The COVID-19 pandemic has highlighted the need for highly scalable and sensitive viral diagnostics, together with identification of viral variants. One-Seq is a novel diagnostic method with three key advantages: it is highly scalable, allowing a throughput of 100,000-1,000,000 tests per day in a single clinical lab, with a turn-around time of 7.5-15 hr; it is extremely cheap at scale, with an estimated amortized reagent cost of $3 per test and significantly reduced personnel costs; and it can report on a number of hotspot viral mutations at equal scalability with no extra cost. These advantages are not balanced by decreases in sensitivity: One-Seq has sensitivity similar to that of the "gold standard" method, RT-PCR, and preserves the ability to distinguish samples with high viral loads from those with low viral loads.

The advances that make One-Seq possible include a one-pot reaction for efficient reverse transcription (RT) and upfront barcoding, without any extraction steps, and a “protector” strategy in which carefully designed competing oligonucleotides prevent barcode crosstalk and preserve detection of the high dynamic range of viral load in clinical samples. Together, these advances allow clinical samples to be pooled before amplification, so that all subsequent manipulations, as well as sequencing, can be done in bulk.

One-Seq can be rapidly adapted to detect any single-stranded RNA virus with equal efficiency, and can even detect multiple viruses in a single run.