Recent advances in microfluidic technologies for circulating tumor cell isolation: from separation strategies to clinical translation

Circulating tumor cells (CTCs) are promising liquid-biopsy biomarkers for cancer diagnosis, treatment monitoring, metastasis assessment, and precision therapy. However, their clinical utility is constrained by extreme rarity, pronounced heterogeneity, and substantial interference from blood cells. Microfluidic technologies have emerged as powerful platforms for CTC isolation because they enable precise fluid control, continuous processing, low sample consumption, and facile integration. This review surveys recent advances in microfluidic CTC isolation, with emphasis on physical force-based strategies, including size-based separation, hydrodynamics, dielectrophoresis, and acoustofluidics, as well as affinity-based approaches relying on antibodies, aptamers, or other recognition ligands. Particular attention is given to surface-engineered microfluidic systems, where micro/nanostructures, antifouling chemistries, and biomimetic interfaces reduce nonspecific blood-cell adhesion and improve isolation purity and reproducibility. We further discuss key barriers to clinical translation, including limited adaptability to real patient samples, performance variability, insufficiently defined clinical scenarios, lack of standardized evaluation criteria, and challenges in engineering integration. Overall, microfluidic platforms offer versatile solutions for high-efficiency and high-purity CTC isolation, and future progress will depend on multimodal integration, standardized design, and clinically oriented optimization.