Advance in Novel Methods for Enrichment and Precise Analysis of Circulating Tumor Cells

Abstract The dissemination of circulating tumor cells (CTCs) in peripheral blood is an important intermediate step for cancer metastasis. It has become one of the most promising targets of “liquid biopsy”, on account of providing complete information of cell biology. However, due to the extremely rarity, complex environment and strong heterogeneity of CTC in peripheral blood, the development of efficient enrichment and separation methods are the key in the accurate detection of CTC. Currently reported CTC enrichment and analysis techniques are mainly based on the physical or biological characteristics of CTC. They are commonly combined with the traditional techniques including density gradient centrifugation, superfine membrane filtration and immunomagnetic separation, the novel methods such as microfluidic chip separation and two-dimensional electrophoresis-field separation, and the analysis techniques such as reverse transcription-polymerase chain reaction, flow cytometry, immunocytochemistry, photoacoustic imaging, surface-enhancement Raman scattering and electrochemistry to realize accurate detection of CTC. In this review, we summarized the recent processes on enrichment and novel detection methods of CTC and discussed the challenges and their clinical application status, which could provide reference for the further improvement of the technology of enrichment, accurate counting and molecular phenotype analysis for CTC, as well as the application in scientific research and clinical practice.