This article was originally published Aug. 19.
As the sequencing services sector grows ever more competitive, Beckman Coulter Genomics is betting that its liquid-handling and automation expertise will be a differentiator in the market.
The Beckman Coulter business unit — formed from the combination of Agencourt Biosciences, which it acquired in 2005, and Clinical Data's Cogenics Division, which it picked up in 2009 — recently launched a new targeted sequencing service that relies on the company's automation tools to provide fast turnaround times and reproducible data, according to company officials.
The service uses Agilent SureSelect target enrichment technology, Beckman Coulter's SPRIworks Fragment Library System for automated library construction, and its Biomek Laboratory Automation Workstation for liquid handling. Sequencing is performed on the Illumina GAII and HiSeq 2000 platforms.
In addition, the business unit's product arm is developing a high-throughout version of the SPRIworks library-prep system, called SPRIworks HT, that it plans to launch in the third quarter.
William Donahue, manager of the molecular biology group at Beckman Coulter Genomics, told In Sequence that the company has in recent years seen a shift in customer requirements for targeted sequencing services. "You look back a few years ago, and people were saying we want to do 10 samples, we want to do 20, [but we] started getting requests a few years ago asking can we do hundreds or thousands of samples."
In response, he said the company developed a pipeline that uses several different types of Beckman Coulter automation tools, along with a laboratory information management system in order to track samples throughout the process. "That allows us to basically process a large number of samples in a greatly reduced turnaround time with an increased reproducibility," he said, adding that the pipeline also uses barcoding in order to eliminate sample-handling errors that might arise from manual processing.
The company declined to disclose specifics in terms of turnaround time since it can vary based on the project, though Donahue noted that the sample-processing component is typically on the order of weeks for large orders, while it would require several months for manual processing.
Officials also declined to discuss pricing, but Tom Thompson, director of global commercial operations for Beckman Coulter Genomics, said that it is "competitive with the rest of the market."
The sequencing services market is growing increasingly crowded, with instrument manufacturers like Complete Genomics and Illumina recently joining the ranks of providers such as SeqWright and Expression Analysis. Donahue acknowledged that the company is seeing increasing competition in the services market, but said, "I think we have an advantage in that we're Beckman Coulter and we have a significant footprint in the automation and liquid-handling field."
In addition, he noted that the services group dates back to Agencourt, which was founded in 2000, "so we've been through the entire trajectory from Sanger sequencing into next-gen sequencing, and we have a great deal of experience doing this."
The targeted sequencing service is offered out of the group's next-generation sequencing facility in Danvers, Mass., which includes an undisclosed number of Illumina GA, HiSeq 2000, and Roche 454 GS FLX Titanium systems. The facility, which houses the former Agencourt business that was formerly based in Beverly, Mass., also offers Sanger sequencing on Life Technologies 3730xl systems.
Thompson said the company is considering adding new sequencing platforms, such as the Pacific Biosciences RS, but would have to fully evaluate them before adding them to its services business.
Beckman Coulter Genomics has a second US site, the former Cogenics headquarters in Morrisville, NC, which offers regulated Sanger sequencing services, as well as gene expression genotyping, and other genomic services.
Thompson said that most of the regulated sequencing at the CLIA-certified facility is for cell bank characterization. The company is "interested in the possibility" of implementing next-gen sequencing in the CLIA lab, but is still evaluating its options in that area, Thompson said.
Beckman Coulter Genomics currently employs around 200 people across its two US sites and three sites in Europe — Takeley, UK; Bernried, Germany; and Grenoble, France. Donahue said that the group does not expect any changes related to Beckman Coulter's acquisition by Danaher, which closed in June.
"It's business as usual as far as we're concerned," he said.
Targeted Sequencing and SPRIworks HT
Donahue said that customers for the targeted sequencing service submit their samples in a 96-well plate. The company performs quality control and quantification of the samples and then shears the DNA with a high-throughput Covaris shearing system.
The Biomek system then loads the plates into cartridges for the SPRIworks library construction step. From there, the liquid-handling systems move the samples into PCR setup, PCR cleanup, quantitation, and hybridization.
After target capture, there is another round of PCR and PCR cleanup, and then the samples are quantified and pooled on the automated platform. "Depending on the level of multiplex that we need we can basically program in how many samples we want to pool together per lane," Donahue said, adding that these steps are all handled through the LIMS.
In addition to its services offering, Beckman Coulter Genomics maintains a product business that develops and commercializes reagents, hardware, and software for genomics research. Key product lines include the Agencourt nucleic acid extraction and purification reagents, which are based on the company's Solid Phase Reversible Immobilization, or SPRI, bead-based technology.
Last year, the company introduced its line of SPRIworks fragment library construction system for the Roche 454, Illumina, and Life Technologies SOLiD platforms, which Donahue described as a "low- to medium-throughout library construction device that has a self-contained reagent cartridge, so all of the reagents — all the enzymes, buffers, the SPRI reagents for size selection and cleanup — everything you need except for your DNA and your adapters are included in the cartridge."
Now, he said, the company is developing methods to do all the library construction on the Biomek automated platform, which will be released as the SPRIworks HT in the third quarter.
"It's a scalability thing" that grew out of the company's service business, he said. "We're a service facility and we also make products, so … essentially we saw this need coming a couple years ago and said, 'Hey look, there's no way that we're going to be able to keep up with the level of multiplexing that we see going on now and the number of libraries that you can run on a sequencer."
The company soon realized that "everyone else is going to be going through these same struggles and that this would be a great idea for a product line," he said.
Donahue said the project has been "a great effort between my group, which has primarily been doing a lot of work with the next-gen sequencers and sample prep, and our reagent team to come together and develop these methods to really simplify library construction."
Beckman Coulter Genomics faces competition from other vendors selling library-prep systems, such as Sage Sciences, which offers the Pippin Prep system, and Illumina, which acquired Epicentre Biotechnologies earlier this year largely for its Nextera library prep technology.
"We were the first to market with automated library construction and there are now a number of other companies that are offering automated methods," Donahue said. "What we're trying to do is offer complete solutions — or as complete as possible — with combined reagent and automation solutions."
He noted that most vendors sell either the automation or the reagents, but not both, "so if something goes wrong, you might be in the middle."
In addition, he said that Beckman Coulter Genomics is "targeting additional parts of the sequencing sample prep workflow beyond the library construction" to enable "an entire target capture workflow … that will allow researchers to solve not just a piece of the puzzle … but a more complete solution."
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