I've heard lots of presentations about novel sequencing technologies, many have never arrived, some have come and gone, all have been pretty neat ideas; but so far not one has arrived that outperforms the Illumina systems many readers of this blog are using.
|Base4's pyrophosphorolysis sequencing technology|
The latest newcomer is Base4's single-molecule microdroplet sequencing technology. The picture above explains the process very well: a single molecule of double-stranded DNA is immobilised in the sequencer, single bases are cleaved at a defined rate from the 3' end by pyrophosphorolysis (the new Pyrosequencing perhaps?), as each nucleotide is cleaved it is captured into a microdroplet where it initiates a cascade reaction that generates a fluorescent signal unique to each base, as microdroplets are created at a faster rate than DNA is cleaved at the 3' end the system generates a series of droplets that can be read out by the sequencer (a little like the fluorescent products being read of a capillary electrophoresis instrument).
Base4 are talking big about what their technology can deliver. They say it will be capable of sequencing 1M bases per second with low systematic error rates. The single-molecules mean no amplification and read-lengths should be long. Parallelisation of the technology should allow multiple single-molecules to be sequenced at the same time. How much and when will have to wait a little longer.
I've been speaking to Base4 over the past few years after meeting their founder Cameron Frayling in a pub in Cambridge. Over the past two years Base4 has been developing their technology and recently achieved a significant milestone by demonstrating robust base-calling of single nucleotides in microdroplets. They are still small, with just 25 employees and are based outside Cambridge. I hope they'll be growing as we start to get our hands on the technology and see what it's capable of.