High-Sensitivity, Bluetooth-Enabled PCB Biosensor for HER2 and CA15-3 Protein Detection in Saliva: A Rapid, Non-Invasive Approach to Breast Cancer Screening

Breast cancer is a leading cause of cancer-related mortality worldwide, requiring efficient diagnostic tools for early detection and monitoring. The human epidermal growth factor receptor 2 (HER2) is a key biomarker for breast cancer classification, typically assessed using immunohistochemistry (IHC). However, IHC requires invasive biopsies and time-intensive laboratory procedures. In this study, we present a biosensor integrated with a reusable printed circuit board (PCB) and functionalized glucose test strips for rapid and non-invasive HER2 detection in saliva. The biosensor achieved a limit of detection of 10⁻¹⁵ g/mL, 4 to 5 orders of magnitude more sensitive than Enzyme-Linked Immunosorbent Assay (ELISA), with a sensitivity of 95/dec and response time of 1 second. In addition to HER2, the biosensor also detects cancer antigen 15-3 (CA15-3), another clinically relevant breast cancer biomarker. The CA15-3 test demonstrated an equally low limit of detection of 10⁻¹⁵ g/mL and a higher sensitivity of 190/dec, further validated using human saliva samples. Clinical validation using 29 saliva samples confirmed its ability to distinguish between healthy, in situ breast cancer, and invasive breast cancer patients. The system, which integrates with a Bluetooth Low Energy (BLE) module, enables remote monitoring, reduces hospital visits, and enhances accessibility for point-of-care and mobile screening applications. This ultra-sensitive, rapid, and portable biosensor offers a promising alternative for breast cancer detection and monitoring, particularly in rural and underserved communities.