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Materials Chemistry Frontiers · 2025 · IF 6.4

Spatiotemporal Identification of Therapeutic Markers via Dual-targeted SERS Bioprobes During Breast Cancer Progression

Xinyu Miao,Xiawei Xu,Li Sun,Xiaoxia Wu,Aochi Liu,Pan Fu,Pengtao Chen,Yujiao Xie,Jiabao Guo,Zhiwei Hou,Dong Xu,Aiguo Wu,Jie Lin

The precise breast cancer treatment heavily relies on the accurate identification of therapeutic markers. Single surface-enhanced Raman spectroscopy (SERS) bioprobes have been demonstrated for tumor primary screening. However, single biomarker detection is insufficient due to tumor heterogeneity and drug resistance with cancer progression. In this study, we have developed a dual-targeted SERS sensing platform using IO NPs@AR@PDA@aPD-L1 and Au NPs@4-MBA@PDA@aHER2 bioprobes for simultaneous detection of dual therapeutic markers (PD-L1 and HER2) in breast cancer, achieving single-cell resolution imaging with a detection limit of 2 cells/mL. Specifically, by digitizing SERS spectra using machine learning, the dual-targeted strategy improved spatial resolution and effectively distinguished the heterogeneous expression of HER2 and PD-L1 in SK-BR-3, MCF-7, and MDA-MB-231 cell lines, improving detection accuracy by ~20% compared to single-marker methods. In the temporal dimension, transforming growth factor-β (TGF-β) was used to induce epithelial-mesenchymal transition (EMT) in MCF-7, simulating the highly invasive and metastatic characteristics of advanced tumors, thereby enabling dynamic monitoring of cancer progression from locally advanced to metastatic disease. This continuous monitoring capability of the dual-targeted strategy offers critical insights into tumor evolution, metastasis risk assessment, and recurrence prediction, thereby playing a vital role in guiding precision cancer management and treatment adaptation.

研究领域: 肿瘤学 · 纳米生物技术 · 分子成像 · 精准医学 · 生物医学工程
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ANALYTICAL CHEMISTRY · 2025 · IF 6.7

Target-Responsive Lanthanide Coordination Nanoparticles for Time-Resolved Photoluminescence and SERS Dual-Mode Biosensing

Bing Qi,Zhao Qi,Lingling Qiu,Chenjie Zhang,Jiayi Chen,Yurong Wei,Jie Wang,Minmin Xu

Lanthanide coordination nanoparticles (Ln-CNPs) have shown significant potential in optical biosensing. However, the conventional self-assembly of lanthanides and ligands generally produces large cross-linked coordination networks with uncontrollable morphologies and poor dispersibility. In this work, we developed a facile coordination-driven self-assembly strategy for preparing Ln-CNPs with tunable properties, demonstrating their exceptional utility in the dual-mode time-resolved photoluminescence (TRPL)/surface-enhanced Raman spectroscopy (SERS) detection of analytes in complex matrices. Specifically, a series of Ln-CNPs were prepared by the coordination-driven self-assembly of adenosine diphosphate (ADP) with Ln3+. The resulting Ln-CNPs exhibited a controllable morphology, excellent monodispersity, long-lived luminescence, and other functionalities. Notably, the luminescence of ADP-Eu and ADP-Tb CNPs remained detectable even at a delay time of 1 ms, making them ideal for TRPL biosensing; while ADP-Gd CNPs showed potential for magnetic resonance imaging. As a proof-of-concept for optical biosensing applications, we engineered a TRPL/SERS dual-mode platform leveraging the specific response of ADP-Eu CNPs to tetracycline (TC). TC binding to ADP-Eu CNPs induced up to 13-fold TRPL enhancement through the antenna effect, while unbound TC molecules enabled 10–9 M-level SERS detection via plasmonic coupling. Quantitative cross-verification between TRPL and SERS significantly enhanced the determination accuracy. This dual-mode platform achieved 97.64–108.90% recoveries for TC detection in serum samples with <3.2% RSD. Our methodology establishes a generalizable paradigm for engineering multifunctional Ln-CNPs and further opens exciting avenues for the accurate detection of analytes in complex biological systems.

