Bruker and the University of Victoria-Genome British Columbia Proteomics Centre said this week that they are collaborating on high-throughput iMALDI mass spec-based assays for determining genetic hemoglobin variants and diabetes risk.
The iMALDI assays, which combine peptide immunoenrichment with mass spectrometry for improved throughput and sensitivity, will be developed to run on Bruker's MALDI Biotyper clinical mass spectrometry platform, said Christoph Borchers, director of the center.
The genetic hemoglobin assays will look for well-known variants linked to diseases including sickle-cell anemia, C disease, and thalassemias, while the diabetes risk assay will measure levels of glycated hemoglobin, hbA1c, an established marker for diagnosing and monitoring the disease.
The tests will be commercialized through University of Victoria spin-out firm MRM Proteomics, where Borchers is chief scientific officer. He told ProteoMonitor that the researchers aim to have the assays ready for market in roughly a year.
The agreement marks a new direction for Bruker's Biotyper device. Launched in 2006, the instrument has been marketed by the company primarily as a tool for proteomic-based microbial identification. With the announcement of the UVic collaboration, though, Bruker is positioning the device for clinical proteomics more broadly.
"Absolutely," said Gary Kruppa, Bruker's vice president for business development, when asked if the agreement signaled an effort by the company to move the Biotyper into the traditional protein diagnostic market.
"The Biotyper has been a very successful product, and we're looking for ways to leverage that success to make it even more widely accepted," he told ProteoMonitor. "The first thing that is of interest is other applications in microbiology... and then the next phase beyond that is obviously the protein diagnostic market."
Borchers, meanwhile, noted that the established clinical acceptance of the Biotyper platform would likely help speed the tests' time to market.
The Biotyper "has been sold mainly for microbiology, but this machine can be used for other clinical assays as well," he said. "It is already in the clinic. It is very robust, and I think this is the way to go right now" in terms of moving mass spec-based protein assays to market.
The Biotyper is available in a research-use-only version, as well as in a CE-IVD version in various European countries, and as a Class 1 Medical Device to clinical microbiology sites in Canada. Bruker has also obtained clearance for clinical use of the instrument in Australia, New Zealand, Taiwan, and Japan. Currently, the instrument is available solely for research purposes in the US, but the company is currently pursuing US Food and Drug Administration 510(k) approval. According to Bruker, more than 800 Biotypers are installed globally.
According to Borchers, the UVic researchers plan to collaborate with Bruker on a number of additional protein diagnostics for the Biotyper. Such tests could serve as alternatives to existing ELISAs, he said, noting that they can offer sensitivity in the low picogram per mL while requiring only a single antibody as opposed to the two antibodies used in a typical ELISA.
Kruppa likewise suggested the device could find a niche as a new platform for existing protein assays.
"There are some radioimmunoassay-based tests where people want to get rid of the radioisotopes, so mass spec would be very attractive there," he said. The platform could also be an alternative to "ELISA-based tests [where there are] problems with interferences and non-specific binding.
"For a lot of existing tests, mass spectrometry can bring advantages in speed, cost, sensitivity, specificity, and those tests we would want to go after," Kruppa said. "There are a number of existing targets that I think really present significant market opportunities if you convert them to mass spec."
He noted that the company is interested in developing novel protein tests for the platform, as well.
Borchers said that his team has contracts with several large undisclosed in vitro diagnostic firms to develop MALDI-based assays for various proteins – with some of these firms requesting assays developed specifically for the Biotyper.
The instrument, Borchers noted, is not as powerful as higher-end MALDI machines like Bruker's Ultraflextreme, but, he said, this level of performance isn't necessary for routine clinical assays.
"It certainly isn't as powerful as other [MALDI machines], and it doesn't have MS/MS capability, but that's not needed here," he said. "It's simple, very robust, and very fast, and this is ok as long as you have a well-developed assay. The other MALDI instruments are more like research-type devices, and they are good, but we don't need that for these assays."
"If it turns out that the higher performance or higher throughput of the larger instruments is needed, we would go there if we had to," Kruppa said. "But it would be great if we could find more clinical diagnostic tests that could be implemented on the Biotyper platform."
Beyond indicating Bruker's new direction for the Biotyper, the UVic deal represents another example of MALDI's growing potential as a technology for clinical proteomics.
Broadly speaking, the field has viewed multiple-reaction monitoring mass spec on triple quadrupole instruments as the likeliest route for mass spec-based proteomics to move into clinical applications, with MALDI traditionally being dismissed due to concerns about its sensitivity and reproducibility.
However, recent work both by Borchers' group and a separate team including his UVic colleague Terry Pearson, SISCAPA Assay Technologies CEO Leigh Anderson, and Bruker researchers – which also used the Biotyper for some assays – has demonstrated that the technology can be used for sensitive and highly reproducible protein quantitation, with coefficients of variation below five percent (PM 1/30/2012).
In fact, despite his significant experience with and investment in triple quad-based MRM-MS assays through his position at UVic and at MRM Proteomics, Borchers said that he believes MALDI, not MRM-MS is currently the most suitable technology for clinical proteomics.
MRM-MS has made great strides recently toward clinical viability, with the proteomics diagnostic firms Applied Proteomics and Sera Prognostics adopting the technology for their tests (PM 3/29/2013). However, said Borchers, MALDI remains a simpler, more robust method.
Perhaps more importantly, it retains an advantage over MRM-MS in terms of throughput. While rapid chromatography systems can allow researchers to run hundreds of samples per day via MRM-MS, MALDI analysis can be done offline of sample prep and separations, allowing researchers to batch process thousands of samples per day, Borchers said.
He noted that he and his colleagues are currently in the process of validating an iMALDI assay for angiotensin I, which is used as a measure of plasma renin activity, a marker of primary aldosteronism. The assay, he said, appeared to correlate very well with radioimmunoassays for angiotensin I, the current gold standard, and was able to quantitate the protein at low picograms per mL levels.
In addition to its work with Borchers, Bruker is involved in several other clinical mass spec collaborations, including work with the aforementioned Pearson and Anderson-led team on SISCAPA-based clinical MALDI assays.
And, last week, the company announced a collaboration agreement with companion diagnostics firm Biodesix, whose proteomic Veristrat test for identifying likely responders to various cancer therapies runs on a platform based on Bruker's Autoflex and Ultraflextreme MALDI instruments (PM 4/12/2013).