NEW YORK (GenomeWeb) – With the launch last week of its next-generation CyTOF platform, Helios, Fluidigm aims to up capabilities for existing users while drawing new customers into the fold with streamlined and simplified operations.
Notably, the new system features a new sample introduction system that allows for increased sample volumes and better sampling efficiency, Tad George, senior director of applications at Fluidigm, told GenomeWeb this week. It also provides a roughly 50 percent increase in sensitivity and increased multiplexing capabilities.
Fluidigm also released a new barcoding system for use with the platform that enables researchers to combine up to 20 samples in one instrument run.
The company is currently taking orders for the new system, which it plans to begin shipping in the third quarter of this year. George declined to give an exact price for Helios but said that it would cost around 10 percent more than the CyTOF 2, which would place it in the range of $600,000 to $700,000.
Originally developed by DVS Sciences, CyTOF 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.
Fluidigm acquired DVS and the CyTOF technology last year for $207.5 million as part of its ongoing push into single-cell proteomics.
Since the acquisition, sales of the platform have somewhat underperformed Fluidigm's expectations. For instance, in 2014 Fluidigm downgraded its guidances after soft sales early in the year, reducing an initial guidance of $33 million to $35 million in CyTOF sales to between $24 million and $26 million, including $3.8 million in 2014 revenue recognized by DVS prior to the acquisition. On its Q3 2014 earnings call, the company said it had revised this estimate to between $23 million and $25 million.
In Q1 2015, CyTOF sales fell short of company expectations by around $2 million, though Fluidigm President and CEO Gajus Worthington attributed that largely to the timing of new system orders in which several orders expected in Q1 were moved to Q2.
With the new Helios platform, the company hopes to capture new users perhaps put off by the complexity of the original instruments, George said, characterizing the new features as half aimed at delivering on the wishes of existing customers and half at bringing new customers into the fold.
"Obviously we always want to make discovery research with our single-cell proteomics platform as easy as we can," he said.
With that in mind, the company made changes that will make maintenance of the instrument easier, he noted.
Additionally, he said, "the user interface has been what I would call modernized. The first instruments were designed by engineers for engineers. But the interface we have developed here is much more modern."
In terms of delivering on wishes of existing users, George said that highest on the list were the increased sample capacity and the barcoding system.
The two fit together, he noted, in the sense that increased sample capacity is required to enable the analysis of the larger samples created when researchers use the barcoding system to multiplex.
Previous versions of the CyTOF used a sample injection system in which researchers used a syringe to introduce their sample into tubing where it was then moved into the instrument for analysis using a carrier solution. That system had a capacity of around 0.5 ml.
The Helios, on the other hand, uses a pressurized sample introduction chamber to pass the sample into the machine and has a capacity of 5 ml.
"That is important especially if people are going to migrate to the barcoding workflow," George said, noting that barcoding experiments combining a number of samples are commonly in the range of 4 ml in total volume.
The barcoding system Fluidigm introduced is based on work done in the lab of Stanford University researcher Garry Nolan, who has worked extensively — though independently — on technology and software development for the system. It uses combinations of three palladium isotopes to encode up to 20 different samples, allowing researchers to run them in a single experiment.
The main advantage of this sort of multiplexing is better reproducibility, George said, noting that by running 20 samples in a single batch researchers can eliminate variation due to sample prep steps and instrument drift.
Multiplexing can also increase throughput by streamlining sample prep and instrument operation, George noted, but Helios' improved throughput — roughly double that of the CyTOF 2 — is primarily attributable to the instrument's improved sampling efficiency.
Mass cytometry's low sampling efficiency — the percentage of cells that are ultimately turned into data — has been one reason researchers, particularly those accustomed to flow cytometry, have been hesitant to take up the technique, George said.
"The sampling efficiency in a flow cytometer is probably about 90 percent or more," he said. Meanwhile, "mass cytometry is traditionally around 30 percent."
The Helios' new sample loading system has nearly doubled that rate, George said, adding that the company hoped this would help win over some new users.
When sampling efficiency is over 50 percent, "people are less worried about it," he said. "Down around 30 percent is where it becomes an objection."
The Helios also features an increased mass range which improves the platform's multiplexing capacity in terms of the number of analytes that can be measured simultaneously — 135 compared to 122 in the CyTOF 2. George noted, however, that the company does not currently sell metal-conjugated antibody reagents that could take advantage of that increased range.
"So this doesn't necessarily buy you any advantage today, but if we develop [reagents] into that region in the future you will be able to use those," he said.
Fluidigm currently offers more than 450 metal-conjugated antibodies to between 250 and 300 unique targets out of its standard reagents catalog, George said. The company also sells kits that allow researchers to make their own reagents and offers custom conjugation services.