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Fluidigm Seeks New Users as it Launches Higher-Throughput Single-Cell mRNA Sequencing Chip

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NEW YORK (GenomeWeb) – Fluidigm is hoping it can draw new customers to its C1 platform with a new chip and workflow that can prepare up to 800 single cells for mRNA sequencing at a time.

Last week, Fluidigm launched a new integrated fluidic circuit (IFC) and reagent kit which increases throughput and decreases per-cell cost for sequencing preparation. The company had previewed the product earlier this year at the Advances in Genome Biology and Technology meeting.

"People wanted to be able to do more cells and more chemistries," Fluidigm VP of Research and Development Marc Unger explained. With that in mind, Fluidigm designed the chip with similar but smaller capture architecture. "We can fit a whole bunch more capture sites on a single chip," he said.

Unger said the new workflow implements a "smarter" chemistry based on barcoding and cell pooling. "We discovered everyone doing mRNA sequencing is actually looking to measure gene expression. For that, 3' end counting chemistry is just fine," he said.

"What scientists are often trying to do is take a fresh look at a tissue type," Fluidigm field application scientist Manisha Ray said. "The ability to do single-cell sequencing opens the door into all different kinds of biology." Often, research concerns the simple question of the number of cell types present, identified by their unique gene expression signatures. "You need to know the numbers of each gene. Counting is all you need."

Unger suggested that scientists interested in gene expression matrices or splice variants would want to continue using Fluidigm's first chip for mRNA sequencing, which can handle up to 96 cells.

"One of the challenges to increasing throughput was figuring out how to miniaturize the cell capture sites," Unger said.  "We had to figure out how to jam 800 of them into a space that previously had only 96. The chemistry is different to address that; it combines all the cells together, pooling them using a barcoding strategy."

Fluidigm introduced a new scheme to apply "two-dimensional" barcoding. Transcripts are barcoded once, and then a second time when the cells are collected and pooled. When the mRNAs are sequenced, the barcoding allows the researchers to match them to their cell of origin.  "Before, we had to do one library prep reaction for every cell product that came out. Now when we do it by pools, [so] despite having 800 cells, we have to only do 20 reactions," Unger said.

The benefits of pooling bear out in a number of ways. The price per cell is 85 percent lower, Unger said, since fewer reactions require fewer reagents. In February, Fluidigm told GenomeWeb that the chip would cut the per-cell costs of RNA sequencing by 50 percent to $10.50. Ray added that pooling reduces batch effects as well as the potential for sample mix-up.

"We can combine up to 800 cells in a single lane of [an Illumina] Hi-Seq instrument," she said. The new chip can also run two different cell types at the same time, side by side. That makes it easier to perform studies comparing a disease state or treatment group versus a normal case or control group.

Ray pointed to research into rare cell types as another possibility enabled by the new workflow. Previously, researchers looking for cells that were found at a rate of one in 100 would only find one cell per 96-cell plate. The 800-cell format provides a more statistically robust way of studying those cells because it analyzes more of them.

The new chip can also benefit studies where the imperative is to process as many cells as soon as possible. "If researchers are doing things where they're sacrificing mice, they want as many cells as they can get at one time from the brain, the spleen, the heart," Ray said.

Fluidigm is hoping that the new workflow will entice new customers to buy the C1 platform. Howard High, a Fluidigm spokesperson, said he had spoken with several customers who were waiting to purchase a Fluidigm instrument because their volume requirements were too great for the 96-cell format.

"Some people had been sitting on the sideline waiting for the ability to run more samples, more cells, so hopefully we've given them a reason to step off that sideline," High said.

In an early access program, customers in both pharma and academia were able to test-drive the new workflow. Fluidigm said it expects its partners to publish data from those studies soon.

The firm is selling the new chips through its existing direct sales model. Fluidigm had "quite a few orders before we did the official launch," High said, and has received additional orders since.

Already, Fluidigm is planning for even higher throughput for this and other applications. Competition for mRNA sequencing preparation is set to be fierce, with multiple technologies looking to compete with the C1 system. In February, Wafergen launched an early-access program for its SmartChip technology, which offers a 5,184-well format. Cellular Research is also developing a platform for mRNA barcoding that it says will be able to run 5,000 to 10,000 single cells in parallel. And scientists from Columbia University recently published a paper on a microwell device for single-cell RNA capture, which has garnered some commercial interest.

"We're not stopping here," Unger said. "We are already working on the next- and next-next-generation of chips for higher throughput for mRNA sequencing preparation.

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