We report on separations of ion isotopologues and isotopomers using ultrahigh-resolution traveling wave-based Structures for Lossless Ion Manipulations with serpentine ultralong path and extended ...routing ion mobility spectrometry coupled to mass spectrometry (SLIM SUPER IMS-MS). Mobility separations of ions from the naturally occurring ion isotopic envelopes (e.g., M, M+1, M+2, ... ions) showed the first and second isotopic peaks (i.e., M+1 and M+2) for various tetraalkylammonium ions could be resolved from their respective monoisotopic ion peak (M) after SLIM SUPER IMS with resolving powers of ∼400–600. Similar separations were obtained for other compounds (e.g., tetrapeptide ions). Greater separation was obtained using argon versus helium drift gas, as expected from the greater reduced mass contribution to ion mobility described by the Mason–Schamp relationship. To more directly explore the role of isotopic substitutions, we studied a mixture of specific isotopically substituted (15N, 13C, and 2H) protonated arginine isotopologues. While the separations in nitrogen were primarily due to their reduced mass differences, similar to the naturally occurring isotopologues, their separations in helium, where higher resolving powers could also be achieved, revealed distinct additional relative mobility shifts. These shifts appeared correlated, after correction for the reduced mass contribution, with changes in the ion center of mass due to the different locations of heavy atom substitutions. The origin of these apparent mass distribution-induced mobility shifts was then further explored using a mixture of Iodoacetyl Tandem Mass Tag (iodoTMT) isotopomers (i.e., each having the same exact mass, but with different isotopic substitution sites). Again, the observed mobility shifts appeared correlated with changes in the ion center of mass leading to multiple monoisotopic mobilities being observed for some isotopomers (up to a ∼0.04% difference in mobility). These mobility shifts thus appear to reflect details of the ion structure, derived from the changes due to ion rotation impacting collision frequency or momentum transfer, and highlight the potential for new approaches for ion structural characterization.
Ion Mobility Separations Using Cocentric Architecture Kwantwi-Barima, Pearl; Hollerbach, Adam L.; Attah, Isaac K. ...
Journal of the American Society for Mass Spectrometry,
07/2024, Letnik:
35, Številka:
7
Journal Article
Recenzirano
Ion mobility separations, especially using drift tube ion mobility spectrometers, are usually performed in linear channels, which can have a large footprint when extended to achieve higher resolving ...powers. In this work, we explored the performance of an ion mobility device with a curved architecture, which can have a more compact form. The cocentric ion mobility spectrometer (CoCIMS) manipulates ions between two cocentric surfaces containing a serpentine track. The mobility separation inside the CoCIMS is achieved using traveling waveforms (TWs). We initially evaluated the device using ion trajectory simulations using SIMION, which indicated that when ions traveled circularly inside the CoCIMS they resulted in similar resolving powers and transmitted m/z range as traveling in a straight path. We then performed experimental validation of the CoCIMS in conjunction with a TOF MS. The CoCIMS was made of two flexible printed circuit board materials folded into cocentric cylinders separated by a gap of 2.8 mm. The device was about 50 mm diameter ×152 mm long and provided 1.846 m of serpentine path length. Three sets of mixtures (Agilent tune mixture, tetraalkylammonium salts, and an eight-peptide mixture) and four traveling waveform profiles (square, sine, triangle, and sawtooth) were used. The sawtooth TW profile produced a slightly higher resolving power for the Agilent tuning mixture and tetraalkylammonium ions. The average resolving power for Agilent tune mixture ions ranged from 37 (using sawtooth TW) to 27 (using square TW). The average resolving powers ranged from 45 (sawtooth TW) to 31 (square TW) for tetraalkylammonium ions. The resolving power of the peptide mixture ions was similar among the four TW profiles and ranged from 51 to 56. The average percent error in TWCCS for the peptide mixture ions was about 0.4%. The new device showed promising results, but improvements are needed to further increase the resolving power.
To address the challenges associated with glycan analyses, we have implemented a structures for lossless ion manipulations (SLIM) serpentine ultra-long path with extended routing (SUPER) ion ...mobility-mass spectrometry (i.e. SLIM SUPER IM-MS) platform to achieve much higher resolution of isomeric glycoforms. We have demonstrated the potential of this platform as a future component of the glycomics toolbox.
Clothianidin, an insecticide with a novel mode of action, has been deployed in the annual indoor residual spraying programme in northern Ghana since March 2021. To inform pragmatic management ...strategies and guide future studies, baseline data on local Anopheles gambiae sensu lato (s.l.) susceptibility to the clothianidin insecticide were collected in Kpalsogu, a village in the Northern region, Ghana.
Phenotypic susceptibility of An. gambiae mosquitoes to clothianidin was assessed using the World Health Organization (WHO) insecticide resistance monitoring bioassay. The WHO cone bioassays were conducted on mud and cement walls sprayed with Sumishield 50 wettable granules (WG) (with clothianidin active ingredient). Daily mortalities were recorded for up to 7 days to observe for delayed mortalities. Polymerase chain reaction (PCR) technique was used to differentiate the sibling species of the An. gambiae complex and also for the detection of knock down resistance genes (kdr) and the insensitive acetylcholinesterase mutation (ace-1).
