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

Abstract

Here, we describe a digital-waveform dual-quadrupole mass spectrometer that enhances the performance of our drift tube FT-IMS high-resolution Orbitrap mass spectrometer (MS). The dual-quadrupole analyzer enhances the instrument capabilities for studies of large protein and protein complexes. The first quadrupole (q) provides a means for performing low-energy collisional activation of ions to reduce or eliminate noncovalent adducts, viz., salts, buffers, detergents, and/or endogenous ligands. The second quadrupole (Q) is used to mass-select ions of interest for further interrogation by ion mobility spectrometry and/or collision-induced dissociation (CID). Q is operated using digital-waveform technology (DWT) to improve the mass selection compared to that achieved using traditional sinusoidal waveforms at floated DC potentials (>500 V DC). DWT allows for increased precision of the waveform for a fraction of the cost of conventional RF drivers and with readily programmable operation and precision (Hoffman, N. M. et al.. A comparison-based digital-waveform generator for high-resolution duty cycle. Review of Scientific Instruments 2018, 89, 084101).

Optimization of a Digital Mass Filter for the Isolation of Intact Protein Complexes in Stability Zone 1,1

“…Previously, an 85.0/15.0 duty cycle and ∼15 V offset was used to isolate single-charge states of protein complexes . It was hypothesized that this isolation was performed in zone 3,1 which has a q value of 4.5 and an a value close to 0.…”

“…Using digital waveforms, the stability diagram can be manipulated by changing the duty cycle to move stability zones to a = 0. , This removes the requirement for scanning the DC voltage to perform ion isolation in a mass filter. By removing the necessity for generating very high voltages, high mass-to-charge ions can be readily detected. − …”

Influence of Pseudopotential Well Depth on the Performance of Hybrid Linear Ion Trap/Time-of-Flight Mass Spectrometry Driven by Square and Sinusoidal Waveform

“…Moreover, the quadrupole ion trap is usually used for ion storage and MS n operation in hybrid instruments, such as QIT/TOF, LIT/TOF, − and QIT/orbitrap . The rf parameters of quadrupole devices have an important impact on the performance of hybrid instruments.…”

“…Moreover, the quadrupole ion trap is usually used for ion storage and MS n operation in hybrid instruments, such as QIT/TOF, 17 LIT/TOF, 18−20 and QIT/orbitrap. 21 The rf parameters of quadrupole devices have an important impact on the performance of hybrid instruments. spectrometer in a well-collimated ion beam to obtain high resolution and mass accuracy for studies of large protein.…”

“…spectrometer in a well-collimated ion beam to obtain high resolution and mass accuracy for studies of large protein. 18,21,22 Brabeck and Reilly reported that a digital ion trap can modulate the duty cycle of the applied rectangle waveforms to operate as traps and mass filters, realizing the isolation, fragmentation, and preconcentration of single charge states ion before mass analysis by a TOF analyzer. 23 We reported that a square waveform phase modulation strategy can simultaneously improve the resolution and sensitivity of LIT/TOF.…”