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构建磁核-大介孔卫星免疫传感器用于长寿命化学发光和高灵敏肿瘤标志物测定。

Construction of Magnetic Core-Large Mesoporous Satellite Immunosensor for Long-Lasting Chemiluminescence and Highly Sensitive Tumor Marker Determination.

机构信息

Department of Chemistry, Department of Gastroenterology, Zhongshan Hospital of Fudan University, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, iChEM, Fudan University, Shanghai, 200433, China.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.

出版信息

Small. 2023 Nov;19(45):e2304631. doi: 10.1002/smll.202304631. Epub 2023 Jul 12.

DOI:10.1002/smll.202304631
PMID:37438544
Abstract

Chemiluminescence immunoassay exhibits high sensitivity and signal-to-noise ratio, thus attracting great attention in the early diagnosis and dynamic monitoring of diseases. However, the collection of conventional flash-type chemiluminescence signal (<5 s) relies heavily on automatic sampling and reading instrument. Herein, a novel core-satellite multifunctional chemiluminescence immunosensor is designed for the efficient enrichment and highly sensitive determination of cancer biomarker carcinoembryonic antigen (CEA) with enhanced and long-lasting output signal that can be conveniently recorded by a simple microplate plate reading instrument. Anti-CEA monoclonal antibody 2 (Ab2) modified Fe O @SiO microspheres (Fe O @SiO -Ab2, 370 nm in diameter) are synthesized as the core for selectively capturing and enriching target CEA in solution, and anti-human CEA monoclonal antibody 1 (Ab1) and horseradish peroxidase (HRP) co-immobilized dendritic large-mesoporous silica nanospheres (MSNs-HRP/Ab1, 80 nm in diameter, pore size: 17 nm) are synthesized as the satellite for efficient immunological recognition and signal amplification. The as-designed core-satellite magnetic chemiluminescence immunosensors exhibit a broad linear range of 0.01-20 ng mL and a low detection limit of 3.0 pg mL for the convenient, highly specific, and sensitive determination of CEA in human serum. Such core-satellite chemiluminescence immunosensors are expected to act as a powerful tool for in vitro detection of various biomarkers, overcome the defect of conventional chemiluminescence relying heavily on expensive and bulky automatic instruments and popularize chemiluminescence analysis to primary medical institutions and remote areas.

摘要

化学发光免疫分析具有灵敏度高、信噪比高的特点,因此在疾病的早期诊断和动态监测中引起了极大的关注。然而,传统的闪烁型化学发光信号(<5s)的采集严重依赖于自动采样和读取仪器。在此,设计了一种新型的核-卫星多功能化学发光免疫传感器,用于高效富集和高灵敏度测定癌标志物癌胚抗原(CEA),具有增强和持久的输出信号,可通过简单的微孔板读取仪器方便地记录。将抗 CEA 单克隆抗体 2(Ab2)修饰的 Fe3O4@SiO2 微球(Fe3O4@SiO2-Ab2,直径 370nm)作为核心,用于选择性地捕获和富集溶液中的靶标 CEA,同时将抗人 CEA 单克隆抗体 1(Ab1)和辣根过氧化物酶(HRP)共固定在树枝状大介孔硅纳米球(MSNs-HRP/Ab1,直径 80nm,孔径:17nm)上作为卫星,用于高效的免疫识别和信号放大。所设计的核-卫星磁性化学发光免疫传感器在人血清中对 CEA 的方便、高特异性和灵敏测定表现出较宽的线性范围(0.01-20ngmL)和较低的检测限(3.0pgmL)。这种核-卫星化学发光免疫传感器有望成为体外检测各种生物标志物的有力工具,克服了传统化学发光严重依赖昂贵且庞大的自动仪器的缺陷,并将化学发光分析推广到基层医疗机构和偏远地区。

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