Kang Hanyue, Xiong Yuting, Ma Liang, Yang Tongqing, Xu Xiaobin
School of Materials Science and Engineering, Tongji University Shanghai 201804 China
State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University Hangzhou 310058 China
RSC Adv. 2022 Dec 6;12(54):34892-34903. doi: 10.1039/d2ra06339e.
Circulating tumor cells (CTCs) released from the primary tumor to peripheral blood are promising targets for liquid biopsies. Their biological information is vital for early cancer detection, efficacy assessment, and prognostic monitoring. Despite the tremendous clinical applications of CTCs, development of effective separation techniques are still demanding. Traditional separation methods usually use batch processing for enrichment, which inevitably destroy cell integrity and affect the complete information acquisition. Considering the rarity and heterogeneity of CTCs, it is urgent to develop effective separation methods. Microfluidic chips with precise fluid control at the micron level are promising devices for CTC separation. Their further combination with micro-/nanostructure arrays adds more biomolecule binding sites and exhibit unique fluid barrier effect, which significantly improve the CTC capture efficiency, purity, and sensitivity. This review summarized the recent advances in micro-/nanostructure array integrated microfluidic devices for CTC separation, including microrods, nanowires, and 3D micro-/nanostructures. The mechanisms by which these structures contribute to improved capture efficiency are discussed. Two major categories of separation methods, based on the physical and biological properties of CTCs, are discussed separately. Physical separation includes the design and preparation of micro-/nanostructure arrays, while chemical separation additionally involves the selection and modification of specific capture probes. These emerging technologies are expected to become powerful tools for disease diagnosis in the future.
从原发性肿瘤释放到外周血中的循环肿瘤细胞（CTCs）是液体活检很有前景的靶点。它们的生物学信息对于癌症早期检测、疗效评估和预后监测至关重要。尽管CTCs在临床上有大量应用，但开发有效的分离技术仍很有必要。传统的分离方法通常采用批量处理进行富集，这不可避免地会破坏细胞完整性并影响完整信息的获取。考虑到CTCs的稀有性和异质性，迫切需要开发有效的分离方法。具有微米级精确流体控制的微流控芯片是用于CTCs分离很有前景的装置。它们与微/纳米结构阵列的进一步结合增加了更多生物分子结合位点，并展现出独特的流体屏障效应，这显著提高了CTCs的捕获效率、纯度和灵敏度。本文综述了用于CTCs分离的微/纳米结构阵列集成微流控装置的最新进展，包括微棒、纳米线和三维微/纳米结构。讨论了这些结构有助于提高捕获效率的机制。基于CTCs的物理和生物学特性，分别讨论了两大类分离方法。物理分离包括微/纳米结构阵列的设计和制备，而化学分离还涉及特定捕获探针的选择和修饰。这些新兴技术有望在未来成为疾病诊断的有力工具。
