The　ubiquitous　biomembrane　interface,　with　its　dynamic　lateral　fluidity,　allows　membrane-bound　components　to　rearrange　and　localize　for　high-affinity　multivalent　ligand-receptor　interactions　in　diverse　life　activities.　Inspired　by　this,　we　herein　engineered　a　fluidic　multivalent　nanointerface　by　decorating　a　microfluidic　chip　with　aptamer-functionalized　leukocyte　membrane　nanovesicles　for　high-performance　isolation　of　circulating　tumor　cells　(CTCs).　This　fluidic　biomimetic　nanointerface　with　active　recruitment-binding　afforded　significant　affinity　enhancement　by　4　orders　of　magnitude,　exhibiting　7-fold　higher　capture　efficiency　compared　to　a　monovalent　aptamer　functionalized-chip　in　blood.　Meanwhile,　this　soft　nanointerface　inherited　the　biological　benefits　of　a　natural　biomembrane,　minimizing　background　blood　cell　adsorption　and　maintaining　excellent　CTC　viability　(97.6%).　Using　the　chip,　CTCs　were　successfully　detected　in　all　cancer　patient　samples　tested　(17/17),　suggesting　the　high　potential　of　this　fluidity-enhanced　multivalent　binding　strategy　in　clinical　applications.　We　expect　this　bioengineered　interface　strategy　will　lead　to　the　design　of　innovative　biomimetic　platforms　in　the　biomedical　field　by　leveraging　natural　cell-cell　interaction　with　a　natural　biomaterial.