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Extracellular acidosis caused by metabolic reprogramming of cancer cells is a reliable marker for tumor infiltrative regions. Although the acidic margin\u2010guided surgery shows promise in improving surgical prognosis, its clinical transition is delayed by having the exogenous probes approved by the drug supervision authority. Here, an intelligent surface\u2010enhanced Raman scattering (SERS) navigation system delineating glioma acidic margins without administration of exogenous probes is reported. With assistance of this system, the metabolites at the tumor cutting edges can be nondestructively transferred within a water droplet to a SERS chip with pH sensitivity. Homemade deep learning model automatically processes the Raman spectra collected from the SERS chip and delineates the pH map of tumor resection bed with increased speed. Acidity correlated cancer cell density and proliferation level are demonstrated in tumor cutting edges of animal models and excised tissues from glioma patients. The overall survival of animal models post the SERS system guided surgery is significantly increased in comparison to the conventional strategy used in clinical practice. This SERS system holds the promise in accelerating clinical transition of acidic margin\u2010guided surgery for solid tumors with infiltrative nature.<\/jats:p>","DOI":"10.1002\/advs.202104935","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T02:01:18Z","timestamp":1642039278000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Intelligent SERS Navigation System Guiding Brain Tumor Surgery by Intraoperatively Delineating the Metabolic Acidosis"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3115-7225","authenticated-orcid":false,"given":"Ziyi","family":"Jin","sequence":"first","affiliation":[{"name":"Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Medical Neurobiology School of Pharmacy Fudan University  Shanghai 201203 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