabrication techniques to fabricate ordered nanophotonic structures and their biomedical applications. Several top‐down approaches used in the semiconductor industry and other fields requiring micro‐ and nanopatterns are used, including electron beam lithography/ion beam lithography, photolithography, interference lithography, nanoimprint lithography, nanosphere lithography, nanotransfer lithography, and nano‐electrodeposition. Various current and emerging biomedical applications of the ordered nanophotonic structures are also covered: i) surface‐enhanced Raman scattering, ii) plasmonics, including surface plasmon resonance and localized surface plasmon resonance, and iii) fluorescence enhancement. Finally, a future perspective of nanophotonic structures fabricated by top‐down techniques in biomedical applications is also summarized.

Abstract Glycans are the most abundant fundamental biomolecules, but profiling glycans is challenging due to their structural complexity. To address this, a novel glycan detection platform is developed by integrating surface‐enhanced Raman spectroscopy (SERS), boronic acid receptors, and machine learning tools. Boronic acid receptors bind with glycans, and the reaction influences molecular vibrations, leading to unique Raman spectral patterns. Unlike prior studies that focus on designing a boronic acid with high binding selectivity toward a target glycan, this sensor is designed to analyze overall changes in spectral patterns using machine learning algorithms. For proof‐of‐concept, 4‐mercaptophenylboronic acid (4MBA) and 1‐thianthrenylboronic acid (1TBA) are used for glycan detection. The sensing platform successfully recognizes the stereoisomers and the structural isomers with different glycosidic linkages. The collective spectra that combine the spectra from both boronic acid receptors improve the performance of the support vector machine model due to the enrichment of the structural information of glycans. In addition, this new sensor could quantify the mole fraction of sialic acid in lactose background using the machine learning regression technique. This low‐cost, rapid, and highly accessible sensor will provide the scientific community with another option for frequent comparative glycan screening in standard biological laboratories.

Abstract Tumor cells display heterogenous molecular signatures during the course of cancer and create distinct tumor cell subpopulations which challenge effective therapeutic decisions. Detection and monitoring of these heterogenous molecular events at single cell level are imperative to identify tumor cell subpopulations and to engage the best therapeutic options for the individual patient. Herein, a microfluidic liquid biopsy platform to analyze circulating tumor cells (CTCs) at single cell level is reported. The individual CTCs are captured in an alternating current‐induced microfluidic platform and analyzed by using surface‐enhanced Raman scattering spectroscopy. This platform selectively captures single CTCs from the patient's peripheral blood mononuclear cells. Using cell line models and patient samples, it is shown that the assay can simultaneously detect multiple protein biomarkers on a single CTC. The platform can stratify the CTCs into different subpopulations based on their cancer‐associated protein signature changes in response to drug treatment. This enables the identification of CTC subpopulations that are probably not responding to treatment and may assist clinicians in specifically monitoring and eliminating therapy‐resistant cancer cells within a lesion. This single CTC monitoring chip will likely have high clinical importance in disease diagnosis and treatment monitoring, and advance the knowledge of cancer heterogeneity.

Abstract The development of reliable, cost‐effective molecular detection at the attomolar level on analyte‐immobilizing surfaces fabricated without lithographic patterning remains a major challenge in chemical sensing technology. This issue is addressed using custom‐designed adhesive superhydrophobic silicon nanograss surfaces produced via plasma etching. When applied to ultrasensitive surface‐enhanced Raman scattering, the nanograss surface enables effective immobilization of water droplets containing Ag nanoparticles and R6G target molecules. Upon water evaporation, the R6G analytes are confined at the edge of the self‐organized coffee‐ring‐like stains with the plasmonic hot spots of the Ag nanoparticles, thus providing a reliable Raman scattering platform for detecting trace analytes. Even at an ultralow concentration of 10−16 m, the corresponding relative standard deviation is 17.57%. A novel plasma‐enabled approach for precise interface nanostructuring, potentially leading to unprecedented capabilities in molecular‐level sensing technologies, is presented.

A general polymerization‐induced strategy is developed to synthesize large‐area (100 cm2) transition metal nitride (TMN: TiN, MoN, WN, VN) porous arrays with high specific surface area (187.5–215.5 m2 g−1) for the first time, which also can be used to prepare TMN porous arrays uniformly doped with multiple elements. The formation of homogeneous organic/inorganic hybrid polymer precursors is a key factor in forming such TMN porous arrays. The TiN porous arrays exhibit an intense blue‐light localized surface plasmon resonance effect centered at 508 nm. The TiN porous arrays also show a remarkable surface‐enhanced Raman scattering (SERS) effect with a Raman enhanced factor of 5.7 × 107 and the lowest detection limit of 1.0 × 10−12 m. They show ultrahigh corrosion resistance and oxidation resistance, which are not available on traditional noble metal and semiconductor SERS substrates. These results suggest the possibility of the development of effective SERS substrates by using cheap TiN to replace the expensive commercial Au substrates.

Abstract The formation of well‐defined, functional surfaces that incorporate the unique properties of inorganic nanoparticles (NPs) requires robust and scalable fabrication strategies. Herein, we report a methodology for the decoration of polymer molds with plasmonic (gold) nanoparticle arrays. Wrinkled soft templates were used to assemble gold NPs (74 nm) into line arrays. These pre‐formed nanoparticle arrays were transferred in a subsequent step onto polycarbonate molds via an injection molding process. Scanning electron microscopy analysis revealed the structural fidelity of the pattern structure upon transfer. The preservation of the optical functionality of the gold nanoparticle line arrays was proven by surface‐enhanced Raman scattering (SERS) experiments. The reported strategy of nanoparticle pattern transfer to polymer bodies by this robust process is expected to prove useful for the fabrication of polymer surfaces with tailored optical functionality.

