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However, current sensors are unable to function in unprocessed whole blood due to limitations in chemical stability and cell\u2010targeting capability. Here, we engineer a cell\u2010resolved ultrastable sensor for hematology (CRUSH) via spherical\u2010nucleic\u2010acid (SNA) technology, which enables live\u2010cell detection of leukemia fusion transcripts in unprocessed whole blood. CRUSH employs stoichiometrically controlled thiol protector to achieve a defect\u2010free thiol monolayer on AuNPs. This design feature endows CRUSH with a record\u2010breaking stability, withstanding 0.1\u00a0M dithiothreitol, a 10,000\u2010fold improvement over conventional SNAs. We also demonstrate that the phagocytic bias of myeloid cells over lymphoid cells drives selective internalization of CRUSH in myeloid lineages in whole blood. Leveraging cellular selectivity and engineered stability, CRUSH offers a mixed\u2010and\u2010read diagnostic test, where lyophilized sensors are directly mixed with whole blood samples, followed by standard flow cytometry analysis. This one\u2010step test detects BCR\u2010ABL1 fusions in living myeloid cells with high specificity and robustness, enabling accurate discrimination of multilineage acute lymphoblastic leukemia within 1 h. Our study bridges biosensing innovation with urgent diagnostic needs, offering a rapid, specific, and robust tool for accurate diagnosis and treatment of hematologic malignancies.<\/jats:p>","DOI":"10.1002\/anie.1339483","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:05:32Z","timestamp":1776229532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Cell\u2010Resolved Ultrastable Biosensor Enables One\u2010Step Detection of Gene\u2010Fusion Transcripts in Unprocessed Whole Blood"],"prefix":"10.1002","volume":"65","author":[{"given":"Chuipeng","family":"Kong","sequence":"first","affiliation":[{"name":"Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Analytical &amp; Testing Centre Sichuan University  Chengdu Sichuan P. R. 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