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BIOSENSORS & BIOELECTRONICS · 2018 · IF 8.173

Amplified electrochemiluminescence detection of CEA based on magnetic Fe3O4@Au nanoparticles-assembled Ru@SiO2 nanocomposites combined with multiple cycling amplification strategy

Guifen Jie,Junjun Ge,Xiaoshan Gao,Chunli Li

In this work, we designed a new strategy for ultrasensitive detection of CEA based on efficient electrochemiluminescence (ECL) quenching of Ru(bpy) 3 2+ -doped SiO 2 nanocomposite by ferrocene using target recycling amplification technique. A large number of [email protected] 2 ECL signal probe were firstly assembled on the novel magnetic core−shell Fe 3 O 4 @Au nanoparticles (NPs), then the ferrocene-labeled ECL quenching probe (Fc-probe) was linked to the magnetic NPs. Finally, numerous DNA1 sequences were produced by target CEA-triggered multiple recycling amplification and displaced the Fc-probe on the magnetic NPs, leading to significantly enhanced ECL signal for CEA detection. Because of the designed cascade signal amplification strategy, the newly developed method achieved a wide linear range of 10 fg/mL to 10 ng/mL with a low detection limit of  3.5 fg/mL. Furthermore, taking advantages of the magnetic Fe 3 O 4 @Au NPs for carring abundant signal probes, sensing target and ECL detection, the developed ECL strategy is convenient, rapid and displayed high sensitivity for CEA detection, which has great potential for analyzing the clinical samples in practical disease diagnosis applications.

研究领域: 分析化学 · 生物传感器 · 纳米技术 · 癌症诊断
✓ 已验证 DOI PubMed 高影响因子
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Materials Advances · 2022 ·Vol. 3 ·期 11 ·4707-4717 · IF 0

Dual CEA/CD44 targeting to colorectal cancer cells using nanobody-conjugated hyaluronic acid-modified mesoporous silica nanoparticles with pH- and redox-sensitivity

Xiying Fan,Tingting Wang,Min Han,Yi Gu,Guochuan Sun,Xinying Peng,Qinghui Shou,Haipeng Song,Wenshuai Liu,Rui Nian

Colorectal cancer (CRC) is the second leading cause of cancer death among all malignancies. Drug delivery targeting tumor surface receptors improve therapeutic effects and lower side-effects since they can increase the drug accumulation in target tissues and cellular uptake. In this study, we established a pH- and redox-responsive drug delivery system based on mesoporous silica nanoparticles (MSNs) for the delivery of the anticancer drug doxorubicin hydrochloride (DOX). In this drug delivery system, MSNs-NH2 were modified with hyaluronic acid (HA) to form a highly loaded anticancer drug core; they were further coated with 11C12, a nanobody against carcinoembryonic antigen (CEA) to form a guiding outer layer (DOX@MSNs-HA-11C12). The accurate localization of nanoparticles would be mediated by two targeting molecules HA and nanobody 11C12, which target the CD44 receptor and the proximal membrane end of CEA on the surface of CRC cells, respectively. The release amount of DOX observed from in vitro drug release profiles increased as follows: pH 7.4 < pH 6.8 < pH 5.4, and (pH 7.4 + GSH) < (pH 6.8 + GSH) < (pH 5.4 + GSH), illustrating that the drug release could be accelerated in a weakly acidic environment as well as in the presence of reduced glutathione (GSH). In vitro cytotoxicity experiments showed that MSNs-HA-11C12 nanoparticles exhibited good biocompatibility and safety. Drug loaded nanoparticles modified by dual targeting molecules HA and 11C12 (DOX@MSNs-HA-11C12) led to higher LoVo CRC cell apoptosis in vitro, compared with DOX@MSNs-NH2 and DOX@MSNs-HA. Confocal laser scanning microscopy and fluorescence spectrophotometry further confirmed that the dual-targeting system significantly enhanced the uptake of DOX@MSNs-HA-11C12 by LoVo cells and the internalization of DOX was the highest, followed by DOX@MSNs-HA, DOX@MSNs-NH2, and DOX, subsequently. In this study, the nanobody targeting CEA was combined with the HA targeting CD44 receptor for the first time, which proved that the dual CEA/CD44 formulation can promote a more accurate drug delivery mode for CRC cells, and provide a basis for subsequent drug development for treating CRC and related cancers.

