NEW YORK – The summer of 2017 was a seemingly promising moment for mass spectrometry's move into the clinic, as both Thermo Fisher Scientific and Sciex introduced new, more streamlined machines aimed at the clinical market, and Roche announced its plans to develop a mass spec-based clinical analyzer with Hitachi.
Three years later, the promise has faded somewhat. Sciex has discontinued sales of its system, the Topaz, after seeing limited adoption.
Thermo Fisher, meanwhile, brought its clinical system, the Cascadion SM Clinical Analyzer, to market in the US this March just as the SARS-CoV-2 pandemic was beginning to peak, and while some observers remain enthusiastic about its potential, adoption will likely depend on the scope of the instrument's test menu, which at the moment remains limited in the US to Vitamin D.
Roche declined an interview request, with a company spokesperson noting that a launch of its mass spec analyzer is still a ways off.
These launches and announcements were part of a long effort among vendors to develop simpler instruments that could bring mass spec to a broader clinical audience. Mass spec is commonly used in clinical laboratories, but it still requires significant expertise, and many of the tests run on these instruments are laboratory developed. The goal was to offer more user-friendly instruments that would interest smaller labs without the in-house experience needed to run mass spec assays as well as larger labs who could use the instruments for more routine tests while focusing more time on building their menu of laboratory-developed tests.
The level of user friendliness varied. Sciex's Topaz was essentially a simplified version of its existing 4500MD LC-MS instrument with a sample prep module and analysis software designed for clinical use. The company offered US Food and Drug Administration-cleared assays for the system, but users could also develop their own tests on it.
The Cascadion, on the other hand, is a fully automated, turnkey system designed to be analogous to the clinical analyzers currently used by labs for various chemistry and immunoassays. The system is significantly easier for inexperienced users to learn and operate than either traditional mass spectrometers or the Topaz. The tradeoff is a lack of flexibility — the Cascadion can only run tests developed for it by Thermo Fisher, and currently only one test, for vitamin D, is available in the US. In Europe, the company launched a CE-IVD marked immunosuppressants panel that measures four immunosuppressants in blood in April.
Recently retired, James Ritchie was formerly the director of the core laboratory at Emory Crawford Long Hospital and an early-access user of the Topaz. He suggested that a number of factors contributed to the instrument's failure to gain traction in the market, perhaps most prominently the fact that despite Sciex's efforts at simplification, the system still required a fair amount of expertise to use.
"They couldn't get into the primary core lab as they still needed a trained [mass spec] technical person," he said.
He also noted that Beckman Coulter, one of Sciex's Danaher stablemates, undercut the Topaz by selling Sciex's traditional clinical mass spec instruments as part of equipment deals "at prices even medium to large hospitals could not justify walking away from."
Additionally, Ritchie said that the decline of the pain drug testing market had "flooded" the market with used mass spec instruments that created further difficulties for the Topaz.
Dominic Gostick, VP of LCMS at Sciex, said in an email that the company had seen its users "pivoting to in-house methodologies to further expand their existing mass spectrometry menus" and that the company "continues to support their method development and workflows."
He said that the company is now focusing its clinical mass spec efforts on its 4500MD and Citrine systems "due to the flexibility and versatility these instruments offer."
The Topaz "has the advantage that it was an open platform, so you could develop your own test on it," said Paul Jannetto, director of the clinical mass spectrometry laboratory at the Mayo Clinic. "However, if you're looking at trying to bring it into that small- or medium-sized market, if you don't have the expertise to do all that and manage that and do all the validations and troubleshooting… this wasn't going to help you."
"Yeah, [Topaz] had kits that you could use for some assays, but if you were already going to be developing your own assays, maybe you could develop your own assays for those [kit-based] assays," he said.
Joe El-Khoury, assistant professor of laboratory medicine and director of clinical chemistry, laboratory medicine at Yale School of Medicine, thought there was potentially a place for the Topaz, however. In an interview before Sciex said that it had taken the instrument off the market, El-Khoury said that his lab had not ruled out getting a Topaz.
