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To address this, a 3D gold nanogranule decorated gold\u2010silver alloy nanopillar (AuNG@Au\u2010AgNP) based surface\u2010enhanced Raman scattering (SERS) biosensor is developed, capable of quantitatively profiling immune\u2010related soluble proteins (interleukin three receptor, alpha chain: CD123, programmed cell death ligand 1: PD\u2010L1, human leukocyte antigen\u2013DR isotype: HLA\u2010DR, and chitotriosidase: ChiT) in serum samples. The 3D bimetallic nanoarchitecture, fabricated using anodized aluminum oxide (AAO), features a uniform structure with densely packed nanogaps on the heads of Au\u2010Ag alloy nanopillars, enabling fast, simple, and replicable production. The proposed biosensor achieves accurate results even with low detection limits (4\u20136 fM) and high signal consistency (relative standard deviation (RSD)\u00a0=\u00a01.79%) within a one\u2010step multi\u2010analytes identification chip with a directly loadable chamber. To enhance the diagnostic performance, a support vector machine (SVM) based machine learning algorithm is utilized, achieving 95.0% accuracy and 95.8% precision in classifying healthy controls, infections with and without sepsis, and septic shock. This advanced 3D plasmonic bimetallic alloy nanoarchitecture\u2010based SERS biosensor demonstrates clinical usefulness for sepsis diagnosis and severity assessment, providing timely and personalized treatment.<\/jats:p>","DOI":"10.1002\/advs.202414688","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T09:26:07Z","timestamp":1739784367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Rapid and Differential Diagnosis of Sepsis Stages Using an Advanced 3D Plasmonic Bimetallic Alloy Nanoarchitecture\u2010Based SERS Biosensor Combined with Machine Learning for Multiple Analyte Identification"],"prefix":"10.1002","volume":"12","author":[{"given":"Woo Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering Korea University  145, Anam\u2010ro, Seongbuk\u2010gu Seoul 02841 Republic of 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