Abstract Novel low‐cost materials to uptake and detect vestigial amounts of pesticides are highly desirable for water quality monitoring. Herein, are demonstrated, for the first time, surface‐enhanced Raman scattering (SERS) sensors enabled via additively manufactured lattices coated with plasmonic nanoparticles (NPs) for detecting pesticides in real water samples. The architected lattices comprising polypropylene (PP) and multiwall carbon nanotubes (MWCNTs) are realized via fused filament fabrication (FFF). In the first stage, the SERS performance of the PP/MWCNT filaments coated with distinct metallic NPs (Ag NPs and Au NPs) is evaluated using methylene blue (MB) as molecular probe. Thereafter, distinctly architected hybrid SERS sensors with periodic porous and fully dense geometries are investigated as adsorbents to uptake MB from aqueous solutions and subsequent detection using SERS. The spatial distribution of MB and Ag NPs on the FFF‐printed lattices is accomplished by SERS imaging. The best hybrid composite is used as SERS probing system to detect low amounts of pesticides (thiram and paraquat) and offers a detection limit of 100 nm for both pesticides. As a proof‐of‐concept, FFF‐enabled test strips are used to detect in loco paraquat molecules spiked on real water samples (Estuary Aveiro water and tap water) using a portable Raman spectrometer.

Abstract Immunotherapy has received wide attention in recent years as a new avenue for the effective treatment of cancer. However, due to the lack of detection limit and sensitivity of immune checkpoint molecule (such as Programmed cell death 1 ligand 1, PD‐L1) in established clinical methods, the immunotherapy evaluation during anti‐PD‐L1/PD‐1 (Programmed cell death receptor 1) treatment is difficult to be guided accurately. In this study, a highly sensitive and maneuverable Surface‐Enhanced Raman Scattering (SERS)‐based immunoassay platform is developed for the analysis of exosomal PD‐L1, a highly potential biomarker for immunotherapy. Excellent detection of exosomal PD‐L1 with good linear fit over a wide concentration range is achieved. In addition, the detection and discrimination of exosomal PD‐L1 in the peripheral blood of cancer patients and healthy controls are successfully achieved. Moreover, the platform has also been successfully used to distinguish common diseases, cancer, and healthy control (such as liver cancer, liver cirrhosis, and normal individuals). The detection platform can be successfully used for the trace detection of PD‐L1 on exosomes, which has excellent potential for clinical development in cancer diagnosis and treatment guidelines.

Prostate specific antigen (PSA) is widely used in liquid biopsy of prostate cancer (PCa) but still faces challenges due to the poor specificity. Herein, this study reports a double-SERS satellite immunoassay, made of an Au-Ag dealloyed intra-nanogap nanoflower (Au-Ag DINF) with strong SERS signals and Au magnetic nanoparticles (AuMNPs) with magnetic capture and SERS amplification, for sensing multiple PSA (free PSA (fPSA), complexed PSA (cPSA) and [-2]proPSA (p2PSA)) toward potential PCa screening. Unlike the previous studies focus on the tPSA and fPSA/tPSA ratio (f/t PSA%), this work introduces a multiple PSA-mediated Prostate Health Index (PHI) assay with significantly increased the predictive accuracy and specificity of PCa, especially the patients with a tPSA level in the "diagnostic gray zone". Practical analysis of clinical samples demonstrated the SERS immunoassay is capable of identifying the PCa subjects from healthy candidates (N = 13), and monitoring PCa patients before and after surgery (N = 5), as well as screening suspicious ones who are in the "gray zone" (N = 10). Overall, benefiting from the PSA-responsive satellite immuno-nanoassemble strategy, dual-SERS magnification effect, and multiple PSA-based PHI assessment, this proposes bioassay held enormous potential for the early diagnosis, screening, monitoring, and prognosis of PCa., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The field of semiconductor surface-enhanced Raman scattering (SERS) substrates has experienced significant advancements, leading to a wide range of applications in several fields. However, the quest for new ultra-sensitive semiconductor SERS materials is still of utmost importance. In this regard, an efficient and novel substrate, F 4 TCNQ/MoS 2 heterostructure is introduced, assisted by V-shaped aluminum anodic oxide (AAO) nanocavities with different depths. Utilizing the efficient charge transfer of organic/inorganic semiconducting heterostructure and the photoconfinement capability of the nanocavity structure of the AAO nanotemplate, excellent stability, fast sensing, enhanced Raman, and photodegradation activities are achieved. Due to its unique 3D structure, the optimized F 4 TCNQ/MoS 2 /AAO with 1500 nm depth achieves ultra-high sensitivity detection of 9.0×10 -16 M for conventional probe molecules. Furthermore, precise detection of water contaminants is observed for the first time with a V-shaped heterostructure due to combined organic/inorganic features that differ significantly from conventional MoS 2 structures or other metal/inorganic or inorganic/inorganic semiconductors. This research presents a novel and versatile strategy for SERS and demonstrates its diverse potential performance in practical applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Immunotherapy represents a promising therapeutic strategy for cancer treatment, but its clinical applications are currently hindered by insufficient therapeutic potency, nonspecific delivery, and adverse side effects. Herein, a novel near-infrared II (NIR-II) photo-triggered plasmonic hyperthermia immunomodulator (RP@IR-pcNS@HA nanoparticles (NPs)) for anticancer treatment of both primary and distant cancers is reported. This immunomodulator comprises an IR-1061 dye-encoded NIR-II porous cubic AuAg nanoshell (pcNS) loaded with a Toll-like receptor 7 agonist - R837 in phase change materials (PCMs), further modified with hyaluronic acid (HA). In response to NIR-II photoirradiation, the RP@IR-pcNS@HA NPs controllably deliver and release R837 to tumor sites, subsequently perform plasmonic hyperthermia therapy for direct ablation of primary tumors, and elicit robust anticancer immune responses. It is demonstrated that upon NIR-II irradiation, such a plasmonic hyperthermia immunomodulator combined with anti-programmed death 1 antibody (αPD-1) completely eradicates both primary and distant cancers. In addition, this combination treatment successfully elicits robust immune memory responses for effective suppression of recurrence and distant metastasis of cancer. With the excellent NIR-II surface-enhanced Raman scattering (SERS) detection ability, the RP@IR-pcNS@HA NPs combined with αPD-1 represent an efficient way to develop high-performance theranostic agents for SERS-guided combination cancer photoimmunotherapy., (© 2024 Wiley‐VCH GmbH.)

