A scalable high-throughput serolomics platform for profiling serum antibody responses in large-scale population-based cohorts.

Abstract

Seroepidemiological assays play a crucial role in tracking immunity and infectious disease exposure across populations. Here we describe an automated assay platform that robustly quantifies antibodies against up to 100 antigens in a single reaction, using Luminex suspension array technology, alongside generating ample quality control measures. This automated multiplex serology workflow is an advancement of our previously developed manual and hybrid multiplex serology platforms. It combines multiple liquid handling systems (Biomeki7, BioTek 405 LS) and bead separation technology (KingFisher Flex) to improve scalability and reproducibility and facilitate its application in large-scale population-based cohorts. Study samples undergo automated processing, and antibody levels are quantified using the Luminex Flexmap3D instrument. A custom R-based application monitors process parameters and visualizes readouts in real time. Daily quality control samples allow subsequent normalization over extended periods of time and across reagent batches. Compared with previous assay versions, the higher degree of automation requires fewer laboratory operators and results in improved robustness and a more continuous throughput. Assay robustness is excellent, with median coefficients of variations between 2.8% and 11.7%, with no relevant batch effects over a 6-month period. Reproducibility across 47 antigens and 91 duplicate samples is remarkably high (R² = 1.00). Using the automated platform, 1,820 study samples can be processed in a typical assay week. We have successfully completed the analysis for ~38,000 cohort samples, including comprehensive quality control data, in 88 assay days. Automated multiplex serology sets the foundation to generate high-quality serolomics data for large-scale cohorts in a reproducible, scalable and cost-effective fashion.