Researchers have developed a portable diagnostic system that evaluates an individual’s antibody protection against COVID-19 using just one microliter of fingertip blood. The Tip Optofluidic Immunoassay (TOI) combines high-sensitivity chemiluminescence detection with microfluidic biosensing to assess antibody protection from both pathogen binding and virus inhibition perspectives—all in just 40 minutes. While many platforms measure antibody levels, few capture the functional aspect of immunity: neutralization. TOI incorporates a renovated in vitro inhibition assay (RIVIA), enhanced through rational protein design to achieve high sensitivity and reproducibility. Unlike conventional methods that require large blood volumes and centralized lab facilities, TOI enables comprehensive immune profiling with minimal resources. Validated in over 100 volunteers, the platform shows strong potential for both public health surveillance and personalized immune assessment. This innovation bridges the gap between laboratory diagnostics and real-world healthcare, offering a practical tool for monitoring vaccine effectiveness and tracking immunity against emerging viral variants.