Aptamer‐Based Galvanic Potentiometric Sensor for Real‐Time Monitoring of Serotonin Signaling Under Psychosocial Stress

Psychosocial stress, a pervasive factor in mental health disorders, is tightly linked to serotonin (5-HT) dysregulation. Real-time electrochemical monitoring of 5-HT in vivo is challenged by interference from vitamin C (Vc) and biofouling, requiring invasive pretreatments. We present a self-powered aptamer-engineered galvanic sensor (aptGRP_5-HT) that integrates phosphorothioate aptamers with a redox potentiometric mechanism, achieving 21.5-fold higher selectivity and 98.3-fold enhanced sensitivity against Vc over conventional sensors while resisting electrochemical biofouling. The aptGRP_5-HT operates in complex biological environments without pretreatment, enabling direct monitoring in a rodent psychosocial stress model. Using this tool, we uncover a neurochemical signature of social hierarchy: high-ranking mice exhibit elevated 5-HT release in the medial prefrontal cortex (mPFC) and dorsal raphe nucleus (DRN), with region-specific correlations to neuronal activity-reduced spontaneous firing in the mPFC and increased activity in the DRN. This work resolves long-standing challenges in neurochemical sensing and establishes aptGRP_5-HT as a transformative platform for probing brain function and stress-related disorders.