Fluidigm said this week that it has agreed to acquire mass cytometry firm DVS Sciences for roughly $207.5 million in company common stock and cash.
The acquisition will add DVS Sciences' multi-parameter single-cell protein analysis platform, the CyTOF 2, to Fluidigm's portfolio, giving the company a foothold in both the high-end flow cytometry and single-cell proteomics markets.
It also marks Fluidigm's further expansion into the protein analysis space. While Fluidigm has traditionally focused on the single-cell genomics market, the company has recently begun applying its technology toward proteomics. For example, in July it signed a co-marketing deal with Olink Biosciences that combined the two firms' tools to create a high-throughput proteomics platform.
Fluidigm has, in fact, had its eye on the single-cell proteomics space for several years, President and CEO Gajus Worthington told ProteoMonitor.
"We started doing single-cell genomics ... going back to 2007, 2008, and it wasn't long after that that we realized that the solutions for single-cell proteomics were lacking, he said, noting that from a technical standpoint, protein analysis is considerably more challenging than genomic work.
"There's no amplification for proteins, antibodies are tricky, and there are efficiency losses, so doing single-cell proteomics is really very challenging," Worthington said. "We've been on a quest to find a robust, scalable, really enabling single-cell protein expression solution for years now."
He called the DVS acquisition "just the beginning of what our ambitions are with respect to this field."
DVS's CyTOF technology combines capabilities of flow cytometry and atomic mass spectrometry, allowing it to measure large numbers of proteins in single cells with high throughput. Atomic mass spectrometry detects proteins using antibodies linked to stable isotopes of elements, which can then be read with high resolution via time-of-flight mass spectrometry. The platform is able to simultaneously quantify as many as 100 protein biomarkers in individual cells at a rate of roughly 1,000 cells per second.
Markham, Ontario-based DVS launched the CyTOF platform in 2009. Since then it has placed roughly 70 instruments, which sell for around $620,000 each. Roughly 80 percent of those instruments have gone to academic and government customers with the remaining 20 percent going to biopharma.
In the first three quarters of 2013, DVS generated revenues of $18.5 million, up 123 percent from $8.3 million in the first three quarters of 2012. On an investor call following announcement of the purchase, Fluidigm Chief Financial Officer Vikram Jog said the company expects DVS to contribute between $33 million and $35 million in revenue in calendar year 2014.
The CyTOF platform is potentially useful for a range of proteomic applications, but it has in particular made inroads into the high-end flow cytometry market – a space that Fluidigm said represents a roughly $300 million opportunity.
While the CyTOF can theoretically measure more than 100 analytes simultaneously, traditional flow cytometers typically max out in the range of 10 to 20 parameters due to overlaps in the emission spectra of the fluorophores used in such instruments.
One drawback to the CyTOF compared to conventional flow cytometry is its relatively slow speed. A typical flow cytometer can read around 20,000 cells per second. Mass cytometry, on the other hand, tops out at around 1,000. In exchange, though, the CyTOF provides a significant advantage in profiling depth.
Fluidigm first became aware of DVS through conversations with customers who used both companies' instruments, Worthington said, noting that "at an institutional level, that overlap was probably about 80 percent."
Contact with these customers made it "abundantly clear that to really do single-cell biology it is a requirement to have genomic and protein analysis," he said.
He added that this requirement was apparent across a wide variety of research areas.
"The need was common really regardless of the application," he said. "You had to have protein expression with genomics regardless of the biological question."
Worthington noted that while in the short term Fluidigm plans to sell and support the CyTOF as a system separate from its existing offerings, longer term "there is ample opportunity to use our microfluidics on the front end of [the CyTOF]."
He cited workflows implementing the company's integrated cell culturing technology as one potential application. "You can easily imagine a microfluidic solution that would allow substantially more control and flexibility around [cell] culturing solutions and then feed into [the CyTOF]," he said. "We're really just in the very beginning stages of analysis of what we can do."
In an email to ProteoMonitor, Bernd Bodenmiller, a University of Zurich researcher specializing in single-cell proteomics, said that "exploiting [Fluidigm's] microfluidics technology will enable truly exciting new experiments with the CyTOF."
For instance, he suggested, "one could envision that time lapse imaging analysis of single cells is performed using a microfluidics system, and that these very same cells are then processed and introduced into the CyTOF using the microfluidic system to determine their protein levels and signaling state."
"The microfluidics tool box to manipulate and then study live or otherwise processed cells is enormous," said Bodenmiller, who is not associated with either company but uses the CyTOF extensively. "Combining such analyses with the CyTOF-based single-cell proteomic readout is unique and will provide a completely new perspective on single-cell function and cell-to-cell variability."
He cited, as well, the potential for combining single-cell genomics and proteomics analyses.
"Workflows could be implemented in which the single-cell DNA/RNA is isolated in the microfluidics systems for genomic/transcriptomic analysis, but the leftover single-cell content is used for subsequent CyTOF analysis," he said. "Alternatively, DNA probes could be labeled with isotopes instead of fluorophores, and then both genomic and proteomic analyses could be done on the CyTOF. Many combinations of workflows can be envisioned. It should be only a matter of time until this happens."
Fluidigm's DVS acquisition is the second example in recent weeks of a single-cell genomics firm moving to secure access to proteomic technology. This month, NanoString obtained an exclusive option to license IP to a proteomic assay developed by researchers at Massachusetts General Hospital that uses DNA-barcoded antibodies to simultaneously measure in the range of 100 proteins at single-cell sensitivity.
Fluidigm's DVS purchase is expected to close in February 2014, at which point DVS will become a wholly-owned subsidiary of Fluidigm.
The company said that it plans to fund the cash portion of the acquisition – which will account for roughly $125 million of the deal's total $207.5 million price – primarily using proceeds from a proposed convertible notes offering.
Several members of DVS's management and R&D teams, including Co-founders Scott Tanner, currently the firm's chief technology officer, Dmitry Bandura, and Vladimir Baranov, will join Fluidigm upon completion of the deal.