Sensors and Actuators Reports
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2024
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IF 6.5
Song Ge,Mingxin Wang,Shunhua Zhu,Han Wu,Jing Li,Dongsheng Liu,Qingli Huang,Shibao Li,Xiaojing Sun
Purpose As an important reference index for the early diagnosis of non-small cell lung cancer (NSCLC), CYFRA21-1 still lacks the detection of low equipment cost, wide linear range and high sensitivity. Surface-enhanced Raman scattering (SERS) is a vibration spectrum technology based on the surface plasma of precious metal nanoparticles, which has been effectively applied to the detection of tumor markers. The combination of SERS technology and sensors has great potential in the ultrasensitive detection of tumor markers. The purpose of this study was to develop a sensitive method using SERS to quantitatively detect CYFRA21-1 for early diagnosis of NSCLC. Methods A double-antibody sandwich immunoassay based on SERS was designed and tested to implement the ultrasensitive detection of CYFRA21-1 in the serum of NSCLC patients. Results Gold @Ag nanorods (Au @Ag NRs) with higher Raman signals were prepared and used as probes, while magnetic graphene oxide was used as a magnetic substrate. The immunized probe, immune substrate and CYFRA21-1 standard substance in the buffer system formed a double-antibody sandwich structure. The standard curve displayed a liner range from 1pg mL −1 to 10 ng mL −1 , and the detection limit (LOD) is 0.8943pg mL −1 . The Raman intensity exhibited a wide linear relationship with the logarithm of CYFRA21-1 concentration. Conclusion Our study successfully established a double-antibody sandwich immunoassay based on SERS. This method demonstrated high specificity and sensitivity for detecting CYFRA21-1 protein content in serum. It has the potential to be applied for early detection of lung cancer biomarkers.
研究领域:
肿瘤学
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医学诊断
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纳米技术
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DOI
高影响因子
Journal of Materials Chemistry B
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2022
·Vol. 10
·期 9
·1386-1392
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IF 7.571
Ling Yang,Ping’an Ma,Xiaorui Chen,Ziyong Cheng,Jun Lin
Sensitive detection of circulating tumor DNA (ctDNA) in vitro has attracted growing attention owing to its potential application in diagnostics of cancer. In this study, we synthesized hydrophilic AgInS2@ZnS core–shell quantum dot nanocrystals and magnetic Fe3O4 nanoparticles, and then the ctDNA triggered hybridization chain reaction was used to detect the CYFRA21-1 DNA associated with lung cancer. In the presence of CYFRA21-1 DNA, three hairpin structures were activated to turn on successively, resulting in the accumulation of quantum dots and eliciting considerable changes of the fluorescence signal. Compared with the conventional fluorescence detection, Fe3O4 provides magnetic adsorption properties and a large surface area for immobilizing and aggregating quantum dot nanoparticles attached to single-stranded DNA. The concentration of CYFRA21-1 is closely related to the number of quantum dots remaining after magnetic adsorption, which provides a promising approach for ctDNA quantification.
研究领域:
生物化学
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分子诊断
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纳米医学
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DOI
PubMed
高影响因子
Analytical Methods
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2020
·Vol. 12
·期 22
·2827-2834
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IF 2.596
Kai Hu,Jiamin Cheng,Jinge Li,Shan Ye,Huaixia Yang,Yanju Liu,Jinming Kong
The sensitive detection of biomarker cytokeratin fragment antigen 21-1 (CYFRA21-1) is crucial for early diagnosis and screening of non-small cell lung cancer (NSCLC). In this work, an electrochemical biosensor based on Nafion-initiated eATRP has been built for ultrasensitive detection of CYFRA21-1 DNA for the first time. Specifically, peptide nucleic acid (PNA) probes are immobilized onto a gold electrode surface and then hybridized with target DNA to form PNA/DNA heteroduplexes for the subsequent attachment of Nafion by the identified carboxyl–Zr4+–phosphoric acid chemistry. Finally, polymer chains are obtained by linking the monomer of ferrocenylmethyl methacrylate to the PNA/MCH/DNA/Zr4+/Nafion probes via eATRP. Under optimized steady-state conditions, the sensor offers a wide current response for CYFRA21-1 DNA from 10−11 to 10−16 M with a detection limit of 6.42 × 10−17 M. The proposed method of using Nafion as the eATRP initiator exhibits high sensitivity, reproducibility and stability and is a promising strategy for early diagnosis of NSCLC.
