Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia in the elderly. Total tau in the blood is a potentially useful biomarker for predicting early AD. However, during detection, the non-specific adsorption of high-abundance biomolecules in the sample will block the detection signal and reduce the detection sensitivity. Based on this, this work described an electrochemical biosensor with high antifouling performance based on loach mucus-inspired guanosine-based hydrogel for the specific detection of tau protein. The exploited electrochemical biosensor shows high sensitivity and selectivity for tau protein detection, with a wide linear response range from 1.00 × 10−2 to 1.00 × 102 ng/mL and a low limit of detection (LOD) of 1.31 × 10−3 ng/mL. This LOD is lower than the critical tau protein concentration (0.2 ng/mL) that distinguishes AD cases, indicating that this simple tau protein immunoassay has the potential for clinical application. Furthermore, due to the facile fabrication, good biocompatibility, facile biofunctionalization, and antifouling property of this hydrogel film, hydrogel-based biosensors also have the potential to detect other biomarkers in complex biological samples.
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