Pyridylboronic Acid- and Poly(ethylene glycol)-Functionalized PEDOT Copolymers for Electrochemical Detection of Sialic Acid-Rich Cancer Biomarkers in Serum

The detection of carbohydrate antigen 19-9 (CA199), a critical biomarker for pancreatic, colorectal, and gastric cancers, is essential for early diagnosis and disease monitoring. Traditional antibody-based assays for CA199 detection are limited by high costs, time-consuming procedures, and susceptibility to nonspecific interference. This study presents an electrochemical biosensor based on a multifunctional poly(EDOT-PyBA-<i>co</i>-EDOT-PEG) copolymer designed to overcome these limitations. The biosensor integrates pyridylboronic acid (PyBA) moieties for specific recognition of sialic acid residues and poly(ethylene glycol) (PEG) chains for antifouling properties within a conductive PEDOT framework. By eliminating antibody dependency, the biosensor reduces costs, enhances stability, and simplifies the diagnostic process. Surface characterization confirmed the successful incorporation of PyBA and PEG units, while electrochemical impedance spectroscopy enabled sensitive detection of CA199 with a limit of detection of 0.05 U·mL^-1 and a linear response range from 0.05 to 40 U·mL^-1. Recovery tests in spiked human serum samples demonstrated excellent accuracy (97-109% recovery), validating the biosensor's reliability in complex biological matrices. The rationally designed copolymer provides both high sensitivity and specificity while maintaining resistance to biofouling in serum samples. This work establishes a scalable, cost-effective platform for glycoprotein biomarker detection, advancing the field of clinical diagnostics and cancer monitoring.