循环肿瘤细胞(CTCs)出现于癌症患者的外周血中,是一种重要的游离态组织样本,对于癌症的早期诊断和预后评估具有非常重要的临床诊断价值。由于血液中CTCs含量极少,对其进行分选富集是CTCs检测和分析的一个重要预处理步骤。传统的宏观方法虽然也能实现细胞分离,但存在耗时长、样品需求量大、目标细胞损失严重及硬件设备依赖性高等不足。近年来兴起的微流控技术可在微米尺度范围内集成物理、化学及生物手段,易于实现整体器件的微型化和低成本便携式发展,为稀有CTCs的高灵敏度、高效分选提供重要的潜在技术手段。本文综述了微流控技术实现CTCs分选的最新研究进展,详细阐述了各种被动、主动分选方法的原理及成功应用实例,分析各方法的优缺点,提出一种新型的多级分选芯片结构,并最后探讨了微流控CTCs分选芯片在临床应用中面临的挑战及未来的发展趋势。
Circulating tumor cells( CTCs),a "liquid biopsy "circulating in the cancer patients' peripheral blood,play an important role in the therapeutic and diagnostic of cancer. Due to the extremely low concentration of CTCs in blood,enrichment has been regarded as an essential pre-treament step for efficient detection of CTCs.Traditional macroscopic separation schemes have achieved a large success in CTCs enrichment. How ever,these methods still suffer from some disadvantages such as time consuming,large volume blood samples required,easy to lose target cells and labor-intensive. M icrofluidics, w hich integrates physical, chemical and biological technologies at microscale level, provides a miniaturized, low-cost and protable tool for efficient CTCs separation. In this review,w e cover the recent advances in passive and active microfluidic CTCs separation methods. The detail w orking principles,biomedical applications,advantages and draw backs of these methods are discussed,and a novel multistage microfluidic chip for CTCs separation is also proposed. Finally,w e discuss the critical concerns and the future trends of CTCs separation microfluidic devices in clinical applications.