具有刺激响应性纳米结构的芯片技术用于循环肿瘤细胞的检测研究

Detection of circulating tumor cells has important clinical value in the prognosis of cancer diagnosis due to their efficient, real-time and non-invasive advantages. Current characterization is often restricted to the time-consuming, low sensitivity and blood volume problems, which still exists big challenges. This application is about the development of stimuli-responsive nano-structured chip technology for detecting CTCs. We expand research using reflux precipitation polymerization and living polymerization techniques to prepare a series of multiple stimuli-responsive magnetic composite microspheres with high magnetic content and SERS coded microspheres. We focus on the role and efficiency of stimuli-responsive interaction between the polymer shell and tumor cells, leading to the development of new type of magnetic microsphere suspension chips for fast, efficient enrichment and separation of circulating tumor cells in the blood. On this basis, the use of the relevant modification technology obtained earlier can further use for the modification of silicon nanowire array. In this part, we focus on surface-initiated living polymerization techniques to fabricate stimuli-responsive polymer linear chains in order to form multiple stimuli-responsive "NanoVelcro". We finally integrate stimuli-responsive nanostructured microfluidic chips by PDMS soft lithography technology with the goal of improving the detection of circulating tumor cells and their viability, and ultimately capture and detection of circulating tumor cells with high sensitivity as well as high purity in real complex samples.

循环肿瘤细胞（CTCs）的检测因其高效、实时、无创等优势，在癌症预后诊断方面具有十分重要的临床应用价值，现有检测技术在检测时间、灵敏度和采血量等方面仍存在较大挑战。本申请围绕发展具有刺激响应性纳米结构的芯片技术用于CTCs检测研究这一核心目标展开，运用回流沉淀聚合和活性聚合技术，制备一系列高磁含量、具有多重刺激响应的磁性复合微球和SERS编码微球，重点研究刺激响应性聚合物壳层与CTCs的作用效率，发展一类新型磁性微球悬浮芯片，实现快速、高效富集分离CTCs的目标。在此基础上，利用微球表面修饰获得的相关技术用于硅纳米柱晶阵列的表面修饰，重点研究表面引发活性聚合生长刺激响应性聚合物线性链，形成具有多重刺激响应性的“纳米毡”，并由此集成一系列具有刺激响应性纳米结构的微流控芯片。将两种芯片分别通过免疫荧光成像检测技术应用于CTCs检测，最终实现对复杂样本中CTCs高灵敏、高纯度捕获与检测。

液体活检因其高效、实时、无创等优势在肿瘤早期诊断具有十分重要的临床应用价值，本项目围绕发展具有刺激响应性纳米结构的芯片技术这一核心目标展开，运用回流沉淀聚合和活性聚合技术，制备一系列高磁含量、具有pH、GSH、超声、光等多重刺激响应的磁性复合微球和SERS编码微球，发展了一类新型磁性微球悬浮芯片，研究了聚合物壳层与肿瘤细胞的相互作用。在此基础上，发展了硅纳米柱晶阵列的表面修饰，在硅片表面引发活性聚合生长刺激响应性聚合物线性链，形成具有刺激响应性聚合物链的“纳米毡”，并由此集成一系列具有刺激响应性纳米结构的微流控芯片用于CTCs的分离检测。在此基础之上，进一步构筑超分子自组装纳米粒子诊疗一体化平台，使得肿瘤细胞在筛选检测过程中，能够同时将抗癌药物或基因快速、精准传递到肿瘤细胞中，实现诊疗一体化，这在疾病诊治、肿瘤免疫治疗中具有十分重要的临床应用价值。