The WHO susceptibility bioassay revealed a delayed killing effect of clothianidin. Mosquitoes exposed to the cone bioassays for 5 min died 120 h after exposure. Slightly higher mortalities were observed in mosquitoes exposed to clothianidin-treated cement wall surfaces than mosquitoes exposed to mud wall surfaces. The kdr target-site mutation L1014F occurred at very high frequencies (0.89-0.94) across all vector species identified whereas the ace-1 mutation occurred at moderate levels (0.32-0.44). Anopheles gambiae sensu stricto was the most abundant species observed at 63%, whereas Anopheles arabiensis was the least observed at 9%.
Anopheles gambiae s.l. mosquitoes in northern Ghana were susceptible to clothianidin. They harboured kdr mutations at high frequencies. The ace-1 mutation occurred in moderation. The results of this study confirm that clothianidin is an effective active ingredient and should be utilized in malaria vector control interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The accumulation of very large ion populations in traveling wave (TW)-based Structures for Lossless ion Manipulations (SLIM) has been studied to better understand aspects of “in-SLIM” ion ...accumulation, and particularly its use in conjunction with ion mobility spectrometry (IMS). A linear SLIM ion path was implemented that had a “gate” for blocking and accumulating ions for arbitrary time periods. Removing the gate potential caused ions to exit, and the spatial distributions of accumulated ions examined. The ion populations for a set of peptides increased approximately linearly with increased accumulation times until space change effects became significant, after which the peptide precursor ion populations decreased due to growing space charge-related ion activation, reactions, and losses. Ion activation increased with added storage times and the TW amplitude. Lower amplitude TWs in the accumulation/storage region prevented or minimized ion losses or ion heating effects that can also lead to fragmentation. Our results supported the use of an accumulation region close to the SLIM entrance for speeding accumulation, minimizing ion heating, and avoiding ion population profiles that result in IMS peak tailing. Importantly, space charge-driven separations were observed for large populations of accumulated species and attributed to the opposing effects of space charge and the TW. In these separations, ion species form distributions or peaks, sometimes moving against the TW, and are ordered in the SLIM based on their mobilities. Only the highest mobility ions located closest to the gate in the trapped ion population (and where the highest ion densities were achieved) were significantly activated. The observed separations may offer utility for ion prefractionation of ions and increasing the dynamic range measurements, increasing the resolving power of IMS separations by decreasing peak widths for accumulated ion populations, and other purposes benefiting from separations of extremely large ion populations.
Structures for lossless ion manipulations (SLIM) technology has demonstrated high resolving power ion mobility separation and flexibility to integrate complex ion manipulations into a single ...experimental platform. To enable IMS separations, trapping/accumulating ions inside SLIM (or in-SLIM) prior to injection of a packet for separations provides ease of operation and reduces the need for dedicated ion traps external to SLIM. To fully characterize the ion accumulation process, we have evaluated the effect of TW amplitudes, ion collection times, and storage times on the "in-SLIM" accumulation process. The study utilized a SLIM module comprising 5 distinct tracks, each with a specific ion accumulation configuration. The effect of the TW conditions on the accumulation process was investigated for a 3-peptide mixture: kemptide, angiotensin II, and neurotensin at a TW speed of 106 m/s. The effect of ion accumulation time/collection time and storage time was investigated, in addition to TW amplitude. Overall, the signal of the analyte ions increased when the ion collection time increased from 49 to 163 ms but decreased when the ion collection time increased further to 652 ms due to the space charge effects. Ion losses were observed at high TW amplitudes (e.g., 15 V
and 20 V
). In addition, under space charge conditions (e.g., collection times of 163 and 652 ms), the signal of the analyte ions decreased with an increase in storage times for all TW amplitudes applied to the trapping region. For ion accumulation, the data indicate that gentler TW conditions must be utilized to minimize ion losses and fragments to benefit from the "in-SLIM" accumulation process. Wider SLIM tracks provided better performance than those with narrower tracks.
