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Fluidigm Targets 'Production Genomics' Space with Four New Integrated Fluidic Circuit Products

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Fluidigm is launching four new consumable chips based on its integrated fluidic circuit technology, PCR Insider has learned.

The new offerings, all of which will run on the BioMark HD real-time PCR system, are intended to provide customers conducting large-scale digital PCR, genotyping, and gene expression experiments with maximum throughput, accuracy, and flexibility.

In addition, with the new products Fluidigm hopes to shape a larger emerging market that it refers to as "production genomics," which is distinct from but includes production genotyping, and in general describes the use of genomics technologies in applied markets that demand high throughput and high accuracy.

"What we see emerging is a series of production applications that are not just genotyping, but include gene expression, digital PCR … and it could ultimately be sequencing, too," Fluidigm CEO Gajus Worthington told PCR Insider this week. "But the broad umbrella is what we're now calling production genomics. It's very different from research, a very different set of requirements, and is addressed by this set of [new] product offerings."

The first new product from the South San Francisco-based company is a digital PCR chip called the qdPCR 37K Integrated Fluidic Circuit, or IFC. The 37K label represents the chip's ability to create up to 770 reactions for as many as 48 samples for 36,960 (rounded to 37,000) reactions; while the 'qd' moniker represents both quantitative and digital PCR. "That means that while you're collecting the fluorescent signal from each of the digital reactions, you're actually looking at it in real time," Worthington said.

This in turn allows users to determine whether they are actually amplifying their target of interest or whether the fluorescence signal is merely an artifact of some sort. "When you're amplifying individual molecules, and every molecule counts, that ability to read the data points in real time is critical," Worthington said.

In addition, the new digital PCR chip contains "a series of manufacturing breakthroughs … and design changes" that lower the cost per sample to as little as $2, Worthington noted, adding that this was about half of the lowest cost per sample available with a droplet-based digital PCR system such as Bio-Rad's QX100 Droplet Digital system. In an interview last month with PCR Insider, a Bio-Rad representative said that the cost of running a digital PCR experiment on its platform is about $3 per reaction, but did not provide a per-sample cost (PCR Insider, 10/11/12).

All told, the new chip provides "substantially lower cost with a performance edge that we think is going to be really important as digital PCR moves from initial discovery work into true production," Worthington said. "The problem with today's digital PCR solutions in a production environment is that it's hard to tell whether you actually found the needle in a haystack, they're too expensive on a per-sample basis, and they're not high-throughput enough. So we've addressed that with this new device, enabling some of the first production applications for digital PCR, for instance [studying genetically modified organisms]."

The second new product is a genotyping chip called the High Precision 96.96 Genotyping IFC. Of the new products, this one is most akin to current Fluidigm consumable chips, for instance its Dynamic Array 96.96.

With the new chip, Fluidigm has "pushed the … call rate up by a substantial margin," Worthington said.

"The call rate that we expect on the chip is minimum 99.9 percent, and that's the highest that you'll find anywhere in the industry," he said. "Some competing PCR-based systems actually have a 95 percent call rate, and that difference may not seem like a lot … but when you need calls for every single SNP it actually makes a huge difference in the amount of rework you might have to do, or the number of samples you might have to throw away or not get paid for. Again, this is something that we learned from our customers, that they needed calls for every single SNP."

Both the qdPCR 37K and High Precision 96.96 Genotyping IFC are currently available for sale from Fluidigm.

The third new product is a 192.24 Gene Expression IFC, which features the ability to run 192 samples in parallel across 24 genes.

"This is really targeted, again, to production environments where they need to plow through huge numbers of samples in very short periods of time," Worthington said. "So 192 samples, exactly twice what the 96.96 does, and four times what the former 48.48 does. With a single run, you're able to get nearly 200 samples through the system. In an eight-hour day you could easily do three runs on the BioMark, so you're up to a throughput of nearly 600 samples a day with one machine and very little hands-on time."

The 192.24 Gene Expression IFC will be available in mid-December, Worthington said.

The last of the new products is called the FLEXsix Gene Expression IFC, and features a "completely new" flexible architecture, Worthington said.

"This is a multi-use device that has six different partitions, and each partition is a 12-by-12 array … so you have six 12-sample-by-12-assay partitions, and you can use them in any configuration, and do up to six runs on the chip," he explained.

Thus, customers could use the chip in a 12-sample-by-48-assay configuration; then use it as a 24-sample-by-12-assay device; or could simply run six separate 12-sample-by-12-assay reactions.

"That allows customers to run a wide range of a small number of samples against a large number of assays, or [vice versa], or anything in between, so they can do their validation work," Worthington said.

He noted that Fluidigm's customers have noted that they often initially have a limited number of samples, limited number of assays, or both to work with in order to validate an assay before moving it into a higher-throughput mode. Now, he said, customers will be able to do this validation work on the FLEXsix, and "after you've got that nailed, you can move it to production with one of the [new] devices … or one that we currently sell."

That scale-up is often done on different platforms, he noted, and the company is hoping that customers will find it easier to perform this "technology bridging" by being able to conduct validation work and high-throughput production work on the same system, the BioMark, using the same workflow.

The FLEXsix product will be available in January, Worthington said.

Producing a Market

With its existing products, such as the various configurations of the Dynamic Array IFC, Fluidigm has already carved out a niche in what has traditionally been called the production genotyping market, where it competes with platforms primarily from Sequenom or Life Technologies, Worthington said.

"This is actually a pretty substantial growth area for us," he added. "I think it's fair to say that we've been taking share of this market for a while, it's been a nice area for us. We've had success with the 96.96, for sure, and all the times that our chip numbers have gone through the roof, it's because of the business we have here. But what we learned as a result of being in the market is that there is a way to make, depending on the application, substantial contributions to people's work. We want to be as advantageous as possible relative to the competition so we can convince customers to switch. And that's what we're trying hard to do … particularly with these new innovations."

But the new chip offerings play into more than just production genotyping, encompassing a field that Fludigm calls production genomics.

"They address a pretty wide range of requirements for labs that are doing really high-throughput work, whether that be in genotyping, expression profiling, or digital PCR," he said.

Worthington declined to disclose any of Fluidigm's existing customers in the production genotyping or broader production genomics space, but noted that the Broad Institute uses its products for DNA fingerprinting applications, which Worthington said has a lot in common with the types of production applications Fluidigm is targeting.

With the emergence of a new market also comes the challenge of getting customers to switch from what Fluidigm may view as outdated, inefficient techniques compared to its product offerings. But many of these customers may have large investments in their current technologies or are deeply entrenched in their current workflows.

"One of the things you see in this kind of market is that when somebody establishes a workflow, it's hard to displace them out of that because the company doesn't want to go back into discovery, into reworking their whole workflow," Fluidigm spokesperson Howard High said.

Worthington echoed these thoughts, noting that the market for most production applications "is pretty well established, there are a lot of techniques out there. This market exists already and is one in which we think we can make a major contribution. So our objective is to be a leader here, but that's going to take some time. There are a lot of machines out there already in this space."

Fluidigm releases its third-quarter financial results on Nov. 7.