研究领域: 材料科学 · 光学生物传感 · 纳米技术 · 分析化学 · 配位化学
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Journal of Pharmaceutical Analysis · 2025 · IF 8.9

SERS detection of osteoarthritis-linked microRNA-204 via a DNAzyme-catalyzed self-amplifying circuit

Zhe Ni,Xingshi Yuan,Zhengliang Luo,Xiaoqi Zhang,Min Chen,Lee Jia,Jie Wang,Xifu Shang

Sensitive detection of microRNA-204 (miR-204) is critical for the early diagnosis and management of osteoarthritis (OA). This work presents a novel surface-enhanced Raman scattering (SERS) biosensor for the ultrasensitive and specific detection of OA-associated miR-204. The platform integrates a self-amplifying nucleic acid circuit with DNAzyme-catalyzed etching of a plasmonic nanoprobe. At its core is a single, rationally designed overhang-containing hairpin probe (O-HP) that functions as both the recognition element and amplification initiator. Upon binding to miR-204, the O-HP triggers polymerase-mediated extension, generating G-quadruplex structures. These structures bind hemin to form DNAzymes that catalyze the localized production of reactive oxygen species (ROS), which subsequently etch the silver shell of the AuNS/Ag@4-ATP SERS nanoprobe. This etching causes the desorption of Raman reporters and a quantifiable 'signal-off' response. This biosensor achieves a remarkably low detection limit of 8.13 fM with a broad dynamic range from 10 fM to 150 nM, and exhibits high specificity, capable of discriminating single-nucleotide variants. Furthermore, it successfully quantified miR-204 in clinical cartilage samples, showing a strong correlation with real-time quantitative polymerase chain reaction results. The modular design of the O-HP also facilitated the adaptation of the platform for detecting miR-21, demonstrating its generalizability. This work provides a robust and versatile biosensing strategy with significant potential for clinical miRNA diagnostics.

CAS / MDL: 16961-25-4
研究领域: 生物传感器 · 分子诊断 · 纳米生物技术 · 微小RNA检测 · 即时检测
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MICROCHIMICA ACTA · 2025 ·Vol. 192 ·期 10 ·1-11 · IF 5.3

Magnetic nanoparticle SERS sensor for rapid and selective detection of ClO− in drinking water

Wang Liu,Wang Mingli

A selective detection strategy is  proposed for the determination of residual hypochlorite in drinking water. Flower-like Fe 3 O 4 @SiO 2 @Ag magnetic nanoparticles can aggregate on a silver film-coated magnetic substrate surface under a magnetic field, enabling the separation and enrichment of the analyte from the sample. 4-Mercaptophenol is functionalized on magnetic nanoparticles enabling quantitative detection of ClO − through a “signal off” mechanism. This substrate exhibits high sensitivity, with an analytical enhancement factor calculated using Rhodamine B (RhB) as an example reaching 1.89 × 10 5 , and a detection limit for ClO − as low as 0.0125 mg/L. The substrate also demonstrates good uniformity, reproducibility, and selectivity. Detection in actual drinking water samples indicates the potential application of this detection strategy in food safety. Graphical

CAS / MDL: 5949-29-1
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

High-Stability Defect Engineering in MOFs via Chemical Induction for Advanced SERS Substrate Preparation

Xiaoyang Fan,Chao Qu,Ziqian Shi,Jun Tian,Chaoyue Wei,Longyun Lin,Tingting You,Yukun Gao,Penggang Yin

Induced vacancy defects have been strategically employed to enhance the performance of semiconductor substrates for surface-enhanced Raman scattering (SERS) applications such as chemical sensing and biosensing. However, maintaining these induced vacancy defects over prolonged use remains a significant challenge, as they tend to rapidly self-heal when exposed to air. In this study, we demonstrate that chemically induced oxygen vacancy (CIVO) defects can stabilize defect sites in the metal–organic framework (MOF) SERS substrate. Due to steric hindrance and the coordination environment surrounding the CIVO defects, these vacancies remain stable in atmospheric conditions for 100 days, in stark contrast to the short-lived photoinduced defects in conventional metal oxide semiconductors, which typically persist for only a few minutes. More significantly, the CIVO defect MOF substrates present a 3 orders of magnitude detection limit lower than the pristine MOF. Practical applications were tested by the CIVO defect MOF substrates, in which rhodamine 6G and p-aminoazobenzene molecules can be sensitively and quantitatively detected. This strategy of chemically induced stable oxygen vacancy defects exhibits broad applicability and is expected to further enhance the performance of MOF-based SERS substrates.

