29 August 2011

Helicos Cries Out “I'm Not Dead! I'm Getting Better!”

Helicos, the first company to launch a single molecule DNA sequencer (a class sometimes called “3rd Generation”), has been hanging on to a thread for a while. They've been delisted from NASDAQ and their cash supply is dwindling (down to $1.6M as by June 30th). They are going through another round of cash-saving layoffs that will bring their headcount down to 10. They have apparently stopped selling the HeliScope and their ability to supply reagents and service support to their current customers has been called into question.

When they launched their HeliScope in 2009, they went head to head with the more established players (Illumina, ABI and 454) focusing almost exclusively on being the first 'true single molecule sequencer' for genomic sequencing. It was a tough sell given that they were a bit late to the party and that their reads are shorter and have a higher error rate. They might have been better served to focus on RNA-Seq and ChIP-Seq where the lower quality reads wouldn't have hurt as much and they could have touted their (at the time) industry-leading # of reads per run.

For the past few months their main strategy seemed to center around litigation – they're suing Life Technologies, Illumina and Pacific Biosciences for patent infringement. Just recently, however, they've expanded this strategy by borrowing a page from Complete Genomics – they have launched a sequencing services program to increase their revenues. They've also launched an interesting targeted sequencing solution in which the capture sequences are attached directly to the flow cell (rather than their standard poly dT sequences). They've demonstrated this technology by creating a flow cell for the direct sequencing of the BRCA1 gene.

I fear it may be a bit too little too late, but at least Helicos is still kicking and demonstrating that it doesn't want to go on the cart.

12 August 2011

Ion Torrent's Roadmap to the $500 Genome

Ion Torrent has made some bold claims about making 10x improvements every 6 months, and so far they've kept to that schedule (albeit only over a single 6 month period). In a recent Nature paper (covered by In Sequence 7/26/11) they detailed how they could shrink their features and increase the chip size to achieve first 165M and then 1100M sensors per chip. I've used this information, along with some really useful 'real world' feedback on the 314 and 316 chip from Nick Loman's blog (@pathogenomenick), to create a speculative roadmap for how Ion Torrent might achieve the 10x improvements through the middle of 2013. Assuming they are able to achieve the higher density chips in the timeframe I've listed (I don't think any timeframe was listed in the paper), that they can extend their reads out to 1000b (which seems reasonable given where 454 is today) and that they can improve the number of 'effective beads' (based on fill efficiency, # of 'live' beads, and # of reads passing the filters), it doesn't seem too unreasonable that they might maintain their '10x improvements every 6 months' goal out through the middle of 2013.

I also took a stab at what future chips might cost based on Rothberg's statement that they would hit a $1000 genome by 1/1/13 and a $500 genome by 7/1/13 (In Sequence 6/14/11). I'm assuming 90Gb per genome and $250 in reagents per run. (The prices listed are the initial prices at launch, but they've already demonstrated that the prices for 'old' chips may come down once the new chips are released.) Everything seems pretty reasonable until you get out to the (theoretical) 324 chip at $5000. Since Rothberg only predicted a 2x drop in price/genome from 1/1/13 to 7/1/13, they're either going to charge a lot more for this chip, or the 10x improvements will have started to peter out.

It should be fun to see how accurate this roadmap is. As always, comments and criticisms are welcome.

Chip1 Release Date Output Spec Sensors Fill Eff. 2 Live Beads Passing Filter Read length Calc Output Est. Chip Price
314 01/01/11 10Mb 1.2M 41% 67% 67% 100 20Mb $250
316 07/01/11 100Mb 6.1M 80% 67% 67% 100 200Mb $250
318 01/01/12 1Gb 11M 80% 67% 67% 250 1Gb $500
320 07/01/12 10Gb 60M3 80% 67% 67% 400 10Gb $?
322 01/01/13 100Gb 165M 100% 100% 100% 600 100Gb ~$750
324 07/01/13 1Tb 1100M 100% 100% 100% 1000 1Tb ~$5,000

1The chip names 320, 322, and 324 and release dates are purely speculative. I haven't seen Ion Torrent claim a new chip every 6 months, just that there would be 10x improvements every 6 months.
2The 'fill efficiency', 'live beads' and 'passing filter' metrics for the 314 and 316 chips came from Nick Loman. The values for the other chips are pure speculation on my part. The values for the 322 and 324 chips are surely a little optimistic, but they could be counterbalanced with longer reads to achieve the same output.
3The 60M sensor chip is also pure speculation on my part. Ion Torrent didn't mention this 'intermediate' chip in the Nature paper.