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BD Expands Rhapsody System to Include Single-Cell Protein Analysis


NEW YORK (GenomeWeb) – BD has expanded the capabilities of its BD Rhapsody system to include protein analysis, enabling the platform to simultaneously measure RNA and proteins at the single-cell level.

With the expansion, BD becomes one of the first companies to offer technology for simultaneous single-cell RNA and protein analysis.

BD launched the Rhapsody system last year for single-cell transcriptomic analysis, with Stephen Gunstream, the company's vice president of genomics, noting at that time that the company planned to add protein detection capabilities in 2018.

Launched last month, the Rhapsody's protein analysis component, which BD is calling the AbSeq assay, makes available antibodies to roughly 100 protein targets. This initial portfolio is based on BD's Pharmingen antibody collection, which the company has traditionally offered for flow cytometry work.

Currently, the available antibodies target only cell-surface proteins, said Stephen Kulisch, senior director, applied markets at BD, but he added that the company would likely offer antibodies to intracellular proteins in the future.

"There are a lot of groups we know that are interested in that kind of work," he said, noting that from a technical perspective there is little difference between targeting cell surface or intracellular proteins.

"But from a commercial [antibody] portfolio perspective, BD's strength is in cell surface markers," he said. "Our knowledge of applications in that space is good and most of our business has been in cell surface markers, so from a business perspective the choice was to go that route first."

The Rhapsody 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 (for RNA detection) or oligonucleotide-linked antibodies (for protein detection) that feature well-specific barcodes that can be used to track target molecules coming from the cell occupying a particular well. Target molecules bind to the barcoded probes or oligo-antibodies constructs, and the captured molecules from all the cells can then be combined and amplified together.

Kulisch said BD researchers have multiplexed as many as 46 protein targets in internal work and that outside groups have multiplexed more than 100.

He said the initial panel of antibodies are focused largely on immunology — the legacy of BD's focus on that field in its flow cytometry offerings.

"We've got a pretty strong presence in immunology research and immune profiling," he said. "The first [AbSeq] targets were based largely on our experience and knowledge in that space."

He added that BD also has "additional application areas of interest around immune-oncology and immunotherapy that are helping to drive some of the decision making around the next waves of antibodies" the company plans to release.

Kulisch said the company will eventually offer custom antibodies and panels for the system, as well.

BD initially previewed the Rhapsody system at the Advances in Genome Biology and Technology conference in February of 2017. At that time it was promoting the platform as a tool for whole-transcriptome sequencing of single cells. However, since then the company has shifted to focus on more targeted assays measuring around 400 to 500 transcripts, which enable higher sensitivity while keeping costs down.

BD also introduced earlier this year its BD Single-Cell Multiplexing kit and its Rhapsody Express system. The former allows researchers to multiplex up to 12 samples per experiment, which increases throughput and reduces batch effects.

The Express system is a less expensive benchtop version of the Rhapsody platform that is intended for more rapid, routine assays.

Kulisch noted that the full Rhapsody platform comes with a scanner component used to count cells and measure their viability. This is useful, he said, when researchers are working with a new or challenging sample as it allows them to gather information on things like cell concentration, cells per well, and cell co-localization, which can help with controlling experiment quality.

If, though, "you have a pretty well-behaved cell line and a pretty well-established protocol," the scanner isn't necessarily needed, Kulisch said.

"When we talked to some of our customers and some [researchers] within BD who are using the system, we found that if they have a protocol that is established, they would just skip the scanning steps," he said. "So, we did a little bit more internal investigation and customer work and found that we had a solution that would allow us to put the technology in the hands of more researchers."

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