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一种用于有效捕获和高纯度回收循环肿瘤细胞的三维导电支架微芯片。

A Three-Dimensional Conductive Scaffold Microchip for Effective Capture and Recovery of Circulating Tumor Cells with High Purity.

机构信息

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.

Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.

出版信息

Anal Chem. 2021 May 11;93(18):7102-7109. doi: 10.1021/acs.analchem.1c00785. Epub 2021 Apr 28.

Abstract

Effective acquirement of highly pure circulating tumor cells (CTCs) is very important for CTC-related research. However, it is a great challenge since abundant white blood cells (WBCs) are always co-collected with CTCs because of nonspecific bonding or low depletion rate of WBCs in various CTC isolation platforms. Herein, we designed a three-dimensional (3D) conductive scaffold microchip for highly effective capture and electrochemical release of CTCs with high purity. The conductive 3D scaffold was prepared by dense immobilization of gold nanotubes (Au NTs) on porous polydimethylsiloxane and was functionalized with a CTC-specific biomolecule facilitated by a Au-S bond before embedding into a microfluidic device. The spatially distributed 3D macroporous structure compelled cells to change migration from linear to chaotic and the densely covered Au NTs enhanced the topographic interaction between cells and the substrate, thus synergistically improving the CTC capture efficiency. The Au NT-coated 3D scaffold had good electrical conductivity and the Au-S bond was breakable by voltage exposure so that captured CTCs could be specifically released by electrochemical stimulation while nonspecifically bonded WBCs were not responsive to this process, facilitating recovery of CTCs with high purity. The 3D conductive scaffold microchip was successfully applied to obtain highly pure CTCs from cancer patients' blood, benefiting the downstream analysis of CTCs.

摘要

有效获取高纯度的循环肿瘤细胞(CTC)对于 CTC 相关研究非常重要。然而,由于各种 CTC 分离平台中白细胞(WBC)与 CTC 非特异性结合或 WBC 耗尽率低,因此通常会与 CTC 一起被共采集,这是一个巨大的挑战。在此,我们设计了一种用于高纯度高特异性捕获和电化学释放 CTC 的三维(3D)导电支架微芯片。该导电 3D 支架是通过将金纳米管(AuNT)密集固定在多孔聚二甲基硅氧烷上来制备的,并通过 Au-S 键功能化,然后嵌入微流控装置中。空间分布的 3D 大孔结构迫使细胞从线性迁移转变为混沌迁移,而密集覆盖的 AuNT 增强了细胞与基底之间的形貌相互作用,从而协同提高了 CTC 的捕获效率。AuNT 涂层的 3D 支架具有良好的导电性,Au-S 键可在电压暴露下断裂,因此可以通过电化学刺激特异性释放捕获的 CTC,而非特异性结合的 WBC 对此过程没有响应,从而有利于高纯度 CTC 的回收。该 3D 导电支架微芯片成功地从癌症患者的血液中获得了高纯度的 CTC,有利于 CTC 的下游分析。

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