CAS / MDL: 919-30-2
研究领域: 药学 · 纳米技术 · 癌症研究 · 生物医学工程
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MICROCHIMICA ACTA · 2018 ·Vol. 185 ·期 6 ·1-8 · IF 5.705

Dye sensitized photoelectrochemical immunosensor for the tumor marker CEA by using a flower-like 3D architecture prepared from graphene oxide and MoS2

Song Kaijing,Ding Chuanmin,Zhang Bing,Chang Honghong,Zhao Zhihuan,Wei Wenlong,Wang Junwen

The authors describe a dye-sensitized photoelectrochemical immunoassay for the tumor marker carcinoembryonic antigen (CEA). The method employs the rhodamine dye Rh123 with red color and absorption maximum at 500 nm for spectral sensitization, and a 3D nanocomposite prepared from graphene oxide and MoS 2 acting as the photoelectric conversion layer. The nanocomposite with flower-like 3D architectures was characterized by transmission electron microscopy, scanning electron microscopy, X-ray powder diffraction, and UV-vis diffuse reflectometry. A photoelectrochemical sandwich immunoassay was developed that is based on the use of the nanocomposite and based on the specific binding of antibody and antigen, and by using a secondary antibody labeled with Rh123 and CdS (Ab 2 -Rh123@CdS). Under optimal conditions and at a typical working voltage of 0 V (vs. Hg/HgCl 2 ), the photocurrent increases linearly 10 pg mL −1 to 80 ng mL −1 CEA concentration range, with a 3.2 pg mL −1 detection limit. Flower-like GO-MoS 2 complex with high efficiency of electron transport was synthesized to construct photoelectrochemical platform. The sandwich-type immunoassay was built on this platform based on specific binding of antigen and antibody. Carcinoembryonic antigen in sample was detected sensitively by using sensitization of rhodamine dye Rh123 as signal amplification strategy.

研究领域: 生物化学 · 分析化学 · 材料科学 · 癌症诊断
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2020 ·Vol. 187 ·期 10 ·1-10 · IF 6.232

Electrochemical immunosensor based on binary nanoparticles decorated rGO-TEPA as magnetic capture and Au@PtNPs as probe for CEA detection

Cao Liangli,Xiao Haolin,Fang Cheng,Zhao Feijun,Chen Zhencheng

Using gold and magnetic nanoparticles co-decorated reduced graphene oxide-tetraethylenepentamine (rGO-TEPA/Au-MNPs) as the magnetic platform for capturing the primary antibody (Ab 1 ), separation and preconcentration of immunocomplex, a novel homogeneous electrochemical immunosensor was successfully developed. The newly prepared magnetic rGO-TEPA/Au-MNPs, compared with MNPs, exhibited better stability and enhanced electrical conductivity attributed to rGO-TEPA, and showed higher biorecognition efficiency due to AuNPs. In addition, Au@PtNPs were prepared and modified with secondary antibody (Ab 2 ) as an efficient signal probe for signal readout. Using carcinoembryonic antigen (CEA) as a model analyte, the prepared immunosensor demonstrated satisfactory properties like high stability, good repeatability and selectivity, wide linear range (5.0 pg mL −1 ~200.0 ng mL −1 ) as well as low detection limit (1.42 pg mL −1 ). The homogenous electrochemical immunosensor was applied to the detection of CEA in human serum and was found to exhibit good correlation with the reference method. Thus, the proposed rGO-TEPA/Au-MNPs-based homogenous immunoassay platform might open up a new way for biomarker diagnosis. Graphical Abstract

研究领域: 分析化学 · 生物传感器 · 纳米技术 · 生物医学工程 · 癌症诊断
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CLINICAL AND EXPERIMENTAL ALLERGY · 2025 · IF 5.2

Excessive Endoplasmic Reticulum Stress in B Cells Associates With the Local Immunoglobulin Production in Severe Type 2 Chronic Rhinosinusitis With Nasal Polyps

Yanran Huang,Zhaofeng Xu,Yan Yan,Chunbo Li,Jieying Yan,Yi Wei,Jian Li,Luo Zhang,Nan Zhang,Claus Bachert,Weiping Wen

