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Becton Dickinson Multiomics Product Roadmap to Lean Heavily on Rhapsody Single-Cell System


NEW YORK – BD Biosciences this year is planning to launch several new products for multiomic research designed for use on its BD Rhapsody single-cell analysis platform in an effort to increase its presence in the precision medicine research market.

Over the coming months, the Franklin Lakes, New Jersey-based company will be launching a second-generation version of its VDJ recombination assay offering improved sensitivity in T-cell receptor pairing efficiency, an open chromatin profiling assay for epigenetic regulation studies, and an intracellular CITE-seq assay for profiling intracellular proteins in combination with surface proteins and whole transcriptomes.

"We see … increasing use of single-cell multiomic assays, because [multiomics] really does provide a comprehensive view of what disease mechanisms are," said Aruna Ayer, senior director of R&D, single-cell multiomics, and advanced technologies at BD.

Precision medicine-related applications that BD envisions for its suite of new products include helping academic and industry researchers identify rare subpopulations of cells that influence tumor growth, metastasis, and therapy resistance, as well as facilitating insights into the immune response triggered by various therapeutic interventions such as immune checkpoint blockade, chemotherapy, and cell therapy.

Coupled with the company's existing technology and recent product launches — including a 50-color flow cytometry platform and the Omics-Guard sample preservation buffer for greater flexibility in transcriptomic and proteomic profiling protocols — the firm is well-positioned to further penetrate precision medicine research, in particular immuno-oncology.

"There's been great momentum in immunotherapy and immuno-oncology in the last 10 years," said Ranga Partha, VP of global marketing and strategic growth areas at BD. "Cell analysis is important, and single-cell analysis is even more critical. And then capturing multiple biological analytes in a single cell gets super critical to uncover cellular heterogeneity."

The updated VDJ recombination assay may be the first new product to launch. Partha said that although BD doesn't have an exact launch timeline, the company expects it to become available globally "in the next few months."

The new version will be called the BD Rhapsody TCR/BCR Next Multiomic Assay. This assay profiles full-length T-cell and B-cell receptors (TCR and BCR) with improved sensitivity and pairing efficiency compared to the previous version and supports both whole and targeted transcriptome profiling, as well as surface protein profiling via CITE-seq using BD AbSeq antibody oligonucleotides.

Ayer explained that this new assay achieves TCR pairing efficiency in the high 70s to 80 percent range, without impacting BCR pairing efficiency.

BD plans to launch its new open chromatin profiling assay soon after the TCR/BCR Profiling Assay. This product, based on the assay for transposase-accessible chromatin with sequencing (ATAC-seq), can be used to perform open chromatin and whole-transcriptome profiling as a single integrated assay.

ATAC-seq was first described in 2013 and has since attracted commercial interest as a means of combining epigenomics and transcriptomics.

The method forms the core of 10x Genomics' Chromium Single-Cell Multiome ATAC + Gene Expression assay, for example, and groups from institutions such as Yale University and the New York Genome Center are exploring ways to combine it with spatial RNA-seq and proteomic assays.

Yale licensed its method, called Cleavage Under Targets and Tagmentation (CUT&Tag), to the university's spinout, AtlasXomics, which recently inked a deal with EpiCypher to further develop it for spatial epigenomics applications.

Ayer said that BD's ATAC-seq assay sets itself apart from competitors through its ability to be run on a microwell-based technology platform such as BD Rhapsody.

"The platform technology is a differentiating feature in itself," she said, "as the microwell technology offers minimal batch effects among other benefits [such as] flexibility in throughput, [and] high signal-to-noise."

Following the above two product launches, BD also plans to release a protein-plus-whole-transcriptome profiling assay called Intracellular CITE-seq, which uses BD's AbSeq Antibody-Oligos to combine intracellular and surface protein profiling with whole-transcriptome sequencing.

Originally established at the New York Genome Center, CITE-seq, or cellular indexing of transcriptomes and epitopes by sequencing, essentially consists of oligonucleotide barcode-labeled antibodies which bind to cell-surface proteins. Antibody-bound cells are then isolated and lysed, and single-cell RNA-seq libraries are prepared from them. Complementary DNA (cDNA) derived from both cellular mRNA and the oligonucleotide barcodes can be sequenced simultaneously, providing a combined transcriptome and surface protein readout.

BD's new assay takes this process one step further, profiling intracellular proteins by a proprietary method simultaneously with surface proteins and whole transcriptome.

Ayer and Partha explained that BD's confidence in its ability to successfully commercialize these upcoming products is bolstered by several recent product launches that help round out an integrated, single-cell, multiomic ecosystem.

One of those products is the BD Omics-Guard Sample Preservation Buffer. This PFA-free buffer protects RNA and proteins for up to 72 hours at 4 degrees Celsius, offering researchers greater flexibility in transcriptomic, proteomic, and multiomic protocols.

"Especially in translational and clinical research," Ayer said, "people often collect samples over multiple days."

Ayer sees decentralized sample collection, as might be the case in large population studies, as the primary use case for this buffer, although she expects that it will also help researchers to optimize large, multiple-sample processing protocol.

"Say, for example, you're starting from a tissue and you have multiple tissue samples to process," she said. "Once you've gotten to your single-cell suspension, [it helps to] preserve them in a certain buffer and get to a stopping point rather than killing yourself doing an 18-hour workday."

The company also recently launched an update to its FACSDiscover S8 spectral flow cytometry platform. BD developed a 50-color spectral flow cytometry panel largely through improvements to its proprietary spectral mixing algorithm coupled with the system's five lasers and 70 detectors, Ayer said.

In a study currently undergoing peer review, BD demonstrated the system's capabilities via a panel that captured the differentiation and activation status of T cells and antigen-presenting cells, while also measuring B cell, natural killer cell, and innate lymphoid cell phenotypes.

"FACS is an important front-end tool before single-cell analysis," Ayer said.

The ability to conduct real-time sorting on 50 different protein parameters, she explained, is expected to enable both broader and deeper phenotyping than ever before.

In an agreement inked earlier this year, robotics developer Hamilton is helping to support BD's single-cell multiomics research through bespoke automated solutions, particularly with respect to enabling reproducible, high-throughput systems.

"The collaboration with Hamilton is helping us accelerate our discoveries," Partha said. "The ability to do high-throughput studies is an increasingly unmet need [among] our customers, so this fits well within our ecosystem."