By Julia Karow
2010 might well become known as the dawn of the Cambrian period for next-gen sequencing, as the number of sequencing platforms mushroomed during the year, a trend that's likely to continue.
As new sequencers catering to different types of users appeared on the market, the two biggest players in the industry — Illumina and Life Technologies — continued to battle each other with promises of more DNA bases at lower cost with greater accuracy and speed.
And while newcomers Pacific Biosciences and Complete Genomics raised considerable funds and went public in 2010, publicly traded Helicos Biosciences continued to reduce its headcount. In the meantime, both Life Technologies and Roche, through acquisitions and partnerships, bolstered their sequencing R&D pipelines with new technologies.
And as more competitors appeared on the scene, vendors became embroiled in patent lawsuits, accusing each other of infringing their technologies.
At the beginning of the year, just four flavors of massively parallel sequencers were commercially available: Illumina's Genome Analyzer IIx, Life Tech's Applied Biosystems SOLiD 3 Plus, Roche's 454 Genome Sequencer FLX, and the Helicos Genetic Analysis System. A year later, the number of sequencers already available or soon to be on the market has ballooned into the double digits, with new additions such as the HiSeq 2000, HiSeq 1000, and HiScanSQ from Illumina; the SOLiD 4, SOLID 5500 and SOLID 5500xl from Life Tech; the GS Junior from Roche 454; the Ion Torrent Personal Genome Machine; and the PacBio RS.
Illumina started the trend of platform diversification in January with the launch of the HiSeq 2000, a $690,000 newly-designed sequencer with dual flow cells and a stated output of 200 gigabases per run (IS 1/12/2010). By the fall, the instrument had become extremely popular, prompting Illumina to increase its production repeatedly to fill orders. The company also introduced the HiSeq 1000, with a list price of $550,000 to $600,000, which produces half as much data as the 2000 model on a single flow cell and will be available early this year.
Several large genome centers replaced GAIIx sequencers with the HiSeq 2000 platform or added sizable numbers of HiSeqs to their portfolio, with the largest order coming from China's BGI, which purchased 128 HiSeqs in January for installation throughout 2010 (IS 1/12/2010).
Just days after announcing the HiSeq 2000, Illumina released the GAIIe, a smaller cousin of the GAIIx with a list price of $250,000 and an initial output of 20 gigabases per run (IS 1/19/2010). But the company pulled the plug on that model in the fall, lowering the price for the GAIIx to $300,000 instead.
In March, Illumina also launched the HiScanSQ, which combines a microarray scanner with a sequencing module and targets users interested in both array and sequencing technology (IS 3/23/2010). The platform has a list price in the $400,000 range and produces more than 50 gigabases of data per run.
Throughout the year, Illumina provided scant information about the development of its Avantome sequencing technology, as well as the status of technology under development at partner Oxford Nanopore Technologies.
The company acquired Avantome in 2008 for $25 million and up to $35 in milestone payments. Early in 2010, Illumina said the technology will provide a fast turnaround time, long reads, and have a low instrument price, and that it plans to position it for clinical markets (IS 1/26/2010).
In 2009, Illumina signed an exclusive marketing and distribution agreement for Oxford Nanopore's initial sequencing technology — a label-free real-time single-molecule platform that combines an exonuclease and a protein nanopore — and invested $18 million in the company.
Life Tech's Answer
Life Technologies in late January launched the $495,000 SOLiD 4, an upgrade to the SOLiD 3 Plus that increased the output to 100 gigabases per run. An upgrade package called hq, scheduled for late 2010, would triple the output per run to 300 gigabases, Life Tech promised (IS 2/2/2010).
Seemingly in response to BGI's purchase of 128 Illumina HiSeq instruments, Life Tech also announced that the Ignite Institute, a new research institute founded by former TGen researcher Dietrich Stephan, would acquire 100 SOLiD 4 systems as part of acollaboration with the company. But the nascent institute lost some of its financial backers and as of late 2010, was not yet operational (GWDN 11/17/2010). In the meantime, several genome centers acquired multiple SOLiD 4 instruments — for example BGI, Baylor College of Medicine, Children's Hospital of Philadelphia, the BC Cancer Agency, the German Cancer Research Center, and the National Center for Genome Resources — including some that had previously exclusively run the Illumina platform.
In March, Life Tech announced the SOLiD PI, a smaller version of the SOLiD 4 system geared at individual researchers that would cost $230,000 and generate up to 50 gigabases per run (IS 3/2/2010). The instrument was scheduled to be shipped to early-access customers in late 2010.
But instead, in November, Life Tech launched the 5500 and 5500xl SOLiD sequencers, new platforms designed with partner Hitachi that the company plans to ship widely starting in early 2011. While the 5500, which replaces the SOLiD PI, costs $349,000 and generates 90 gigabases per run, the $595,000 SOLiD 5500xl, which replaces the planned hq update, will deliver 180 gigabases per run.
In a bid to bolster its next-gen sequencing portfolio further, Life Tech announced in August that it would acquire Jonathan Rothberg's Ion Torrent for $375 million in cash and up to $350 million in milestone payments, a deal that closed in October. Rothberg presented details on the technology for the first time at the Advances in Genome Biology and Technology meeting in February, showing off Ion Torrent's electronic benchtop sequencer (IS 3/2/2010), which measures pH changes during DNA synthesis on semiconductor chips.
Life Tech said it hopes that the Ion Torrent technology, with its fast turnaround time, will help it "unlock the big diagnostic market" (IS 11/2/2010).
