Tip Optofluidic Immunoassay: Evaluating COVID-19 Antibody Protection with 1μL Fingertip Blood

Infectious diseases such as COVID-19 pose continuous threats to global health. Effective re-infection management relies heavily on maintaining high circulating binding and neutralizing antibody levels. Traditional methods for antibody protection evaluation such as ELISA and VNT face significant challenges including complicated sample preparation, long assay time, and large sample consumption, hindering their applications in timely and routine disease control. This study introduces a house-developed Tip Optofluidic Immunoassay (TOI), featuring industrial-grade micro-fabricated immuno-reactors and a portable chemiluminescent imaging station, capable of evaluating humoral immunity comprehensively within 20 minutes. The system quantifies SARS-CoV-2 binding and neutralizing antibodies efficiently, offering a large dynamic range (3-4 orders of magnitude), extremely high signal-to-noise ratio (approximately 10,000), and high sensitivity for IgG binding assays. It also integrates an updated version of the Rapid In-Vitro Inhibition Assay for SARS-CoV-2 neutralizing antibody assessment, significantly reducing the sample-to-answer time and cost. In a study, TOI was utilized for quantifying antibody protection for multiple SARS-CoV-2 strains using just 1 µL of fingertip blood, from both binding, affinity, and neutralization perspectives. With TOI, individuals with broad-spectrum antibody protection against the WT and XBB strains, as well as those with strong immune imprints were identified. The precision, efficiency, and minimal sample requirement make TOI a valuable tool for decentralized surveillance, and infectious disease risk prediction, supporting the development of disease control and personalized immunization strategies.