循环肿瘤细胞富集技术研究进展

doi:10.3969/j.issn.1673-8640.2022.01.019

摘要/Abstract

摘要：

循环肿瘤细胞（CTC）是从原发性或转移性肿瘤部位脱落至循环系统的极少量的肿瘤细胞,与肿瘤的转移密切相关。从血液样本中分离出CTC并对其进行后续分析,对了解细胞水平的肿瘤转移和疾病临床管理都至关重要。由于CTC在血液中含量极少,难以被富集,因此限制了其临床应用。近年来,随着富集分离技术的不断进步,CTC作为肿瘤生物标志物对疾病进行预后评估逐渐成为研究热点。文章综述了CTC分离技术的最新进展,介绍了该类技术的临床应用并讨论其优缺点、未来展望和技术难题,力求为后续开展相关研究提供参考。

关键词: 循环肿瘤细胞, 富集分离, 微流控

Abstract:

Circulating tumor cells（CTC）are a few tumor cells that are shed from the site of a primary or metastatic tumor into the circulatory system. As such,the isolation of CTC from blood samples and their subsequent analysis are of importance not only for understanding cancer metastasis at the cellular level but also for clinical management of the disease. Since the content of CTC in blood is too scarce to be enriched,which has become the bottleneck restricting its clinical application. In recent years,with the development of separation and enrichment techniques,CTC as a tumor biomarker for disease prognosis evaluation has become a hot topic. This review aims to review the latest advances of CTC isolation technology in cancer diagnosis,introduces the application examples of this technology,and discusses its advantages and disadvantages,prospects and technical challenges,to provide a reference for follow-up research.

Key words: Circulating tumor cell, Enrichment and separation, Microfiltration

中图分类号:

R446.1

沈素雅, 黄建钊, 李小怀. 循环肿瘤细胞富集技术研究进展[J]. 检验医学, 2022, 37(1): 91-96.

SHEN Suya, HUANG Jianzhao, LI Xiaohuai. Progress on the enrichment technology of circulating tumor cells[J]. Laboratory Medicine, 2022, 37(1): 91-96.

图/表 3

参考文献 37

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特性	原理	应用方法	优点	缺点
物理特性	大小差异	膜滤过法、密度梯度离心法	设计和操作简单、不受表面标志物影响	纯度低、敏感性低、实用性有限
	流体力学	DLD技术、惯性聚焦技术、涡流捕获技术	通量高、纯度高、无需生物学标志、不易阻塞	准确率低
	超声波	声波细胞分选	温和、无需配体、生物兼容	通量低
	细胞电学特征	电泳富集法	调控简单、可重复性强、纯度高、存活率高	富集效率偏低
化学特性	抗体	免疫磁珠法、固载抗体微通道	特异性高、选择性强、敏感性高	重复性差、保存期短、成本高、过程复杂
	适配体	适配体捕获法	亲和力高、可重复性强、保质期长、条件温和	成本高

特性	原理	应用方法	优点	缺点
物理特性	大小差异	膜滤过法、密度梯度离心法	设计和操作简单、不受表面标志物影响	纯度低、敏感性低、实用性有限
	流体力学	DLD技术、惯性聚焦技术、涡流捕获技术	通量高、纯度高、无需生物学标志、不易阻塞	准确率低
	超声波	声波细胞分选	温和、无需配体、生物兼容	通量低
	细胞电学特征	电泳富集法	调控简单、可重复性强、纯度高、存活率高	富集效率偏低
化学特性	抗体	免疫磁珠法、固载抗体微通道	特异性高、选择性强、敏感性高	重复性差、保存期短、成本高、过程复杂
	适配体	适配体捕获法	亲和力高、可重复性强、保质期长、条件温和	成本高

特性	实验技术	原理	研究结果	文献
物理性质	三角形微柱DLD阵列芯片	尺寸和变形性	细胞发生变形;流速为2 000 μL/min,捕获率为95%。	LUI等^[32]
	直管道微流控芯片	力学性质	流速100~300 μL/min,肿瘤细胞活性高（89%~91%）,可用于后续检测	PARK等^[33]
	放置声波传感器	声波分选	临床分离效果好;分选速度达7.5 mL/h,捕获率>86%	DING等^[34]
	Cluster-Chip	物理捕获CTC-cluster	实现CTC-cluster的高效物理捕获,保持了细胞簇的完整性	SARIOGLU等^[35]
化学特性	鱼骨形微流控分选平台	阳性分选法	捕获效率高、CTC可以在原位进行基因分析,可实现单细胞分离	BRINKMANN等^[36]
	CTC-iChip芯片	阴性分选法	敏感度高,能进一步分析细胞的性质	OZKUMUR等^[37]

特性	实验技术	原理	研究结果	文献
物理性质	三角形微柱DLD阵列芯片	尺寸和变形性	细胞发生变形;流速为2 000 μL/min,捕获率为95%。	LUI等^[32]
	直管道微流控芯片	力学性质	流速100~300 μL/min,肿瘤细胞活性高（89%~91%）,可用于后续检测	PARK等^[33]
	放置声波传感器	声波分选	临床分离效果好;分选速度达7.5 mL/h,捕获率>86%	DING等^[34]
	Cluster-Chip	物理捕获CTC-cluster	实现CTC-cluster的高效物理捕获,保持了细胞簇的完整性	SARIOGLU等^[35]
化学特性	鱼骨形微流控分选平台	阳性分选法	捕获效率高、CTC可以在原位进行基因分析,可实现单细胞分离	BRINKMANN等^[36]
	CTC-iChip芯片	阴性分选法	敏感度高,能进一步分析细胞的性质	OZKUMUR等^[37]