研究领域:
癌症诊断
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生物化学
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电化学
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分子生物学
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PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2020
·Vol. 412
·期 17
·4155-4163
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IF 3.637
Li Jinge,Zhao Liying,Wen Dongxiao,Li Xiaofei,Yang Huaixia,Wang Dazhong,Kong Jinming
In this work, a new method of CYFRA21-1 DNA (tDNA) detection based on electrochemically mediated atom transfer radical polymerization (e-ATRP) and surface-initiated reversible addition-fragmentation chain transfer polymerization (SI-RAFT) cascade polymerization and AgNP deposition is proposed. Firstly, the peptide nucleic acid (PNA) probe is captured on a gold electrode by Au-S bonds for specific recognition of tDNA. After hybridization, PNA/DNA strands provide high-density phosphate groups for the subsequent ATRP initiator by the identified carboxylate-Zr 4+ -phosphate chemistry. Then, a large number of monomers are successfully grafted from the DNA through the e-ATRP reaction. After that, the chain transfer agent of SI-RAFT and methacrylic acid (MAA) are connected by recognized carboxylate-Zr 4+ -carboxylate chemistry. Subsequently, through SI-RAFT, the resulting polymer introduces numerous aldehyde groups, which could deposit many AgNPs on tDNA through silver mirror reaction, causing significant amplification of the electrochemical signal. Under optimal conditions, this designed method exhibits a low detection limit of 0.487 aM. Moreover, the method enables us to detect DNA at the level of PCR-like and shows high selectivity and strong anti-interference ability in the presence of serum. It suggests that this new sensing signal amplification technology exhibits excellent potential of application in the early diagnosis of non-small cell lung cancer (NSCLC).
Electrochemical detection principle for CYFRA21-1 DNA based on e-ATRP and SI-RAFT signal amplification technology.
研究领域:
生物化学
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分析化学
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癌症诊断
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纳米技术
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产品关联
DOI
PubMed
高影响因子
BIOELECTROCHEMISTRY
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2017
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IF 3.346
Yan Zeng,Jing Bao,Yanan Zhao,Danqun Huo,Mei Chen,Yanli Qi,Mei Yang,Huanbao Fa,Changjun Hou
Many studies confirm that the aberrant expression of Cytokeratin 19 fragment 21-1 (CYFRA21-1) is highly correlated with non-small cell lung cancer (NSCLC), especially for squamous cell carcinoma. Herein, we report a sandwich-type electrochemical immunosensor based on signal amplification strategy of multiple nanocomposites to test CYFRA21-1 selectively and sensitively. The proposed immunosensor fabricated by three-dimensional graphene (3D–G), chitosan (CS) and glutaraldehyde (GA) composite on the glass carbon electrode (GCE) with a large surface area is prepared to immobilize primary antibodies (Ab 1 ) and provide excellent conductivity . To further amplify the electrochemical signal, the trace tag on the foundation of gold nanoparticles (AuNPs) is coated with amino-functionalized carbon nanotube (MWCNT-NH 2 ) nanocomposite through thionine linking, which provides more amino groups to capture more horseradish peroxidase-labeled antibodies (HPR-Ab 2 ) and enhances the conductivity. Under optimal conditions, the developed immunosensor exhibits excellent analytical performance for the determination of CYFRA21-1 with a wide linear range from 0.1 to 150 ng·mL − 1 and a low detection limit (LOD) of 43 pg·mL − 1 . Furthermore, satisfactory results are obtained for the determination of CYFRA21-1 in real clinical serum samples, indicating the potential of the immunoassay to be applied in clinical analysis.
