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. However, these methods still suffer from some disadvantages such as time consuming, large volume blood samples required, easy to lose target cells and labor-intensive. Microfluidics, which integrates physical, chemical and biological technologies at microscale level, provides a miniaturized, low-cost and protable tool for efficient CTCs separation. In this review, we cover the recent advances in passive and active microfluidic CTCs separation methods. The detail working principles, biomedical applications, advantages and drawbacks of these methods are discussed, and a novel multistage microfluidic chip for CTCs separation is also proposed. Finally, we discuss the critical concerns and the future trends of CTCs separation microfluidic devices in clinical applications.

Contents
1 Introduction
2 Passive separation techniques
2.1 Microscale filtration
2.2 Field flow and hydrodynamic fractionation
2.3 Deterministic lateral displacement
2.4 Inertia separation
2.5 Biomimetic separation
2.6 Affinity separation
3 Positive separation techniques
3.1 Dielectrophoresis separation
3.2 Magnetic separation
3.3 Acoustic separation
3.4 Optical separation
4 Multistage separation
5 Conclusion and outlook