Swiss proteomics firm Biognosys and Swiss Federal Institute of Technology Zurich researcher Reudi Aebersold have received CHF 1.5 million ($1.57 million) from the Swiss Commission for Technology and Innovation to bring hyper-reaction monitoring mass spectrometry, or HRM-MS, to market.
The technique is a new proteomics technology based on the data-independent acquisition, or SWATH, mass spec method that Aebersold introduced at the American Society for Mass Spectrometry's annual meeting in June (PM 6/10/2011). According to a statement from Biognosys, the new technique “enables simultaneous measurement of thousands of known and unknown proteins in a sample and subsequent extraction of protein profile data."
Aebersold developed the SWATH technique on AB Sciex’s TripleTOF 5600 machine, which, he said in an interview with ProteoMonitor at ASMS, was the only Q-TOF instrument on the market offering high enough performance to run the method.
"We need very good sensitivity, large dynamic range, fast scan speed," he said. "It's a complicated relationship between all these things, and when you tweak somewhere it affects the other things. Right now, the 5600 has the optimal combination."
Like selected-reaction monitoring mass spec, SWATH targets for fragmentation particular precursor ion windows where it expects a peptide of interest to be present and then looks at the level of fragment ions to detect and quantify that peptide.
The difference, according to Aebersold, is that, enabled by the speed of the 5600, SWATH selects a wide precursor window of 25 mass units and moves through the entire precursor ion mass range in segmented windows of 25 mass units, allowing it to "basically generate fragment ions from everything that is eluting from the [LC] column."
Then, using the SRMAtlas developed in an effort led by Aebersold and the Institute for Systems Biology's Rob Moritz, researchers search the fragment ion spectra captured by the machine against the reference spectra in the SRMAtlas to make the peptide IDs.
The unique search strategy is necessary, Aebersold said, because the large composite fragment ion spectra generated by the technique would "choke" a typical search engine.
"So we use the SRM libraries to select and find specific patterns in these composite spectra that correspond to target peptides," he said. "We don't try to explain every spectrum like we would with sequence database searching, we simply want to find patterns that tell us whether or not a particular peptide is present and in what quantity."
In July Aebersold said that an initial study using the technique showed it could identify proteins in a complex sample over four orders of magnitude of dynamic range with quantitation equivalent to that provided by SRM-MS (PM 7/22/2011).
"In terms of sensitivity of detection, [SWATH is] probably a factor of three or four off from SRM, but it's approaching the performance of SRM," he said.
Biognosys was spun out of the Swiss Federal Institute of Technology in 2008. In November 2011 it raised CHF2.7 million ($3 million) in a Series A funding round (PM 11/4/2011). According to its website its customers include Novartis, Pfizer, Integrated Diagnostics, and Philips.