Many of the readers of this blog will have seen the announcements from Oxford Nanopore Technologies on their MinIon early access program. The people I talk to are almost universally excited; if a little sceptical about how quickly we’ll be getting rid of our HiSeq’s and Proton’s.
ONT’s big promise is long-reads and the science we’ll be able to do with these is likely to be transformative. The opportunities for big-bucks are highly motivational and everyone appears to be developing different nanopore sequencing technologies as a result. The strategies are highly varied and we’re likely to see even more effort when ONT prove a commercial sequencer is a real possibility.
What about other Nanopore companies: A new nanopore might offer benefits to sequencing as it slows down the passage of DNA to a speed at which it might be possible to read multiple data-points from each base - less than a base pair per microsecond. Meni Wanunu’s group in the department of physics and chemistry at Northeastern University are making nanopores from hafnium oxide.
Unfortunately
it takes ten minutes to “drill” each nanopre. Fancy a 1,000,000 pore
chip? You’ll need to wait 19 years f they are drilled one at a time!
Obviously they're not going to make 1,000,000 nanopores one at a time, and 1,000,000 nanopores might not be needed. Each nanopore stays open for a period of time long enough to allow 100’s, 1000’s or perhaps even 1,000,000’s of DNA molecules to pass through. One thing lacking in the press-releases from ONT were detailed specs that allow us to think about the kinds of experiments that might be possible. I’m sure we’ll hear more when we get selected to participate in the EA program though!
Meni Wanunu commented on the advantages of their slow-pores over ONT’s enzymatically controlled translocation method, saying eventually ONT's pores give up; "The biggest advantage we have is that we don't rely on anything except the battery, the voltage to drive the DNA through the pore," he said according to GenomeWeb.
Waiting till 2030 for a Hafnium nanopore sequencer is just too long, I'm looking forward to hearing all about user experiences with MinION at AGBT next year.
I am so tired of both academic and commercial entities overstating the value of their widget and underplaying the competition. Nanopores will never be a "sample in-data out" deal. Careful attention to temperature, salt concetration, sample purity, etc will be required. In that the light, ONT's addition of a motor, hairpin, and insertion adapter via a transposon are inconveniences on par with Illumina's Nextera sample prep, which everyone seems to love so much. I have always felt that ONT's Achilles heel is the lipid bilayer and the limited scale-up headroom. There are many ways to EVENTUALLY overcome these in a synthetic pore. It will still be 2020 at least for that though, not because we will be drilling holes sequentially in a TEM (only an academic with an army of slave labor - aka grad students - can contemplate that but because it will take that long for the technology to develop the precision required.
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