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基于表面增强拉曼光谱与表面分子印迹聚合物技术集成的无干扰、高精度生物传感器,用于检测人血液中的肿瘤生物标志物。

Interference-free and high precision biosensor based on surface enhanced Raman spectroscopy integrated with surface molecularly imprinted polymer technology for tumor biomarker detection in human blood.

机构信息

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Digital Fujian Internet-of-Things Laboratory of Environment Monitoring, Fujian Normal University, Fuzhou, 350007, PR China.

Fujian Pien Tze Huang Cosmetics Co., Ltd, Zhangzhou, 363000, PR China.

出版信息

Biosens Bioelectron. 2019 Oct 15;143:111599. doi: 10.1016/j.bios.2019.111599. Epub 2019 Aug 21.

DOI:10.1016/j.bios.2019.111599
PMID:31476600
Abstract

The reliable quantitative analysis of tumor biomarkers in circulating blood is crucial for cancer early screening, therapy monitoring and prognostic prediction. Herein, a novel biosensor combing surface-enhanced Raman spectroscopy (SERS) and surface molecularly imprinted polymer (SMIP) technology was developed for quantitative detection of carcinoembryonic antigen (CEA) that is closely related to several common cancers. Owing to the use of SMIP, recognition sites with high affinity to the target of interest can be well imprinted on the surface of SERS substrate, leading to a more stable and specific capture ability. In addition, two layers of core-shell nanoparticles were integrated to this SERS substrate to form highly efficient electromagnetic enhancement for SERS measurement via the generation of lots of "hot spot". Besides, a unique Raman reporter (CC) with silent Raman signals at 2024 cm was capsulated in the nanoparticles to avoid the optical noises originating from endogenous molecules at fingerprint region (300-1800 cm). Meanwhile, we employed an internal standard molecular (CN) to real time correct the fluctuating signals of Raman reporter when performing the quantitative analysis. Due to these features, a limit of detection (LOD) of 0.064 pg mL with the detection range of 0.1 pg mL - 10 μg mL can be achieved by this assay. Excitingly, this technology even showed wonderful performances for CEA detection in real blood from cancer patients, demonstrating great potential for biomarker-based cancer screening.

摘要

循环血液中肿瘤标志物的可靠定量分析对癌症早期筛查、治疗监测和预后预测至关重要。在此,我们开发了一种将表面增强拉曼光谱(SERS)和表面分子印迹聚合物(SMIP)技术相结合的新型生物传感器,用于定量检测癌胚抗原(CEA)。CEA 与几种常见癌症密切相关。由于使用了 SMIP,可以在 SERS 基底表面很好地印迹对目标具有高亲和力的识别位点,从而获得更稳定和特异的捕获能力。此外,两层核壳纳米粒子被整合到该 SERS 基底中,通过产生大量“热点”,形成高效的电磁增强用于 SERS 测量。此外,一种独特的拉曼报告分子(CC)被封装在纳米粒子中,其在 2024cm处具有静默的拉曼信号,以避免来自指纹区域(300-1800cm)内源性分子的光学噪声。同时,我们采用内标分子(CN)实时校正定量分析中拉曼报告分子的波动信号。由于这些特点,该方法的检测限(LOD)为 0.064pg/mL,检测范围为 0.1pg/mL-10μg/mL。令人兴奋的是,该技术甚至在来自癌症患者的真实血液中对 CEA 检测表现出优异的性能,为基于生物标志物的癌症筛查展示了巨大的潜力。

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