摘要:SummaryCirculating tumor cells (CTCs) enter the vasculature from solid tumors and disseminate widely to initiate metastases. Mining the metastatic-enriched molecular signatures of CTCs before, during, and after treatment holds unique potential in personalized oncology. Their extreme rarity, however, requires isolation from large blood volumes at high yield and purity, yet they overlap leukocytes in size and other biophysical properties. Additionally, many CTCs lack EpCAM that underlies much of affinity-based capture, complicating their separation from blood. Here, we provide a comprehensive introduction of CTC isolation technology, by analyzing key separation modes and integrated isolation strategies. Attention is focused on recent progress in microfluidics, where an accelerating evolution is occurring in high-throughput sorting of cells along multiple dimensions.Graphical abstractDisplay OmittedHighlights•Circulating tumor cells (CTCs) spread cancer through the bloodstream (metastasis)•CTC-based liquid biopsy enables minimally invasive sampling of cancer cells in blood•Their extreme rarity requires all CTC types to be enriched from large blood volumes•CTC isolation technology is analyzed, with a focus on high-throughput microfluidicsBiotechnology; Cell biology; Technical aspects of cell biology