Decoding the molecular mechanisms of sour and salty sensation using biomimetic taste-based biosensors.

This critical review examines the molecular processes that govern the perception of sour and salty tastes and their application in biomimetic sensor technologies. Sour and salty tastes are unique among the five basic taste modalities because they are mediated by ion channels rather than G-protein-coupled receptors. This critical review examines how proton (H+)-dependent sour mechanisms (OTOP1, KIR2.1) and sodium (Na+) dependent salty mechanisms (ENaC) have inspired four classes of biomimetic taste sensors: membrane-mimetic, ion-channel-based, cell-based, and nanomaterial enhanced. A quantitative comparison reveals a central unmet challenge: no existing sensor platform has simultaneously achieved biological selectivity, long-term stability (>1 month), and cross sensitivity below 10% in complex matrices. Ion-channel-based sensors offer molecular fidelity but degrade within days; cell-based sensors are physiologically relevant but irreproducible (CV >30%), whereas nanomaterial sensors are highly sensitive but non-selective. We identify specific failed approaches (e.g., ASIC channels for sour sensing) and persistent gaps, including overpromised biological mimicry and underreported interference effects. Emerging directions including memristor-based neuromorphic circuits and reservoir computing architectures are critically assessed for their potential to bridge the gap between mechanistic understanding and deployable technology. This framework aims to guide the rational design of next-generation taste sensors for food quality control, pharmaceutical testing, and diagnostic applications related to medical conditions and environmental monitoring.