Will the Digital Mass Filter Be the Next High-Resolution High-Mass Analyzer?

Abstract

Mass filter operation in higher stability zones is known to provide better resolution. Unfortunately, for sine driven instruments, higher stability zone operation reduces the accessible mass range and increases the degenerative effects of fringe fields. Conversely, digitally driven mass filters do not suffer from loss of mass range, and the fringe field effects do not increase significantly by switching stability zones because the AC voltage is always constant and the DC voltage is always zero. This work catalogues 12 stability zones that are accessible with the new digital waveform generation technology. These zones have theoretical baseline resolving powers that range from 22 to 1 300 000 with pseudopotential well depths that range from 3.5 to 43 V. Operation in higher stability zones also has the advantage of aligned axial stability wells. That alignment maximizes the pseudopotential well depth for each higher stability zone, making them more than an order of magnitude greater than the standard ∼0.2 V well of a sine filter operating in the first stability zone at unit resolution. Increased pseudopotential well depth correlates with better ion transmission and sensitivity. Our theoretical examination suggests that the digital mass filter can obtain both high resolution and high sensitivity with essentially unlimited mass range.

Implementing Digital-Waveform Technology for Extended m/z Range Operation on a Native Dual-Quadrupole FT-IM-Orbitrap Mass Spectrometer

“…Additional activation techniques (e.g., CID, ECD/ETD, and SID) can be added to this platform to expand the current platform to probe subunit interfaces. Notably, for the first time, DWT has been shown to transmit, isolate, and filter large protein complexes (approaching the MDa size) supporting the previously described theory …”

“…Figure C–E illustrates the selection capabilities of Q using model protein systems CRP, AmtB, and GroEL. With the isolation of a single-charge state for these complexes and with support by previous theory, evidence suggests that the (3,1) stability zone (the intersection of the third stability zone along the X -axis and first stability zone on the Y -axis) can be accessed without a significant loss in throughput or sensitivity . Collectively, the data shown in Figure illustrate the isolation of a single charge state of native protein complexes CRP (115 kDa), AmtB (127 kDa), and GroEL (801 kDa), thereby making it possible to perform more detailed experiments, IMS, CID, both top-down and complex-down, on specific charge states of proteins and protein complexes.…”

“…The overall performance of DWT for isolation of With the isolation of a single-charge state for these complexes and with support by previous theory, evidence suggests that the (3,1) stability zone (the intersection of the third stability zone along the X-axis and first stability zone on the Y-axis) can be accessed without a significant loss in throughput or sensitivity. 58 Collectively, the data shown in Figure 2 illustrate the isolation of a single charge state of native protein complexes CRP (115 kDa), AmtB (127 kDa), and GroEL (801 kDa), thereby making it possible to perform more detailed experiments, IMS, CID, both top-down and complexdown, on specific charge states of proteins and protein complexes. Mass spectra illustrating how mild collisional activation in the q of the qQ-FT-IM-PF-DT Orbitrap can be used to remove adducted species (salts, endogenous lipids, and other small molecules) from (A) the trimeric ammonia transport channel (AmtB, 127 kDa) and (B) GroEL (801 kDa, tetradecamer (n = 14)).…”

“…Notably, for the first time, DWT has been shown to transmit, isolate, and filter large protein complexes (approaching the MDa size) supporting the previously described theory. 58 ASSOCIATED CONTENT * sı Supporting Information…”

Effect of Jitter on Digital Mass Filter Analysis in Higher Stability Zones

“…Operations in the higher stability zones were performed with parameters (i.e., duty cycle, well depth, q-value, etc.) defined in ref . All analyses were performed with perfluorotributyl amine (PFTBA) purchased from Scientific Instrument Services Inc. (Ringoes, NJ).…”