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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

Flexible SERS substrate based on active nanoparticle enrichment for ultra-trace in situ detection

Shaoshuai Han,Yangyang Yu,Di Lian,Xin Yang,Ning Li,Tangcheng Huang,Shaojing Duan,Meijing Du,Jun Ren,Zhenlin Wu

Surface-enhanced Raman spectroscopy (SERS) has emerged as a powerful technique for applications in food safety testing, environmental monitoring, disease diagnosis, and molecular characterization. However, conventional SERS substrates frequently suffer from limited sensitivity, poor signal uniformity, and dependence on skilled operators. In this study, a flexible and high-performance SERS sensing strategy is proposed, which is based on surface acoustic wave (SAW)-induced clustering of 50 nm gold nanoparticles (AuNPs). When a 5 μ L AuNP colloidal droplet is dispensed onto the SAW propagation region, acoustic streaming drives the aggregation of nanoparticles. Upon complete evaporation of the droplet, densely packed SERS-active hotspots are formed, enabling strong Raman signal enhancement. By optimizing the thickness of the PDMS flexible film and the input power, the resulting Raman substrate exhibits minimum detectable concentration reaching 10 −13   M for rhodamine 6G (R6G), 10 −10   M for 4-aminothiophenol (4-ATP), and 10 −11   M for crystal violet (CV)—as well as excellent reproducibility. The relative standard deviation (RSD) for CV detection decreased from 45.32% (SAW-free) to 3.59% under SAW-assisted enrichment, confirming the significant improvement in signal uniformity. Finally, the flexible SAW-SERS sensor demonstrates a sensitivity of up to 10 −8   M for detecting Thiram residues on apple surfaces. This flexible SAW-assisted SERS substrate offers a promising strategy for portable, efficient, and reliable environmental and food safety monitoring.

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BIOSENSORS & BIOELECTRONICS · 2025 · IF 10.5

PlasmoBridge: Stable hotspot engineering and targeted Surface-enhanced Raman spectroscopy (SERS) monitoring of methotrexate

Wen Cao,Guangyao Huang,Yue Fang,Jingyuan Shao,Sensen Hao,Ying Wang,Tinfei Tan,Zhenxing Li,Mancun Zhao,Liujie Hou,Junping Wang,Hongzhi Wang

Surface-enhanced Raman spectroscopy (SERS) offers unique molecular fingerprinting capability and enhanced sensitivity. However, the application of SERS in therapeutic drug monitoring (TDM) is limited due to the occurrence of unstable plasmonic hotspots, poor reproducibility, and the lack of molecular specificity. In this study, we present “PlasmoBridge”, a dual-function aptamer–nanoparticle assembly that bridges adjacent silver nanoparticles with thiolated methotrexate (MTX) aptamers. This design generates uniform nanogaps (∼6.5 nm) that enable stable and reproducible hotspot formation while selectively enriching MTX molecules in the electromagnetic field. Consequently, PlasmoBridge achieves ultrasensitive MTX detection (10 −8  M) with relative standard deviations below 10 % and the requisite linearity across clinically relevant concentration ranges. Integrating liquid–liquid and solid-phase extraction delivers recoveries in serum that exceed 90 %. Convolutional neural network–assisted spectral analysis serves to further enhance quantitative accuracy (R 2  > 0.99). In a preclinical osteosarcoma model, PlasmoBridge-guided TDM preserved antitumor efficacy while reducing systemic toxicity via optimized dosing. When compared with enzyme-multiplied immunoassay technique (EMIT) and liquid chromatography-tandem mass spectrometry (LC–MS/MS) procedures, PlasmoBridge uniquely balances sensitivity, speed, and clinical practicality, enabling near-real-time and point-of-care monitoring. Moreover, this generalizable biosensing framework, combining nanoscale engineering, molecular recognition, and AI-driven quantification, offers a promising route to precision pharmacotherapy of a range of small-molecule drugs.

