By Diagnostics World Staff
November 25, 2015 | Quanterix, the Lexington, Mass.-based creator of a high-throughput protein analysis instrument, is overhauling its hardware and software as it prepares for a more commercial stage in its development. The company’s Simoa instruments have been in early customers’ labs for around 18 months, giving Quanterix a first look at how they will hold up under continuous use and what features users will be looking for in the future.
The Simoa is built to detect proteins at minute concentrations in blood or other biological samples. It uses the same combination of targeted antibodies and fluorescent markers as an ELISA experiment, a process that has been common since the 1970s. In the Simoa, however, hundreds of thousands of these reactions can be performed and measured in parallel, inside microwells etched into disc-shaped cartridges. (For a more detailed look at the Simoa technology, see, “Quanterix Aims for Early Clinical Adoption with High-Throughput Protein Assays.”)
The instrument is agnostic to which ELISA assays are performed, so while Quanterix sells a limited menu of test kits to its customers, many users are running homebrewed tests with their own libraries of antibodies. Most of these tests support basic research, but Quanterix hopes clinical labs will eventually use the Simoa for diagnostic testing, searching for biomarkers at trace levels in the bloodstream that could be early indicators of disease.
“[Our business] is probably a third diagnostic discovery, and two thirds pharmaceutical drug development and companion diagnostics,” says CEO Kevin Hrusovsky. “The most rapid growth in the last nine months has been from the pharmaceutical and biotechnology industry, realizing the incredible objectivity that our technology is bringing to bear for a lot of disease categories.”
Thanks to a well-publicized grant from the NFL, Quanterix is most closely associated with efforts to invent a blood test for concussion, based on biomarkers that may cross the blood-brain barrier in small quantities following head trauma. But Hrusovsky says this is only a small branch of the company’s work in neurology, with users investigating disorders from Alzheimer’s to Parkinson’s. “Tau, amyloid beta, these are areas where there’s a lot of both drug discovery and diagnostic interest,” he says.
Another large area of demand is the analysis of cytokines involved in inflammation and immune responses.
Because any standard ELISA test can be adapted to run on the Simoa, Quanterix often works with users to create assays the company did not anticipate. (Most recently, Clinical Chemistry published a use case detecting the p24 antigen of HIV.) Some users have even veered away from protein analysis to detect specific microRNAs or DNA sequences, replacing antibodies with different kinds of capture probes to isolate their targets in the Simoa’s microwells.
As a result, Quanterix has run into bugs that never came up in the company’s own experiments, especially as users have started running multiple in-house tests in parallel.
“The power users have done a lot of multiplexing of homebrew, and what we find is that everyone’s problems are a little bit different and unique,” Hrusovsky says. “We’ve seen a lot of one-off issues.”
The New Simoa
Now, Quanterix is releasing the Simoa 2.0, with upgrades that will let customers create their own tests with less troubleshooting. The Simoa 2.0 is not an entirely new instrument, but it does involve new software installs and some hardware retrofits, which are being offered for free to existing customers.
“We’ve already got about 50 to 70% of the install base modified with all the hardware changes,” says Hrusovsky. “We’ve had to beef up our service and application organization, so we’ve been building a pretty formidably sized company in order to implement this.”
The biggest change will be to the sample volumes required for Simoa experiments. Quanterix claims it will be possible to use half the volume of sample, and just one-fifth the quantity of reagents, to run an assay on the Simoa 2.0, compared to the previous version. This is a result of a revised sample preparation process, in which less sample is left as dead volume that cannot mix with antibodies for analysis.
However, working with smaller samples led to unforeseen hurdles. For instance, Quanterix found that, with less sample available to begin with, evaporation became a serious impediment to experiments. The Simoa 2.0 therefore uses new sample plates with redesigned lids that prevent evaporation.
Similarly, Quanterix learned that certain assays, when repeated over time, were causing salt to build up inside the Simoa, requiring the company to redesign its washing system to deal more effectively with salt.
Meanwhile, Quanterix is taking the opportunity to add software features requested by its early customers. Some of these will let the Simoa better monitor how it’s being used, by adding new prompts and letting the instrument stop runs if its database is full. “The software is now much more intuitive, for instance, when [users] load up their reagents,” says Hrusovsky. “The software will tell them if there’s some issue they’re creating, where the system might shut down later because reagents weren’t loaded properly.”
Other features make homebrewed test more programmable. Users have sometimes found that they need to customize their reagent levels to make a new assay run properly. Now they will be able to specify those requirements when they prepare a test, and the Simoa will remember their custom protocols when it gives prompts and performs quality control during a run.
“Our technology runs really bleed-to-read,” says Hrusovsky. “You’re putting in the blood sample, and the entire ELISA experiment is being run inside our equipment. [So we’re] making sure that the more generic algorithms we had for off-the-shelf assays can also be applied to homebrew assays.”
The updated software of the Simoa 2.0 will also feature an electronic record keeping system compliant with 21 CFR part 11 regulations ― meaning users will for the first time be able to submit data generated by the Simoa to the FDA.
That reflects Quanterix’ efforts to quickly mainstream its technology for the same uses as other broad testing platforms. As a few pharmaceutical companies have gotten acquainted with the Simoa in their early discovery work, some will likely want to move their assays on to preclinical studies where data has to be prepared for regulators. “A lot of these companies have antibody drugs, and want to use our technology to run PK/PD [pharmacokinetic/pharmacodynamic] studies,” says Hrusovsky. “To do those, they really did need to have the 21 CFR part 11 compliance.”
The second big area for growth the Quanterix team sees is in laboratory developed tests, where clinical labs design their own diagnostics in-house, usually for patients in their parent hospitals. This has traditionally been the fastest route to bringing new types of testing into clinical use, before mass-market diagnostics can be prepared and submitted to the FDA.
No diagnostic uses of the Simoa have been proven out in clinical settings yet. But Hrusovsky is hugely optimistic about the disease areas the instrument might cover with laboratory developed tests. “Our technology not only can help in concussions, but can provide early detection of a lot of different diseases, whether it be heart disease, whether it be cancers,” he says. “Can we look at these low-abundance markers early, in an annual physical?... I think that is the future of medicine.”
To reach these kinds of markets with Quanterix’ new, more commercial-ready instrument, Hrusovsky is looking for the funds to expand production and distribution. His company is now in the middle of a new funding round, pitching crossover investors in preparation for a planned initial public offering in 2016.