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Illumina, Bio-Rad Form Alliance for Single-Cell Sequencing System

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NEW YORK (GenomeWeb) – Bio-Rad and Illumina have formed an exclusive partnership to develop a next-generation sequencing workflow for single cells, the firms said this week at the JP Morgan Healthcare conference in San Francisco. The single-cell analysis field has been expanding over the past few years and this new partnership may affect a number of companies with competing technologies.

The result of the collaboration is expected to be a "cost-effective, end-to-end, high-throughput, and scalable platform for single-cell analysis," Illumina's CEO Jay Flatley said in a presentation at JP Morgan. The firms expect the project to be completed by early 2017.

"We think the combination of our respective know-how and intellectual property will allow us to jointly create a foundational product offering in this market," he said.

At launch, the system will be capable of preparing up to 10,000 single cells at $1 per cell with only a few hours of hands-on time, according to Flatley. Estimated total run time was not reported by the firms.

Under the agreement, Bio-Rad will develop a modified version of its QX200 instrument and consumable cartridge that creates droplets, Flatley said. These droplets will contain single cells and barcoded beads.

Specifically, the firm is "developing an instrument that will encapsulate cells leveraging our core droplet partitioning technology," Bio-Rad's senior vice president and general manager of the Digital Biology Center, Annette Tumolo, told GenomeWeb in an email.

Following cell lysis and hybridization of the cellular RNA to the bead within the droplet, the emulsion is broken, and after a few more sample prep steps the mixture enters a sterile library prep process developed by Illumina, Flatley explained.

After sequencing, the data will stream to Illumina's BaseSpace — a recently expanded cloud-based platform that provides third-party and internally developed bioinformatics applications — to be analyzed and reported.

"This workflow will represent the market's most integrated end-to-end single-cell solution, and could be expanded in the future to include many new applications," Flatley said.

He noted that the commercialization plan will leverage the firms' respective channels, with Bio-Rad selling the modified droplet-generating instrument, and Illumina selling all consumables, including the droplet cartridge, in a single kit.

Bio-Rad and Illumina seem to have made preliminary progress in this project already, with Flatley noting that several proof-of-principle experiments have been conducted, "demonstrating cell purity of over 90 percent with samples containing up to 450 single cells, in excellent concordance with bulk RNA-seq methods."

Illumina is generally focused on improving the standardization of the development toolset around digital fluidics, Flatley also said. It is the firm's intention to "open up that technology to third-party developers to create applications that they can build using digital fluidics technology."

Flatley explained that much of the work in single cells has of necessity been done using small cell numbers, with scientists developing their own workflows "at cost points that have prevented them from scaling to large cell collections." To further catalyze the market requires a strategy for scaling the cell preparation, he said.

Bio-Rad acquired droplet-based sequencing firm GnuBio in 2014 with the goal of commercializing a clinical NGS system,  but "this co-development with Illumina is not related in any way to the work going on with the technology we acquired from GnuBio," Tumolo said.

Competition in the single-cell sequencing space

There are a number of players already in the single-cell sequencing space. Notably, Fluidigm was one of the first vendors to develop and market products specifically for the field.

The firm views recent announcements of companies entering this market as "confirmation of the emergence and importance of this key area of biological discovery," Howard High, a spokesperson for Fluidigm, told GenomeWeb in an email, adding that the company is "committed to continuing to lead the market in providing the largest range of applications to researchers investigating single-cell biology."

Fluidigm anticipates more companies will "enter this fast growing market, broadening the number of available solutions."

High said Fluidgim's C1 system enables researchers to rapidly isolate, process, and profile individual cells for genomic analysis. The C1 can analyze up to 800 cells at a time, and it enables single-cell mRNA sequencing, targeted DNA sequencing, whole exome sequencing, and whole genome sequencing on Illumina sequencers, in addition to performing targeted gene expression and miRNA expression profiling.

Fluidigm has also formed global partnerships to open single-cell genomics centers in Sweden and Australia.

Becton Dickinson recently launched a cell sorter and assays for single-cell genomics, and Qiagen has partnered with Cell Microsystems to commercialize a technology for isolating and analyzing single cells. WaferGen, meanwhile, launched a single-cell system for single-cell genomics called ICell8 in October of last year.

Cellular Research's Resolve system, which the firm originally said it planned to launch in 2016, is also similar to the proposed Illumina and Bio-Rad workflow in that it can analyze up to 10,000 cells in parallel for $1 per cell. Becton Dickinson acquired Cellular Research last year.

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