High-throughput, low-cost and rapid DNA sequencing using surface-coating techniques

Abstract

The speed1–3, expense1–4 and throughput2 of genomic sequencing impose limitations on its use for time-sensitive acute cases, such as rare4,5 or antibiotic resistant infections6, and large-scale testing that is necessary for containing COVID-19 outbreaks using source-tracing7–9. The major bottleneck for increasing the bandwidth 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 200510–12. Here we report a new method for sourcing reagents based on surface coating technology (SCT): the DNA adhered onto the biochip is directly contacted by a reagent-coated polymeric strip. Compared with flow cells the reagent layers are an order of magnitude thinner while both the reagent exchange rate and biochip area are orders of magnitude greater. These improvements drop the turn-around time from days to twelve hours and the cost for whole genome sequencing (WGS) from about $1000 to $15, as well as increase data production by several orders of magnitude. This makes NGS more affordable than many blood tests while rapidly providing detailed genomic information about microbial and viral pathogens6,13, cancers14 and genetic disorders for targeted treatments6 and personalized medicine6,15. This data can be pooled in population-wide databases for accelerated research and development as well providing detailed real-time data for tracking and containing outbreaks, such as the current COVID-19 pandemic.