A dual-module molecularly imprinted polymer-based cellular electrochemical sensing platform for multiplexed profiling...

Simultaneous quantification of multiple structurally similar purines, including guanine (G), xanthine (X), adenine (A), and hypoxanthine (H), remains a fundamental challenge in electroanalysis and metabolomics. To address this issue, a spatially resolved dual-module cellular electrochemical platform (GA/XH-DMCEP) was developed. The core innovation of this platform lies in the synergistic integration of two complementary strategies at the material and system levels: a "precise individual imprinting followed by functional compositing" approach for fabricating dual-template molecularly imprinted polymer (MIP) composites with orthogonal recognition, enabling simultaneous detection of the GA and XH pairs; and a dual-working-electrode "spatial signal isolation" architecture that allocates physically independent signal acquisition channels to each purine pair. This design fundamentally overcomes electrochemical signal overlap, transforming convoluted responses into four distinct and simultaneously quantifiable signals. The GA/XH-DMCEP exhibits high sensitivity, selectivity, and stability, facilitating multiplexed quantification of purine levels in human breast adenocarcinoma (MCF-7) cells. When applied to profile the metabolic impact of the genotoxin ethyl methanesulfonate (EMS), the platform reveals a purine-specific metabolic fingerprint, namely a preferential decrease in intracellular G and X at sub-cytotoxic doses, which is invisible to single-parameter assays. This work provides a generalizable system-level engineering strategy for multiplexed chemosensing.