Carboxylic Acid–Functionalized β‐Ketoenamine Linked Porous Organic Polymer Based Fluorescent Immunoassay for Prostate Cancer Detection

ABSTRACT Prostate‐specific antigen (PSA) serves as a critical biomarker for the early diagnosis and monitoring of prostate malignancies. In this work, we report the fabrication of a carboxy‐functionalized porous organic polymer (POP) as a highly sensitive and selective fluorescent immunosensor for PSA detection. The POP was synthesized via a solvothermal Schiff base condensation, which bears free –COOH functionalities to facilitate covalent antibody immobilization through classical EDC/NHS coupling chemistry. The resulting POP–antibody bioconjugate exhibited a pronounced fluorescence quenching response upon PSA binding, attributed to static quenching via ground‐state complex formation, as confirmed by steady‐state and time‐resolved photoluminescence studies. Under optimized conditions, the sensor achieved a limit of detection (LOD) of 14 pg/mL, demonstrating a wide linear dynamic range and minimal cross‐reactivity with nontarget biomolecules. The high surface area and hierarchical porosity of the POP matrix contributed to enhanced probe–analyte interactions and signal amplification. Notably, the sensor retained excellent performance in complex matrices, with successful PSA quantification in artificial urine and blood samples, highlighting its potential for real‐world clinical diagnostics. The synergistic integration of structural surface functionality and photostability in this POP‐based platform underscores its promise for ultrasensitive, low‐cost, and point‐of‐care biosensing of cancer biomarkers.