Nested data independent MS/MS acquisition

Abstract

Data independent acquisition (DIA) attempts to provide comprehensive MS/MS data while providing a cycle time that is capable of following the elution profile of chromatographic peaks. Currently available MS technology is not yet fully capable of fulfilling these expectations. This paper suggests a new multiplex-based approach to more closely achieve this objective. Customized scans have been programmed for a Q Orbitrap instrument. Multiple nonadjacent mass range segments are sequentially collected (cut out) by the quadrupole. These combined mass ranges undergo fragmentation, and the resulting product ions are analyzed as a whole by the Orbitrap analyzer. The systematical variation of the mass range segments (nested design) permits the mathematical assignment of the observed product ions within a narrow precursor mass range. The proposed approach allows the use of mass windows that are narrower than those in conventional DIA (SWATH). A unique aspect of the proposed approach is the fact that halving the mass window width requires the addition of only a single multiplexed scan. This is different from conventional DIA, which requires the number of mass windows to be doubled in order to achieve the same objective. This paper shows that for a given cycle time, the proposed nested DIA technique produces significantly less chimeric product ion spectra than conventional DIA. However, further improvements from the programming, and most likely the hardware side, are still required in order to achieve the aim of comprehensive MS/MS. Graphical Abstract Schematic of nested design.

Comparison of data acquisition modes with Orbitrap high‐resolution mass spectrometry for targeted and non‐targeted residue screening in aquacultured eel

“…An intermediate strategy between AIF and "Top N" DDMS2 for non-targeted data acquisition termed "data-independent acquisition" (DIA) has been developed with hybrid HRMS instruments for the analysis of food contaminants. [19][20][21][22][23][24][25][26][27][28][29][30] In general, with DIA data collection, a limited group of precursor (MS1) ions are sequentially filtered through a quadrupole (with a wide isolation window) and then introduced into the collision cell to produce product (MS2) ions. DIA can also be performed with TOF instruments.…”

A Quantitative and Confirmatory Method Employing Liquid Chromatography Coupled to Hybrid High-Resolution Mass Spectrometry and QuEChERS for the Determination of Thirty-Seven Growth Promoter Residues in Bovine Urine

“…In this way, the FS-AIF and FS-DIA modes showed not to be appropriate for quantitative analysis. It should be taken into account that these modes might still be applied to screening and untargeted purposes. − A lower resolution power (17,500 FWHM) was selected in the PRM mode in order to increase the number of detected signals for each product ion. However, it should be taken into account that all of the detected ions (precursors and products) have been identified using a mass extraction window of 5 ppm.…”

Simulated-to-real Benchmarking of Acquisition Methods in Metabolomics

“…Various different DDA and DIA strategies have been introduced [Guan et al, 2020, Guo et al, 2021, Davies et al, 2021,Kaufmann and Walker, 2016] and although each new method is compared with other approaches, no clear consensus has emerged as to which overall strategy is best in which situation [Guo and Huan, 2020a,b, Fernández-Costa et al,2020]. An advantage of DDA is that MS2 spectra are generated nearly ready to use, as each MS2 spectrum targets a particular ion, and we can be reasonably confident that the fragment ions observed do indeed come from the targeted ion.…”