The stepwise hydration of the benzonitrile•+ radical cation with one–seven H2O molecules was investigated experimentally and computationally with density functional theory in C6H5CN•+(H2O) n ...clusters. The stepwise binding energies (ΔH n–1,n °) were determined by equilibrium measurements for C6H5CN•+(H2O) and for •C6H4CNH+(H2O) n with n = 5, 6, and 7 to be 8.8 and 11.3, 11.0, and 10.0 kcal/mol, respectively. The populations of n = 2 and 3 of the C6H5CN•+(H2O) n clusters were observed only in trace abundance due to fast depletion processes leading to the formation of the hydrated distonic cations •C6H4CNH+(H2O) n with n = 4–7. The observed transition occurs between conventional radical cations hydrated on the ring in C6H5CN•+(H2O) n clusters with n = 1–3 and the protonated radical •C6H4CNH+ (distonic ion) formed by a proton transfer to the CN nitrogen and ionic hydrogen bonding to water molecules in •C6H4CNH+(H2O) n clusters with n = 4–7. The measured binding energy of the hydrated ion C6H5CN•+(H2O) (8.8 kcal/mol) is similar to that of the hydrated benzene radical cation (8.5 kcal/mol) that involves a relatively weak CHδ+···O hydrogen bonding interaction. Also, the measured binding energies of the •C6H4CNH+(H2O) n clusters with n = 5–7 are similar to those of the protonated benzonitrile (methanol) n clusters C6H5CNH+(CH3OH) n , n = 5–7 that involve CNH+···O ionic hydrogen bonds. The proton shift from the para-•C ring carbon to the nitrogen of the benzonitrile radical cation is endothermic without solvent but thermoneutral for n = 1 and exothermic for n = 2–4 in C6H5CN•+(H2O) n clusters to form the distonic •C6H4CN···H+(OH2) n clusters. The distonic clusters •C6H4CN···H+(OH2) n constitute a new class of structures in radical ion/solvent clusters.
Accumulation of β-amyloid (Aβ) is one of the hallmarks of Alzheimer’s disease. The deposition of β-amyloid plaques is likely to start years in advance of manifestation of clinical symptoms, although ...the exact timing is unknown. Over the years, Aβ peptides undergo both post-translational modification and stereoisomerization. Analysis of the resulting stereoisomers is particularly challenging because of their identical elemental composition and similar physicochemical properties. Herein, we have utilized our recently developed structures for lossless ion manipulations ion mobility-mass spectrometry platform (SLIM IM-MS), in conjunction with serpentine ultralong path with extended routing (SUPER), to baseline resolve four distinct sets of Aβ17–28 tryptic peptide epimers on a rapid (∼1 s) time scale. We discovered that sodium adduct ions, M + H + Na2+, allowed baseline SLIM SUPER IM resolution for all Aβ epimer sets assessed, while such baseline separations were unachievable for their M + 2H2+ doubly protonated ions.
The collision cross section (CCS) is an important property that aids in the structural characterization of molecules. Here, we investigated the CCS calibration accuracy with traveling wave ion ...mobility spectrometry (TWIMS) separations in structures for lossless ion manipulations (SLIM) using three sets of calibrants. A series of singly negatively charged phospholipids and bile acids were calibrated in nitrogen buffer gas using two different TW waveform profiles (square and sine) and amplitudes (20, 25, and 30 V0‑p). The calibration errors for the three calibrant sets (Agilent tuning mixture, polyalanine, and one assembled in-house) showed negligible differences using a sine-shaped TW waveform. Calibration errors were all within 1–2% of the drift tube ion mobility spectrometry (DTIMS) measurements, with lower errors for sine waveforms, presumably due to the lower average and maximum fields experienced by ions. Finally, ultrahigh-resolution multipass (long path length) SLIM TWIMS separations demonstrated improved CCS calibration for phospholipid and bile acid isomers.
The stepwise hydration of the benzonitrile
radical cation with one-seven H
O molecules was investigated experimentally and computationally with density functional theory in C
H
CN
(H
O)
clusters. The ...stepwise binding energies (Δ
) were determined by equilibrium measurements for C
H
CN
(H
O) and for
C
H
CNH
(H
O)
with
= 5, 6, and 7 to be 8.8 and 11.3, 11.0, and 10.0 kcal/mol, respectively. The populations of
= 2 and 3 of the C
H
CN
(H
O)
clusters were observed only in trace abundance due to fast depletion processes leading to the formation of the hydrated distonic cations
C
H
CNH
(H
O)
with
= 4-7. The observed transition occurs between conventional radical cations hydrated on the ring in C
H
CN
(H
O)
clusters with
= 1-3 and the protonated radical
C
H
CNH
(distonic ion) formed by a proton transfer to the CN nitrogen and ionic hydrogen bonding to water molecules in
C
H
CNH
(H
O)
clusters with
= 4-7. The measured binding energy of the hydrated ion C
H
CN
(H
O) (8.8 kcal/mol) is similar to that of the hydrated benzene radical cation (8.5 kcal/mol) that involves a relatively weak CH
···O hydrogen bonding interaction. Also, the measured binding energies of the
C
H
CNH
(H
O)
clusters with
= 5-7 are similar to those of the protonated benzonitrile (methanol)
clusters C
H
CNH
(CH
OH)
,
= 5-7 that involve CNH
···O ionic hydrogen bonds. The proton shift from the
-
C ring carbon to the nitrogen of the benzonitrile radical cation is endothermic without solvent but thermoneutral for
= 1 and exothermic for
= 2-4 in C
H
CN
(H
O)
clusters to form the distonic
C
H
CN···H
(OH
)
clusters. The distonic clusters
C
H
CN···H
(OH
)
constitute a new class of structures in radical ion/solvent clusters.
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