Functionalized Pillar[6]arene Nanomembrane Probe for Ultrasensitive Sensing of Clinically Valuable 1-Methylnicotinamide in Mouse Urine

Analyzing 1-methylnicotinamide (1-MNA), a nicotinamide metabolite implicated in metabolic disorders, in biological systems is challenging owing to its trace-level concentrations and matrix effects. Herein, we report an electrochemical sensor featuring a micropipette functionalized with charge-tunable nanomembranes consisting of carboxylated pillar[6]arene-modified poly(vinyl alcohol) (CAP6A-PVA) for rapid metabolite detection. The covalently cross-linked CAP6A-PVA nanomembrane demonstrates exceptional 1-MNA detection capability with a LOD of approximately 1.16 nM,400-fold higher than that of conventional fluorescence-based detection methods. We also achieved real-time 1-MNA detection over a wide concentration range (10 nM-1000 μM) at a broad range of physiologically relevant pH (6.0-9.0). The CAP6A-PVA platform was successfully used to quantify 1-MNA in unprocessed mouse urine samples, demonstrating its real clinical utility by eliminating the need for sample pretreatment.