Cyclodextrin-integrated molecularly imprinted polymer-based QCM sensor for sensitive, label-free detection of Gal3

The global prevalence of heart failure (HF) poses a significant public health challenge. Elevated serum levels of Galectin-3 (Gal3) are a reliable biomarker for the early detection and monitoring of HF progression. Given the high mortality and morbidity associated with HF, early diagnosis is critical, necessitating a rapid, sensitive, and straightforward method for Gal3 detection. This study presents an innovative, label-free quartz crystal microbalance (QCM) sensor designed for Gal3 detection. The sensor uses hexakis-(6-mercapto-6-deoxy)-β-cyclodextrin (mCD) to facilitate the oriented immobilization of the Gal3 template through self-assembly and employs a molecularly imprinted polymer (MIP) for Gal3-specific detection. The mCD-integrated MIP was synthesized by electropolymerizing poly-aniline-3-carboxylic acid (ANI3C), chosen from 20 candidate polymers via molecular docking. Under optimal conditions, the MIP-based QCM sensor demonstrated an imprinting factor (IF) of 4.71 and an equilibrium dissociation constant (K_D) of 2.03 nM. This indicates a stronger binding affinity compared to the non-molecularly imprinted polymer (NIP), which exhibited a K_D of 26.75 nM. The sensor exhibits a linear detection range of 1–30 ng/mL, with a limit of detection (LOD) of 1.08 ng/mL (S/N = 3) and a limit of quantification (LOQ) of 3.61 ng/mL (S/N = 10). It demonstrated excellent accuracy and precision with no interference, and successfully detected Gal3 in lipid-free human serum, highlighting its potential for in heart failure diagnostics and monitoring.