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BIOORGANIC CHEMISTRY · 2025 · IF 4.7

Dual-responsive SERS nanoprobe for real-time imaging of pH and ROS dynamics in wound healing

Hanbin Deng,Shanyu Yang,Huwen Wu,Han Zhou,Peishen Zhang,Shaowen Cheng,Fabiao Yu,Rui Wang

In the complex process of wound healing, real-time and dynamic monitoring of key indicators such as pH and reactive oxygen species (ROS) in the microenvironment can effectively evaluate the inflammatory status and therapeutic effect of the wound. In this study, a dual-responsive surface-enhanced Raman scattering (SERS) probe was developed, which could simultaneously detect the changes of pH and ROS levels during the wound healing process. The gold–silver core–shell nanoparticles (Au@Ag NPs) were utilized as the active substrate, and 4-mercaptobenzoic acid (4-MBA) and 2,5-dihydroxythiophenol (DHBT) were modified as Raman reporter molecules, which were further coated with polyethylene glycol and bovine serum albumin to improve the biocompatibility and stability. In the Raman spectra, the peak of DHBT at 876 cm −1 was used to indicate the ROS level, while the intensity ratio at 1360 and 1075 cm −1 (I 1360 /I 1075 ) of 4-MBA reflected the pH change. The SERS probe exhibited good ratiometric response characteristics, high selectivity, and low cytotoxicity. In vitro SERS imaging experiments demonstrated that the probe could dynamically monitor ROS generation and pH changes, while SERS imaging in the mouse wound model further confirmed its ability to monitor pH and ROS in the wound microenvironment in vivo. Histological analysis also verified its biosafety. In summary, the dual-responsive SERS probe designed in this study has potential application value in evaluating wound healing effects and provides a new approach for monitoring the wound microenvironment.

CAS / MDL: 1074-36-8 9004-74-4
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2025 · IF 4.6

Liquid-liquid interfacial self-assembly of ordered CuS@cu core-shell heterostructure for synergistic SERS enhancement

Yi Zhong,Jie Li,Pei Xu,Yantao Lou,Xingchen Zhang,Haibing Ji,Yuanjie Teng

Semiconductors offer advantages as surface-enhanced Raman scattering (SERS) substrates, including high stability and low cost. However, their intrinsic plasmonic resonance is inherently weak due to bandgap limitations, where valence electrons can only be excited to the conduction band under specific conditions. Consequently, their SERS enhancement mechanism primarily relies on charge transfer processes at the material-molecule interface, resulting in enhancement factors typically 1–3 orders of magnitude lower than those of conventional noble metal substrates (e.g., Au, Ag). To address this limitation, this study proposes a semiconductor-metal heterojunction synergistic enhancement strategy. A SERS substrate was designed by constructing a core-shell heterostructure of CuS and metallic Cu (CuS@Cu), aiming to combine efficient charge transfer with strong electromagnetic field enhancement. The results demonstrate that the synthesized CuS@Cu core-shell heterojunction exhibits significantly enhanced Raman activity. The optimization of SERS performance were systematically investigated by tuning precursor concentrations (e.g., CuS colloidal concentration, CuSO₄ concentration). Utilizing a liquid-liquid interfacial self-assembly technique, with n-butyl acetate as the oil phase and an aqueous colloidal dispersion of CuS@Cu nanoparticles as the aqueous phase, large-area, ordered CuS@Cu core-shell heterojunction films were fabricated. Leveraging a selective interfacial CT mechanism between the CuS semiconductor and probe molecules (e.g., Rhodamine B (RhB), Methylene Blue (MB), Malachite Green (MG)), this substrate enables specific enhancement of their SERS signals (EF ∼ 10 5 for RhB). Quantitative limits of detection reached 1 × 10 −7  mol/L, 3.16 × 10 −7  mol/L, and 3.16 × 10 −6  mol/L for RhB, MB, and MG, respectively. Also, the substrate exhibits high reproducibility and homogeneous SERS response (RSD < 4.5 %), ensuring reliable and robust sensing performance. The combination of the controllable liquid-liquid interfacial self-assembly and the heterojunction enhancement effect highlights the significant potential of this substrate for application in portable SERS sensing devices.

