Enrichment of Hyaluronic Acid Binding Tumor Cells by Modulation of Selective Adhesion on Microgel Surfaces

Liquid biopsy‐based detection of cells with specific biomarker profiles is critical for cancer diagnostics and treatment. Here, we present a novel method for the selective enrichment of CD44‐expressing tumor cells from blood using thermoresponsive microgel surfaces functionalized with hyaluronic acid (HA). A key feature of our approach is the precise modulation of CD44–HA interactions through the microgels’ volume phase transition temperature (VPTT). Lowering the temperature from 37°C to 30°C induces swelling of the microgel layer, thereby diminishing adhesive interactions and promoting the detachment of weakly adhering white blood cells (WBCs), while strongly adherent tumor cells remain captured. Flow cytometry analysis studies further reveal that tumor cells with elevated CD44 expression exhibit persistent adhesion on HA‐functionalized surfaces. Given the straightforward fabrication process and the versatility for incorporating various biomarkers via chemical synthesis, this temperature‐responsive microgel platform holds promise for the efficient capture of circulating tumor cells (CTCs) present in the blood of cancer patients and other challenging diagnostic applications.