A Cell-Compatible Polyethylene Glycol Sensor for Dual-Mode Cu2+ Tracking: In Vivo Biosensing and Smartphone-Based High-Sensitivity Detection In Vitro

Polyethylene glycol (PEG) plays a key component in functional materials due to its exceptional water solubility, biocompatibility, and chemical versatility. However, the absence of π-conjugation in PEG's molecular structure prevents fluorescence emission, limiting its utility in fluorescent material applications. In this study, a novel PEG-based sensor ( P ) was synthesized by covalently linking PEG to a coumarin fluorophore. P exhibited significantly enhanced green fluorescence compared to unmodified PEG. It allows rapid (~5 s), highly sensitive, and specific copper (Cu 2+ ) detection through fluorescence quenching, achieving 97.40% quenching efficiency with a 0.52 nM detection limit. Nuclear magnetic resonance ( 1 H NMR) titration, inductively coupled plasma mass spectrometry (ICP-MS), and density functional theory (DFT) calculations confirmed the detection mechanisms, revealing the P –Cu 2+ interaction mechanism. Furthermore, fluorescence imaging results demonstrated that P exhibited a fluorescence quenching response upon the addition of Cu 2+ to HeLa cells, providing a potential new method for detecting Cu 2+ in vivo. In addition, the incorporation of a smartphone color recognition application enables approximate quantification of Cu 2+ concentrations in test samples. This approach not only extends PEG's applicability in sensing and smart technology integration but also offers an efficient, low-cost solution for on-site Cu 2+ detection.