研究领域:
生物标志物检测
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电化学
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纳米技术
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癌症诊断
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2021
·Vol. 414
·期 3
·1389-1402
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IF 4.157
Lv Xiaoyi,Bi Mengmeng,Xu Xiaoyun,Li Yanping,Geng Chao,Cui Bo,Fang Yishan
Aggregation-induced electrochemiluminescence reagent, a distyrylbenzene derivative with donor–acceptor conjugated nanosheet structure, namely TPAPCN, was used as a trace label and modified on the electrode through the formation of classical sandwich complex of antibody-antigen–antibody in this work. In aggregate state, TPAPCN with twisted structure was limited in nanometer space through intermolecular π − π stacking interactions, which not only restricts the intramolecular motions but also combines a large number of singlet excitons to greatly trigger electrochemiluminescence (ECL). The ECL signal of this system enhanced with more captured cytokeratin 19 fragment 21–1 (CYFRA21-1) on the modified electrode. Three-dimensional graphene/platinum nanoparticles with large specific surface, and excellent electroconductivity and biocompatibility were prepared and acted as excellent carriers for thionine handling (3D-GN/PtNPs/Th), which was employed for improving the loading of antibodies and generating internal electrochemical signal. Consequently, a novel ratiometric sandwich immunosensor for CYFRA21-1 detection was fabricated based on TPAPCN and 3D-GN/PtNPs/Th, that is, a rapid and reliable detection was achieved through the ratio between ECL and electrochemical signals. The prepared sensor performed good linearity in the range of 50 fg/mL to 1 ng/mL with a detection limit as low as 16 fg/mL. Moreover, the detection results revealed well in the analysis of human serum samples, demonstrating a significant application for clinical monitoring and biomolecules detection. Graphical abstract
研究领域:
分析化学
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生物化学
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纳米技术
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生物传感器
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PubMed
高影响因子
MICROCHIMICA ACTA
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2019
·Vol. 186
·期 12
·1-8
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IF 5.479
Meng Xiangying,Chen Xiao,Wu Weihua,Zheng Wei,Deng Haohua,Xu Luyao,Chen Wei,Li Zhulai,Peng Huaping
Molybdenum oxide quantum dots (MoO x QDs) were synthesized by a one-pot method and used as a versatile probe in an electrochemiluminescent (ECL) immunoassay of the non-small cell lung cancer biomarker cytokeratin 19 fragment 21–1 (CYFRA21-1) as a model analyte. The MoO x QDs exhibited stable and strong cathodic green ECL, with an emission peak at 535 nm, in the presence of K 2 S 2 O 8 within the potential range of −2.0 to 0 V. On exposure to CYFRA21-1, the ECL decreases because of the immunoreaction between CYFRA21-1 and its antibody which generates a barrier for electron transfer. The determination of CYFRA21-1 with favorable analytical performances was successfully realized under the optimal conditions. ECL decreases linearly in the 1 pg mL −1 to 350 ng mL −1 CYFRA21-1 concentration range, and the detection is as low as 0.3 pg mL −1 . Excellent recoveries from CYFRA21-1-spiked human serum indicate that the assay can be operated under physiological conditions.
Schematic representation of the fabrication of molybdenum oxide quantum dots (MoO x QDs) and the electrochemiluminescent (ECL) immunoassay based on the use of the MoO x QDs ECL probe for cytokeratin 19 fragment 21–1 (CYFRA21-1).
