We describe a scalable, highly parallel sequencing system with raw throughput significantly greater
than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel 60×60
mm2
fibreoptic slide containing 1,600,000 individual wells and is able to sequence 25 million bases,
at 99% or better accuracy (phred 20), in a 4 hour run. To provide sequencing templates, we clonally
amplify DNA fragments on beads in the droplets of an emulsion. The template-carrying beads are
loaded into the wells to convert each into a picoliter-scale sequencing reactor. We perform sequencing
by synthesis using a pyrosequencing protocol optimized for solid support and the small dimension
of the open reactors. Here we show the utility, throughput, accuracy and robustness of this system
by shotgun sequencing and de novo assembling the Mycoplasma genitalium genome with 96%
coverage at 99.96 % accuracy in one run of the machine.