Excimer-Based Fluorescence Sensor Array for Glycosaminoglycans Quality Control

The structural heterogeneity, critical therapeutic applications, and associated clinical risks of glycosaminoglycans (GAGs) necessitate rigorous quality control. However, discriminating between different GAGs remains challenging due to their structural complexity and the limited sensitivity of current sensor array-based methods. In this study, four complexes consisting of sodium 4-(pyren-1-yl) butane-1-sulfonate (PBSS) and functionalized polyethylenimine (PEI)─PEI–PBSS 5, PEI–PBSS 10, PEI–PBSS 15, and PEI–PBSS 20 ─were designed based on the excimer fluorescence principle. These complexes, prepared via electrostatic adsorption of anionic PBSS onto the cationic PEI backbone, constitute a sensor array capable of discriminating different GAGs through their distinct fluorescence response patterns. Five GAGs─heparin (HP), low-molecular-weight heparin (LMWH), chondroitin sulfate (CS), dermatan sulfate (DS), and oversulfated chondroitin sulfate (OSCS)─were successfully differentiated at concentrations ranging from 50 to 5000 ng/mL with 100% accuracy. More notably, a simplified three-complex array (PEI–PBSS 10, PEI–PBSS 15, and PEI–PBSS 20 ) not only retains the capability to effectively identify HP adulterated with OSCS or DS but also enables the discrimination of OSCS with varying sulfation levels. This approach provides valuable insights for the quality control of GAG-based pharmaceuticals and the differentiation of structurally similar analogues.