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BIOSENSORS & BIOELECTRONICS · 2025 · IF 10.5

Multicolor SERS-Encoded Immuno-cocktail for Longitudinal Precise Tracking of CTCs Phenotypes in Lung Cancer Therapeutics

Min Fan,Zongyang Yu,Kan Luo,Ping Chen,Duo Lin,Yating Lin,Xueliang Lin,Jingbo Chen,Shangyuan Feng

Tumor heterogeneity and drug resistance remain major obstacles to the implementation of personalized therapeutic strategies in lung cancer. Circulating tumor cell (CTC)-based liquid biopsy provides a powerful, minimally invasive tool for tracking dynamic changes in tumor heterogeneity and elucidating mechanisms of treatment response and drug resistance. Herein, we present a portable, field-deployable surface-enhanced Raman scattering (SERS) immunoprobe platform capable of multiplexed detection of CTC membrane biomarkers to monitor tumor heterogeneity throughout the course of therapy. Utilizing a cocktail of multicolor-encoded immunoprobes, the platform achieves single-cell phenotypic resolution via antigen-specific spectral fingerprinting, validated by flow cytometry. It demonstrates ultra-sensitive CTC quantification (limit of detection of 1.7 cells/mL) and precise molecular subtyping across four cell lines (HCC827, A549, BEAS-2B, and HeLa). Integrated with orthogonal partial least squares discriminant analysis (OPLS-DA), the platform accurately distinguishes clinically relevant cell types with 99% classification accuracy, successfully stratifying metastatic versus non-metastatic lung cancer ( n = 24) and capturing treatment-driven CTC evolution in longitudinal studies ( n = 7). Our results highlight a transformative strategy for real-time interception of drug resistance trajectories, positioning dynamic CTC phenotyping as a critical tool for adaptive therapy and prognostic assessment in precision oncology.

CAS / MDL: 16961-25-4 50-81-7
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Nanoscale · 2021 ·Vol. 13 ·期 31 ·13344-13352 · IF 7.79

Ultrasensitive SERS detection of exhaled biomarkers of lung cancer using a multifunctional solid phase extraction membrane

Yi Huang,Tianhua Xie,Kun Zou,Yingqiu Gu,Guohai Yang,Fanli Zhang,Lu-Lu Qu,Shikuan Yang

The construction and clinical application of a surface-enhanced Raman scattering (SERS) platform for the early diagnosis of lung cancer could improve the survival rate of patients and would be of great significance. Nevertheless, a sensitive and reusable method for the detection of aldehydes, as biomarkers of lung cancer, in exhaled breath is still an enormous challenge. Aldehydes generally have a low cross section in Raman scattering and have a weak specific affinity to plasmonic nanoparticle surfaces, meaning that sensing them at low concentrations is incredibly difficult. Herein, an ultrasensitive SERS strategy, that can be recycled for further use, for the detection of lung cancer biomarkers in the form of aldehydes was realized by fabrication of a multifunctional Ag NPs@ZIF-67/g-C3N4 solid phase extraction (SPE) membrane. Based on the change in the vibrational fingerprints of 4-ATP before and after reaction with the aldehydes, the SPE membrane was successfully used for the ultrasensitive detection of aldehydes with a detection limit of 1.35 nM. The excellent SERS performance was attributed to the synergistic effect of the densely and closely distributed Ag NPs (providing SERS “hot spots”), ZIF-67 (concentrating the analyte molecules) and g-C3N4 (forming a membrane to prolong the contact time between the aldehydes and the substrate). In addition, recycling of the SPE membrane was achieved by utilizing the self-cleaning ability of the Ag NPs@ZIF-67/g-C3N4 membrane originating from the photocatalytic properties of g-C3N4. The proposed SERS membrane was easy to operate, rapid and portable, thus providing a potential tool for a point-of-care test in clinical and diagnostic practice.

