Ion Torrent: Hype cycle status "disillusionment"

I'm as guilty as anyone about buying into the hype. When I labelled the Ion Torrent an "agile gazelle" earlier this year, a reader admonished me for not being skeptical enough. Well, he was right, I was wrong. The tediously useful hype cycle has come into play and we've hit disillusionment rather earlier than expected with Ion Torrent.

I heard the launch specs for Ion Torrent in November at the ELRIG meet-up in Hinxton. The information we got there was that the shipping "314" chip would permit 100k reads of 100 bases length, i.e. 10 megabases per run. To put that in perspective, it's 1/40th of a 454 run or 0.00005 of a HiSeq run. This is disappointing for those who, like me, had believed 100-200 megabases was going to be the shipping specification, useful enough for bacterial genomics. 10 megs is useful pretty much only for amplicons and viral genomes.

Even more of a blow to this instrument's prospects is the sample preparation workflow - once shrouded in secrecy - this turns out to be virtually identical to 454's. That means fragmentation, adapter ligation and amplification using a bead-based emulsion PCR stage. This is a major hassle and makes a mockery of the instrument's 2 hour run time. A 454 only takes 8 hours to run but the user is tied up for days making libraries. The Ion Torrent, like the 454 will therefore be idle most of the time. Some of this can be improved by automation, but the presently available automation solutions cost more than the Ion Torrent!

Rothberg explains this away "If it takes a machine two weeks to sequence [a genome], it doesn’t matter if the sample prep takes 1.5 days. But if you’re getting sequence in two hours, it does!”, conveniently forgetting the 454, his own invention! Is it significant that 454 has had no major innovations for 2 years now, still generating 400-600Mb and 1m reads. Let's hope the chip can outperform the 454 optics -based system.

Lastly, and not surprisingly, the instrument suffers the same "read-forward" issues as 454 which means homopolymers can't be called accurately, and the reads are full of indels. This is inevitable with a flow-based approach. When questioned on whether Ion Torrent performed worse or better than with 454 in this regard, I got a "no comment".

Specs are supposed to improve with the announced but unavailable "316" chip which is supposed to bring output up to 100 megabases. But despite the promises of infinite scaleability through semiconductors, the launch spec is poor.  It is instructive that the 314 chip has 1.4m "sensors" but that this doesn't yet seem to translate into read count. Is the argument for semiconductor scaleability fragile?

Anyway, turned out I didn't need to blog on this because Life Tech have publicised the limitations of their technology themselves, in the form of their $7M contest to "democratise" sequencing. The plan is to outsource the technical development to the community. This is a genius move - if it works - if these 3 drawbacks can be fixed quickly (and so cheaply) then the machine has a great future ahead of it.

But I would urge caution for those people thinking of taking part -  the market value of your successful invention will be greater than the prize money on offer! Maybe you can sell it to Roche who desperately need to overcome the same problems with the 454!

Remember Solexa was sold to Illumina for $600m because of the genius of their solid-surface cluster based DNA chemistry. That genius has permitted Illumina to comprehensively beat Moore's Law since the introduction of their technology, scaling greater heights daily (at ELRIG, they announced a ~400Gb run from a HiSeq!).

I love the idea of out-sourcing method development to the community, its very zeitgeisty and Web 2.0. But the community should get a cut of the profits, not a cash prize. Although (as far as I can see) the T&Cs have not been published yet, you can bet that Life take ownership of the intellectual property. Please correct me if I'm wrong, Life Tech!

There's also a worry here, don't Life Tech have a solid roadmap to juice throughput, improve sample workflow and reduce error rates? Alarm bells are sounding.

In the meantime, the jury is out for the Ion Torrent. It's got a great price tag at $50k, but a lot of problems need to be overcome quickly.

What do you think? Is this helping democratise sequencing, or is it a cynical tactic to get cheap R&D?