Microchemical Journal, vol.214, 2025 (SCI-Expanded)
HE4 is a clinically significant biomarker for ovarian cancer; however, current detection methods are hindered by poor sensitivity and high costs, underscoring the urgent need for more advanced, rapid, and sensitive detection platforms. In this study, an ultra-sensitive and highly selective electrochemical immunosensor is presented based on the novel polyferrocene-thiophene (PT) and MoS2@PDA@CuCoFe2O4 (MPC) nanoparticle in chitosan (CS) modified electrodes. PT was synthesized to modify the electrode surface by electrospinning to provide high electrochemical response and stability by porous structure. The CuCoFe2O4 (CCF) nanoparticles, with magnetic and catalytic properties, were encapsulated in a carbon shell and further functionalized with MoS2 nanosheets to improve the bioactivity and surface area of the immunosensor system. The sensor exhibited excellent electrochemical performance with significant signal amplification due to the unique combination of materials. The developed sensor demonstrated a low detection limit of 2.82 pg/mL and a linear detection range from 1 pg/mL to 10 ng/mL. The sensor showed high specificity against interfering biomarkers (HER2, CRP, IL6, HSA, PSA, CA19-9, and CA125) and exhibited excellent repeatability (relative standard deviation < 2 %) and long-term stability (signal loss < 10 % after 15 days). Real sample validation in spiked serum and urine matrices resulted in recovery rates between 97.0 % and 99.6 %. The developed platform offers a promising approach for early diagnosis of ovarian cancer, combining simplicity, efficiency, and high performance in real-world sample analysis, including artificial serum and urine samples. The performance of the developed electrochemical HE4 immunosensor was also evaluated with an ELISA test for comparison.