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Materials Research Express · 2020 ·Vol. 7 ·期 9 ·095012 · IF 1.929

Preparation of Ag@PDA@SiO2 electrospinning nanofibrous membranes for direct bacteria SERS detection and antimicrobial activities

Menghui Wan,Haodong Zhao,Zhihua Wang,Yanbao Zhao,Lei Sun

In this paper, a convenient method to fabricate flexible and free-standing surface-enhanced Raman scatting (SERS) substrates for direct bacteria detection without aptamer bonding is presented. SiO2 nanofibers were prepared via electrospinning and calcination by using tetraethyl orthosilicate as the precursor. Subsequently, it was coated with polydopamine (PDA) by self-polymerization. Finally, Ag@PDA@SiO2 nanofibrous membranes were obtained through in situ growth of Ag nanoparticles in Tollens' reagents. The as-prepared Ag@PDA@SiO2 composite nanofibrous membranes were characterized by techniques of scanning electron microscopy, transmission electron microscopy, X-ray powder diffraction, energy-dispersive x-ray spectroscopy and thermo gravimetric analysis. The flexibility of the as-prepared nanofibrous membranes were verified simply through manual folding. Small molecule probes of 4-mercaptophenol (4-MPh) and 4-mercaptobenzoic acid (4-MBA) were chosen to investigate the SERS sensitivity of the as-prepared Ag@PDA@SiO2 as free-standing substrates. Furthermore, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), as typical strains of Gram-negative and Gram-positive bacteria, were performed to directly SERS detection by dropping bacteria suspension onto the fibrous membranes without any previous treatment, such as aptamer combination. In addition, the antimicrobial properties of the as-prepared Ag@PDA@SiO2 electrospinning nanofibrous membranes were tested by inhibition zone and turbidity methods. The results show that Ag nanoparticles with an average diameter of 50 nm are uniformly deposited on the surface of electrospinning nanofibers, and the as-prepared Ag@PDA@SiO2 nanofibrous membranes are flexible. As SERS substrates, it shows a rather high detection limitation of 10−11 mol l−1 for 4-MPh and 4-MBA. More importantly, this substrate can be applied for bacteria label-free SERS detection, i.e., complicated procedures are avoided. Meanwihile, the as-prepared Ag@PDA@SiO2 nanofibrous membranes exhibit excellent antibacterial properties. Thus, it has application prospects in trace bacteria detection and water purification.

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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2023 · IF 4.4

Preparation of 3D nano silver trees/sea urchin-like gold and SERS detection of uric acid

Xin Lin,Li-Jun Li,He-Yuan-Xi Guo,Rui Li,Jun Feng

In this paper, 3D nano-silver trees/sea urchin-like gold Surface Enhanced Raman Spectroscopy (SERS) substrates were prepared by chemical reduction method, characterized by SEM, EDS, UV–Vis and XRD et.al, and the preparation process was optimized using Rhodamine B (RB) as the Raman signal molecule. The SERS characteristics of Uric Acid on this substrate were investigated and the results showed that the SERS substrate had a Raman enhancement factor of 1.9 × 10 7 for RB, and also had a significant Raman enhancement effect on Uric Acid. The SERS intensity ( I SERS ) at 1400 cm −1 showed a good linear relationship with the logarithm value of uric acid concentration (log C ) between the range of 5 × 10 −4 M to 1 × 10 −7 M. The linear fitting equation was I SERS  = 890 (log C ) + 8066 (R 2  = 0.983), and the LOD = 2.8 × 10 − 8 M. The spiked test was performed in human serum with recoveries ranging from 82.86% to 125.13% and RSD (n = 3) < 3.5%.

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APPLIED SURFACE SCIENCE · 2020 · IF 6.182

Integrated accurate extraction and fast detection of analyte: Capillarity-Based SERS substrate using in effluent monitoring

Chundong Liu,Fengcai Lei,Jia Li,Yisheng Wei,Zhen Li,Chao Zhang,Baoyuan Man,Jing Yu

In order to realize integration of directional extraction and Raman detection for analytes in effluent, a capillarity-based surface-enhanced Raman spectroscopy (SERS) structure of CuO@Ag nanocapillaries (NCs) has been designed and prepared in this paper. Benefitting from the capillaries formed inside the CuO@Ag NC, probe molecules can be spontaneously transferred and concentrated from the CuO@Ag NC bottom to the top. Further processed with infrared irradiation, the CuO@Ag NC changes from amphiphilic state to hydrophobic-oleophilic state, which can accurately extract molecules that dissolved in oil-phase liquid from the mixed oil/water solution. Numerical simulations by finite-difference time domain method illustrate theoretically that the CuO@Ag NC top is also the position where the strongest electric flied located in this structure, demonstrating the integration feasibility of high-efficient extraction, enrichment and detection in one structure. Experimentally, the enhancement factor and relative standard deviation for R6G molecule of this structure are 1.67 × 10 11 and 15.7% respectively, with other Raman properties also showing remarkable performance. In the simulated wastewater detection test, this structure realizes the fast recognition of trace Sudan I dyes (10 -7 M) in the mixed hexane/water solution composed of both target analyte Sudan I and interferent molecule rhodamine 6G, indicating its promising prospect using in effluent monitoring.

