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Herein, we present a programmable molecular device that integrates Boolean logic computation with spatial confinement to overcome these limitations. Our system employs valence\u2010controllable, split DNAzyme modules assembled on a tetrahedral DNA nanostructure (TDN). The peroxidase\u2010mimicking activity is stringently gated by a cell\u2010surface AND logic, requiring the co\u2010localization of two adjacent modules on target protein clusters for activation. This spatial constraint effectively eliminates stochastic or unintended signal leakage originating from solution\u2010phase reactions or nontarget cells. Upon activation, the DNAzyme catalyzes the biotinylation of neighboring membrane protein clusters, generating stable multivalent adhesion sites. Quantitative dissociation kinetics reveal that the trivalent design of the DNAzyme modules promotes highly cooperative binding, resulting in uniform, long\u2010lived complexes on target cells. We demonstrate that this approach enables specific recognition and highly efficient isolation of target cells from mixed cell populations and clinical samples, showcasing a strategy for programming high\u2010fidelity molecular interactions on interested cell surfaces.<\/jats:p>","DOI":"10.1002\/anie.5650963","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:21:53Z","timestamp":1784888513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Co\u2010Localization\u2010Gated Multivalent DNA Logic Gate for Programmable Cell Recognition"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4997-2663","authenticated-orcid":false,"given":"Miao","family":"Mao","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010Sen University  Guangdong 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