Antibody‐Functionalized DNA Hydrogels Recognize and Isolate Living Tumor Cells

Abstract DNA nanostar hydrogels are a novel class of biocompatible and programmable materials with promising applications as a cell matrix for tissue engineering or cancer diagnosis. Yet, precise isolation of specific cell types with these hydrogels has remained elusive without specific interaction between DNA and cell membrane. Here, a DNA nanostar hydrogel–based method is reported for cell isolation, achieved by interfacing living cells with the hydrogel via an antibody‐functionalized DNA motif. As a proof of concept, epithelial cell adhesion molecule (EpCAM)‐positive cells are isolated—a model of circulating tumor cells—whose separation from white blood cells is crucial for early cancer diagnosis. By optimizing the antibody‐DNA conjugate, a specific binding is achieved between target cells and the DNA gel, enabling the capture of up to 90% of cells. The cells are selectively enriched from a mixture of different cell types using parallelized and iterative capture. The cells recover by dissociating the gel using strand displacement, retain their viability and capacity to proliferate, which supports their future use for culture or analysis. This generalizable method allows coupling of any cell type to DNA gels —supporting future applications ranging from cancer research to recapitulate cellular tumor models in vitro or regenerative medicine to grow designer tissues.