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CARBOHYDRATE POLYMERS · 2018 · IF 5.158

Jellylike flexible nanocellulose SERS substrate for rapid in-situ non-invasive pesticide detection in fruits/vegetables

Jie Chen,Meizhen Huang,Lili Kong,Mengshi Lin

This study aimed to develop a jellylike flexible substrate based on nanocellulose decorated with Ag nanoparticles (Ag/NC substrate) and explore its applications for rapid in-situ pesticide detections in fruits and vegetables by surface-enhanced Raman spectroscopy (SERS). The performances of Ag/NC substrate were characterized by rhodamine 6G (R6G). The limit of detection recorded by a portable Raman spectrometer is 10 −8 M. The substrate still exhibited satisfactory sensitivity after 60-day preservation. Jellylike and slightly sticky Ag/NC substrate demonstrated good adaptabilities in attaching to sample surfaces and is suitable for in-situ SERS detection. Two types of pesticides on apple peels and cabbages were detected by rapid in-situ and non-invasive SERS method coupled with Ag/NC substrate. The lowest detectable level was 0.5 ng/cm 2 for thiram and 5 ng/cm 2 for thiabendazole, which were well below the maximum residue levels. These results demonstrate that Ag/NC substrate is sensitive for rapid in-situ multi-pesticide detection in food.

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NANOTECHNOLOGY · 2022 ·Vol. 33 ·期 13 ·135501 · IF 3.953

Nanoscale engineering of ring-mounted nanostructure around AAO nanopores for highly sensitive and reliable SERS substrates

Jun Dong,Yan Wang,Qianying Wang,Yi Cao,Qingyan Han,Wei Gao,Yongkai Wang,Jianxia Qi,Mengtao Sun

Surface-enhanced Raman scattering (SERS) is recognized as one of the most favored techniques for enhancing Raman signals. The morphology of the SERS substrate profoundly affects molecular Raman spectra. This study aimed to construct a ring-mounted nanostructured substrate via liquid–liquid two-phase self-assembly incorporated with anodic aluminum oxide (AAO) membrane transfer techniques. High-density nanoparticles (NPs) assembled on AAO membranes were ascribed to reduce the diameters of the nanopores, with Au–Ag alloy NPs to regulate the dielectric constant so as to reveal the local surface plasmon resonance tunability. SERS engineered in this way allowed for the fabrication of a ring-mounted nanostructured substrate where the distribution density of NPs and dielectric constant could be independently fine-tuned. High SERS activity of the substrate was revealed by detecting the enhanced factor of crystal violet and rhodamine 6G molecules, which was up to 1.56 × 106. Moreover, SERS of thiram target molecules confirmed the supersensitivity and repeatability of the substrate as a practical application. The results of this study manifested a low-cost but high-efficiency ring-mounted nanostructured SERS substrate that might be suitable in many fields, including biosensing, medical research, environmental monitoring, and optoelectronics.

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RSC Advances · 2015 ·Vol. 5 ·期 84 ·68668-68675 · IF 3.84

Hydrothermal synthesis of gold polyhedral nanocrystals by varying surfactant concentration and their LSPR and SERS properties

Yanting Liu,Jun Zhou,Xiaocong Yuan,Tao Jiang,Lucia Petti,Lu Zhou,Pasquale Mormile