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PubMed
高影响因子
ANALYST
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2026
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IF 3.6
Xiaojing Zhang,Hongyang Guo,Li Sin Wong,Hangming Xiong,Liubing Kong,Li Zhang,Yanjie Hu,Yong Zhou,Hao Wan,Ping Wang
Decentralized biomarker testing is pivotal for cancer screening, risk evaluation, and longitudinal surveillance, yet most established assays remain laboratory-centric that are not suitable for point-of-care testing (POCT). Saliva has attracted extensive attentions owing to its redundant bioinformation, non-invasive collection and easy sampling for disease screening. Herein, we developed a highly sensitive Love-wave surface acoustic wave (Love-SAW) immunosensor for the quantification of Cyfra21-1 in saliva, a clinically established cytokeratin-19 fragment widely used in epithelial cancer management, and advanced it toward a chip-scale sensing platform that can be readily integrated into portable POCT devices. The immunosensor employs a sandwich immunoassay, with signal amplification by gold nanoparticle–labeled antibodies. The sensing interface is engineered via cysteamine self-assembly on gold through Au–S coupling, followed by glutaraldehyde activation to enable covalent immobilization of the Cyfra21-1 coating antibody. Cyfra21-1 was measured in both PBS and artificial saliva samples, with a total assay time of approximately 20 min per sample. The Love-SAW immunosensor provided a dynamic detection range of 7.81–62.5 ng/mL and a limit of detection of 4.9 ng/mL for Cyfra21-1 detection in PBS, and demonstrated matrix-tolerant detection in spiked artificial saliva (15.62–125 ng/mL, LOD: 13.9 ng/mL). Quantification in spiked artificial saliva agreed well with ELISA, yielding good recoveries of 82.36%–106.60%. These results demonstrate that the gold-enhanced Love-SAW immunosensor enables highly sensitive, rapid and portable quantification of salivary biomarkers, providing a promising foundation for the development of compact and non-invasive POCT systems for disease screening.
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PubMed
高影响因子
Experimental and Therapeutic Medicine
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2023
·Vol. 25
·期 2
·1-10
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IF 2.7
Qing Chen,Shaojin Zhu,Nanlin Jiao,Ziyu Zhang,Guangjian Gao,Wenqiang Zheng,Gang Feng,Wenzheng Han
The early diagnosis of lung cancer is closely associated with the decline of mortality. A panel consisting of seven lung cancer‑related autoantibodies (7‑AABs) has been shown to be a reliable and specific indicator for the early detection of lung cancer, with a specificity of ~90% and a positive predictive value of ~85%. However, its low sensitivity and negative predictive value limit its wide application. To improve its diagnostic value, the diagnostic efficiencies of 7‑AABs in combination with non‑specific tumor markers were retrospectively investigated for the detection of early‑stage lung cancer. A total of 217 patients with small lung nodules who presented with ground‑glass opacity or solid nodules as well as 30 healthy controls were studied. The concentrations of 7‑AABs and heat shock protein 90a (HSP90a) were assessed using ELISA. Automated flow fluorescence immune analysis was used for the assessment of CEA, CYFRA21‑1, CA199 and CA125 levels. The results showed that 7‑AABs + HSP90a possessed a remarkably improved diagnostic efficiency for patients with small pulmonary nodules or for patients with lung nodules of different types, which suggested that 7‑AABs in combination with HSP90a could have a high clinical value for the improvement of the diagnostic efficiency of early‑stage lung cancer.
研究领域:
肿瘤学
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医学诊断学
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免疫学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2026
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IF 5.2
Fengjun Lv,Jinyi Chen,Shengxi Wu,Ran Sun,Lu Zhang,Yawen Luo,Hao Zhang,Doudou Xu
This study developed a stable, label-free AuNPs/Fe-MOFs/COOH-GO electrochemical immunosensor for the detection of Cytokeratin 19 fragment (CYFRA21-1), a critical biomarker for the early screening and diagnosis of non-small cell lung cancer (NSCLC). The nanocomposites of AuNPs/Fe-MOFs/COOH-GO was synthesized using a combination of hydrothermal synthesis, chemical reduction, and ultrasonic dispersion. AuNPs and COOH-GO components contributed high conductivity and a large specific surface area, which significantly enhanced the sensitivity of the sensor. The three-dimensional mesoporous structure of the Fe-MOFs further improved the stability of the immunosensor. Firstly, our novel nanocomposites was modified by using a glassy carbon electrode (GCE). CYFRA21-1 antibodies were then immobilized on the modified surface via interactions with thiol and carboxyl groups present on the nanomaterial. Bovine serum albumin (BSA) was employed to block non-specific binding sites. The constructed immunosensor exhibited a wide detection range for CYFRA21-1 from 1 pg mL −1 to 100,000 pg mL −1 , with a correlation coefficient (R 2 ) of 0.9989 in differential pulse voltammetry, and the limit of detection was defined as 0.35 pg mL −1 . The sensor also demonstrated high sensitivity, excellent specificity, good reproducibility, and remarkable stability, indicating its potent application potential for the early screening and diagnosis of NSCLC.
