新型POSS基纳米生物探针构建及基于微流控技术的肿瘤标志物多分子检测研究

As popular awareness of the importance of cancer early diagnosis increases, the controllable nanodevices and detection methods which based on new functional nanomaterials and can perform accurate tumor biomarkers detection are becoming more and more compelling. Microfluidic biochip with multiple advantages，such as low sample consumption, fast response time and high throughput, appears to be a promising alternative. In this program, new strategy for the design of conjugated molecules with special functionalization and good optical properties will be developed. Furthermore, surface amendable conjugated oligomer-substituted POSS, which is a special family of inorganic-organic hybrid materials with nanocage structure (POSS NPs)，will be designed and synthesized. Various bioconjugation technique, ordered assembly of biomolecules on the nanoparticles, and the interaction of the nanoparticles and biomolecules will be investigated comprehensively to fabricate organic/inorganic hybrid materials with high stability and good biocompatibility. The successful conjugation of biomolecules to star-shaped POSS NPs also suggests that such POSS NPs formation has a bright future in interaction with tumor biomarkers to construct high-quality POSS bio-nanoprobe. Moreover, a novel microfluidic protein biochip based on POSS bio-nanoprobe will be developed for simultaneous detection of multiple tumor biomarkers in buffer solution and serum, which may be useful for early cancer diagnosis and proteomics. Taking advantage of the microfluidic biochip technology, the excellent structure and fluorescence properties of POSS bio-nanorobe, and the ordered assembly of biomolecules, this strategy may achieve ultrasensitive and selective detection of multiple tumor biomarkers. Moreover, this new platform of POSS bio-nanoprobe based microfluidic biochip will inspire new application opportunities of microfluidic biochip in many fields such as biomedical research.

针对“恶性肿瘤的早期诊断”这一科学问题，设计、构建以新型功能性纳米材料为基础的肿瘤标志物多分子联合检测模式及可控微纳器件，对肿瘤的早期检测和临床治疗具有十分重要的意义。本项目拟利用分子工程方法优化有机共轭分子结构设计，并在分子水平上将有机共轭分子和无机倍半硅氧烷有效结合在一起，制备各项性能优异、高稳定性和高生物相容性的枝状（星型）POSS/有机发光共轭分子纳米杂化材料；通过探索及优化多类生物耦合技术及生物有序组装方法，并进一步研究纳米粒子与生物分子的相互作用机制，构建高性能（高稳定性、高灵敏度、高靶向性、低交叉反应性）的POSS/有机发光寡聚物纳米生物复合探针；进而与纳米微流器件相结合，设计与开发用于肿瘤多分子标志物检测的微流控生物芯片平台；希望通过结合POSS/有机发光寡聚物纳米生物探针和微流控芯片技术的优势，并提出利用生物分子介导的有序组装方法，提高肿瘤标志物诊断的敏感性、特异性和靶向性，开发一种高灵敏和高特异性的多肿瘤标志物纳米微流控芯片检测系统；并通过对缓冲溶液或血清样本中肿瘤多分子标志物的联合检测，评估它们对肿瘤早期诊断及预后疗效的应用价值。

恶性肿瘤已成为目前严重危害人类健康的主要疾病之一，是造成人类死亡的主要原因之一，发展肿瘤标志物检测与早期治疗新方法对克服癌症,提高患者治愈率和生存率具有重要意义。基于有机共轭分子的新型纳米生物探针具有很高的摩尔吸光系数，良好的生物相容性，荧光强度高，发光时间长，光化学稳定性好等特性，在生物传感、荧光成像及肿瘤诊疗等方面逐渐成为热点研究领域。本项目旨在开发具有优异光学性能的有机共轭分子探针，用于肿瘤的早期检测和治疗。在项目的资助下，课题的研究工作主要围绕有机共轭分子光电功能材料设计、制备及应用开展，主要研究内容包括设计制备了几类以倍半硅氧烷为核，水溶性有机共轭分子作为臂的POSS基有机无机杂化材料并对合成方法进行优化。利用AutoCAD设计了微流控芯片通道，将POSS基有机共轭探针与微流控芯片结合用于肿瘤标志物和核酸的检测。同时我们结合新型有机共轭分子具有的优异光学性能，进一步探索了材料在肿瘤检测和治疗领域的应用，并取得了较好的研究成果，表明有机共轭分子在肿瘤检测和治疗领域具有较大的应用潜力，对研发有机无毒肿瘤诊疗试剂具有较高的现实意义。