Noninvasive liquid biopsies can be used for early tumor diagnosis by identifying the methylation level of the tumor suppressor genes (TSGs)-a reliable index for cancer evaluation. However, identifying trace circulating genes from specimens remains challenging. This work introduces a novel method that combines magnetic isolation and surface-enhanced Raman scattering (SERS) to concentrate and detect the methylated TSG promotors. A superparamagnetic iron oxide nanoparticle modified with streptavidin is prepared as a universal magnetic bead. Biotin-terminated probe single-strand DNA (ssDNA) is immobilized on the magnetic beads through biotin-streptavidin bioconjugation. Artificial target ssDNA fragments with various methylation levels are applied as a promoter gene model. Concentrated double-strand DNA (dsDNA) is produced by a hybridizing probe and target ssDNA on magnetic nanobeads, as well as an additional magnetic isolation process. The well-prepared DNA adduct, which consists of 3 nm cisplatin-modified Ag nanoclusters, can specifically bind with guanine-cytosine base pairs of dsDNA. Ag-nanoparticle-induced localized SERS amplified signals of 5-methylcytosine (5-mC) from the dsDNA in Raman spectra, enabling accurate methylation level measurement in mixtures of 0-1 µm methylated DNA, with a detection limit of 0.05 µm. This method shows promise for enabling the methylation level evaluation of various TSGs and promoters in early cancer liquid biopsies., (© 2024 Wiley‐VCH GmbH.)

Real-time polymerase chain reaction (RT-PCR) with fluorescence detection is the gold standard for diagnosing coronavirus disease 2019 (COVID-19) However, the fluorescence detection in RT-PCR requires multiple amplification steps when the initial deoxyribonucleic acid (DNA) concentration is low. Therefore, this study has developed a highly sensitive surface-enhanced Raman scattering-based PCR (SERS-PCR) assay platform using the gold nanoparticle (AuNP)-internalized gold nanodimpled substrate (AuNDS) plasmonic platform. By comparing different sizes of AuNPs, it is observed that using 30 nm AuNPs improves the detection limit by approximately ten times compared to 70 nm AuNPs. Finite-difference time-domain (FDTD) simulations show that multiple hotspots are formed between AuNPs and the cavity surface and between AuNPs when 30 nm AuNPs are internalized in the cavity, generating a strong electric field. With this 30 nm AuNPs-AuNDS SERS platform, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA)-dependent RNA polymerase (RdRp) can be detected in only six amplification cycles, significantly improving over the 25 cycles required for RT-PCR. These findings pave the way for an amplification-free molecular diagnostic system based on SERS., (© 2024 Wiley‐VCH GmbH.)

The exploration of novel functionalized supramolecular coordination complexes (SCCs) can enable new applications in domains that include purification and sensing. In this study, employing a coordination-driven self-assembly strategy, we designed and prepared a series of benzochalcogenodiazole-based metallohelicates as high-efficiency charge-transfer surface-enhanced Raman scattering (SERS) substrates, expanding the range of applications for these metallohelicates. Through structural modifications, including the substitution of single heteroatoms on ligands, replacement of coordinating metals, and alteration of ligand framework linkages, the Raman performance of these metallohelicates as substrates were systematically optimized. Notably, the SERS enhancement factors (EFs) of the metallohelicate-based SERS substrates were significantly enhanced to levels as high as 1.03×10 7 , which rivals the EFs of noble metals devoid of "hot spots". Additionally, the underlying Raman enhancement mechanisms of these metallohelicates have been investigated through a combination of control experiments and theoretical calculations. This study not only demonstrates the utility of metallohelicates as SERS substrates but also offers insights and materials for the development of high-efficiency new charge-transfer SERS substrates., (© 2024 Wiley-VCH GmbH.)

Traditional surface-enhanced Raman scattering (SERS) sensors rely heavily on the use of plasmonic noble metals, which have limitations due to their high cost and lack of physical and chemical stability. Hence, it is imperative to explore new materials as SERS platforms that can withstand high temperatures and harsh conditions. In this study, the SERS effect of molybdenum boride ceramic powders is presented with an enhancement factor of 5 orders, which is comparable to conventional noble metal substrates. The molybdenum boride powders synthesized through liquid-phase precursor and carbothermal reduction have β-MoB, MoB 2 , and Mo 2 B 5 phases. Among these phases, β-MoB demonstrates the most significant SERS activity, with a detection limit for rhodamine 6G (R6G) molecules of 10 -9  m. The impressive SERS enhancement can be attributed to strong molecule interactions and prominent charge interactions between R6G and the various phases of molybdenum boride, as supported by theoretical calculations. Additionally, Raman measurements show that the SERS activity remains intact after exposure to high temperature, strong acids, and alkalis. This research introduces a novel molybdenum boride all-ceramic SERS platform capable of functioning in harsh conditions, thereby showing the promising of boride ultrahigh-temperature ceramics for detection applications in extreme environments., (© 2024 Wiley‐VCH GmbH.)

Breast-conserving surgery is the favorable option for breast cancer patients owing to its advantages of less aggressiveness and better cosmetic outcomes over mastectomy. However, it often suffers from postsurgical lethal recurrence due to the incomplete removal of microscopic tumors. Here, a surface-enhanced Raman scattering (SERS) surgical strategy is reported for precise delineation of tumor margins and intraoperative real-time elimination of microscopic tumor foci, which is capable of complete surgical removal of breast tumors and significantly improve the outcomes of breast-conserving surgery without local tumor recurrence. The technique is chiefly based on the human epidermal growth factor receptor 2 (HER2)-targeting SERS probes with integrated multifunctionalities of ultrahigh sensitive detection, significant HER2 expression suppression, cell proliferation inhibition, and superior photothermal ablation. In a HER2+ breast tumor mouse model, the remarkable capability of the SERS surgical strategy for complete removal of HER2+ breast tumors through SERS-guided surgical resection and intraoperative real-time photothermal elimination is demonstrated. The results show complete eradiation of HER2+ breast tumors without local recurrence, consequently delivering a 100% tumor-free survival. Expectedly, this SERS surgical strategy holds great promise for clinical treatment of HER2+ breast cancer with improved patients' survival., (© 2024 Wiley‐VCH GmbH.)

