Automated implementation of the SwabSeq COVID-19 diagnostic assay on the opentrons flex liquid-handling robot

The SwabSeq COVID-19 diagnostic assay [7] enables scalable SARS-CoV-2 detection using next-generation sequencing (NGS) of barcoded samples without RNA extraction. To adapt this approach for routine clinical use, we developed a fully automated workflow on the Opentrons FLEX liquid-handling platform. Automated pre-PCR setup processed 96 samples in approximately 15 min with minimal hands-on time, while post-PCR thermocycling, pooling, and solid-phase reversible immobilization (SPRI) bead cleanup were completed autonomously in about 2.5 h. The automated workflow produced results highly concordant with the manual method, showing complete agreement among negative samples, very high agreement among positive samples, and no discordant calls. This work demonstrates that a complex NGS-based diagnostic can be translated from a pandemic-scale pipeline into a practical, routine laboratory workflow using an accessible, open-source automation platform.