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用于口腔癌唾液癌胚抗原检测的蛋白石光子晶体增强型上转换关闭荧光免疫分析

Opal photonic crystal-enhanced upconversion turn-off fluorescent immunoassay for salivary CEA with oral cancer.

作者信息

Li Yige, Hu Songtao, Chen Cong, Alifu Nuernisha, Zhang Xueliang, Du Juanrui, Li Chunyan, Xu Lin, Wang Lin, Dong Biao

机构信息

Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China.

State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130021, China.

出版信息

Talanta. 2023 Jun 1;258:124435. doi: 10.1016/j.talanta.2023.124435. Epub 2023 Mar 11.

DOI:10.1016/j.talanta.2023.124435
PMID:36940576
Abstract

The point-of-care test of tumor markers in saliva with high specificity and sensitivity for early diagnosis of oral cancer is of great interest and significance, but remaining a daunting challenge due to the low concentration of such biomarkers in oral fluid. Herein, a turn-off biosensor based on opal photonic crystal (OPC) enhanced upconversion fluorescence is proposed to detect the carcinoembryonic antigen (CEA) in saliva by applying fluorescence resonance energy transfer sensing strategy. Hydrophilic PEI ligands are modified on upconversion nanoparticles to enhance the sensitivity of biosensor by promoting sufficient contact between saliva and detection region. As a substrate for the biosensor, OPC can also provide a local-field effect for greatly enhanced upconversion fluorescence by coupling the stop band and excitation light, and a 66-fold amplification of the upconversion fluorescence signal was obtained. For the CEA detection in spiked saliva, such sensors showed a favorable linear relationship at 0.1-2.5 ng mL and more than 2.5 ng mL, respectively. The limit of detection was down to 0.1 ng mL. Moreover, by monitoring real saliva, the effective discrepancy between patients and healthy people was confirmed, indicating remarkable practical application value in clinical early diagnosis and home-based self-monitoring of tumors.

摘要

用于口腔癌早期诊断的具有高特异性和灵敏度的唾液肿瘤标志物即时检测具有极大的研究价值和意义,但由于口腔液中此类生物标志物浓度较低,仍然是一项艰巨的挑战。在此,基于蛋白石光子晶体(OPC)增强上转换荧光的猝灭型生物传感器被提出,通过应用荧光共振能量转移传感策略来检测唾液中的癌胚抗原(CEA)。在纳米上转换颗粒上修饰亲水性聚醚酰亚胺配体,通过促进唾液与检测区域的充分接触来提高生物传感器的灵敏度。作为生物传感器的底物,OPC还可通过耦合禁带和激发光提供局域场效应,以极大增强上转换荧光,上转换荧光信号实现了66倍的放大。对于加标的唾液中的CEA检测,此类传感器在0.1 - 2.5 ng/mL和大于2.5 ng/mL时分别呈现出良好的线性关系。检测限低至0.1 ng/mL。此外,通过监测实际唾液,证实了患者与健康人之间的有效差异,表明其在肿瘤临床早期诊断和居家自我监测中具有显著的实际应用价值。

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