A chemiluminescent imaging immunosensor based on copper-doped NiFe PBA nanozyme for detection of BTN3A2: A candidate biomarker in early stage of gastric cancer.

The early diagnosis of gastric cancer (GC) faces great challenges due to the lack of specific biomarkers. Therefore, it is crucial to discover effective markers and establish highly sensitive detection methods. This study validated the potential of BTN3A2 protein as an early GC biomarker by analyzing serum samples from patients with GC, benign gastritis, other digestive system cancers, and healthy controls across three clinical centers. Furthermore, a chemiluminescent (CL) imaging immunosensor based on copper-doped NiFe PBA (Cu-NiFe PBA) nanozyme probe was developed to achieve highly sensitive detection of BTN3A2 protein in serum of patients with GC and healthy controls. The high detection sensitivity for BTN3A2 was achieved by copper doping to enhance peroxidase-like activity of nanozyme for signal amplification. The proposed sensor exhibits a broad linear range from 0.5 to 5000 pg/mL, and achieves a detection limit of 0.15 pg/mL (S/N = 3). In addition, the established sensor is successfully utilized for BTN3A2 detection in serum samples from GC and healthy individuals across three clinical centers, and demonstrates perfect correlation with clinical outcomes when compared with traditional enzyme-linked immunosorbent assay. This study provides a candidate serum biomarker in the early stage of GC and offers a convenient, highly sensitive method for its detection.