Background Immunoglobulin overproduction was observed in type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). Endoplasmic reticulum (ER) stress is linked to aggregation in various inflammatory diseases, yet its presence and extent in nasal polyps remain to be elucidated. Objective To assess the impact of B-cell ER stress on local immunoglobulin production in CRSwNP and investigate its correlation with disease severity. Methods Single-cell mapped transcriptional profiles at cellular resolution. Electron microscopy revealed ultrastructural features, complemented by immunohistochemistry/immunofluorescence mapping marker localisation. Western blotting quantified protein expression, with QuantiGene Plex and Luminex enabling multiplex cytokine analysis. Bulk RNA sequencing and targeted protein expression validation in ex vivo experiments confirmed critical findings. Results HSPA5 and HSP90B1 were found to be two major elevated ER stress markers in type 2 CRSwNP, compared to the control nasal tissue, and their expression correlated with the expression of IGHE and type 2 inflammatory markers. In CRSwNP, the ER stress signature score and increased marker expression predominantly originated from B and plasma cells. Electron microscopy revealed dilated ER and enlarged lumen in sorted B cells from nasal polyps. MZB1 exhibited co-localisation with plasma cells and mature B cells. Immunofluorescence staining demonstrated that MZB1 co-localised with HSPA5 and HSP90B1. In vitro, stimulation with MZB1 upregulated mRNA expression of ER stress markers and IgE. Increased IGHE expression was detected in response to ER stress induced in vitro. Finally, anti-IgE treatment inhibited the expression of ER stress-related genes. Conclusion ER stress markers were significantly upregulated in CRSwNP. Specifically, ER stress levels were significantly elevated in B cells of CRSwNP compared to controls. In type 2 CRSwNP, B-cell ER stress may play a role in promoting local IgE production. Graphical The ER stress burden was significantly upregulated in type 2 CRSwNP tissues compared to both healthy controls and non-type 2 polyp tissues. This elevated stress was linked to more severe type 2 inflammation and increased local IgE production. In vitro studies of B cells derived from nasal polyp tissues demonstrated that MZB1 upregulated endoplasmic reticulum stress, which was associated with enhanced IgE level. Furthermore, in vivo treatment with Omalizumab reduced endoplasmic reticulum stress levels. ER, endoplasmic reticulum; HC, healthy controls; CRSwNP, chronic rhinosinusitis with nasal polyps; MZB1, Marginal Zone B1 protein.

CAS / MDL: 11089-65-9
研究领域: 耳鼻喉科学 · 免疫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CLINICAL AND EXPERIMENTAL ALLERGY · 2021 ·Vol. 52 ·期 1 ·46-58 · IF 5.018

Substance P-induced lung inflammation in mice is mast cell dependent

Nan Wang,Jue Wang,Yongjing Zhang,Shiling Hu,Tianxiao Zhang,Yuanyuan Wu,Xiuzhen Sun,Tao Zhang,Shuanying Yang,Langchong He

Background Allergic asthma is a common inflammatory lung disease and a major health problem worldwide. Mast cells (MCs) play a key role in the early-stage pathophysiology of allergic asthma. Substance P (SP) functions in neurogenic inflammation by activating MCs, and therefore, it may to participate in the occurrence and development of asthma. Objective We examined the relationship between SP and lung inflammation, and also whether SP can directly trigger asthma. Methods We measured the number of peripheral blood eosinophils, neutrophils and basophils and evaluated the levels of IgE and SP in blood samples of 86 individuals with allergic asthma. Serum IgE and SP levels were also determined in 29 healthy individuals. C57BL/6 mice were subjected to different doses of SP, and bronchoalveolar lavage fluid (BALF) was collected to count the inflammatory cells. Lung tissues were analysed using histopathological methods to evaluate lung peribronchial inflammation, fibrosis and glycogen deposition. Levels of IgE, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-13, IL-17 and IFN-γ were determined in mouse serum. Results Substance P levels were increased in the serum samples of patients with asthma. SP induced mouse lung peribronchial inflammation, fibrosis and glycogen deposition, with high levels of Th2-related cytokines such as IL-4, IL-5 and IL-13 observed in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kit W-sh/W-sh mice. Conclusions & clinical relevance Substance P levels increased significantly in serum of asthmatic patients and independently associated with the risk of asthma. Furthermore, SP induced Th2 lung inflammation in mice, which was dependent on MCs. Graphical Here, we found that SP levels were increased in the serum samples of patients with asthma, which was independently associated with the risk of asthma. In mice model, SP induced lung peribronchial inflammation, fibrosis, and glycogen deposition, with high levels of Th2-related cytokines in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kit W-sh/W-sh mice, which indicated that SP induced Th2 lung inflammation in mice was dependent on MCs.

