Redox-encoded molecular recognition enables enzyme-free potentiometric sensing of electroinactive glutamate

Anal Chim Acta. 2026 Dec 15;1427:346383. doi: 10.1016/j.aca.2026.346383. Epub 2026 Oct 15.

ABSTRACT

Glutamate (Glu), the major excitatory neurotransmitter in the central nervous system, is intrinsically electroinactive, making its direct electrochemical detection challenging and often requiring enzyme-mediated signal transduction. Here, we introduce a redox-encoded molecular recognition strategy that converts selective binding of electroinactive Glu into a potentiometric signal without enzymatic catalysis. The resulting glutamate potentiometric redox-encoded sensor (Glu-PRES) integrates a molecularly imprinted polydopamine (PDA) recognition layer with a Prussian Blue (PB) redox transducer on a bipolar carbon fiber electrode. Selective Glu binding within the imprinted cavities modulates the local interfacial environment and ionic accessibility of the underlying PB layer, inducing a PB-associated potential shift that is measured against a stable IrCl₆^3-/IrCl₆^2- redox interface through galvanic potentiometry. Glu-PRES provides a broad linear range of 0.10-400 μM with a detection limit of 31 nM, while responses to physiologically relevant interferents remain below 14% of that to 10 μM Glu. The sensor also exhibits reversible potential responses upon repeated switching between 100 nM and 1 μM Glu, together with strong resistance to protein fouling. The sensor further resolves graded Glu-release dynamics in a brain hematoma-mimicking hydrogel model. These results demonstrate a recognition-to-redox potential encoding strategy for enzyme-free potentiometric sensing of electroinactive molecular targets.

PMID:43003583 | DOI:10.1016/j.aca.2026.346383