A review of recent progress toward the efficient separation of circulating tumor cells via micro-/nanostructured microfluidic chips

Circulating tumor cells (CTCs) are closely correlated with cancer diagnoses, and their early detection can help patients receive accurate prognoses in a noninvasive manner. However, the rarity, fragility, and heterogeneity of CTCs introduce significant technical challenges to their separation from blood. Recent advances in micro-/nanofabrication techniques have made microfluidic chips better for CTC separation. In this review, we mainly focus on recent progress made in the development of microfluidic chips incorporating micro-/nanostructures for the CTC separation. Specifically, we reviewed two major CTC separation mechanisms, that is, physical and chemical approaches. Representative works on physical mechanism-based approaches (include pillar filtration, cross-flow filtration, deterministic lateral displacement, smart materials, and bionics); immunomagnetic beads, and surface modification; and chemical mechanism-based approaches include diversity of affinity ligand selection, are reviewed. Their advantages and disadvantages are compared and discussed, and a perspective on the future direction of CTC is provided.