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DOI
高影响因子
Biosensors-Basel
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2022
·Vol. 12
·期 7
·435
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IF 5.743
Cui Fan,Bingyan Jiang,Wenjia Shi,Dan Chen,Mingyong Zhou
Current methods for the early diagnosis of cancer can be invasive and costly. In recent years, exosomes have been recognized as potential biomarkers for cancer diagnostics. The common methods for quantitative detection of exosomes, such as nanoparticle tracking analysis (NTA) and flow cytometry, rely on large-scale instruments and complex operation, with results not specific for cancer. Herein, we present a tri-channel electrochemical immunobiosensor for enzyme-free and label-free detecting carcino-embryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragments (Cyfra21-1) from exosomes for specific early diagnosis of lung cancer. The electrochemical immunobiosensor showed good selectivity and stability. Under optimum experimental conditions, the linear ranges were from 10−3to 10 ng/mL for CEA, 10−4to 102ng/mL for NSE, and 10−3to 102ng/mL for Cyfra21-1, and a detection limit down to 10−4ng/mL was achieved. Furthermore, we performed exosome analysis in three kinds of lung cancer. The results showed a distinct expression level of exosomal markers in different types. These works provide insight into a promising alternative for the quantification of exosomal markers in specific diseases in the following clinical bioassays.Keywords:electrochemical immunobiosensor;exosome detection;multiple biomarkers;lung cancer
研究领域:
生物医学工程
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癌症诊断
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电化学
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生物标志物分析
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DOI
PubMed
高影响因子
TALANTA
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2024
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IF 5.6
Ruifang Liu,Hang Song,Hao Wu,Zhihao Yang,Surong Fang,Jing Zhu,Long Ba
Lung cancer is the main cancer that endangers human life worldwide, with the highest mortality rate. The detection of lung tumor markers is of great significance for the early diagnosis and subsequent treatment of lung cancer. In this study, a vertical graphene field effect transistor (VGFET) immunosensor based on graphene/C 60 heterojunction was created to offer quantitative detections for the lung tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), and neuron-specific enolase (NSE). The experimental results showed that the sensitive range for standard antigen is between 1 pg/ml to 100 ng/ml, with a limit of detection (LOD) of 5.6 amol/ml for CEA, 33.3 amol/ml for Cyfra 21–1 and 12.8 amol/ml for NSE (1 pg/ml for all). The detection accuracy for these tumor markers was compared with the clinically used method for clinical patients on serum samples. Results are highly consistent with clinically used immunoassay in its efficient diagnosis concentration range. Subsequently, the mesoporous silica nanospheres (MSNs) with an average size of 90 nm were surface modified with glutaraldehyde, and a second antibody was assembled on MSNs, which fixes nanospheres on the antigen and amplified the field effect. The LODs for three markers are 100 fg/ml (0.56 amol/ml for CEA) under optimal circumstances of detection. This result indicates that specific binding to MSNs enhances local field effects and can achieve higher sensing efficiency for tumor marker detection at extremely low concentrations, providing effective assistance for the early diagnosis of lung cancer.
研究领域:
生物医学工程
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纳米技术
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癌症诊断
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材料科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）