柔性静电纺丝传感界面用于汗液中疾病标志物IL-6的可视化检测和成像

The noninvasive, high sensitive and real-time monitor of disease markers plays a significant role in tumor early diagnosis, disease monitoring and drug research. However, due to relatively low sensitivity, short of detectable analytes and much more sweat volume, it remains a challenge to apply the flexible sensing interfaces to continuously monitor disease markers in sweat. Herein, we propose to further study and fabricate flexible electrospun sensing interfaces for imaging and visual detection of disease markers in sweat. First of all, to improve the flexibility of electrospun sensing interfaces that can directly act on the skin to quickly and efficiently capture protein molecules of sweat. Second, understanding the color change mechanism of polymers responding to amino acids, try to regulate the fluorescence signal of electrospun sensing interfaces. Third, using disease marker IL-6 as target model, aptamer with a high affinity is utilized to develop double-fluorescence signal strategy to get improved detection with high confidence level and high Signal to Noise Ratio. In addition, to develop the method to rapidly, real-time, ultra-sensitively detect IL-6 in sweat, and further monitor its concentration change after drug treatment. We seek a great potential of this project in the fields of early diagnosis of tumor, disease monitoring and drug research.

非侵入式、高灵敏、实时监测疾病标志物浓度变化对肿瘤的早期诊断、疾病监测和药物研究有着重要意义。柔性传感界面已用于连续监测汗液中疾病标志物，但目前还存在一些限制，如灵敏度不足，检测对象有限，需汗液体积过多等。本项目拟深入进行柔性传感界面的基础研究：（1）发展改善静电纺丝柔性的策略，直接用于皮肤表面纳升汗液中蛋白质的快速高效富集；（2）研究氨基酸诱导聚合物颜色变化机制，发展荧光调控方法，构建氨基酸响应型柔性静电纺丝荧光传感界面；（3）以细胞因子IL-6为疾病标志物模型，利用核酸适配体的高效识别能力，与柔性静电纺丝传感界面相结合，发展双荧光信号策略用于原位识别传感界面上的靶分子，提高检测信噪比和可信度。（4）运用柔性传感界面和双荧光信号策略，发展快速实时检测汗液中IL-6的超灵敏传感方法，探讨药物刺激与IL-6浓度变化的关联。本项目预期成果有望为肿瘤早期诊断、疾病监测和药物研究提供有力分析手段。

非侵入式、高灵敏、实时监测疾病标志物浓度变化对肿瘤的早期诊断、疾病监测和药物研究有着重要意义。本项目的主要工作如下：（1）基于静电纺丝纳米纤维膜发展了一种简单、无标记的多重放大纳米传感平台，实现了疾病 DNA 标志物的超灵敏可视化检测。如利用HCV核心蛋白(HCVcp)、G-四联体/hemin DNAzyme和静电纺丝膜表界面的催化发夹组装(CHA)扩增反应，设计了一种等离子体纳米平台，实现了对HCVcp等的检测。（2）发展了多种在静电纺丝传感平台上特异性生物识别事件进行信号转换和放大策略，如结合新型PiDSD反应设计、膜表界面的CHA放大反应和ThT荧光信号报告，实现一步法检测凝血酶及核酸标志物。（3）利用静电纺丝的局域效应调控分子结构，实现了可视化检测致龋pH临界点等。（4）发展了新型单分子水平分析策略，设计了包括共臂分子信标和锁核酸等多种分子探针，成功实现了肿瘤标志物ctDNA及单核苷酸差异的同时区分，T790M序列和野生型序列的同时区分。本项目预期成果有望为肿瘤早期诊断、疾病监测和药物研究提供有力分析手段。