Just before the end of the year, Life Tech launched the first Ion Torrent sequencer, called Personal Genome Machine, shipping it to "select sites" initially (IS 12/14/2010). The first version of the $49,500 instrument, which had been in the hands of early-access customers throughout the year, will deliver 10 to 20 megabases per run and read lengths of 100 to 200 bases, with updates scheduled for later this year (IS 12/7/2010).
Early in 2010, Life Tech also publicly unveiled its single-molecule real-time sequencing technology, dubbed "Starlight", which uses quantum dot nanocrystals attached to DNA polymerase and FRET to measure DNA synthesis (IS 3/2/2010). Later last year, the company also outlined how the technology could be used to deliver both DNA sequence and long-range structural information (IS 9/14/2010). But especially after its acquisition of Ion Torrent, Life Tech has been mum about its commercialization plans for the technology.
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Roche's 454 Life Sciences launched the GS Junior in May, a smaller version of its GS FLX sequencer that targets individual researchers. The instrument has an output of about 35 megabases per run, with an average read length of about 400 base pairs, and a list price on the order of $100,000.
Early this year, the company plans to launch a chemistry upgrade for the GS FLX that will increase the read length to an average of 800 bases, and up to 1,000 bases.
Roche also placed a couple of new bets last year on sequencing technologies to succeed its Genome Sequencer. In July, the company announced a partnership between 454 and IBM to co-develop a nanopore sequencer that will use IBM's DNA transistor technology (IS 7/6/2010). Roche estimated that it will take approximately five years to commercialize the technology.
Then, in November, 454 partnered with UK-based DNA Electronics to develop a low-cost, high-throughput DNA sequencing platform that combines 454's sequencing chemistry and its partner's electrochemical detection technology (IS 11/2/2010). Life Tech's Ion Torrent also licenses sequencing-related IP from DNA Electronics. Roche provided no timeline for commercialization at the time.
Pacific Biosciences spent 2010 both preparing for the commercial launch of its first instrument, the PacBio RS, and putting itself on solid financial footing.
In February, the company first presented its $695,000 instrument at the AGBT meeting (IS 3/2/2010). It also named its first 10 early-access customers — all located in North America — and later added the Sanger Institute as its European test site (IS 2/23/2010). All sites received their instruments by the end of November, and the company now plans to launch the system commercially during the first half of this year, rather than at the end of 2010. The current beta instrument produces data with an average read length of 500 to 550 bases and a raw read accuracy of 80 to 85 percent (IS 12/7/2010).
In 2014, PacBio plans to launch a higher-throughput platform, called "V2", which will integrate sequencing reactions, optical detection, and signal processing into a microchip (IS 2/23/2010).
In July, PacBio raised $109 million in a Series F financing round (IS 7/20/2010), which included a $50 million strategic investment from Gen-Probe, which is collaborating with PacBio on developing sequencing-based integrated clinical diagnostics systems. The following month, the company filed for an initial public offering (IS 8/24/2010). It started trading on the Nasdaq Global Select Market in October, raising $200 million in the IPO, not including over-allotments.
Following several delays, Complete Genomics launched its commercial human genome sequencing service last year and became a publicly traded company in the fall.
In early 2010, the firm cut its target for the year from 10,000 to 5,000 human genomes (IS 1/19/2010), resulting from a delay in its commercial operations. In February, it had orders for more than 500 genomes from more than 30 customers.
Complete Genomics filed for an initial public offering in the summer (IS 8/3/2010) and closed a $39 million Series E financing round shortly afterwards (IS 8/24/2010). In November, the company started trading on the Nasdaq Global Market, raising $54 million in its IPO, not including over-allotments (IS 11/16/2010).
During the first nine months of the year, Complete Genomics sequenced about 400 human genomes and planned to analyze another 300 genomes during the remainder of the year, bringing the total to about 700. In early 2011, the company expects to be able to sequence about 400 human genomes per month and is currently seeking to fill its order books (IS 12/14/2010).
Helicos started the year with additional sales of its Helicos Genetic Analysis system, to Stanford University and a private research institute (IS 2/9/2010). But as its cash reserves dwindled, the company's fortunes turned, and in May, Helicos said it had laid off half its staff and repositioned its technology from research to diagnostic applications (IS 5/18/2010).
Another round of layoffs followed in September, when Helicos also disclosed that it would scale back support and reagent supplies for its current customers (IS 9/28/2010). In November, after being delisted from the Nasdaq, Helicos secured a $4 million bridge loan, abandoning its plans to open a CLIA-certified lab (IS 11/30/2010).
As vendors' sequencing platforms are competing in the marketplace, the companies are also battling in court about intellectual property rights to the technologies.
In a lawsuit that started in 2009, Illumina and Life Technologies both claim that their Genome Analyzer and SOLiD systems infringe several of each others' patents. Last month, the court issued a claim construction order, and a jury trial is currently scheduled for November (IS 12/21/2010).
Helicos sued Pacific Biosciences, Life Technologies and Illumina last August, claiming the PacBio SMRT technology, Illumina's Genome Analyzer and HiSeq instruments, and Life Tech's Starlight technology infringe several of its patents. All three defendants countersued, and a scheduling conference is ordered for Jan. 13 (IS 12/21/2010).
Finally, Illumina sued Complete Genomics in August, claiming that Complete's sequencing technology infringes three of its patents. A case management conference is currently scheduled for March 15 (IS 12/21/2010).
Have topics you'd like to see covered in In Sequence? Email the editor at jkarow [at] genomeweb [.] com.