Thursday, January 13, 2011

Whither Ion Torrent?

In a comment on yesterday's piece, Matthew Herper asks how the Ion Torrent might be better than Illumina's MiSeq. That's a head-scratcher, and I'm sure the Ion Torrent folks are scrambling to figure out what to tell people.

The problem is, looking at it honestly, is that Illumina is claiming they'll beat or meet Ion Torrent on every dimension. Similar startup cost (once you thrown in necessary gadgets for the Ion Torrent), similar run cost, similar raw read lengths (but paired!), similar numbers of reads, double the total output, faster runs and less hands on time or trouble. Did I leave anything out?

So where does Ion Torrent go to keep from being stillborn? Now, they say they have 60 instruments sold, which isn't quite stillborn -- but will MiSeq choke off further growth?

The one potential gap is that Ion Torrent is (almost) here now whereas MiSeq won't show up for about 6 months. That's not a big window, but some folks will be anxious enough that they'll want their sequencer NOW. But, how many sequencers can they really churn out without quality going haywire? The last thing Ion Torrent needs to put itself behind a reputational eight ball. Of course, pushing hard to place sequencers could pay off huge if Illumina is delayed in rolling out MiSeq -- or can't meet demand.

Upfront cost similarity is for one sequencer. For a variety of reasons, some folks will want more than one (e.g. to make sure at least one is already operating). Presumably the $50K increment starts applying here, though it's not clear how many Ion Torrent's can be supported by that $50K-$75K in auxiliary gear. And, it's sobering that you don't beat MiSeq on throughput until you buy the third one. Indeed, for similar amounts you could buy 5 Ion Torrents or 2 MiSeq and have similar throughput.

Giving away sequencers would be another way to grab an edge -- or cut the price even lower. Obviously, they could start with complimentary placements with a few key genomics bloggers (grin). Seriously, this is not an unprecedented model. Kodak took the world by storm giving away cameras -- processing & reload on the original Brownie was doable only at Kodak. This would be an expensive strategy, but would presumably tie down a bunch of users from going with the competition.

How quickly can Ion Torrent up their specs? That would be the best way to win -- up Illumina's ante in a huge way. This is what their contests are around, but they need the boost now. Again, it is sobering what a challenge has been put before them. Illumina has roughly 2X the read length, though as paired ends rather than one read -- but for many applications paired ends are equivalent or superior (I have one tiny one where you need a monolithic read, but I don't see it as a "killer app"). Longer reads, requiring more cycles, would also exacerbate the speed issue -- putting even more pressure on shortening cycle times.

The sample prep issue is potentially a tough nut. Illumina's slurp of Epicentre means quick-and-easy fragment library preps. For PCR amplicons, any platform will do. But, emulsion PCR seems to be something nobody loves. I haven't seen it done & I think some folks see the trouble as overblown -- but have you ever heard someone say "I love the smell of emulsion breaking in the morning! It smells of victory!"? Illumina's bridge PCR approach certainly looks easy. Can Ion Torrent get access to some non-emulsion clonal amplification (rolling circle?) and get it in place quickly enough?

The ultimate leap past Illumina would be to roll out a new chip beyond the 2nd generation one Ion Torrent just announced. Presumably Illumina has MiSeq's specs near the limits of what the great masses of users will be able to routinely get, but perhaps they left some slack in -- but 5X slack? If Ion Torrent could launch another 10X in number of sensors -- or quickly roll out a way to get more of those sensors working -- that could keep people excited.

Ion Torrent might also try some sort of ante upping in integrating with another player or a novel sample prep approach. Nothing leaps to mind as really fitting the bill, but perhaps something is out there. Hard to beat low input fragment libraries with just a bunch of pipetting, but who knows?

Finally, there is pure cool factor. Ion Torrent had it, iPod dock and all. Apple makes a mint selling cool stuff (with very slick user interfaces and integration) at a premium price. I doubt this will work in the scientific arena, but who knows?

Yep, it's quite a rabbit which Jay Flatley pulled out of his hat this week. Knocking your opponent off-balance before they actually rolled out is something executives must dream of. I think Ion Torrent will survive (and hope it will; Illumina continuing to expand its 70% market share really wouldn't be good for the market), but their trajectory is looking a lot flatter at the moment.


Anonymous said...

Would be nice to see panels of primers for certain targets with sample barcode. You could sell those like Taqman assays or panels, expect 100x coverage and shove that in an Access Array, highly multiplexed and BANG in the PGM machine (choose your genes and your 48 patients barcodes). You must get rid of the library, there is no question about that.

AB needs serious allies, not another emulsion solution...

Unknown said...

+ we still need to see a paper about the PGM. while we have thousands with the Illumina chemistry / technology in the materials n methods section.
+ are we sure the error rate is comparable?
+ Paired end is still essential for >>most of the experiments since the bioinformatic part of the genomics games is still a mess.....n trust me ... doing even resequencing w/o PE makes u need >> than 30X coverage to allign the short reads n call the variants for real i guess ion torren won t go much far unless they go "all in" with what they ve in their R&D department right now, and bring it immediatelly to market.

kris said...

A bit confused with the MiSeq specifications. It seems there is yet unpublished improvement to the sequencing chemistry which the CEO of Illumina made a passing mention. If you compare the specifications of HiScanSQ with that of MiSeq you would notice that it takes 1.5 day for a 36 bp single read run on HiScanSQ compared to 4h on MiSeq. Similarly, it takes 8 days for a 2 x 100 bp paired-end run on HiScanSQ compared to 19 h on MiSeq. Obviously there is no comparable run to 2 x 150 bp paired-end run, which gives >1Gb/day on MiSeQ. This improvement if translated to HiSeq 2000 would blow away every other sequencer in terms of throughput. May be the MiSeq is designed from scratch and signals a new product line from Illumina. In that case the community still needs a publication with MiSeq as is the case with PGM. It should happen any time now from the early access labs.

Keith Robison said...

Nick Loman actually talked to an Illumina person in the know & the fast times on the MiSeq are in many ways specific to the very small flowcell on the instrument -- no scanning (which I had guessed) but also very rapid chemistry enabled by that space.

So, unfortunately, there aren't a lot of obvious ways to translate these to the other platforms -- MiSeq is designed from the ground up to be a very small & nimble gazelle.

On the other hand, Illumina does seem (from recent announcements) to have all sorts of tricks to squeeze more data out of the rest of the line.

Anonymous said...

Further more (it is true for the scanning), cluster generation could be bypassed all together very soon, you will see many sample prep methods out there who will target that.

Anonymous said...

Illumina also had a coup buying Epicentre for the Nextera sample prep. I have used it and for unfragmented DNA input, it works very well. The Ion PGM sequencing time needs to be compared from sample in to data out. Even with standard library prep input to MiSeq, not having emPCR is a much bigger deal than most people realize. emPCR kills any use of the instrument for clinical use, while the ease of use of the MiSeq will have them everywhere. An iPod doc is just a representation of misplace effort into something not useful.