Recent advances in the use of stable isotopes necessitate novel synthesis techniques for isotope separation and enrichment that are scalable and offer high throughput. Stable-isotope-enriched nanostructures can offer unique advantages as nanomedicines, safe tracers, and labels and are critical for applications in various industrial processes, metabolic research, and medicine. So far, there exists no method to synthesize miniature isotope-enriched materials at the nanoscale. In this study, an ultrafast Laser-induced isotope enrichment at nanoscale (LIIEN) is put forward to synthesize isotope-enriched nanostructures, eliminating the need for large equipment and expenses, thereby demonstrating a lab-scale isotope enrichment process. A significant isotope enrichment for Carbon nanostructures is observed. The isotope enrichment can be attributed to the redistribution of isotope ions in the plasma plume explained by the plasma centrifuge model. The LIIEN synthesized structures exhibit excellent Surface-Enhanced Raman Scattering (SERS) signal enhancement and reproducibility, making them potential candidates for SERS-based biomolecule sensing. This technique is an efficient method to fabricate nanosized isotope-enriched structures of characteristic properties by carefully tuning laser parameters at ambient conditions., (© 2024 Wiley‐VCH GmbH.)

Accurate detection of trace tetracyclines (TCs) in complex matrices is of great significance for food and environmental safety monitoring. However, traditional recognition and amplification tools exhibit poor specificity and sensitivity. Herein, a novel dual-machine linkage nanodevice (DMLD) is proposed for the first time to achieve high-performance analysis of TC, with a padlock aptamer component as the initiation command center, nucleic acid-encoded multispike virus-like Au nanoparticles (nMVANs) as the signal indicator, and cascade walkers circuit as the processor. The existence of spike vertices and interspike nanogaps in MVANs enables intense electromagnetic near-field focusing, allowing distinct surface-enhanced Raman scattering (SERS) activity. Moreover, through the sequential activation between multistage walker catalytic circuits, the DLMD system converts the limited TC recognition into massive engineering assemblies of SERS probes guided by DNA amplicons, resulting in synergistic enhancement of bulk plasmonic hotspot entities. The continuously guaranteed target recognition and progressively promoted signal enhancement ensure highly specific amplification analysis of TC, with a detection limit as low as 7.94 × 10 -16  g mL -1 . Furthermore, the reliable recoveries in real samples confirm the practicability of the proposed sensing platform, highlighting the enormous potential of intelligent nanomachines for analyzing the trace hazards in the environment and food., (© 2024 Wiley‐VCH GmbH.)

The fabrication of a highly controlled gold (Au) nanohole (NH) array via tip-based lithography is improved by incorporating a sacrificial layer-a tip-crash buffer layer. This inclusion mitigates scratches during the nano-indentation process by employing a 300 nm thick poly(methyl methacrylate) layer as a sacrificial layer on top of the Au film. Such a precaution ensures minimal scratches on the Au film, facilitating the creation of sub-50 nm Au NHs with a 15 nm gap between the Au NHs. The precision of this method exceeds that of fabricating Au NHs without a sacrificial layer. Demonstrating its versatility, this Au NH array is utilized in two distinct applications: as a dry etching mask to form a molybdenum disulfide hole array and as a catalyst in metal-assisted chemical etching, resulting in conical-shaped silicon nanostructures. Additionally, a significant electric field is generated when Au nanoparticles (NPs) are placed within the Au NHs. This effect arises from coupling electromagnetic waves, concentrated by the Au NHs and amplified by the Au NPs. A notable result of this configuration is the enhancement factor of surface-enhanced Raman scattering, which is an order of magnitude greater than that observed with just Au NHs and Au NPs alone., (© 2024 Wiley‐VCH GmbH.)

Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive surface analysis technique that is widely used in chemical sensing, bioanalysis, and environmental monitoring. The design of the SERS substrates is crucial for obtaining high-quality SERS signals. Recently, 2D transition metal dichalcogenides (2D TMDs) have emerged as high-performance SERS substrates due to their superior stability, ease of fabrication, biocompatibility, controllable doping, and tunable bandgaps and excitons. In this review, a systematic overview of the latest advancements in 2D TMDs SERS substrates is provided. This review comprehensively summarizes the candidate 2D TMDs SERS materials, elucidates their working principles for SERS, explores the strategies to optimize their SERS performance, and highlights their practical applications. Particularly delved into are the material engineering strategies, including defect engineering, alloy engineering, thickness engineering, and heterojunction engineering. Additionally, the challenges and future prospects associated with the development of 2D TMDs SERS substrates are discussed, outlining potential directions that may lead to significant breakthroughs in practical applications., (© 2024 Wiley‐VCH GmbH.)

Efficient separation, enrichment, and detection of bacteria in diverse media are pivotal for identifying bacterial diseases and their transmission pathways. However, conventional bacterial detection methods that split the separation and detection steps are plagued by prolonged processing times. Herein, a multistage annular functionalized carbon nanotube array device designed for the seamless integration of complex biological sample separation and multimarker detection is introduced. This device resorts to the supersmooth fluidity of the liquid sample in the carbon nanotubes interstice through rotation assistance, achieving the ability to quickly separate impurities and capture biomarkers (1 mL sample cost time of 2.5 s). Fluid dynamics simulations show that the reduction of near-surface hydrodynamic resistance drives the capture of bacteria and related biomarkers on the functionalized surface of carbon nanotube in sufficient time. When further assembled as an even detection device, it exhibited fast detection (<30 min), robust linear correlation (10 1 -10 7 colony-forming units [CFU] mL -1 , R 2 = 0.997), ultrasensitivity (limit of detection = 1.7 CFU mL -1 ), and multitarget detection (Staphylococcus aureus, extracellular vesicles, and enterotoxin proteins). Collectively, the material and system offer an expanded platform for real-time diagnostics, enabling integrated rapid separation and detection of various disease biomarkers., (© 2024 Wiley‐VCH GmbH.)

