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A label-free dual immunosensor for the simultaneous electrochemical determination of CA125 and HE4 biomarkers for the early diagnosis of ovarian cancer

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Abstract

The blood levels of cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are measured in the diagnosis and progression monitoring of ovarian cancer (OC), and the Risk of Ovarian Malignancy Algorithm (ROMA) score% values are calculated for cancer risk assessment. For the first time, disposable dual screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles were used to fabricate label-free electrochemical dual CA125-HE4 immunosensors for the sensitive, fast, and practical simultaneous determination of CA125 and HE4. DPV and SWV methods were used to simultaneously determine antigens in two different linear ranges (1–100 pg mL−1 and 1–50 ng mL−1). High sensitivity, low LOD, and LOQ were obtained for two linear ranges with a correlation coefficient above 0.99. The application stability of the dual CA125-HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. The dual immunosensors exhibited high selectivity in eight different antigen mixtures. The reusability of the dual immunosensors has been tested up to 9 cycles. ROMA score% values for pre-menopausal and post-menopausal status were calculated using the concentration of CA125 and HE4 in the blood serum and assessing OC risk. The disposable dual immunosensors can be used in point-of-care tests for rapid and practical simultaneous determination of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

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Funding

This work was supported by the Scientific and Technological Research Institution of Turkey (TUBITAK), 1001- Scientific and Technological Research Projects Support Program (project number: 118R030).

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Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Çankırı Karatekin University, Çankırı, 18100, Turkey

    Melike Bilgi Kamaç, Muhammed Altun & Merve Yilmaz

  2. Bioengineering Department, Faculty of Engineering, Çanakkale Onsekiz Mart University, Çanakkale, Turkey

    Mustafa Kemal Sezgintürk

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  1. Melike Bilgi Kamaç
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  2. Muhammed Altun
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Contributions

Melike Bilgi Kamaç: conceptualization, methodology, investigation, validation, formal analysis, data curation, supervision, writing—original draft, funding acquisition, resources, and project administration. Muhammed Altun: methodology, investigation, validation, visualization, formal analysis, and writing—original draft. Merve Yılmaz: methodology, investigation, validation, visualization, formal analysis, and writing—original draft. Mustafa Kemal Sezgintürk: conceptualization, methodology, and writing—review and editing.

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Correspondence to Melike Bilgi Kamaç or Mustafa Kemal Sezgintürk.

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Bilgi Kamaç, M., Altun, M., Yilmaz, M. et al. A label-free dual immunosensor for the simultaneous electrochemical determination of CA125 and HE4 biomarkers for the early diagnosis of ovarian cancer. Anal Bioanal Chem 415, 1709–1718 (2023). https://doi.org/10.1007/s00216-023-04569-y

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