基于多种肿瘤标志物同时检测的双信号免疫层析试纸条及装置的研制

With the increasing incidence of malignant tumors, new requirements and challenges have been put forward for the timely tumor diagnosis. Clinical detection of tumor markers in serum samples plays crucial role in tumor screening, tumor diagnosis and prognosis monitoring. There are many kinds of tumor markers of lung cancer. And it is difficult to obtain accurate results by only detecting a single tumor marker. Some lung cancer tumor markers can be used to specifically distinguish non-small cell lung cancer and small cell lung cancer, which is benefit for the early diagnosis of lung cancer type and proposing an effective treatment. In this project, immunochromatographic test strip based on gold nanoparticles (GNP) and upconverting nanoparticles (UCNP) will be constructed for simultaneous detection of various lung cancer tumor markers, and the corresponding upconversion luminescence signal acquisition device will also be developed. It is mainly studied on the following three aspects: (1) the synthesis of GNP and UCNP labelled NP-antibody conjugates with different luminescent colors; (2) the construction of immunochromatographic test strips with dual signal for simultaneous detection of various lung cancer tumor markers; (3) the development of upconversion luminescence test strip detector. Therefore, it can realize the real-time and on-site detection of tumor markers, providing a rapid, simple and effective detection method for early diagnosis and prognosis monitoring of tumors.

随着恶性肿瘤的发病率越来越高，对肿瘤的及时诊断提出了新的要求和挑战。临床上检测肿瘤标志物的血清水平对于肿瘤筛查、诊断及预后监测复发都具有十分重要意义。肺癌的肿瘤标志物种类较多，单独检测一种标志物很难得到准确结果，其中某些肿瘤标志物可用于特异性地区分非小细胞肺癌和小细胞肺癌，从而有助于肺癌的早期分型诊断并准确地提出治疗方案，进而改善治疗效果。本项目拟构建用于多种肺癌肿瘤标志物同时检测的具有比色和上转换发光的双信号免疫层析试纸条，并研制相应的上转换发光信号采集装置。探索和解决以下三个方面的问题：（1）金纳米粒子和上转换纳米粒子双标记的纳米抗体偶联物的合成；（2）多种肺癌肿瘤标志物同时检测的免疫层析试纸条的构建；（3）上转化免疫发光检测仪的研制。进而实现对肺癌肿瘤标志物的现场即时检测，为肿瘤的早期诊断和预后监测提供一种快速、简便、高效的检测手段。

癌症已经成为威胁全球健康的主要公共问题之一，也是目前中国居民死亡的主要原因之一。发展对肿瘤标志物快速、简便、高效的现场即时检测方法，对肿瘤的预防、早期诊断和预后监测具有非常重要的意义。本项目中，（1）构建基于金纳米棒（GNR）的免疫层析试纸条用于疾病标志物（包括肿瘤标志物）的比色-光热联合检测；（2）搭建一台荧光-光热双模成像系统，兼具荧光成像和热成像双功能，用于免疫层析试纸条荧光信号和热信号的采集；（3）构建基于AuPd@FexOy金属复合纳米粒子的免疫层析试纸条用于疾病标志物的检测；（4）合成系列上转换发光纳米粒子并应用于肿瘤的成像诊断和治疗。上述研究成果可为包含肿瘤在内的重大疾病的早期快速诊断提供新方法。相关研究工作自2020年1月到2022年12月共在Sensors & Actuators: B. Chemical, Acta Biomaterialia, Analyst等SCI期刊发表论文12篇（影响因子大于5的6篇），申请中国发明专利4项。