To tackle the challenge of discovering and analyzing low-abundance proteins in complex samples, Bruker recently launched the timsTOF pro MS system, an update of its timsTOF system, which was launched last year (see IBO 6/15/16). The system is currently shipping at a list price of $899,000.

The timsTOF pro employs dual TIMS (Trapped Ion Mobility Spectrometry) funnels to trap ions in the first section, while simultaneously eluting them from the second section. The system is designed for Parallel Accumulation Serial Fragmentation (PASF), a method developed by Matthias Mann, PhD, of the Max Planck Institute of Biochemistry, for shotgun proteomics. PASF allows the collection of MS/MS spectra from multiple ion precursors.

As Rohan Thakur, PhD, executive vice president at Bruker Daltonics, who heads the company’s Life Science MS business, told IBO, “The dual TIMS allows us to do parallel accumulation and serial fragmentation, enabling very high scan rates at high MS resolution. It’s the only technology out there that allows you to separate ions in the gas phase, after chromatographic separation and before they enter the mass analyzer.” To chromatography, MS and MS/MS, this adds a new dimension for analysis. “On the timsTOF Pro, this additional dual TIMS separation mechanism allows you to separate the co-eluting species in the ion mobility dimension. So it’s like a fourth dimension of separation before triggering mass analysis.”

The result is close to 100% duty cycle and a fast scan rate, with a resolution of 50,000, according to Bruker. Asked how this compares to other advanced MS systems, Dr. Thakur noted, “The best Orbitraps’ published scan rate is <30 Hz, with resolution of R=7,500 in the MS/MS mode. QTOFs without TIMS capability cannot be fairly compared.”

These capabilities specifically address challenges facing quantitative proteomics. “If you do bottom-up proteomics, the peptide mixtures are still extremely complex, and the elution of peptides is unpredictable. So you needed something that would scan very fast, is sensitive and would acquire data at high resolution,” explained Dr. Thakur. This allows greater characterization and quantification of low-abundant peptides.

As Dr. Thakur told IBO, “We are not wasting ions due to the very high duty cycle of the dual TIMS funnel, allowing the timsTOF Pro to uncover more ions; for example, biologically significant low-level peptides in bottom-up proteomics.” The fast scan rate is key. “So we get one extra opportunity to sort through the complex mixture of ions coming in, and that’s key. And we do it at R=50,000 resolution in the mass analyzer, so we’re not compromising on mass resolution, resulting in a scan rate faster than any mass spec out there.”

Applications include PTM research and large cohort studies.