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Bio-Rad Expands Single-Cell Library Prep Platform With New scATAC-seq Assay


SAN FRANCISCO (GenomeWeb) – Bio-Rad continues to push into the next-generation sequencing with droplet-based technologies, in particular with new assays that make use of the ddSeq single-cell preparation platform it developed in conjunction with Illumina and launched last year.

This week, the firm said that it has developed a single-cell assay for transposase accessible chromatin by sequencing (scATAC-seq) product to add to its existing single-cell RNA sequencing assay. The product is now available for early-access users and Bio-Rad plans a full commercial launch for the first quarter of 2019, according to Carolyn Reifsnyder, director of life science marketing in the company's digital biology group.

The scATAC-seq solution runs on Bio-Rad's ddSeq system, but instead of isolating and encapsulating single cells, it traps individual nuclei into droplets. Reifsnyder said on each instrument run there are four reactions, each of which can process up to 5,000 cells for a total of 20,000 cells in a five minute run with a capture efficiency of more than 80 percent.  

That capture efficiency is significantly higher than for its single-cell RNA-seq assay, which researchers from the Association of Biomolecular Resource Facilities reported in April to be around 3 percent.

Reifsnyder noted that the firm had developed a new approach for "cell and barcode encapsulation that allows us to achieve this high capture efficiency with the new kit." Key to the scATAC-seq kit is the company's use of a customized hyperactive transposase, the enzyme that cuts the DNA between the nucleosomes, she said.

Reifsnyder said the scATAC-seq assay would have initial applications in oncology research and provide a way to validate single-cell RNA-seq experiments. "It's a good way to better understand the mechanisms that drive which genes are turned on and off," she said.

The product will likely compete with the one being developed by 10x Genomics, which the firm previously said it would launch in the fourth quarter of this year.

It's not yet clear how the two products will compare to each other. Reifsnyder touted the custom transposase in the Bio-Rad assay and said that its much improved capture efficiency would be an advantage, but did not share other performance specifications. Likewise, 10x Genomics has also not disclosed performance specifications for its ATAC-seq assay yet.

Bio-Rad made its initial foray into the sequencing market when it acquired startup GnuBio in 2014, a Cambridge, Massachusetts firm that had been developing a droplet-based targeted sequencing technology.

Reifsnyder declined to comment on whether Bio-Rad was still developing that platform. Initially, Bio-Rad had said it would develop the GnuBio technology for targeted clinical sequencing applications, and it integrated the startup into its Digital Biology Center Cambridge team. But last year, the company closed the Cambridge facility, consolidating the center into the Digital Biology Group in Pleasanton, California. Bio-Rad did not say at the time what that consolidation meant for the development of the GnuBio technology, however, the company said in an earnings call last year that it planned to redirect some of the savings it was recognizing from closing down the facility to areas like liquid biopsy.

Reifsnyder said that Bio-Rad plans to continue to develop products in the single-cell arena. "The area of single-cell library prep is a large untapped market," she said. In particular, the company is focused on applications that make use of the benefits of droplet technology. "Droplet partitioning is a very fast, scalable way to partition and encapsulate single cells," she said, and the firm is looking to develop other types of single-cell assays that make use of that technology.

Over the last several years, there has been enormous growth in the single-cell sequencing market as plummeting sequencing costs have made analyzing single cells no longer cost prohibitive and as advancements in methods for isolating and analyzing single cells have proliferated. 

A recent market research reported by Grand View Research estimated the global market for single-cell sequencing at $730 million in 2016 and projected it would reach $2.49 billion by 2025.

Given the interest, there are now a number of single-cell technologies on the market. Aside from Bio-Rad and 10x Genomics, WaferGen Bio-systems (now part of Takara Bio), Fluidigm, Becton Dickinson, and 1CellBio have all launched commercial instruments.

In addition, some academic groups, looking for low-cost options or more open systems, have developed their own technologies. Researchers from the New York Genome Center, for instance, have developed a microfluidic system, which they estimated costs $575 to build, on which they run Drop-seq for single-cell RNA-seq as well as an internally developed method called CITE-seq, which looks at the transcriptomes and surface proteins of cells. Researchers in Jay Shendure's lab at the University of Washington, meanwhile, have developed single-cell methods that are based on combinatorial indexing and do not require any specialized equipment.