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LC Sciences Joins Agilent, NimbleGen, Febit, and Others in the Nascent Target Enrichment Market

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LC Sciences, a Houston, Texas-based genomics and proteomics company, last week launched a custom target enrichment service for next-generation sequencing applications.

LC Sciences now provides a service called Target-Specific Selection for the capture of a defined genomic region or RNA sequences. The service is based on the firm's µParaflo biochip technology, and LCS claims its service enables researchers to take "full advantage" of second-gen, high-throughput sequencers by achieving "more coverage and deeper sequencing by reducing sample complexity, and focusing reads on the areas of interest."

By launching its service, LCS has decided to enter a market varyingly referred to as sequence capture, target enrichment, and sequence enrichment. While firms playing in this area — which, in addition to LCS, include Agilent technologies, Roche NimbleGen, Febit, and RainDance Technologies — cannot agree on a name for it, they all agree that the market has the potential to become, in LCS' words, "very large."

Second-gen sequencing technologies have "provided many new opportunities for researchers, and we can already see that market growing very quickly; it's going to be huge," Chris Hebel, LCS' director of business development told BioArray News last week.

"It makes sense that the target-specific selection market will be very large as well," Hebel said. "This market is a logical extension of our technology. I think it makes sense that this application of microarrays or this technology is very complementary to sequencing," he said. "If you can reduce the sample complexity to a point where you can run multiple samples in one read sequencing reaction, and you are getting all the reads you need, then you have saved yourself a lot of money."

According to Hebel, the new market for target-specific selection is a "perfect example" of how arrays are being adapted to serve researchers moving to second-gen sequencing platforms.

"There has been a lot of talk about sequencing replacing arrays, and this is a clear example that they are complementary to each other; arrays can make sequencing more cost effective," he said.

Other array vendors agree. Last week, Agilent launched its SureSelect Target Enrichment System to compete in a market that Fred Ernani, Agilent’s product manager of emerging genomics applications, called "substantial."

Agilent's target-enrichment kit contains a customer-specified mixture of up to 55,000 biotinylated RNA probes delivered in a single tube. Users can design their own custom SureSelect mixtures using Agilent’s eArray online design tool, which contains many genomes and allows users to upload their own sequences.

“The sequencing community has been expressing a need for this type of tool since the advent of next-generation sequencing,” Ernani told BioArray News last month. “Agilent already possessed a high level of expertise in custom oligo synthesis, so we saw this as a logical entry into the next-gen sequencing workflow" (see BAN 2/10/2009).

Febit, too, plans to throw its hat in the ring later this month with a full commercialization of its HybSelect application. The HybSelect method, available in early access since last year, makes use of Febit's Geniom instrument and will be made available both as a service and as a standalone application for Geniom owners. Defined oligonucleotides can be synthesized within the eight channels of a Geniom biochip, and then used as capture probes for the targeted genomic DNA loci within a sample.

"I think that [second-generation sequencing] itself is performing very well, and the combination of sequencing with this extraction technology turns our offering into a brute-force, disruptive tool," Peer Stähler, the Heidelberg, Germany-based company's chief scientific officer, said last month. "HybSelect, together with [second-gen sequencing], will fill a gap that microarrays cannot fill" (see BAN 2/17/2009).

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µParaflo

According to Hebel, LCS’ offering revolves around its ability to custom synthesize oligonucleotide sequences in situ on a programmable high-density microfluidics chip as capture probes designed to target specific regions of interest in any genome or transcriptome.

Samples are hybridized to the chip, undesired sequences are washed off, and the captured target sequences are recovered by eluting them from the chip. The selected target sequences are then ready for sequencing or further processing.

LCS also offers target selection in solution. Biotinylated or phosphorylated oligonucleotides are synthesized and designed to target specific genomic sequence regions of interest. After hybridization with a sample, magnetic beads are added, and the capture probes are affinity linked to the beads. The captured target sequences are separated from other sequences by washing the beads, after which the target sequences can be recovered.

LCS' service is designed to work with any second-gen sequencer on the market, and LCS is platform agnostic, according to Hebel. While the company does not offer sequencing services in house, it has "ready access" to second-gen instruments in adjacent companies and core facilities.

"This market is a logical extension of our technology ... and I think the two main advantages of our array in general are the flexibility of the platform, and the quality of the synthesis we are able to achieve, based on our chemistry and microfluidic design," said Hebel.

Hebel said that, given its technology, LCS treats each project as a custom project. "Every order is different. Every customer is unique. So I think the flexibility of our product is really great for this application that is evolving," Hebel said. "The synthesis in particular is completely custom, we can do any sequence and genome," he said. "We have no additional set-up issues and everything is digital, so a single array is very quick," he added.

He argued that this flexibility could give LCS an edge over its rivals. "At this early stage of the application’s development, it is rare that a customer requests an array, it's designed, they get their results, and they are done," Hebel said. "More typically, the results from a first-run experiment lead them to want more arrays with new designs," he said. "To be able to quickly design and make one array after another is essential for this application."

In terms of its own offering, Hebel said the firm anticipates its in-solution option will be more attractive to users over time. "Our long-term view is that in-solution capture will make more makes sense … for standard design selection projects," Hebel said. "At not much more cost, we can synthesize capture probes [that] can also be used in solution for tens or hundreds of samples, without having to do array after array for each sample."

Hebel admitted that LCS already faces competition from several firms, but likened the target selection market to the market for microRNA arrays. LCS, Agilent, and Febit also sell miRNA arrays, for instance.

"We are at the point in the market where there is a lot of interest from different companies, but the cream will rise to the top," Hebel said. "The market will be defined by who can provide the reliable results and satisfy the needs of customers. We feel that we can do that."

Hebel added that LCS has decided to focus on selling a service, rather than a catalog product, because its customers are "not necessarily experts" on the use of the tools. "A lot of people are still intimidated by arrays; they would rather just focus on the results, rather than have to figure out how to run the protocol for a new application," he said.

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