Microwave-based label-free immunosensor to detect anti-p53 autoantibodies

Anti-p53 autoantibody concentrations in the bloodstream have been linked to early tumor formation, making this molecule a promising cancer biomarker, including early colorectal cancer (CRC) diagnosis. Herein, a microwave-based label-free biosensor was designed for the first time by microstrip transmission line technology to detect anti-p53 autoantibodies (anti-p53 Aabs). The biosensor integrates a p53 antigen-functionalized copper surface that interacts with anti-p53 Aabs from samples and utilizes a 50-Ω microstrip line with stepped impedance resonators (SIRs) optimized to resonate at 5.2 GHz to transduce the p53-anti p53 Aabs interaction. Experimental evaluations showed that the biosensor could detect binding events with a linear response from 250 up to 1250 pg/mL, a sensitivity of 0.104 MHz*mL/pg, and a limit of detection (LOD) of 316.5 pg/mL. Leveraging the inherent advantages of microstrip-based biosensors of high sensitivity, miniaturization, and real-time monitoring could provide a transformative approach to non-invasive and label-free detection of not only anti-p53 Aabs but other cancer-related biomarkers, helping fill a significant gap in current biosensor technology and addressing an unmet need in oncology diagnostics. • First microwave-based immunosensor for label-free detection of anti-p53 Aabs. • Disruptive microwave-based immunosensor for precise biomarker monitoring. • Clinically relevant limit of detection. • High specificity, selectivity, and reliability validated with real samples. • Outstanding clinical performance correlated with the gold-standard ELISA method.