Voltage sweep ion mobility spectrometry.

PubMed

Davis, Eric J; Williams, Michael D; Siems, William F; Hill, Herbert H

2011-02-15

Ion mobility spectrometry (IMS) is a rapid, gas-phase separation technique that exhibits excellent separation of ions as a standalone instrument. However, IMS cannot achieve optimal separation power with both small and large ions simultaneously. Similar to the general elution problem in chromatography, fast ions are well resolved using a low electric field (50-150 V/cm), whereas slow drifting molecules are best separated using a higher electric field (250-500 V/cm). While using a low electric field, IMS systems tend to suffer from low ion transmission and low signal-to-noise ratios. Through the use a novel voltage algorithm, some of these effects can be alleviated. The electric field was swept from low to high while monitoring a specific drift time, and the resulting data were processed to create a 'voltage-sweep' spectrum. If an optimal drift time is calculated for each voltage and scanned simultaneously, a spectrum may be obtained with optimal separation throughout the mobility range. This increased the resolving power up to the theoretical maximum for every peak in the spectrum and extended the peak capacity of the IMS system, while maintaining accurate drift time measurements. These advantages may be extended to any IMS, requiring only a change in software.

Overtone Mobility Spectrometry (Part 2): Theoretical Considerations of Resolving Power

PubMed Central

Valentine, Stephen J.; Stokes, Sarah T.; Kurulugama, Ruwan T.; Nachtigall, Fabiane M.; Clemmer, David E.

2009-01-01

The transport of ions through multiple drift regions is modeled in order to develop an equation that is useful for an understanding of the resolving power of an overtone mobility spectrometry (OMS) technique. It is found that resolving power is influenced by a number of experimental variables, including those that define ion mobility spectrometry (IMS) resolving power: drift field (E), drift region length (L), and buffer gas temperature (T). However, unlike IMS, the resolving power of OMS is also influenced by the number of drift regions (n), harmonic frequency value (m), and the phase number (ϕ) of the applied drift field. The OMS resolving power dependence upon the new OMS variables (n, m, and ϕ) scales differently than the square root dependence of the E, L, and T variables in IMS. The results provide insight about optimal instrumental design and operation. PMID:19230705

Field applications of ion-mobility spectrometry

NASA Astrophysics Data System (ADS)

Brown, Patricia A.

1997-02-01

Ion mobility spectrometry (IMS) is an excellent tool for detection of controlled substances under field conditions. Plasmagrams and tables showing the results of field applications will be discussed. Residues of drugs, such as cocaine and heroin, can be left anywhere including vehicles, boats, and houses. In houses, the carpets, walls, and floors are good locations for residues to adhere. Individual clothing can also be contaminated with drug residue. Vehicles that are suspected of having previously smuggled illegal substances can be vacuumed and screened. Tablets that look similar and respond the same when screened with the Marquis reagent can be differentiated by IMS. With Southern California being the 'methamphetamine capital of the world' and the resurgence of phencyclidine, IMS has proven extremely valuable in the screening of abandoned clandestine laboratory sites and vehicles in which the clandestine laboratories; chemicals and glassware were transported. IMS is very responsive to ephedrine/pseudophedrine, a precursor of methamphetamine and 1-piperidinocyclohexanecarbonitrile, an intermediate of phencyclidine. Once residues are detected, vacuum samples, and/or methanol wipes are collected and analyzed at the DEA Laboratory for confirmation of the suspected substance using GC-IRD or Mass Spectrometry.

Application of ion mobility-mass spectrometry to microRNA analysis.