Early and accurate diagnosis of cystic echinococcosis (CE) with existing technologies is still challenging. Herein, we proposed a novel strategy based on the combination of label-free serum surface-enhanced Raman scattering (SERS) spectroscopy and machine learning for rapid and non-invasive diagnosis of early-stage CE. Specifically, by establishing early- and middle-stage mouse models, the corresponding CE-infected and normal control serum samples were collected, and silver nanoparticles (AgNPs) were utilized as the substrate to obtain SERS spectra. The early- and middle-stage discriminant models were developed using a support vector machine, with diagnostic accuracies of 91.7% and 95.7%, respectively. Furthermore, by analyzing the serum SERS spectra, some biomarkers that may be related to early CE were found, including purine metabolites and protein-related amide bands, which was consistent with other biochemical studies. Thus, our findings indicate that label-free serum SERS analysis is a potential early-stage CE detection method that is promising for clinical translation., (© 2024 Wiley‐VCH GmbH.)

Functional disorders of the thyroid remain a global challenge and have profound impacts on human health. Serving as the barometer for thyroid function, thyroid-stimulating hormone (TSH) is considered the single most useful test of thyroid function. However, the prevailing TSH immunoassays rely on two types of antibodies in a sandwich format. The requirement of repeated incubation and washing further complicates the issue, making it unable to meet the requirements of the shifting public health landscape that demands rapid, sensitive, and low-cost TSH tests. Herein, a systematic study is performed to investigate the clinical translational potential of a single antibody-based biosensing platform for the TSH test. The biosensing platform leverages Raman spectral variations induced by the interaction between a TSH antigen and a Raman molecule-conjugated TSH antibody. In conjunction with machine learning, it allows TSH concentrations in various patient samples to be predicted with high accuracy and precision, which is robust against substrate-to-substrate, intra-substrate, and day-to-day variations. It is envisioned that the simplicity and generalizability of this single-antibody immunoassay coupled with the demonstrated performance in patient samples pave the way for it to be widely applied in clinical settings for low-cost detection of hormones, other molecular biomarkers, DNA, RNA, and pathogens., (© 2023 Wiley-VCH GmbH.)

Rapid and precise acute myocardial infarction (AMI) diagnosis is essential for preventing patient death. In addition, the complementary roles of creatine kinase muscle brain (CK-MB) and cardiac troponin I (cTnI) cardiac biomarkers in the early and late stages of AMI demand their simultaneous detection, which is difficult to implement using conventional fluorescence and electrochemical technologies. Here, a nanotechnology-based one-stop immuno-surface-enhanced Raman scattering (SERS) detection platform is reported for multiple cardiac indicators for the rapid screening and progressive tracing of AMI events. Optimal SERS is achieved using optical property-based, excitation wavelength-optimized, and high-yield anisotropic plasmonic gold nanocubes. Optimal immunoassay reaction efficiencies are achieved by increasing immobilized antibodies. Multiple simultaneous detection strategies are implemented by incorporating two different Raman reports with narrow wavenumbers corresponding to two indicators and by establishing a computational SERS mapping process to accurately detect their concentrations, irrespective of multiple enzymes in the human serum. The SERS platform precisely estimated AMI onset and progressive timing in human serum and made rapid AMI identification feasible using a portable Raman spectrometer. This integrated platform is hypothesized to significantly contribute to emergency medicine and forensic science by providing timely treatment and observation., (© 2023 Wiley-VCH GmbH.)

Green fabrication of superhydrophobic surface by water-based processing is still challenging, because introduction of the substances with hydrophilic moieties compromises its superhydrophobicity. Herein, a plasmon-driven photochemical reduction reaction under ultraviolet light (UVA) irradiation is first discovered and is applied to deoxygenation of hydrophilic organic adsorbates on rough nano-Ag coating for the formation of stable superhydrophobic surface. A nano-Ag coating with strong localized surface plasmon resonance in the UVA region is prepared by a water-based silver mirror reaction and results in a unique chemical reduction reaction on its surface. Consequently, the low residual hydrophilic functionalities and the formed cross-linked structure of the adsorbate on Ag nanoparticles (NPs) enables the coating to exhibit stable superhydrophobicity against to both air and water. The superhydrophobic Ag NP-coated sandpaper can also be used as a surface-enhanced Raman scattering (SERS) substrate to concentrate aqueous analytes for trace detection., (© 2023 Wiley-VCH GmbH.)

Molecular recognition of complex isomeric biomolecules remains challenging in surface-enhanced Raman scattering (SERS) spectroscopy due to their small Raman cross-sections and/or poor surface affinities. To date, the use of molecular probes has achieved excellent molecular sensitivities but still suffers from poor spectral specificity. Here, we induce "charge and geometry complementarity" between probe and analyte as a key strategy to achieve high spectral specificity for effective SERS molecular recognition of structural analogues. We employ 4-mercaptopyridine (MPY) as the probe, and chondroitin sulfate (CS) disaccharides with isomeric sulfation patterns as our proof-of-concept study. Our experimental and in silico studies reveal that "charge and geometry complementarity" between MPY's binding pocket and the CS sulfation patterns drives the formation of site-specific, multidentate interactions at the respective CS isomerism sites, which "locks" each CS in its analogue-specific complex geometry, akin to molecular docking events. Leveraging the resultant spectral fingerprints, we achieve > 97 % classification accuracy for 4 CSs and 5 potential structural interferences, as well as attain multiplex CS quantification with < 3 % prediction error. These insights could enable practical SERS differentiation of biologically important isomers to meet the burgeoning demand for fast-responding applications across various fields such as biodiagnostics, food and environmental surveillance., (© 2023 Wiley-VCH GmbH.)

