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BD Sees Rhapsody Platform as Key Part of Larger Single-Cell Multi-Omics Portfolio

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NEW YORK (GenomeWeb) – BD continues its move into single-cell multi-omics with the release this month of its BD Rhapsody platform.

The platform, which the company previewed earlier this year at the Advances in Genome Biology and Technology conference, allows for single-cell transcriptomic analysis of tens of thousands of individual cells. Next year, the company plans to add protein detection capabilities, according to Stephen Gunstream, vice president of genomics for BD.

He added that BD believed combining the Rhapsody system with other parts of the company's portfolio — its flow cytometers, for instance — will give it a competitive edge over other firms in the single cell omics space.

During the AGBT preview, BD discussed the use of the Rhapsody system (then called the Resolve) for whole-transcriptome sequencing. However, since then, discussions with early-access users have led the company to focus more on targeted assays, Gunstream said.

This decision stemmed from a variety of reasons, he noted, such as a need foimproved sensitivity and lower costs.

"When you're doing a [whole] transcriptome, you're amplifying all of the RNA there, whether you are interested in those genes or not," he said. "And there's a lot more background noise. So by using a targeted approach, you actually can just pick out the 400 or 500 different genes that are of interest, and you amplify those. It's a much more sensitive approach."

On the cost side, Gunstream said that while the price of sequencing continues to go down, it remains a "pretty major driver of experimental costs."

"With the targeted approach, you can actually end up lowering your sequencing costs by up to fivefold per experiment," he said. "And that becomes a pretty big driver in allowing people to run more samples and really start to understand some of those more complex diseases."

"When we started putting this out there and talking to customers… we found that sequencing cost was a big barrier, as well as performance in terms of sensitivity," Gunstream said. "So we think with the targeted approach, we actually address both of those things."

He added that, as omics research moves closer to the clinic, demand for targeted assays will likely rise. "Not just because it lowers costs, but because you just want to analyze what you want to use from a clinical perspective," he said.

BD has developed several panels in areas like immunology that researchers can order for use on the Rhapsody. The company also offers a custom panel service as well as what Gunstream described as a hybrid model, where it will customize existing panels to include certain additional targets customers are interested in.

Gunstream said he expected much of the interest in the device to come from researchers in immunology, oncology, and neurology.

The system uses an array of microwells and a bead barcoding system to enable single-cell analyses. Suspensions of the cells of interest are loaded onto 200,000-microwell arrays in concentrations that make it unlikely that multiple cells will occupy the same well.

Each well contains a magnetic bead with functionalized oligonucleotide probes that feature well-specific barcodes that can be used to track RNA molecules coming from the cell occupying a particular well. A lysis buffer is added to the array, allowing the mRNA to bind to the barcoded probes, and the captured molecules from all the cells can then be combined and amplified together.

Gunstream said that BD plans to add protein detection capabilities by mid-2018, taking advantage of the large antibody library the company has built up over its years in the flow cytometry business.

"We've been analyzing single cells and their protein expression for the last 40 years," he said. "So we're taking this antibody portfolio that we have at BD and allowing customers to order those and actually measure protein and RNA expression on the Rhapsody system at the same time."

He declined to say what level of protein multiplexing the system would be capable of, but said he expected it could be on the order of hundreds of proteins.

In a way, the company is coming to single-cell multi-omics from the opposite direction of firms like Nanostring and Fluidigm, which have moved into protein work after starting on the genomic side.

"I think people have been wanting to do [single cell protein and genomic analyses] for a very long time and have been limited by technology in many cases," Gunstream said. "Maybe 10 to 15 years ago, we had flow cytometry cores, and then we had sequencing cores, but now when you start talking about applications and understanding what's happening, you really need both. And so, as researchers are starting to realize that and see the data and what you can interpret by putting these two together, there's a real drive for that [kind of analysis]."

Gunstream noted, though, that cost remains a limiting factor, and suggested that researchers could leverage BD's larger portfolio to design more targeted experiments — potentially giving the company an advantage over other single-cell omics firms.

"It's not like these are $300 experiments," he said. "If you want to analyze, say, 10 proteins, and hundreds of RNAs, or a whole transcriptome, these [experiments cost] tens of thousands of dollars."

One potential way to bring this cost down is by more narrowly targeting the cells you analyze, Gunstream suggested. For instance, if in a population of 10,000 cells, a researcher is actually interested in just a subset of 1,000, they might use flow cytometry to isolate that subpopulation of 1,000 before running them on the Rhapsody system.

"We're a leader in flow cytometry, so we have all that knowledge," he said. "If someone says, 'I want to isolate these subtypes of T cells,' we can say, 'okay, these five markers are the ones to use.' And then you add the RNA on top."

The process could also be reversed to use the Rhapsody to identify subsets of cells of interest via highly-multiplexed protein analyses, followed by more targeted RNA analysis using flow cytometry, Gunstream said. "You can get your results [using flow cytometry] in a day, and for a lot lower cost than having to go through sequencing."

"There are a lot of different ways that we can put these pieces together," he said. "We see it as a really nice fit."

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