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Becton Dickinson Launches New Cell Sorter, Assays for Single-Cell Genomics

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NEW YORK (GenomeWeb) – Becton Dickinson this week launched its first major products designed specifically for genomics research as it unveiled the BD FACSseq cell sorter and BD Precise Assays for high-throughput single-cell gene-expression analysis studies at the American Society of Human Genetics annual meeting in Baltimore.

The product launch, which is technically the start of an early-access program, comes just a month-and-a-half after BD announced it was acquiring San Francisco Bay Area single-cell genomics firm Cellular Research, whose barcoding technology underlies the BD Precise Assay product.

However, BD and Cellular Research had been exploring the marriage of their respective technologies since at least February, when they disclosed that they had inked a co-marketing agreement for single-cell sequencing applications.

BD has made a spate of recent acquisitions and partnerships to solidify its presence in the genomics research market, especially sample preparation for next-generation sequencing, as covered by GenomeWeb in August. However, single-cell genomics applications in particular appear to be the most natural extension of the company's 30-plus years of experience in the flow cytometry and fluorescence-activated cell sorting market.

"I think people understand the value of single-cell analysis … it's about the heterogeneity of cells and the ability to actually analyze individual cells," Stephen Gunstream, vice president of global genomics at BD, told GenomeWeb this week. "It's really uncovering major biological differences that might be masked by doing a group analysis — you really want to study every individual cell."

The current challenge facing the field is developing technology that allows researchers to study large numbers of individual cells "accurately, quickly, easily, and affordably," something BD feels it has achieved with its new products, Gunstream said.

"We feel like the combination of BD's flow cytometry capabilities with Cellular Research's … technology for measuring gene expression of single cells allows us to provide that fully automated, easy-to-use, and affordable single-cell analysis that allows customers to get that high-resolution data that they haven't had in the past," he noted.

Other companies have also begun to take notice of increased researcher interest in single-cell genomics. Fluidigm is arguably the market leader, and one of the first vendors to develop and market products specifically for the field. Its C1 single-cell auto-prep system has been available for a few years and has generally driven revenue growth at the company, despite recent rocky financial results. Fluidigm continues to note, though, that single-cell research applications comprise the majority of its gene expression platform sales, and that it doesn't see that changing in the near future. In late August, the company also introduced a new workflow for the C1 to simultaneously prepare up to 800 single cells for mRNA sequencing.

Another competitor is WaferGen Biosystems, which just this week launched its ICell8 single-cell genomics system, also at ASHG. Based on the company's SmartChip technology, the ICell8 system is designed to isolate, identify, and process thousands of individual cells using a multi-sample nanodispenser, automated imaging, and dedicated software.

BD's Gunstream declined to comment on the specific capabilities of those platforms, but noted that the BD FACSseq and Precise assays don't use expensive microfluidics. "The cost of consumables is essentially sort of a 96-well plate as opposed to some of the other technologies on the market with consumables you have to buy," Gunstream said.

"The other part of that is, instead of being a passive cell capture or anything like that, this is individual cell sorting," he added. "We can actually sort [on the BD FACSseq] and get the phenotypic information from the cell just like you would on any other cell sorter, and then compare that to the genomic data downstream that you get out of the Precise assays. We really feel like … when you combine that phenotypic and genomic information, it kind of puts [FACSseq] out on its own."

Gunstream declined to provide detailed pricing information for the new products, but noted that customers could use the Precise assays with essentially any BD cell sorter, which can already be found in many core labs. However, he also noted the FACSseq has been streamlined and simplified so that "you don't have to be a flow expert to get going. This takes away a lot of the barriers that have been out there for FACS already."

According to a poster presented by BD at ASHG this week, the FACSseq features one laser for illumination and four parameters for detection (one composite channel and three fluorescence channels). The system uses total internal reflection to enable automatic alignment of the sort head to simplify cell sorting. Cells are sorted directly into 96-well plates or other consumables of choice. In the poster, BD described how company researchers used the system to eliminate dead cells from collection by propidium iodide and isolate single cells from different cell cycle phases using Hoechst dye staining.

Meantime, the BD Precise plates are pre-loaded with a detergent-based single-cell lysis buffer along with RNA stabilizers, as well as Cellular Research's molecular indices and sample-specific barcodes. In another experiment described in the poster, researchers sorted single cells from a mixed cancer cell sample into the Precise assay plates, then generated libraries for sequencing on an Illumina MiSeq instrument. They were then able to analyze gene expression of specific single cells using a computation pipeline performed on the Seven Bridges genomics platform.

BD would now like to get its platform into the hands of early-access users to replicate some of these experiments and develop and test new applications. As that happens, the company will also start to put more of the pieces in place for its broader genomics strategy, including the anticipated 2016 launch of a microdroplet-based automated NGS library preparation platform based on technology it acquired along with Irish startup GenCell Biosystems last year.

"Single-cell analysis is just one piece of that puzzle that we're working on," Gunstream said. "We have a number of other pieces in play where we're sort of trying to [enable] customers [to do] sample collection, preservation, cell isolation, [and] library prep for sequence readiness. We're really focused on simplifying the workflow, making it more efficient, making it higher throughput, and offering more value with higher-quality data to researchers and clinicians alike. This is a major bottleneck for customers, and it fits very well with our capabilities at BD and some of these technologies we've acquired."