Precise Capture and Dynamic Release of Circulating Liver Cancer Cells with Dual‐Histidine‐Based Cell Imprinted Hydrogels

Abstract Circulating tumor cells (CTCs) detection presents significant advantages in diagnosing liver cancer due to its noninvasiveness, real‐time monitoring, and dynamic tracking. However, the clinical application of CTCs‐based diagnosis is largely limited by the challenges of capturing low‐abundance CTCs within a complex blood environment while ensuring them alive. Here, an ultrastrong ligand, l ‐histidine– l ‐histidine (HH), specifically targeting sialylated glycans on the surface of CTCs, is designed. Furthermore, HH is integrated into a cell‐imprinted polymer, constructing a hydrogel with precise CTCs imprinting, high elasticity, satisfactory blood compatibility, and robust anti‐interference capacities. These features endow the hydrogel with excellent capture efficiency (>95%) for CTCs in peripheral blood, as well as the ability to release CTCs controllably and alive. Clinical tests substantiate the accurate differentiation between liver cancer, cirrhosis, and healthy groups using this method. The remarkable diagnostic accuracy (94%), lossless release of CTCs, material reversibility, and cost‐effectiveness ($6.68 per sample) make the HH‐based hydrogel a potentially revolutionary technology for liver cancer diagnosis and single‐cell analysis.