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However, proteomic coverage for trace samples is constrained by adsorption loss during repeated elution at sample pretreatment. Here, we demonstrated superparamagnetic composite nanoparticles functionalized with molecular glues (MGs) to enrich proteins in trace human biofluid. We showed high protein binding (&gt;95\u2009%) and recovery (\u224890\u2009%) rates by anchor\u2010nanoparticles. We further proposed a Streamlined Workflow based on Anchor\u2010nanoparticles for Proteomics (SWAP) method that enabled unbiased protein capture, protein digestion and pure peptides elution in one single tube. We demonstrated SWAP to quantify over 2500 protein groups with 100 HEK 293T cells. We adopted SWAP to profile proteomics with trace aqueous humor samples from cataract (<jats:italic>n<\/jats:italic>=15) and wet age\u2010related macular degeneration (<jats:italic>n<\/jats:italic>=8) patients, and quantified \u22481400 proteins from 5\u2005\u03bcL aqueous humor. SWAP simplifies sample preparation steps, minimizes adsorption loss and improves protein coverage for label\u2010free proteomics with previous trace samples.<\/jats:p>","DOI":"10.1002\/anie.202309806","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T03:29:20Z","timestamp":1693538960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Superparamagnetic Composite Nanobeads Anchored with Molecular Glues for Ultrasensitive Label\u2010free Proteomics"],"prefix":"10.1002","volume":"62","author":[{"given":"Shuang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Surgical Intensive Care Unit Xinhua Hospital, School of Medicine and School of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200030 P. R. 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