用于CTCs高效俘获与无损脱附的温敏形变PNIPAm-PDMS复合纳米柱阵列微通道芯片研究

Circulating tumor cells (CTCs) have important applications in early diagnosis of tumor metastasis. The recent technologies for CTCs capturing and separating are based on cell size or specific immunoadsorption of cell-surface molecules, and usually have many defects such as lower detection rate, slower speed and uneasily separated mainly due to the cell heterogeneity.According to the previous reports and our earlier studies, we find that poly (dimethylsiloxane) (PDMS) nano-column array have highly and specific capacity for CTCs adhesion and capture. In our proposal we will firstly empoly temperature-sensitive poly (N-isopropylacrylamide) (PNIPAm) to modify PDMS nano-column array in order to get the better CTCs which are temperature-sensitive and non-damage desorption; Secondly, we will improve the temperature-sensitive and cell adherence rate by optimizing the nano-column diameter，height and the separation distance of each other; Finally, nano-column arrays were covered and packaged to construct microchannel-array chips,which have the higher reaction rate and efficacy.These proposal will therefore construct a new, effective and specific micro-channel chips based on CTCs' adsorption or non-damage desorption, meanwhile it will provide scientific proof for biological study and clinical assessment of tumor metastasis, relapse ,therapeutic and gene mutation for predicting the drug resistance by CTCs.

循环肿瘤细胞(CTCs)在肿瘤转移早期诊断等方面有重要研究意义与应用价值。现行基于细胞大小或表面特异分子免疫吸附的CTCs检测技术受细胞异质性影响而具有检出率低、速度慢和不易分离获取等不足。相关文献及我们研究表明聚二甲基硅氧烷(PDMS)纳米柱阵列可高效、特异的黏附性俘获CTCs。据此本课题拟采用温敏智能材料-聚N-异丙基丙烯酰胺(PNIPAm)接枝修饰PDMS纳米柱阵列，对CTCs进行温敏性无损脱附；经优化纳米柱直径、柱高、间距、PNIPAm接枝量、温敏性以提高PNIPAm-PDMS纳米柱阵列的CTCs俘获率、特异性及脱附效率；再封装纳米柱阵列以构建微通道芯片，以提高CTCs俘获效率，加快反应速度。本课题旨在建立一种快速、高效、特异的CTCs黏附俘获与温敏无损脱附的微通道芯片检测技术。最终为CTCs在肿瘤转移早期诊断、术后复发、疗效评估及基因突变预测肿瘤患者药物耐等方面的应用提供科学依据。

循环肿瘤细胞(CTCs)在肿瘤转移等方面有重要研究意义与应用价值。基于细胞大小或表面特异分子免疫吸附的CTCs检测受细胞异质性影响而具有检出率低、速度慢等不足。本项目利用1）聚二甲基硅氧烷(PDMS)纳米柱阵列和3D纳米粗糙面实现对CTCs高效而特异的黏附俘获；2）采用温敏智能材料-聚 N-异丙基丙烯酰胺(PNIPAm)接枝修饰PDMS表面，实现对CTCs的温敏性脱附，通过优化纳米柱直径、柱高、间距、PNIPAm 接枝量、温敏性，提高了CTCs的俘获效率及脱附效率；3）封装成微通道芯片系统以提高 CTCs 俘获效率，加快反应速度。最终建立了一种高效的 CTCs 黏附俘获与温敏脱附技术，为 CTCs 用于肿瘤转移诊断、疗效评估等方面提供科学依据。本项目资助下，课题组现已研发制备出一套基于PNIPAm-PDMS纳米3D表面的CTCs微通道芯片检测系统和一套基于切向流-微米孔阵列的循环肿瘤微栓子（CTM）微通道芯片检测系统；现已发表SCI论文1篇（talanta, IF=4.0），在投SCI论文1篇，并有1篇SIC论文撰写中；另发表核心期刊论文1篇，接收1篇。本项目总投入经费23万元，现已支出经费13.32万元，剩余经费9.68万将用于本项目已产生但未结算费用以及后续研究支出。

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