CAS / MDL: 148470-19-3
研究领域: 免疫学 · 肺科学 · 过敏学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Advanced Sensor Research · 2023 ·Vol. 2 ·期 8 ·2200050 · IF 0

Coronary Au@Bi Nanospheres for Highly Impedance-Sensitive Immunosensing toward CEA

Caihong Wang,Ruizhuo Ouyang,Jinyao Liu,Yuefeng Zhao,Yuhao Li,Ning Guo,Baolin Liu,Yuqing Miao

Novel coronary Au@Bi nanospheres (NSs) are simply synthesized by sparkling gold nanoparticles (Au NPs) on the surface of bismuth (Bi) NSs and successfully used as highly impedance-sensitive immunosensing platform to develop a new label-free electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA). Firstly, Bi NSs are prepared by one-pot hydrothermal method, showing uniform sphere morphology with a dense oxide film formed outside Bi NSs due to the easy oxidation of Bi in the air. The oxide film significantly hinders the transmission of electrons and effectively improves the sensitivity of the proposed electrochemical impedance immunosensor. The surface functionalization of Bi NSs with Au NPs enhances the biocompatibility, stability, as well as active surface area of the produced Au@Bi NSs, preferable for the efficient loading of antibody molecules. The electrochemical impedance spectroscopy (EIS) is selected as the optical technique to measure CEA with the constructed immunosensor based on Au@Bi NSs. Because of the excellent impedance-responsive performance, this new immunosensor displays highly sensitive detection toward CEA in a linear range of 50 fg mL −1 –100 ng mL −1 with an extremely low detection limit of 9.83 fg mL −1 and could be potentially used in early clinical detection of cancer.

研究领域: 生物医学工程 · 分析化学 · 纳米技术 · 肿瘤学
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ANALYTICAL CHEMISTRY · 2020 · IF 6.785

Nanopore-based Strategy for Selective Detection of Single Carcinoembryonic Antigen (CEA) Molecules

Haoran Tang,Hao Wang,Cheng Yang,Dandan Zhao,Yuanyuan Qian,Yongxin Li

Nanopores have become one of the most important tools for single-molecule sensing, but the challenge for selective detection of specific biomolecules still exists. In this contribution, we develop a new technique for sensing carcinoembryonic antigen (CEA), one of the important cancer biomarkers, using solid-state nanopores as a tool. The method is based on the specific affinity between aptamer (Apt) modified magnetic Fe3O4–Au nanoparticles (MNPs) and CEA, and the formed CEA–Apt–MNPs and remaining Apt–MNPs can transport the nanopores by applying a positive potential after magnetic separation. Due to the obvious particle size difference between CEA–Apt–MNPs and Apt-MPs, their corresponding blockage signals could be distinguished completely by the degree of the current decline. Moreover, the frequency of the blockage signals for CEA–Apt–MNPs is proportional to the concentration of CEA within certain limits, indicating that our designed nanopore sensing strategy can quantitatively detect CEA in complex samples. This work demonstrates that our designed nanopore-based strategy can be used for CEA sensing with good selectivity and sensitivity and also can be used to analyze other protein biomarkers for early diagnosis and monitoring of cancer, though the detection limit (0.6 ng/mL) is not relatively low. In future works, we plan to improve our detection limit by the improvement of the nanopipette preparation technology and detection method.

研究领域: 生物物理学 · 医学诊断 · 纳米技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BMC CANCER · 2018 ·Vol. 18 ·期 1 ·1-11 · IF 3.288

Serum microRNA signatures and metabolomics have high diagnostic value in gastric cancer

Liu Hai-Ning,Wu Hao,Tseng Yu-Jen,Chen Yan-Jie,Zhang Dan-Ying,Zhu Lin,Dong Ling,Shen Xi-Zhong,Liu Tao-Tao

Background Many novel diagnostic biomarkers have been developed for gastric cancer (GC) recently. We chose two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and aimed to establish appropriate models.Methods We reviewed the diagnostic accuracies of all microRNAs identified by previous diagnostic tests. Then appropriate microRNAs and their combinations were validated the diagnostic value. We included 80 patients with GC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was conducted, and we used three multivariate statistical analyses to establish diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19–9) were detected for comparison with the novel models.Results Sixty-seven published studies and 70 microRNAs were finally included in the systematic review. MiR-18a, miR-19a, miR-21, miR-92a, miR-199a and miR-421 were chosen to further validate their diagnostic efficiencies. Five of those microRNAs in GC patients had significantly different expression. The combination of miR-19a and miR-92a had the highest area under the curve (AUC) at 0.850 with a sensitivity of 91.3% and a specificity of 61.0%. The GC/MS analysis performed an excellent diagnostic value and the AUC reached 1.0.Conclusion There is a good potential for microRNAs and GC/MS analysis as new diagnostic methods in view of their high diagnostic value compared with traditional biomarkers.

