纸基三维聚合物刷结构调控与循环肿瘤DNA液体活检快速分析

In this project, in view of the demand for high sensitivity and rapid detection of non-invasive liquid biopsy, flexible polymer brush featuring maintaining the wettability of the paper substrate is fabricated onto paper-chips to establish a low-cost, highly sensitive non-invasive home detection of tumor for early warning diagnosis. Based on the adjustment of main chain and side chain of polymers, a three-dimensionally paper-based flexible organic sensing interface was built up via the matching of network structures of fibers with steric configuration of polymers, which overcomes the defects of the nonspecific protein absorbance when inorganic nanomaterials is utilized and possesses the merits of high loading, oriented control and anti-fouling. A water-tolerated perovskite solar cell structure-like photoelectrode was prepared with the dual-directionally intelligent regulation channels of electrons and holes established to solve the recombination issues of electrons and holes in traditional photoelectric conversion process. Intelligent responsive switch is firstly implanted onto paper substrate to control the transition between hydrophilic and hydrophobic properties of the paper paths and transport the liquid timely, thus breaking through the limitation of irreversible hydrophobic property of paper substrate when treated by hydrophobic wax. By means of such intelligent responsive switch, the liquid flow as well as the area, time, place and rate of the reaction could be accurately controlled and the spatial and timing difference of the matter was easily observed. In addition with the development of in-situ isothermal nucleic acid amplification method, an innovative bimodal detection of ctDNA was realized by the comparison and verification of visually rapid detection and photoelectrical accurate analysis. Finally, three-dimensionally integrated functionalized paper based devices are integrated with other signal reading instruments to pave a path for future development of the popular liquid biopsy detecting technology.

针对非侵入式液体活检高灵敏快速分析需求，本项目在纸芯片上引入有机材料，制备保持纸基浸润性的柔性聚合物刷，实现低成本、高灵敏肿瘤早期诊断的家居式无创检测。调节主、侧链结构，借助纸纤维立体网状结构与聚合物空间构型的匹配与调控，克服无机纳米材料对蛋白质的非特异性吸附，构筑高负载、定向控制、抗污染纸基三维柔性有机传感界面；制备纸基耐水钙钛矿电池结构材料，构建电子-空穴的双向智能调控通道，解决传统光电转换电子空穴复合问题；植入亲水智能响应开关，控制纸纤维亲疏水的切换与液体的适时输送，打破纸基单向疏水的单一传统方法局限；设计自供能内置光源，发展在线生物分子恒温扩增方法，借助智能响应开关控制液体流通与反应的区域、时间、空间与速度，依据物质时空差异的行程轨迹与尺度，实现循环肿瘤DNA可视化快检与光电精检双模式对比与验证检测；研究三维纸芯片集成、一点进样多点输出的“傻瓜式”操作，推动大众化液体活检技术发展。

针对非侵入式液体活检高灵敏快速分析需求，本项目在纸芯片上引入有机材料，构筑了高负载、定向控制、抗污染纸基三维柔性有机传感界面，研究了纸基聚合物刷制备的方法和性能，解决了生物分子非特异性吸附问题，揭示了聚合物刷表面负载生物识别分子机制与影响因素。借助纸纤维立体网状结构，在纸纤维表面生长多种功能纳米材料，在增强纸基材导电性的同时提高其比表面积，以负载更多的生物识别分子。借助溶剂热生长技术，实现了纸基材半导体金属氧化物的功能化，赋予了纸基材优异的光电转换性能。制备纸基耐水钙钛矿电池结构材料，构建电子-空穴的双向智能调控通道，解决传统光电转换电子空穴复合问题，设计开发了新型光电功能材料生长方法及其微观结构优化，引入了载流子传输层、极化电场、晶面异质结等载流子分离新策略。植入亲水智能响应开关，控制纸纤维亲疏水的切换与液体的适时输送，研究了纸基智能响应开关的设计及性能，设计集试剂预埋存储、纳米酶试剂传输、显色直读功能集成芯片。基于杂交链反应及酶促级联反应，利用DNA walker，CRISPR/Cas技术发展在线生物分子恒温扩增方法，借助智能响应开关控制液体流通与反应的区域、时间、空间与速度，依据物质时空差异的行程轨迹与尺度，纸基双模式信号采集、级联光敏结构纸芯片构筑、三维贵金属形貌调控、多级信号放大策略的设计，有效提高纸基传感平台分析性能，研究了三维纸芯片集成、一点进样多点输出的“傻瓜式”操作，推动大众化液体活检技术发展，实现低成本、高灵敏肿瘤早期诊断的家居式无创检测。