基于卟啉ECL的多肿瘤标志物成像新方法研究

With the increasing disclosure of the relationship between tumor and its associated multiple biomarkers, the conventional electrochemiluminescence (ECL) sensing in terms of intensity towards single analyte could barely meet the demands of contemporary biomedical analyses. In this way, being an inevitable tendency in the development of ECL technology, new probing theories along with measuring approaches have been emerging with respect to multiplexed targets. In view of those, this project intends to explore a series of chromatic tagging methods for ECL visual detection, by exploiting the hardly reconciled contradiction between the organic irradiation so consipicuous to naked eyes and its wildly inconsistent quenching in the aqueous phase. Down to the very bottom, manipulating the porphyrin-enclosed biomimetic structures via self-assembly, that facilitates the electro-luminescence conversion as well, comprises the essential idea when being carried forward towards the foregoing motivation. In this sense, it presumes practically the two-dimensional imaging and simultaneous quantification of various kinds of markers, which once realized would consequently promote the specificity and the precision of early cancer diagnostics. The outline of this research contains several successive sections, primarily the porphyrin-based ECL behaviors and mechanisms, the selection of porphyrins with high luminous efficiency, the most optimal coreactant for synergizing their ECL emanation, the ultrasensitive multi-wavelength ECL visualizing strategies by integrating porphyrin complexes, and the tentative early cancer detections in association with classical labels (e.g., Ru(bpy)32+). This project is considered to be an advanced and deepening development of ECL imaging concept in addition to its corresponding technique, meanwhile a quest of innovative analytical means for solutions to ECL-concerned clinical issues. It is believed that the outcome of this investigation would promise a expansive perspective in the fields of medical inspection, health monitoring, bio-″omics″, etc.

鉴于肿瘤的发生发展关系到多种标志物的产生与浓度变化，传统电致化学发光(ECL)体系对单组分的光强传感方式已不能满足现代生物医学分析的要求，面向多肿瘤标志物的新探测理论及检测手段已是ECL技术发展的必然趋势。本项目利用有机相ECL的肉眼可见与其水相易淬灭在生物分析中难以调和的矛盾，拟探索一类基于多色基团标记的ECL成像探测方法，其核心思想是利用保护卟啉的自组装仿生结构促进其电光转换，对多组分标志物进行二维成像定量，从而有效提高癌症诊断的特异性和准确度。研究内容主要包括卟啉基ECL行为和机理、高效ECL卟啉的筛选、最佳共反应物匹配、基于卟啉生物复合物的多波长ECL高灵敏成像方法，及与经典探针(如钌联吡啶)联立的多色标记早期诊断试验研究。本项目是对ECL成像理论与技术研究的进一步深化和发展，为解决ECL临床诊断问题探索新检测策略，研究成果将在医学检验、健康监测和生物组学等领域具有广泛应用前景。

传统电致化学发光(ECL)体系对单组分的光强传感方式已不能满足现代生物医学分析的要求，面向多肿瘤标志物的新探测理论及检测手段已是ECL技术发展的必然趋势。鉴于此，本项目探索并确立了一类基于多色基团标记的ECL成像探测技术。其研究方法的核心是利用保护卟啉的自组装仿生结构促进其电光转换，对多组分标志物进行成像定量，从而有效提高癌症诊断的特异性和准确度。项目执行期内，在本领域SCI期刊发表论文11篇，其中一作/通讯作者9篇，含SCI一区和Nature Index期刊7篇、《中国科技期刊卓越行动计划入选项目》划定的国内高质量学术期刊1篇；影响因子>10的3篇；同时，申请国家发明专利11项，转让3项；参加国际会议7次，做分会场报告4次；培养硕士研究生12名。总体而言，我们发展并揭示了系列新的ECL分析原理，并确立了新的共反应物、光敏剂和局部富集办法；用于开展涉及多个标志物的ECL成像肿瘤诊断，最终实现了生物靶标分子的特异性成像检测。这些新的ECL发光材料、机制、方法和平台有望为ECL生物图像分析提供有效的理论与技术支撑。