Nanostructures intrinsically possessing two different structural or functional features, often called Janus nanoparticles, are emerging as a potential material for sensing, catalysis, and biomedical applications. Herein, we report the synthesis of plasmonic gold Janus nanostars (NSs) possessing a smooth concave pentagonal morphology with sharp tips and edges on one side and, contrastingly, a crumbled morphology on the other. The methodology reported herein for their synthesis - a single-step growth reaction - is different from any other Janus nanoparticle preparation involving either template-assisted growth or a masking technique. Interestingly, the coexistence of lower- and higher-index facets was found in these Janus NSs. The general paradigm for synthesizing gold Janus NSs was investigated by understanding the kinetic control mechanism with the combinatorial effect of all the reagents responsible for the structure. The optical properties of the Janus NSs were realized by corelating their extinction spectra with the simulated data. The size-dependent surface-enhanced Raman scattering (SERS) activity of these Janus NSs was studied with 1,4-BDT as the model analyte. Finite-difference time-domain simulations for differently sized particles revealed the distribution of electromagnetic hot-spots over the particles resulting in enhancement of the SERS signal in a size-dependent manner., (© 2023 Wiley-VCH GmbH.)

Surface-enhanced Raman scattering (SERS) is a sensitive and fast technique for sensing applications such as chemical trace analysis. However, a successful, high-throughput practical implementation necessitates the availability of simple-to-use and economical SERS substrates. In this work, we present a robust, reproducible, flexible and yet cost-effective SERS substrate suited for the sensitive detection of analytes at near-infrared (NIR) excitation wavelengths. The fabrication is based on a simple dropcast deposition of silver or gold nanomaterials on an aluminium foil support, making the design suitable for mass production. The fabricated SERS substrates can withstand very high average Raman laser power of up to 400 mW in the NIR wavelength range while maintaining a linear signal response of the analyte. This enables a combined high signal enhancement potential provided by (i) the field enhancement via the localized surface plasmon resonance introduced by the noble metal nanomaterials and (ii) additional enhancement proportional to an increase of the applicable Raman laser power without causing the thermal decomposition of the analyte. The application of the SERS substrates for the trace detection of melamine and rhodamine 6G is demonstrated, which shows limits of detection smaller than 0.1 ppm and analytical enhancement factors on the order of 10 4 as compared to bare aluminium foil., Competing Interests: There are no conflicts of interest to declare., (© 2023 The Authors. Analytical Science Advances published by Wiley‐VCH GmbH.)

Semiconductors demonstrate great potentials as chemical mechanism-based surface-enhanced Raman scattering (SERS) substrates in determination of biological species in complex living systems with high selectivity. However, low sensitivity is the bottleneck for their practical applications, compared with that of noble metal-based Raman enhancement ascribed to electromagnetic mechanism. Herein, a novel Cu 2 O nanoarray with free carrier density of 1.78×10 21  cm -3 comparable to that of noble metals was self-assembled, creating a record in enhancement factor (EF) of 3.19×10 10 among semiconductor substrates. The significant EF was mainly attributed to plasmon-induced hot electron transfer (PIHET) in semiconductor which was never reported before. This Cu 2 O nanoarray was subsequently developed as a highly sensitive and selective SERS chip for non-enzyme and amplification-free SARS-CoV-2 RNA quantification with a detection limit down to 60 copies/mL within 5 min. This unique Cu 2 O nanoarray demonstrated the significant Raman enhancement through PIHET process, enabling rapid and sensitive point-of-care testing of emerging virus variants., (© 2023 Wiley-VCH GmbH.)

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., (© 2023 Wiley-VCH Verlag GmbH.)

Non-invasive detection and precise localization of deep lesions have attracted significant attention for both fundamental and clinical studies. Optical modality techniques are promising with high sensitivity and molecular specificity, but are limited by shallow tissue penetration and the failure to accurately determine lesion depth. Here the authors report in vivo ratiometric surface-enhanced transmission Raman spectroscopy (SETRS) for non-invasive localization and perioperative surgery navigation of deep sentinel lymph nodes in live rats. The SETRS system uses ultrabright surface-enhanced Raman spectroscopy (SERS) nanoparticles with a low detection limit of 10 pM and a home-built photosafe transmission Raman spectroscopy setup. The ratiometric SETRS strategy is proposed based on the ratio of multiple Raman spectral peaks for obtaining lesion depth. Via this strategy, the depth of the phantom lesions in ex vivo rat tissues is precisely determined with a mean-absolute-percentage-error of 11.8%, and the accurate localization of a 6-mm-deep rat popliteal lymph node is achieved. The feasibility of ratiometric SETRS allows the successful perioperative navigation of in vivo lymph node biopsy surgery in live rats under clinically safe laser irradiance. This study represents a significant step toward the clinical translation of TRS techniques, providing new insights for the design and implementation of in vivo SERS applications., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The Fabry-Perot (FP) resonator is an intuitive and versatile optical structure owing to its uniqueness in light-matter interactions, yielding resonance with a wide range of wavelengths as it couples with photonic materials encapsulated in a dielectric cavity. Leveraging the FP resonator for molecular detection, a simple geometry of the metal-dielectric-metal structure is demonstrated to allow tuning of the enhancement factors (EFs) of surface-enhanced Raman scattering (SERS). The optimum near-field EF from randomly dispersed gold nano-gaps and dynamic modulation of the far-field SERS EF by varying the optical resonance of the FP etalon are systematically investigated by performing computational and experimental analyses. The proposed strategy of combining plasmonic nanostructures with FP etalons clearly reveals wavelength matching of FP resonance to excitation and scattering wavelengths plays a key role in determining the magnitude of the SERS EF. Finally, the optimum near-field generating optical structure with controlled dielectric cavity is suggested for a tunable SERS platform, and its dynamic SERS switching performance is confirmed by demonstrating information encryption through liquid immersion., (© 2023 Wiley-VCH GmbH.)

