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A noninvasive quantitative assay that is capable of identifying prostate cancer biomarkers in untreated urine is an attractive diagnosis tool, but this method is subject to various obstacles. Difficulties presented by untreated urine include varying salt concentrations, and pH levels that may be different even though they are from the same patient. Untreated urine also presents interference from other biomolecules and possesses a fewer number of cancer biomarkers than can be found in serum. As a result, urine preconditioning processes and digital rectal examination (DRE) to increase biomarker secretion are mandatory in current urine assays. To address these challenges, an ion‐responsive urine sensor (IRUS) that measures differential electrical signals is proposed as a self‐normalized detection method. The proposed IRUS is based on a FET biosensor with a disposable sensing gate and has the capability to detect …