Several polyhedral gold nanocrystals (Au NCs) whose geometric morphology belongs to the Platonic solid and Archimedean solid groups are synthesized by modulating the cetyltrimethylammonium bromide (CTAB) concentration in the designed hydrothermal processes. The mechanism of growth of these polyhedral Au NCs is revealed via crystallographic analyses, which suggest that their morphologies mainly depend on the diminishing of the surface energy of the specific facets in the CTAB-directive shape-control process. Furthermore, the localized surface plasmon resonance (LSPR) properties of the as-prepared polyhedral Au NCs are numerically assessed using the finite element method (FEM). The calculations show that these polyhedral Au NCs exhibit geometry-dependence plasmonic properties: specifically, the enormous local field enhancements occur around their vertices and corners. The SERS spectra of 4-mercaptobenzoic acid molecules adsorbed on these polyhedral Au NCs display superior SERS activity with an enhancement factor of 105 to 106 at the excitation wavelength of 785 nm. Particularly, the truncated tetrahedron and bitetrahedron show higher SERS enhancement factors due to their LSPR being closer to the excitation wavelength of 785 nm. Thus, the facile surfactant-assisted synthesis offers the opportunity to design and optimize the shape-dependent SERS activity of polyhedral Au NCs with respect to possible applications in bio-sensing and imaging.

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CRYSTENGCOMM · 2016 ·Vol. 18 ·期 40 ·7805-7813 · IF 3.849

Controlled assembly of one-dimensional MoO3@Au hybrid nanostructures as SERS substrates for sensitive melamine detection

Xiu Liang,Xiao-Juan Zhang,Ting-Ting You,Guang-Sheng Wang,Peng-Gang Yin,Lin Guo

A new, feasible, and highly efficient platform was developed using self-assembly of (3-aminopropyl) diethoxymethylsilane (ATES) to create metallic oxide-based noble metal nanoparticle hybrid materials. The ex situ approach for fabricating 1D MoO3-nanowires (MoO3-NWs) or ZnO-nanorods (ZnO-NRs) @Au-nanoparticles (Au-NPs) hybrid surface-enhanced Raman scattering (SERS) substrates not only provides a simple route for the decoration of noble metal nanoparticle on metallic oxide nanomaterials, but also realizes the controllable assembly/co-assembly of pre-synthesized nanoparticles with distinctively different sizes, compositions, shapes, and properties. Control over the self-assembly synthesis for morphology and SERS activity was demonstrated by several parameters: (i) coupling agent of ATES, (ii) ATES content, (iii) Au-NPs content, (iv) Au-NP sizes, and (v) other metallic oxide such as ZnO-NRs. The finite difference time domain (FDTD) method was employed to visualize the enhancement mechanism distribution of the hybrid substrate. Furthermore, the optimized MoO3-NW@Au-NPs SERS substrate manifests high SERS sensitivity to melamine with a limit of detection (LOD) of 0.1 ppb (0.08 nM) and excellent uniformity (RSD = 9.26%). The LOD was much lower than the maximal residue limit (MRL) of 2.5 ppm in food prescribed by the US Food and Drug Administration (FDA).

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MICROCHIMICA ACTA · 2023 ·Vol. 191 ·期 1 ·1-10 · IF 5.7

Self-assembly flexible SERS imprinted membrane based on Ag nanocubes for selective detection of microcystin-LR

Wang Zedong,Zhang Liang,Sun Lian,Bao Siqi,Liu Dajun,Li Hongji,Liu Yuming

Silver nanocubes monolayer-modified polydimethylsiloxane (Ag NC/PDMS) flexible SERS substrates have been prepared by a three-phase interface self-assembly procedure. The combination of this method with membrane technology brings nanoparticles in close proximity, densely, and regularly arranged in monolayers over a large area, leading to excellent SERS properties. Considering the complexity of practical detection, molecular imprinted polymers (MIPs) were anchored on the surface of SERS substrate and applied to selective detection of microcystin-LR (MC-LR). It is worth mentioning that the SERS imprinted membranes (AP-MIMs) were still clearly detected at a concentration of 0.1 µg·L −1 of MC-LR in drinking water, and the detection limit was as low as 0.0067 µg·L −1 . The substrate exhibited excellent uniformity with a relative standard deviation (RSD) of 6.1%. In the presence of interference molecules, AP-MIMs exhibited excellent selectivity for MC-LR. Furthermore, in the spiking and recovery tests of practical lake water samples, the method showed excellent recoveries ranging from 96.47 to 105.31%. It has been demonstrated that the prepared AP-MIMs can be applied to sensitive and specific detection of trace amounts of MC-LR in drinking water. Graphical

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