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RainDance Preps Launch of ThunderStorm High-Throughput Target Enrichment Platform

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By Julia Karow

Anticipating demand for targeted sequencing in large numbers of samples, RainDance Technologies is preparing to launch ThunderStorm, a high-throughput platform for target sequence enrichment that uses its microdroplet-based PCR technology.

ThunderStorm, slated for launch at the American Society of Human Genetics annual meeting in Montreal this month, will allow users to PCR-amplify targets in up to 96 samples within 24 hours in an automated fashion.

The instrument will have a list price of $295,000 and will begin shipping to customers in November, followed by a broader launch in January. The company offers "several programs" for customers with small capital budgets to gain access to the platform, said chief marketing officer Andy Watson. Customers with projects involving a thousand or more samples can expect the enrichment to cost about $100 per sample, he said.

RainDance developed the new platform because it believes that the demand for large targeted sequencing projects will increase as exome sequencing, whole-genome sequencing, and GWAS projects are being completed, Watson said. Many customers, for example, now want to follow up on interesting regions they found in those studies, "but do it on larger numbers of samples."

Others want to use the system to fill in gaps that remain after exome sequencing studies, and a number of customers are interested in clinical targeted sequencing on many samples.

ThunderStorm will use the same RainStorm microdroplet-based PCR technology as the RDT 1000, RainDance's current platform that it will continue to sell at a reduced list price of just below $100,000. Previously, that instrument cost $225,000.

Like the RDT 1000, the new platform will support custom primer libraries containing between 100 and 20,000 primer pairs, with a total target size of up to about 10 megabases. Amplicons can range in size from 150 to 1,500 base pairs, with GC content between 30 and 70 percent, according to the company's website.

The company has decreased sample input requirements from 1 to 2 micrograms to about 250 nanograms of genomic DNA for certain samples, which Watson said is important for studying tumor or FFPE samples where the amount of material is limited.

In addition to custom targets, ThunderStorm will also support the same catalog target panels as the RDT 1000. These include the ASDSeq panel with 62 genes known to be involved in autism spectrum disorder; the XSeq panel, which contains more than 1,000 genes on the X chromosome; and the HLASeq panel that comprises the HLA super locus, a 3.8-megabase region.

But unlike the RDT 1000, which only processes one sample at a time and up to eight per day, users of the ThunderStorm will be able to load between one and 96 samples at a time, which the instrument processes automatically. While one sample will take about 30 minutes to complete, 96 samples will need about 24 hours.

Users load their samples in 96-well plates, which they can run with any of eight different primer pair panels that can be stored on the instrument. The instrument then sets up microdroplet PCR reactions by merging the sample DNA with the primer pairs and reagents on a chip. Users then collect these reactions in a 96-well output plate, followed by thermal cycling, emulsion breaking, and sequencing.

The process is compatible with a variety of sequencing platforms, including the Illumina HiSeq and MiSeq, Life Technologies' Ion Torrent PGM and 5500 SOLiD, Pacific Biosciences' PacBio RS, and Roche's 454 GS FLX and GS Junior.

According to Watson, several customers are interested in pairing the ThunderStorm with either the Ion Torrent PGM or the Illumina MiSeq, seeing it as a good match because of its fast turnaround time for smaller numbers of samples.

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ThunderStorm will likely compete with Agilent Technologies' and Roche/NimbleGen's hybridization-based custom target enrichment products, which do not require a similar dedicated piece of hardware.

But according to Watson, the workflow with ThunderStorm will be faster and less tedious than for these platforms, which take several days, and the coverage of the intended targets by PCR is more complete than with hybridization-based methods. Unlike those, ThunderStorm also does not require users to make DNA sequencing libraries, he said.

RainDance expects some but not all of its existing RDT 1000 customers — about 50 worldwide — to switch to ThunderStorm, and is providing incentives for them to do so. However, the RDT 1000 "is still an important product for us, especially for lower capacity users," Watson said.

For clinical use, the company also plans to launch a regulated version of ThunderStorm sometime in the future, starting with the CE-IVD market in Europe, but does not have a timeline yet. In preparation for this, it has already implemented "various design controls and other quality procedures needed for regulated instruments," Watson said.

One of the first existing customers to adopt the new platform will be Ambry Genetics, a clinical laboratory and genomic service provider based in Aliso Viejo, Calif. Ambry, which is expected to receive an instrument next month, said in a statement that it plans to use the ThunderStorm system for genetic testing and targeted next-gen sequencing services.

Other current users are cautiously optimistic. "A higher throughput and more automated system is a welcome change," John McPherson, genome technologies director at the Ontario Institute for Cancer Research, told In Sequence by e-mail. He said he does not know much about the new platform yet and needs to evaluate it prior to making a purchase decision.


Have topics you'd like to see covered in In Sequence? Contact the editor at jkarow [at] genomeweb [.] com.

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