Metal nanostructures with a tunable plasmonic gap are useful for photonics, surface-enhanced spectroscopy, biosensing, and bioimaging applications. The use of these structures as chemical and biological sensing/imaging probes typically requires an ultra-precise synthesis of the targeted nanostructure in a high yield, with Raman dye-labeling and complex assay components and procedures. Here, a plasmonic nanostructure with tunable dual nanogaps, Au dual-gap nanodumbbells (AuDGNs), is designed and synthesized via the anisotropic adsorption of polyethyleneimine on Au nanorods to facilitate tip-selective Au growths on nanorod tips for forming mushroom-shaped dumbbell-head structures at both tips and results in dual gaps (intra-head and inter-head gaps) within a single particle. AuDGNs are synthesized in a high yield (>90%) while controlling the inter-head gap size, and the average surface-enhanced Raman scattering (SERS) enhancement factor (EF) value is 7.5 × 10 8 with a very narrow EF distribution from 1.5 × 10 8 to 1.5 × 10 9 for >90% of analyzed particles. Importantly, AuDGNs enable label-free on-particle SERS detection assays through the diffusion of target molecules into the intraparticle gap for different DNA sequences with varying ATGC combinations in a highly specific and sensitive manner without a need for Raman dyes., (© 2023 Wiley-VCH GmbH.)

Non-metallic materials have emerged as a new family of active substrates for surface-enhanced Raman scattering (SERS), with unique advantages over their metal counterparts. However, owing to their inefficient interaction with the incident wavelength, the Raman enhancement achieved with non-metallic materials is considerably lower with respect to the metallic ones. Herein, we propose colourful semiconductor-based SERS substrates for the first time by utilizing a Fabry-Pérot cavity, which realize a large freedom in manipulating light. Owing to the delicate adjustment of the absorption in terms of both frequency and intensity, resonant absorption can be achieved with a variety of non-metal SERS substrates, with the sensitivity further enhanced by ≈100 times. As a typical example, by introducing a Fabry-Pérot-type substrate fabricated with SiO 2 /Si, a rather low detection limit of 10 -16  M for the SARS-CoV-2S protein is achieved on SnS 2 . This study provides a realistic strategy for increasing SERS sensitivity when semiconductors are employed as SERS substrates., (© 2023 Wiley-VCH GmbH.)

Surface-enhanced Raman scattering (SERS) is a feasible and ultra-sensitive method for biomedical imaging and disease diagnosis. SERS is widely applied to in vivo imaging due to the development of functional nanoparticles encoded by Raman active molecules (SERS nanoprobes) and improvements in instruments. Herein, the recent developments in SERS active materials and their in vivo imaging and biosensing applications are overviewed. Various SERS substrates that have been successfully used for in vivo imaging are described. Then, the applications of SERS imaging in cancer detection and in vivo intraoperative guidance are summarized. The role of highly sensitive SERS biosensors in guiding the detection and prevention of diseases is discussed in detail. Moreover, its role in the identification and resection of microtumors and as a diagnostic and therapeutic platform is also reviewed. Finally, the progress and challenges associated with SERS active materials, equipment, and clinical translation are described. The present evidence suggests that SERS could be applied in clinical practice in the future., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Surface-enhanced Raman scattering (SERS), as a rapid and nondestructive biological detection method, holds great promise for clinical on spot and early diagnosis. In order to address the challenging demands of on spot detection of biomedical samples, a variety of strategies has been developed. These strategies include substrate structural and component engineering, data processing techniques, as well as combination with other analytical methods. This report summarizes the recent SERS developments for biomedical detection, and their promising applications in cancer detection, virus or bacterial infection detection, miscarriage spotting, neurological disease screening et al. The first part discusses the frequently used SERS substrate component and structures, the second part reports on the detection strategies for nucleic acids, proteins, bacteria, and virus, the third part summarizes their promising applications in clinical detection in a variety of illnesses, and the forth part reports on recent development of SERS in combination with other analytical techniques. The special merits, challenges, and perspectives are discussed in both introduction and conclusion sections., (© 2022 Wiley-VCH GmbH.)

The identification of blood species is of great significance in many aspects such as forensic science, wildlife protection, and customs security and quarantine. Conventional Raman spectroscopy combined with chemometrics is an established method for identification of blood species. However, the Raman spectrum of trace amount of blood could hardly be obtained due to the very small cross-section of Raman scattering. In order to overcome this limitation, surface-enhanced Raman scattering (SERS) was adopted to analyze trace amount of blood. The 785 nm laser was selected as the optimal laser to acquire the SERS spectra, and the blood SERS spectra of 19 species were measured. The convolutional neural network (CNN) was used to distinguish the blood of 19 species including human. The recognition accuracy of the blood species was obtained with 98.79%. Our study provides an effective and reliable method for identification and classification of trace amount of blood., (© 2022 Wiley-VCH GmbH.)

Accurate identification of malignant lung lesions is a prerequisite for rational clinical management to reduce morbidity and mortality of lung cancer. However, classification of lung nodules into malignant and benign cases is difficult as they show similar features in computer tomography and sometimes positron emission tomography imaging, making invasive tissue biopsies necessary. To address the challenges in evaluating indeterminate nodules, the authors investigate the molecular profiles of small extracellular vesicles (sEVs) in differentiating malignant and benign lung nodules via a liquid biopsy-based approach. Aiming to characterize phenotypes between malignant and benign groups, they develop a single-molecule-resolution-digital-sEV-counting-detection (DECODE) chip that interrogates three lung-cancer-associated sEV biomarkers and a generic sEV biomarker to create sEV molecular profiles. DECODE capturessEVs on a nanostructured pillar chip, confines individual sEVs, and profiles sEV biomarker expression through surface-enhanced Raman scattering barcodes. The author utilize DECODE to generate a digitally acquired sEV molecular profiles in a cohort of 33 people, including patients with malignant and benign lung nodules, and healthy individuals. Significantly, DECODE reveals sEV-specific molecular profiles that allow the separation of malignant from benign (area under the curve, AUC = 0.85), which is promising for non-invasive characterisation of lung nodules found in lung cancer screening and warrants further clinincal validaiton with larger cohorts., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Highly branched gold (Au) nanostructures with sharp tips are considered excellent substrates for surface-enhanced Raman scattering (SERS)-based sensing technologies. Here, a simple synthetic route for producing Au or Au-Ag bimetallic mesostructures with multiple sharpened tips in the presence of carbon quantum dots (CQDs) is presented. The morphologies of these mesostructured plasmonic nanoparticles (MSPNs) can be controlled by adjusting the concentration of CQDs, reaction temperatures, and seed particles. The optimal molar ratio for [HAuCl 4 ]/[CQDs] is found to be ≈25. At this molar ratio, the diameters of MSPNs can be tuned from 80 to 200 nm by changing the reaction temperature from 25 to 80 °C. In addition, it is found that hierarchical MSPNs consisting of multiple Au nanocrystals can be formed over the entire seed particle surface. Finally, the SERS activity of these MSPNs is examined through the detection of rhodamine 6G and methylene blue. Of the different mesostructures, the bimetallic MSPNs have the highest sensitivity with the ability to detect 10 -7  m of rhodamine 6G and 10 -6  m of methylene blue. The properties of these MSPN particles, made using a novel synthetic process, make them excellent candidates for SERS-based chemical sensing applications., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

