A review of enrichment methods for circulating tumor cells: from single modality to hybrid modality

Circulating tumor cell (CTC) analysis as a liquid biopsy can be used for early diagnosis of cancer, evaluating cancer progression, and assessing treatment efficacy. The enrichment of CTCs from patient blood is important for CTC analysis due to the extreme rarity of CTCs. This paper updates recent advances in CTC enrichment methods. We first review single-modality methods, including biophysical and biochemical methods. Hybrid-modality methods, combining at least two single-modality methods, are gaining increasing popularity for their improved performance. Then this paper reviews hybrid-modality methods, which are categorized into integrated and sequenced hybrid-modality methods. The state of the art indicates that the CTC capture efficiencies of integrated hybrid-modality methods can reach 85% or higher by taking advantage of the superimposed and enhanced capture effects from multiple single-modality methods. Moreover, a hybrid method integrating biophysical with biochemical methods is characterized by both high processing rate and high specificity.