CAS / MDL: 548-62-9 75-09-2
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Plasmonics · 2025 · IF 4.3

PDA-MMT/Au@Ag SERS Substrate for Ultrasensitive Thiram Detection and Multiplex Pesticide Screening

Guo Jingtong,Ma Xiaodi,Song Wenjing,Yu Long

This study develops a novel, eco-friendly Surface Enhanced Raman Scattering (SERS) substrate, PDA-MMT/Au@Ag NPs, for ultrasensitive thiram (TRM) detection and pesticide screening. The substrate integrates polydopamine-functionalized montmorillonite (PDA-MMT) with Au@Ag core–shell nanoparticles synthesized via solvent-free photoreduction. MMT enriches analytes and prevents nanoparticle aggregation, while Au@Ag NPs generate high-density plasmonic hotspots. This dual synergy enables exceptional performance: a TRM detection limit of 1.34 × 10⁻⁹ M in solution (far below the FDA limit), with high uniformity (RSD = 9.54%) and stability (> 28 days). The substrate also demonstrates versatility for dyes (R6G, CV, NBA) and other pesticides. Optimization confirmed 30 min UV irradiation and a 1:10 MMT-to-Au@Ag volume ratio as ideal parameters. Characterization by TEM, XRD, XPS, and UV–vis validated the successful synthesis and core–shell structure. Compared to existing SERS platforms, this substrate offers superior sensitivity, reduced noble metal usage, and simpler, chemical-reductant-free fabrication, making it promising for on-site food safety and environmental monitoring.

CAS / MDL: 12108-13-3
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JOURNAL OF HAZARDOUS MATERIALS · 2020 · IF 9.038

A nanozyme-based enhanced system for total removal of organic mercury and SERS sensing

Hao Liu,Yue Guo,Yunxin Wang,Huidan Zhang,Xiaowei Ma,Sisi Wen,Jing Jin,Wei Song,Bing Zhao,Yukihiro Ozaki

Total removal of organic mercury in industrial wastewater is a crucially important task facing environmental pollution in the current world. Herein, we demonstrate the fabrication of Au-NiFe layered double hydroxide (LDH)/rGO nanocomposite as not only an efficient nanozyme with oxidase-like activity but also an efficient surface-enhanced Raman spectroscopy (SERS) substrate to determine organic mercury, with the minimum detection concentration as low as 1 × 10 −8 M. According to the binding energy of X-Ray photoelectron spectrometer (XPS) and the free radicals of electron paramagnetic resonance (EPR) spectra, the mechanism of catalytic enhanced degradation is the production of Au-amalgam on Au surface, accelerating the electron transfer and the generation of O 2 •– radicals from oxygen molecules and •CH 3 radicals from the methyl group in MeHg to participate the oxidase-like reaction. Furthermore, the Au-NiFe LDH/rGO nanocomposite is able to degrade and remove 99.9% of organic mercury in two hours without the secondary pollution by Hg 2+ . In addition, the material can be used for the multiple degradation-regeneration cycles in actual applications, which is significant in terms of the environmental and economic point of view. This work may open a new horizon for both highly sensitive detection and thorough degradation of organic mercury in environmental science and technology .

研究领域: 环境科学与技术 · 纳米生物学 · 分析化学
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APPLIED SURFACE SCIENCE · 2022 · IF 7.392

Interface synthesis of MoS2@ZnO@Ag SERS substrate for the ultrasensitive determination of bilirubin

Yingnan Quan,Jia Li,Mingyue Hu,Maobin Wei,Jinghai Yang,Ming Gao,Yang Liu

A highly sensitive strategy is urgently needed to detect potential cancer biomarkers present at trace levels in the early stages of the disease. Here we report a surface-enhanced Raman spectroscopy (SERS) biosensor that combines enrichment capabilities, MoS 2 @ZnO@Ag, for the ultrasensitive detection of free bilirubin in serum, and was likely to be used for accurate diagnosis of related diseases. The substrate is evolved from the reported MoS 2 @ZnO with Ag nanoparticles attached to it, which integrates the advantages of low cost, simple pretreatment and high sensitivity, and can accurately and quantitatively analyze actual bilirubin samples. The sensing efficiency is evaluated by bilirubin with the detection limit of 10 -8 M. Main emphasis focuses on using MoS 2 @ZnO@Ag SERS substrate to detect the free bilirubin in serum. This substrate exhibits ultrahigh sensitivity in sensing bilirubin in human blood. In this study, the MoS 2 @ZnO@Ag provides a new biosensing technology for the detection of free bilirubin, which is expected to be applied to clinical diagnosis.

