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基于镧系纳米探针发光放大策略的人唾液肿瘤标志物超灵敏即时检测

Ultrasensitive Point-of-Care Test for Tumor Marker in Human Saliva Based on Luminescence-Amplification Strategy of Lanthanide Nanoprobes.

作者信息

Zhou Shanyong, Tu Datao, Liu Yan, You Wenwu, Zhang Yunqin, Zheng Wei, Chen Xueyuan

机构信息

CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Key Laboratory of Nanomaterials Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences Fuzhou Fujian 350002 China.

Fujian Science and Technology Innovation Laboratory for Optoelectronic Information of China Fuzhou Fujian 350108 China.

出版信息

Adv Sci (Weinh). 2021 Jan 6;8(5):2002657. doi: 10.1002/advs.202002657. eCollection 2021 Mar.

Abstract

The point-of-care detection of tumor markers in saliva with high sensitivity and specificity remains a daunting challenge in biomedical research and clinical applications. Herein, a facile and ultrasensitive detection of tumor marker in saliva based on luminescence-amplification strategy of lanthanide nanoprobes is proposed. EuO nanocrystals are employed as bioprobes, which can be easily dissolved in acidic enhancer solution and transform into a large number of highly luminescent Eu micelles. Meanwhile, disposable syringe filter equipped with nitrocellulose membrane is used as bioassay platform, which facilitates the accomplishment of detection process within 10 min. The rational integration of dissolution enhanced luminescent bioassay strategy and miniaturized detection device enables the unique lab-in-syringe assay of tumor marker like carcinoembryonic antigen (CEA, an important tumor marker in clinic diagnosis and prognosis of cancer) with a detection limit down to 1.47 pg mL (7.35 × 10 m). Upon illumination with a portable UV flashlight, the photoluminescence intensity change above 0.1 ng mL (0.5 × 10 m) of CEA can be visually detected by naked eyes, which allows one to qualitatively evaluate the CEA level. Moreover, we confirm the reliability of using the amplified luminescence of EuO nanoprobes for direct quantitation of CEA in patient saliva samples, thus validates the practicality of the proposed strategy for both clinical diagnosis and home self-monitoring of tumor marker in human saliva.

摘要

在生物医学研究和临床应用中,实现对唾液中肿瘤标志物的高灵敏度和特异性即时检测仍然是一项艰巨的挑战。在此,我们提出了一种基于镧系纳米探针发光放大策略的简便、超灵敏的唾液中肿瘤标志物检测方法。采用EuO纳米晶体作为生物探针,其可轻松溶解于酸性增强剂溶液中并转化为大量高发光的Eu胶束。同时,配备硝酸纤维素膜的一次性注射器过滤器用作生物检测平台,可在10分钟内完成检测过程。溶解增强发光生物检测策略与小型化检测装置的合理整合,实现了对癌胚抗原(CEA,癌症临床诊断和预后的重要肿瘤标志物)等肿瘤标志物独特的注射器内实验室检测,检测限低至1.47 pg/mL(7.35×10⁻¹² M)。用便携式紫外线手电筒照射时,肉眼可直观检测到CEA浓度高于0.1 ng/mL(0.5×10⁻⁹ M)时的光致发光强度变化,从而能够定性评估CEA水平。此外,我们证实了使用EuO纳米探针的放大发光直接定量患者唾液样本中CEA的可靠性,从而验证了所提出策略在人体唾液中肿瘤标志物临床诊断和家庭自我监测方面的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cb3/7927602/5d5021d0df0e/ADVS-8-2002657-g006.jpg

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