The surface-enhanced Raman scattering (SERS) technique with ultrahigh sensitivity has gained attention to meet the increasing demands for food safety analysis. The integration of machine learning and SERS facilitates the practical applicability of sensing devices. In this study, a machine learning-driven 3D plasmonic cavity-in-cavity (CIC) SERS platform is proposed for sensitive and quantitative detection of antibiotics. The platform is prepared by transferring truncated concave nanocubes (NCs) to an obconical-shaped template surface. Owing to the triple synergistic enhancement effect, the highly ordered 3D CIC arrays improve the simulated electromagnetic field intensity and experimental SERS activity, demonstrating a 33.1-fold enhancement compared to a typical system consisting of Au NCs deposited on a flat substrate. The integration of machine learning and Raman spectroscopy eliminates subjective judgments on the concentration of detectors using a single feature peak and achieves accurate identification. The machine learning-driven CIC SERS platform is capable of detecting ampicillin traces in milk with a detection limit of 0.1 ppm, facilitating quantitative analysis of different concentrations of ampicillin. Therefore, the proposed platform has potential applications in food safety monitoring, health care, and environmental sampling., (© 2022 Wiley-VCH GmbH.)

Stimulated surface-enhanced Raman scattering (SERS) in combination with engineered nano-tracer offers extraordinary potential in lateral flow immunoassays (LFIAs). Nonetheless, the investigation execution of SERS-LFIA is often compromised by the intricacy and overlap of the Raman fingerprint spectrum as well as the affinity-interference of nano-tracer to antibody. To circumvent these critical issues, an engineered core-shell multifunctional nano-tracer (named APNPs) with precise control of the size of nano-core (AuNPs) and coating of the nano-shell (Prussian blue nanomaterials) is prepared for SERS-LFIA via a modified enlarging particle size and coating modification strategy. Importantly, this nano-tracer exhibits enhanced coupling efficiency, highly retained affinity, reinforced colloid stability, and unique SERS signal (2156 cm -1 ) in the silent region (1800-2800 cm -1 ) with high signal-to-background ratio simultaneously, all of which are beneficial to the enhancement of the analysis performance. With a proof-of-concept demonstration for detection of ractopamine (RAC), a dual-pattern LFIA that synergizes both the enlarged particle size and coating modification supported colorimetric/biological silence Raman dual-response (coined as the ECCRD assay) is demonstrated by integrating APNPs with the competitive-type immunoreaction. This research may contribute to the rational design of multifunctional nano-tracer, and the ECCRD assay can be expanded for a wide spectrum of applications in environmental monitoring and biomedical diagnosis., (© 2022 Wiley-VCH GmbH.)

While immunoassays are pivotal to medical diagnosis and bioanalytical chemistry, the current landscape of public health has catalyzed an important shift in the requirements of immunoassays that demand innovative solutions. For example, rapid, label-free, and low-cost screening of a given analyte is required to inform the best countermeasures to combat infectious diseases in a timely manner. Yet, the current design of immunoassays cannot accommodate such requirements as constraint by accumulative challenges, such as repeated incubation and washing, and the need of two types of antibodies in the sandwich format. To provide a potential solution, herein, a plasmonic Raman immunoassay with single-antibody, multivariate regression, and shift-of-peak strategies, coined as the PRISM assay, for serum biomarkers detection, is reported. The PRISM assay relies on Raman reporter-antibody conjugates to capture analytes on a plasmonic substrate. The ensuing nanomechanical perturbations to vibration of Raman reporters induce subtle but characteristic spectral changes that encode rich information related to the captured analytes. By fusing Raman spectroscopy and chemometric analysis, both Raman frequency shift- and multivariate regression models for sensitive detection of biomarkers are developed. The PRISM assay is expected to find a wide range of applications in clinical diagnosis, food safety surveillance, and environmental monitoring., (© 2022 Wiley-VCH GmbH.)

Gas-phase surface-enhanced Raman scattering (SERS) remains challenging due to poor analyte affinity to SERS substrates. The reported use of capturing probes suffers from concurrent inconsistent signals and long response time due to the formation of multiple potential probe-analyte interaction orientations. Here, we demonstrate the use of multiple non-covalent interactions for ring complexation to boost the affinity of small gas molecules, SO 2 and NO 2 , to our SERS platform, achieving rapid capture and multiplex detection down to 100 ppm. Experimental and in-silico studies affirm stable ring complex formation, and kinetic investigations reveal a 4-fold faster response time compared to probes without stable ring complexation capability. By synergizing spectral concatenation and support vector machine regression, we achieve 91.7 % accuracy for multiplex quantification of SO 2 and NO 2 in excess CO 2 , mimicking real-life exhausts. Our platform shows immense potential for on-site exhaust and air quality surveillance., (© 2022 Wiley-VCH GmbH.)