研究领域: 肿瘤学 · 分子生物学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Omega · 2022 · IF 4.132

Ultrasensitive Detection of Carcinoembryonic Antigen by Chitosan/Polythiophene/CdTe Electrochemical Biosensor

Jiajia Wang,Xin Hua,Baokang Jin

A facile method for the in situ fabrication of chitosan/polythiophene/CdTe (CS/PTh/CdTe) nanocomposite has been developed. It was then connected with anti-CEA (Ab), which was evoked for the electrochemical detection of carcinoembryonic antigen (CEA, Ag) within K4Fe(CN)6. The results indicate that CS/PTh/CdTe/GCE has a high selectivity for the detection of CEA with a wide linear range of 0.0001–10000 ng/mL and excellent sensitivity with a low detection limit of 40 fg/mL. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), and in situ FT-IR spectra are evoked to study the mechanism of detection of CEA via CS/PTh/CdTe/GCE. The high sensitivity of the electrochemical sensor is due to the fact that the electrochemical oxidation products of K4Fe(CN)6 can directly oxidize CdTe from a low energy state to a high energy state (CdTe)*, making CdTe more prone to be oxidized and facilitate electron transfer. The developed electrochemical biosensor can be used for the detection of real samples, providing a precise method for the detection of CEA with potential application in the clinical detection of tumors.

研究领域: 生物医学工程 · 分析化学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2026 · IF 4.6

Flower-like FeMoO4 nanoparticles as a peroxidase mimic for sensitive colorimetric immunoassay of CEA

Yuwei Pan,Xiaoyan Deng,Rong Zhang,Liuyan You,Jiaqing Guo,Youxiu Lin,Dianping Tang,Wenqiang Lai

Early and accessible detection of tumor biomarkers requires robust colorimetric readouts that can operate in complex matrices. We report flower-like hierarchical FeMoO 4 nanoparticles functioning as a peroxidase-like nanozyme and enable a cascade immunoassay for carcinoembryonic antigen. The nanoparticles were obtained by a solvothermal route and exhibit a single crystalline FeMoO 4 phase with uniform Fe, Mo, and O distributions, mixed Fe 3+ and Fe 2+ states, and a measurable fraction of surface non-lattice oxygen species (O_ads, including hydroxyl-related oxygen and adsorbed/weakly bound oxygen). These features support efficient H 2 O 2 activation and TMB oxidation. FeMoO 4 was integrated with a glucose oxidase (GOx)-based enzyme signal reporter, in which GOx and the detection antibody (Ab2) were co-immobilized on gold nanoparticles (AuNPs) to form GOx-AuNP-Ab2 conjugate. In a sandwich immunoassay format, the captured enzyme-labeled conjugate generates H 2 O 2 in proportion to the antigen concentration, which is subsequently converted by FeMoO 4 into a stable colorimetric signal at 652 nm. Reaction conditions were optimized for both the chromogenic branch and the enzymatic branch, and kinetic analysis gave Michaelis-Menten behavior with K m values of 0.78 mM for H 2 O 2 and 0.40 mM for TMB. Radical scavenging identified superoxide and hydroxyl radicals as the main active species, with singlet oxygen as a minor contributor. The CEA assay achieved a linear range of 0.1 to 60 ng mL −1 and a limit of detection of 63 pg mL −1 , with a one month retention of 93% of the initial absorbance. Results for six clinical serum samples showed good agreement with a commercial ELISA at the 95% confidence level, and one CEA-negative serum was included as a negative control. These findings establish FeMoO 4 as a stable and manufacturable nanozyme platform for colorimetric immunoassays.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICAL BIOCHEMISTRY · 2020 · IF 2.877

A sandwich-type electrochemical immunosensor for detecting CEA based on CeO2-MoS2 absorbed Pb2+

Wenjun Li,Xiuwen Qiao,Chenglin Hong,Chaoyun Ma,Yiju Song

A sandwich-type immunosensor for detecting the concentration of carcinoembryonic antigen (CEA) was prepared. In this work, gold nanoparticles (Au NPs) were used as platform to attach more primary antibody (Ab 1 ) due to excellent electrical conductivity and good biocompatibility. Molybdenum disulfide-Cerium oxide (CeO 2 -MoS 2 ) nanohybrid was used as a carrier to absorb lead ions (Pb 2+ ) and the second antibody (Ab 2 ). CeO 2 -MoS 2 -Pb 2+ -Ab 2 was used as a nanoprobe to detect CEA antigen. Under optimal conditions, square wave voltammetry (SWV) successfully displayed the electrical signal of Pb 2+ . The designed electrochemical immunosensor has excellent analytical performance. In addition, the detection range was 0.001–80 ng/mL and the minimum detection limit was 0.3 pg/mL (S/N = 3), which had good selectivity and stability. Finally, the proposed immunosensor successfully detected the concentration of CEA in the serum of the sample, which provided a feasible method for CEA testing.

研究领域: 分析化学 · 生物传感器 · 纳米材料 · 电化学 · 癌症诊断
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