High-Resolution Differential Ion Mobility Separations/Orbitrap Mass Spectrometry without Buffer Gas Limitations

Abstract

Strong orthogonality between differential ion mobility spectrometry (FAIMS) and mass spectrometry (MS) makes their hybrid a powerful approach to separate isomers and isobars. Harnessing that power depends on high resolution in both dimensions. The ultimate mass resolution and accuracy are delivered by Fourier Transform MS increasingly realized in Orbitrap MS, whereas FAIMS resolution is generally maximized by buffers rich in He or H 2 that elevate ion mobility and lead to prominent non-Blanc effects. However, turbomolecular pumps have lower efficiency for light gas molecules and their flow from the FAIMS stage complicates maintaining the ultra-high vacuum needed for Orbitrap operation. Here we address this challenge via two hardware modifications: (i) a differential pumping step between FAIMS and MS stages and (ii) reconfiguration of vacuum lines to isolate pumping of the Orbitrap ultra-high vacuum region. Either greatly ameliorates the pressure increases upon He or H 2 aspiration. This development enables free optimization of FAIMS carrier gas without concerns about MS performance, maximizing the utility and flexibility of FAIMS/MS platforms. SUPPORTING INFORMATION AVAILABLE: Photos of single and tandem ion funnel interfaces, the plot of backing line pressure with SFI.

Identification and quantification of amino acids and related compounds based on Differential Mobility Spectrometry

“…Using methanol as an added modifier to N 2 as carrier gas, we already showed baseline separation of isomeric ions could be obtained in the case of sarcosine, α-and β-alanine, 44 as well as for the α-, β-, and -aminobutyric acid isomers. 45 As reported in the literature, adding of a fraction of He to the carrier gas 20,22,29 or increasing the waveform amplitude 21 should also be considered for high resolution DMS. Quantification of AAs and related compounds were achieved using our 3D quadrupole ion trap despite the intrinsic limitations of these instruments in terms of sensitivity and linear dynamic range.…”

“…30 DMS has also been shown to be more orthogonal to MS/MS than DT-IMS or related time-separation methods, in the case of peptides, for example. 20,31 Coupled to MS/MS, it was shown that the coverage achieved with the DMS is comparable to that achieved with the chromatographic methods. 32 DMS hyphenated to MS/MS has thus been used for analysis of complex biological fluids such as urine and plasma, and especially for the separation of co-eluting isomers.…”

“…17 Efforts toward separation of isobaric and isomeric species led to the development of high resolution instruments and/or methodologies. Within a decade, important progresses have been made with new types of instruments time- 18,19 and spacemobility 20,21 separation. Significant enhancement of the resolving power can also be achieved by introducing a fraction of He 22 or polar molecules 23 in the carrier gas, as found in particular for AAs.…”

Application of zero‐phase digital filtering for effective denoising of field asymmetric waveform ion mobility spectrometry signal

“…For example, in the high‐resolution planar FAIMS, a periodic asymmetric high voltage waveform, defined as dispersion voltage (DV), was applied to one of the two parallel planar electrodes to create an asymmetric alternating electric field ( E D ) in a gap between the two electrodes 21,22 . During each waveform cycle, ions carried by a constant gas flow into the FAIMS gap will be deflected toward either one of electrodes and eventually discharged on the electrodes after many waveform cycles 21–24 . A proper DC compensation voltage (CV) is superimposed on the DV to make ions move in the opposite direction, which can just offset the deflection of ions caused by DV.…”

“…A proper DC compensation voltage (CV) is superimposed on the DV to make ions move in the opposite direction, which can just offset the deflection of ions caused by DV. By this way, ions with the specific Δ K ( E ) can be kept stable in the FAIMS gap, which are subsequently carried by the gas out of the FAIMS 23–25 . A FAIMS spectrum of ions with different Δ K ( E ) can be obtained by scanning the CV across a certain voltage range at a given speed 24,25 …”