Sensitive Detection of the Human Epididymis Protein-4 (HE4) Ovarian Cancer Biomarker through a Sandwich-Type Immunoassay Method with Laser-Induced Breakdown Spectroscopy

Detection of cancer before the appearance of any symptoms is crucial for successful treatment. Early detection is, however, very challenging, particularly for the types of cancer with few or no symptoms at early stages, such as epithelial ovarian cancer (EOC). Developing a user-friendly method that can detect biomarkers with sufficient selectivity, sensitivity, and reproducibility is a promising approach for overcoming the challenges of early detection of EOC. In this study, we report a sandwich-type microparticle immunoassay for sensitive detection of the HE4 biomarker with laser-induced breakdown spectroscopy. Here, we cross-linked elemental particles to a specific functional group of the targeted biomolecules based on a covalent and non-covalent linking chemistry to improve the sensitivity and selectivity of biomarker detection, in which Fe3O4 and SiO2 microparticles were used to conjugate and purify the antibody-antigen in complex media. Simultaneous detection of Fe and Si from a magnetically purified assay significantly improves the HE4 biomarker's detectability, in which HE4 was detected with a limit of detection of 0.0022 pM. We also determined the coupling ratio between HE4 and silica particles using a silicon calibration curve.

Automated summary

Detection of cancer before the appearance of symptoms is crucial for successful treatment. This study developed a user-friendly method using laser-induced breakdown spectroscopy to detect the HE4 biomarker, which is challenging to detect early due to the lack of symptoms. The method improved the sensitivity and selectivity of biomarker detection through cross-linking elemental particles and simultaneous detection of Fe and Si.