Fast, cost-effective, and flexible DNA sequencing by roll-to-roll fluidics

Sequencing data and some analysis. Abstract: Despite decreasing prices per DNA base pair over the past decade, small-scale next-generation sequencing (NGS) remains prohibitive in urgent clinical settings, since the reagent efficiency of sequence-by-synthesis (SBS) is low in the corresponding flow cells. Here we show NGS by roll-to-roll fluidics (r2r-fl), which is cost-effective for flexible biochip sizes. R2r-fl is a practical implementation of plane-Couette flow, with up to 85 times lower reagent consumption (US$ 0.16 per giga base pair), rinsing times of less than 2 seconds, and shortened turnaround times (TAT) for paired-end 100 bp (PE100) sequencing from days to under 12 hours. We maintain over 99.9% precision and 99.3% sensitivity of single nucleotide polymorphisms (SNP) for the human genome, 99.9% mapping rate for E.coli, and minimal nucleotide substitutions, deletions, or insertions in the SARS-CoV-2 Alpha strain. Overall, r2r-fl makes NGS drastically faster and more affordable, thus contributing to revolutions in dealing with pathogens, cancers, genetic diseases, and personalized medicine.