An integrated glycan probe-based colorimetric biosensor for glycoprotein analysis

Glycoproteins are widely involved in physiological processes of eukaryotic cells, and their expression and glycosylation modifications often become aberrant during the early stages of malignant transformation, making them highly promising molecular biomarkers for the early detection and monitoring of cancer. However, the efficient recognition of glycan structures and their translation into sensitive analytical signals remain technical challenges.

In this work, a simple and universal colorimetric biosensing method is proposed based on a designed probe, 4-carboxyphenylboronic acid@bovine serum albumin-MnO₂ (4-CPBA@BSA-MnO₂, CBM), which integrates glycan recognition and signal amplification into a single protein scaffold. With mucin 1 (MUC 1), a representative ovarian cancer biomarker, as a proof-of-concept, the fabricated biosensor achieves a detection limit as low as 0.089 ng/mL and a linear detection range from 0.1 ng/mL to 10 μg/mL. Clinical serum analysis further confirms its capability to accurately distinguish ovarian cancer patients from healthy controls. In addition, the sensitive detection of alpha-fetoprotein (AFP) as well as epithelial cell adhesion molecule (EpCAM) also demonstrates the modularity and universality of this strategy.

Overall, this paper presents an integrated glycan probe that possesses both glycan capture and signal output functionalities. Consequently, we propose and validate a universal paradigm for glycoprotein detection, providing a simple and sensitive strategy for these disease-related biomarkers.