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During the treatment of liver failure, the rapid and efficient adsorption and removal of bilirubin from whole blood via hemoperfusion remain a significant clinical challenge, since whole blood contains not only bilirubin but also other essential components, such as erythrocytes, leukocytes, and platelets. Herein, modified polyethersulfone (PES) microspheres based on the imidazole\u2010functionalized quaternary ammonium salts (IQASs) are fabricated using phase inversion and electrostatic spraying techniques. Subsequently, the adsorption mechanism of the IQASs is systematically investigated, and the modified PES microspheres containing different IQASs are prepared for verification. The prepared hemoperfusion adsorbent (PES\/VI8\u2010AANa) achieves a bilirubin clearance ratio exceeding 95% in PBS. Additionally, it achieves a clearance ratio of over 60% within 120 min in plasma, and demonstrates excellent biocompatibility. Furthermore, in animal model validation, the fabricated microspheres exhibit a bilirubin clearance ratio exceeding 50% in whole blood within 120 min, with no significant reduction in albumin and globulin levels. This study presents a systematic and comprehensive methodology aimed at developing a highly efficient whole\u2010blood adsorbent for bilirubin removal, thereby advancing its potential application in clinical therapeutics.<\/jats:p>","DOI":"10.1002\/adhm.202503176","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T12:19:25Z","timestamp":1767097165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Imidazole\u2010Functionalized Quaternary Ammonium Salts Modified Polyether Sulfone Microspheres for Highly Efficient Bilirubin Removal in Whole Blood"],"prefix":"10.1002","volume":"15","author":[{"given":"Ningyue","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Nephrology Kidney Research Institute West China Hospital of Sichuan University  Chengdu 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