研究领域: 生物医学工程 · 分析化学 · 临床诊断
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MICROCHIMICA ACTA · 2025 ·Vol. 192 ·期 6 ·1-11 · IF 5.3

Ag@Au nanoparticle solid arrays for enhanced SERS detection of enrofloxacin: FDTD simulation insights

Cheng Yuliang,Zhao Yajie,Li Peizhen,Yu Hang,Xie Yunfei,Guo Yahui,Yao Weirong,Qian He

As one of the most extensively used antibiotics in aquaculture in China, enrofloxacin (ENR) tends to accumulate in human body and endanger people’s health. Rapid, sensitive, and facile assays for enrofloxacin are urgently needed. In this study, based on the solid-phase substrate preparation strategy combined with microsphere etching and magnetron sputtering, Ag@Au nanoparticle (Ag@Au NP) solid array (Ag@Au NSA) with high surface-enhanced Raman spectroscopy (SERS) enhancement factor (EF≈8.3 × 10 7 ) was developed. Finite-difference time-domain (FDTD) simulations revealed that the Ag@Au NSA achieved maximum electromagnetic enhancement (EM) under the following optimized conditions: 633 nm excitation wavelength, 7.9 nm Au shell thickness, and 30.5 nm Ag core size. Additionally, SERS mapping results confirmed both the excellent enhancement performance and signal reproducibility of Ag@Au NSA, due to the expected micro-region enhancement with long-term effects accompanied by a larger range of high-density “hot spots.” The proposed SERS sensing for ENR based on Ag@Au NSA had a limit of detection (LOD) of 0.076 ng/mL ( R 2 ≈ 0. 9991) and was further applied to real-sample detection of ENR in crayfish tail meat with good recoveries ranging from 91.36 to 112.60%, indicating its great potential in practice. Graphical

研究领域: 分析化学 · 食品安全 · 纳米技术
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MICROCHIMICA ACTA · 2026 ·Vol. 193 ·期 3 ·128 · IF 5.4

Immunochromatographic SERS sensor-deep learning combined strategy for intelligent diagnosis of chronic kidney disease

Yu Zengshan,Zhang Zhibin,Guo Shan,Li Zelong,Chen Hao,Gai Jichuan,Wei Jiyuan,Xu Shiqi,Wang Mingli,Shi Guochao

A combined “immunochromatographic surface-enhanced Raman scattering (SERS) sensor–deep learning” detection strategy is proposed. Specifically, we first prepared an immunochromatographic SERS sensor with excellent surface enhancement capability for the specific recognition of neutrophil gelatinase-associated lipocalin (NGAL) molecules in serum, significantly enhancing the detection sensitivity of the target molecule. Subsequently, we integrated deep learning algorithms to perform preprocessing, feature extraction, and pattern recognition analysis on complex SERS spectral signals, overcoming the limitations of traditional algorithms in handling high-dimensional nonlinear data. This approach enables rapid, sensitive, and highly specific detection of NGAL. The platform achieves a detection limit as low as 0.1059 ng/mL with a broad linear detection range. For clinical validation, serum samples from 14 volunteers were analyzed. Six deep learning models were employed to classify the acquired clinical spectral data, with the Residual Network (ResNet) model achieving a classification accuracy of 98.81%, a loss value of only 0.0877, and an area under the receiver operating characteristic curve (AUC) of 99.97%. In addition, in the analysis of new samples, the classification and prediction of data from patients and normal individuals were successfully achieved. The proposed “immunoassay surface-enhanced Raman scattering sensor - deep learning” combined detection strategy has demonstrated extraordinary potential in the rapid, sensitive and specific detection of NGAL, providing crucial technical support for the intelligent discrimination of chronic kidney disease. Graphical

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