Nanomechanical systems for the rapid detection of HIV-1 p24 antigen

Early detection of HIV is crucial for reducing transmission and ensuring timely initiation of antiretroviral therapy (ART), significantly improving patient outcomes. Although diagnostic tests have advanced from first-generation antibody detection assays to fourth-generation immunoassays that detect both HIV antibodies and the p24 antigen, these are limited to clinical labs. Their longer processing times, high costs, and the requirement for multiple patient visits highlight the need for rapid, affordable point-of-care (POC) diagnostics. This study introduces a nanomechanical cantilever-based biosensor for the rapid detection of HIV-1 p24 antigen, a key marker for early diagnosis. The platform demonstrated remarkable sensitivity, detecting p24 at concentrations as low as 100 fg/mL in solution and 1 pg/mL in human serum, and was quantitative within several orders of magnitude. After functionalizing the microcantilevers with two broadly cross-reactive monoclonal antibodies (ANT-152 and C65690M), the system was able to detect p24 from a wide range of HIV-1 subtypes. Furthermore, this biosensor was found to be compatible with various blood processing methods and with a direct electronic output. This platform's high sensitivity, specificity, and applicability across multiple HIV subtypes underscores its potential for future development into a next-generation POC diagnostic tool.