A Dual-Encoded Bead-Based Immunoassay with Tunable Detection Range for COVID-19 Serum Evaluation

Serological assay for coronavirus 2019 (COVID-19) patients including asymptomatic cases can inform on disease progression and prognosis. A detection method taking into account multiplex, high sensitivity, and a wider detection range will help to identify and treat COVID-19. Here we integrated color-size dual-encoded beads and rolling circle amplification (RCA) into a bead-based fluorescence immunoassay implemented in a size sorting chip to achieve high-throughput and sensitive detection. We used the assay for quantifying COVID-19 antibodies against spike S1, nucleocapsid, the receptor binding domain antigens. It also detected inflammatory biomarkers including interleukin-6, interleukin-1 beta, procalcitonin, C-reactive protein whose concentrations range from pg mL(-1) to mu g mL(-1). Use of different size beads integrating with RCA results in a tunable detection range. The assay can be readily modified to simultaneously measure more COVID-19 serological molecules differing by orders of magnitude.