<p>Cancer antigen 125 (CA125) is a key biomarker for ovarian cancer, and its concentration level is an important predictor for diagnosis. We&#xa0;developed a novel electrochemical impedance biosensor for CA125 detection based on a dual-signal amplification strategy using 1,1,1-tris(hydroxymethyl)ethane-polytrimethylene carbonate (TME-PTMC) and zeolitic imidazolate framework-8 loaded with gold nanoparticles (ZIF-8@Au). The biosensor was constructed by immobilizing ZIF-8@Au on a gold electrode using 1,6-hexanedithiol (HDT) as a crosslinking agent, followed by the attachment of aptamer 1 (Apt1) via sulfhydryl groups. 6-Mercapto-1-hexanol (MCH) was used to prevent nonspecific binding. Through specific aptamer-antigen recognition, CA125 was captured and anchored onto the electrode surface. After carbodiimide hydrochloride (EDC)/ N-hydroxysuccinimide (NHS) activation, aptamer 2 (Apt2) further recognized CA125, forming an aptamer-antigen-aptamer "sandwich structure". The TME-PTMC polymer was then conjugated via ester bonds, significantly enhancing signal amplification. Electrochemical impedance spectroscopy (EIS) analysis confirmed that under optimized conditions, the sensor exhibited a wide linear detection range (0.01 U mL⁻¹ to 100 U mL⁻¹) and a low detection limit (0.0062 U mL⁻¹). Moreover, the sensor demonstrated excellent selectivity, stability, and reproducibility in the analysis of&#xa0;clinical serum samples, highlighting its potential for early ovarian cancer diagnosis and clinical monitoring.</p> Graphical Abstract <p></p>