Tunable Heparin Detection in Serum via Conjugated Polyelectrolytes with Electrostatic-Hydrophobic Synergy.

Heparin, a clinically essential anionic biomacromolecule, is widely used as an anticoagulant and an antithrombotic agent. Real-time monitoring of heparin concentration is critical for precise dosage adjustment to minimize side effects. In this study, we developed two water-soluble cationic conjugated polyelectrolytes, PCBO-NMe3+ and PCBE-NMe3+, based on polycarbazole backbones, for sensitive and selective heparin detection. Synthesized via Suzuki and Sonogashira coupling polymerizations, followed by quaternization, these polymers demonstrated excellent fluorescence stability in buffer solutions across a broad pH range (4-12). The ethynyl-functionalized PCBE-NMe3+ exhibited superior performance, achieving a detection limit of 34.6 nM, and enhanced anti-interference capability compared to PCBO-NMe3+, attributed to stronger hydrophobic interactions. Both polymers enabled the selective detection of clinically heparin with varying molecular weights including unfractionated heparin and low molecular weight heparin. The linear detection range could be flexibly tuned by adjusting the polymer concentration. In serum samples, PCBE-NMe3+ showed high accuracy, with recoveries of 95.3-98.0% (RSD < 5%). Mechanistic studies revealed that heparin quenches fluorescence via electrostatic-driven polymer aggregation, further assisted by hydrophobic interactions. This strategy offers a promising approach for real-time heparin monitoring in complex clinical settings.