He noted that while his lab already had a mass spec vitamin D assay up and running and has extensive expertise running and developing mass spec assays, the Topaz interested him in that it might provide a less expensive solution.
"Right now I have a Hamilton for the sample preparation, I have an LCMS from Waters for the analysis, and Ascent [from Indigo BioAutomation] for the data analysis," he said. "So, I essentially have something that is very similar to the Topaz system in my lab that is costing a relative fortune because I pay each company separately for service agreements, and I pay the software analysis individually for every sample analyzed."
This, combined with the ability to develop LDTs on the instrument made it potentially attractive, El-Khoury said, given his lab's expertise.
Ultimately, though, it seems the Topaz occupied an awkward spot where it was not simplified enough for an inexperienced user and not differentiated enough from existing clinical mass spec instruments for experienced labs to adopt the system.
The Cascadion, on the other hand, is directly targeting users with little to no mass spec background.
Jannetto said the instrument probably didn't make sense for a reference lab like Mayo that was already up and running with numerous mass spec assays. His lab has experience with the system as it did some of the initial validation work on it with Thermo Fisher, he said.
"I have three different labs that I manage that have mass spectrometers and in one alone I have more than 40 mass specs, so when I have that type of capital equipment already at my disposal, it's much cheaper for me to do my own tests than to pay someone else for the reagents to do it," he said.
Throughput is another major consideration, he said, noting that from that perspective the Cascadion would be better suited to a small to medium lab as opposed to a larger reference lab.
"It couldn't handle my volumes of testing," he said. "My immunosuppressant test volume alone is more than it could handle in a 24-hour period. So it would cost me more money and I would have less throughput."
Like Jannetto, El-Khoury said the Cascadion made the most sense for labs without existing mass spec experience.
"If I have no experience with LCMS, I don't have a PhD [assay] development expert or techs who know how to develop methods and I'm starting fresh, then I would recommend the Cascadion, because it's basically the closest there is to an automated platform that is fully integrated," he said.
He added that the instrument could also make sense for his lab at Yale, depending on the ultimate cost, and noted that he was, in fact, getting a quote on one.
While his lab has the experience and personnel to develop its own tests, these are limited resources, and moving some tests to an automated instrument like Cascadion could free up time for the development of needed LDTs.
"I have a development list that spans five assays that I need to work on that we are slowly building because all of our techs are running these other assays," he said. "So for us, as an experienced lab, the Cascadion would mean I could move at least vitamin D to start to the automated lab where I can teach an autochem tech who doesn't have mass spec experience how to run it, and then I can use my [mass spec-experienced] techs to develop new methods that don't have automated assays."
He added that the SARS-CoV-2 pandemic has affected his thinking around this, as well, because he has been losing mass spec techs to virology.
Jannetto and El-Khoury both said that ultimately whether the Cascadion proved a success would come down to its test menu. Jannetto said that with only vitamin D testing available in the US, it wasn't to his mind a compelling offering at the moment.
"We never buy a piece of equipment for just one test," he said. "I don't have the luxury of money and space and all of those things. Unless you have a lot of vitamin Ds, you're never going to get your return on investment."
El-Khoury agreed but said that he believed that the immunosuppressant panel that Thermo Fisher launched in Europe, and which it will presumably launch in the US (the company declined to comment for this story), could be an important driver of Cascadion sales.
"That is an assay that is needed on a daily basis," he said, noting that this means his lab needs a tech capable of running mass spec immunosuppressant assays scheduled seven days a week.
A Cascadion with immunosuppressants as part of its menu would mean "that I don't have to bring a tech in on the weekend just to run this one assay," he said, adding that this was an issue common to any lab running immunosuppressants given that physicians need results of those tests daily.
"When they have immunosuppressants, [the instrument] will be much more attractive," he said.