New biosensor for the early detection of tPSA in the serum of prostate cancer patients using a Tb-anthracene-9-carboxaldehyde complex embedded in a modified cellulose polymer thin film

Abstract

This study reports the development and validation of a novel optical biosensor for the early detection of total prostate-specific antigen (tPSA) in serum samples from prostate cancer patients, utilizing a terbium-anthracene-9-carboxaldehyde (Tb-A9C) complex embedded within an epoxy-functionalized carboxymethyl cellulose (CMC) polymer thin film. The sensor was systematically optimized by investigating solvent effects and metal-to-ligand molar ratios, with dimethyl sulfoxide (DMSO) and a 1 : 1 (Tb : A9C) stoichiometry identified as optimal conditions yielding maximum luminescence intensity at 545 nm. Surface characterization via SEM confirmed successful layer-by-layer assembly, showing transformation from a cracked polymer surface to a smooth sensor-embedded film, followed by dendritic antibody immobilization patterns, while FTIR spectroscopy validated each fabrication stage through characteristic functional group signatures. Upon functionalization with anti-PSA monoclonal antibodies via glutaraldehyde crosslinking, the thin film sensor exhibited concentration-dependent luminescence quenching upon tPSA binding, enabling quantitative detection across a linear range of 0.025–0.30 ng mL⁻¹ with an exceptionally low detection limit of 0.0159 ng mL⁻¹ and excellent coefficient of determination (R² = 0.995). The biosensor demonstrated outstanding accuracy and precision in both intra-day and inter-day assessments using clinical serum samples from prostate cancer patients, showing strong agreement with standard ELISA methods (sensitivity: 100%, specificity: 100%). Molecular docking and 100-ns molecular dynamics simulations revealed stable binding of the Tb-A9C complex within the PSA pocket C3 (ΔG = −7.5 kcal mol⁻¹), with persistent hydrogen bonding networks and minimal structural fluctuations confirming specific and stable complex formation. The superior photophysical properties of the terbium complex, including large Stokes shift, long luminescence lifetime enabling time-gated detection, combined with the stabilizing CMC polymer matrix and computational validation of binding stability, establish this Tb-A9C thin film biosensor as a simple, sensitive, stable, and cost-effective alternative to conventional diagnostic methods for early prostate cancer detection and clinical monitoring.