High-throughput low-cost DNA sequencing using surface-coating technology

Abstract The speed, expense and throughput of genomic sequencing impose limitations on its use for time-sensitive acute applications, such as rare or antibiotic resistant infections, and large-scale testing that is necessary for population-wide source-tracing, as in the COVID-19 pandemic. A major bottleneck for increasing throughput and decreasing operating costs of next-generation sequencers (NGS) is the flow cell that supplies reagents for the biochemical processes; this subsystem has not significantly improved since 2005. Here we report a new method for sourcing reagents based on surface coating technology (SCT): the DNA adhered onto a biochip that is directly contacted by a reagent-coated polymeric strip. Compared with flow cells, reagent layers are an order of magnitude thinner while both the reagent exchange rate and biochip area are orders of magnitude greater. For whole genome sequencing (WGS), these improvements reduce turn-around time from days to twelve hours, reduce cost from about $1000 to $15, and increase data throughput by orders of magnitude. This makes NGS more affordable than many blood tests while rapidly providing detailed genomic information about microbial and viral pathogens, cancers and genetic disorders for targeted treatments and personalized medicine. The resulting data can be pooled in population-wide databases for accelerated research and development as well for providing detailed real-time data for tracking and containing pandemic outbreaks.