Detection of breast cancer related biomarkers in serum using an electroetching-biosensor with sub-typing recommendations

Abstract

Liquid biopsy is an efficient, real-time method for monitoring cancer progression. In breast cancer sub-typing, it holds potential for providing rapid and comprehensive cancer characterization, including molecular subtypes, predictive prognosis, and personalized treatment options. In this work, we designed an Electroetching-Biosensor that generates output signals from the etching of gold nanoparticles (AuNPs). These nanoparticles are enriched and embedded within a metal–organic framework based on a prussian blue analog, forming a 3D multicavity structure that enhances focused etching and signal amplification. The HKUST-1@PBA@AuNPs can specifically capture the targets, which in turn protect the AuNPs from etching. Thus, the etching response of AuNPs is proportional to the target concentration, enabling the quantitative detection of four biomarkers. The Electroetching-Biosensor offers a detection range spanning at least five orders of magnitude, with a detection limit as low as μU/mL or pg/mL. Its performance is highly consistent with gold standard methods. Furthermore, 24 clinical samples of breast cancer are analyzed. Based on the immunohistochemistry subtyping results, a recommendation for liquid biopsy-based subtyping has been proposed.