Abstract:

The isolation and analysis of circulating tumor cells (CTCs) is an important issue in tumor research. CTCs in peripheral blood, which are important biomarkers of liquid biopsy, are closely related to the occurrence of cancer and are used to monitor the effect of treatment on cancer patients. However, the number of CTCs in the blood samples of cancer patients is very low, usually being present at only 0-10 CTCs/mL. Therefore, prior to the detection of CTCs, it is important to preprocess clinical blood samples for efficient separation and enrichment. With the advantages of low sample consumption, high separation efficiency, ease of automation and integration, microfluidic chips can be a suitable platform for the isolation of CTCs. In the last few years, CTC separation and detection using microfluidic chips have developed rapidly, and a variety of detection methods have been developed. According to the technical principle used, microfluidics for CTC separation can be divided into biological property-based methods and physical property-based methods. The biological property-based methods mainly depend on the interaction between the antigen and antibody, or the specific binding of the aptamer and target. These methods have high selectivity but low efficiency and recovery rates. Physical separation is based on the physical properties of CTCs such as their size, density, and dielectric properties. For example, CTCs can be blocked or captured by the microstructure in the channels of microfluidic chips, sorted by external physical fields (acoustic, electrical, magnetic), or screened by micro-scale hydrodynamics. Physical property-based methods generally have a higher flux but lower separation purity. However, the advantages of biological property-based methods and physical property-based methods can be integrated to provide microfluidic chips having better separation performance. In addition to the direct positive enrichment of CTCs, a negative enrichment strategy can also be adopted. The influence of direct screening on the activity of CTCs can be avoided by selectively removing white blood cells. In this paper, recent advances in microfluidics utilized in the isolation of CTCs, including physical and immune methods and positive and negative enrichment, are reviewed. We summarized the technical principles, detection methods, and research progress in CTC separation and detection using microfluidic chips. Developing trends in microfluidics for CTC separation and analysis are also discussed.

Key words: microfluidics, circulating tumor cells (CTCs), separation and detection