PubMed

Takebayashi, Kosuke; Hirose, Kenji; Izumi, Yoshihiro; Bamba, Takeshi; Fukusaki, Eiichiro

2013-03-01

Liquid chromatography/mass spectrometry is widely used for studying sequence determination and modification analysis of small RNAs. However, the efficiency of liquid chromatography-based separation of intact small RNA species is insufficient, since the physiochemical properties among small RNAs are very similar. In this study, we focused on ion mobility-mass spectrometry (IM-MS), which is a gas-phase separation technique coupled with mass spectrometry; we have evaluated the utility of IM-MS for microRNA (miRNA) analysis. A multiply charged deprotonated ion derived from an 18-24-nt-long miRNA was formed by electrospray ionization, and then the time, called the "drift time", taken by each ion to migrate through a buffer gas was measured. Each multivalent ion was temporally separated on the basis of the charge state and structural formation; 3 types of unique mass-mobility correlation patterns (i.e., chainlike-form, hairpin-form, and dimer-form) were present on the two-dimensional mobility-mass spectrum. Moreover, we found that the ion size (sequence length) and the secondary structures of the small RNAs strongly contributed to the IM-MS-based separation, although solvent conditions such as pH had no effect. Therefore, sequence isomers could also be discerned by the selection of each specific charged ion, i.e., the 6(-) charged ion reflected a majority among chainlike-, hairpin-, and other structures. We concluded that the IM-MS provides additional capability for separation; thus, this analytical method will be a powerful tool for comprehensive small RNA analysis. Copyright © 2012. Published by Elsevier B.V.

Tandem ion mobility spectrometry coupled to laser excitation

NASA Astrophysics Data System (ADS)

Simon, Anne-Laure; Chirot, Fabien; Choi, Chang Min; Clavier, Christian; Barbaire, Marc; Maurelli, Jacques; Dagany, Xavier; MacAleese, Luke; Dugourd, Philippe

2015-09-01

This manuscript describes a new experimental setup that allows to perform tandem ion mobility spectrometry (IMS) measurements and which is coupled to a high resolution time-of-flight mass spectrometer. It consists of two 79 cm long drift tubes connected by a dual ion funnel assembly. The setup was built to permit laser irradiation of the ions in the transfer region between the two drift tubes. This geometry allows selecting ions according to their ion mobility in the first drift tube, to irradiate selected ions, and examine the ion mobility of the product ions in the second drift tube. Activation by collision is possible in the same region (between the two tubes) and between the second tube and the time-of-flight. IMS-IMS experiments on Ubiquitin are reported. We selected a given isomer of charge state +7 and explored its structural rearrangement following collisional activation between the two drift tubes. An example of IMS-laser-IMS experiment is reported on eosin Y, where laser irradiation was used to produce radical ions by electron photodetachment starting from doubly deprotonated species. This allowed measuring the collision cross section of the radical photo-product, which cannot be directly produced with an electrospray source.

Increasing conclusiveness of clinical breath analysis by improved baseline correction of multi capillary column - ion mobility spectrometry (MCC-IMS) data.

PubMed

Szymańska, Ewa; Tinnevelt, Gerjen H; Brodrick, Emma; Williams, Mark; Davies, Antony N; van Manen, Henk-Jan; Buydens, Lutgarde M C

2016-08-05

Current challenges of clinical breath analysis include large data size and non-clinically relevant variations observed in exhaled breath measurements, which should be urgently addressed with competent scientific data tools. In this study, three different baseline correction methods are evaluated within a previously developed data size reduction strategy for multi capillary column - ion mobility spectrometry (MCC-IMS) datasets. Introduced for the first time in breath data analysis, the Top-hat method is presented as the optimum baseline correction method. A refined data size reduction strategy is employed in the analysis of a large breathomic dataset on a healthy and respiratory disease population. New insights into MCC-IMS spectra differences associated with respiratory diseases are provided, demonstrating the additional value of the refined data analysis strategy in clinical breath analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Direct Liquid Sampling for Corona Discharge Ion Mobility Spectrometry.

PubMed

Sabo, Martin; Malásková, Michaela; Harmathová, Olga; Hradski, Jasna; Masár, Marián; Radjenovic, Branislav; Matejčík, Štefan

2015-07-21

We present a new technique suitable for direct liquid sampling and analysis by ion mobility spectrometry (IMS). The technique is based on introduction of a droplet stream to the IMS reaction region. The technique was successfully used to detect explosives dissolved in methanol and oil as well as to analyze amino acids and dipeptides. One of the main advantages of this technique is its ability to analyze liquid samples without the requirement of any special solution.

Rapid screening of abused drugs by direct analysis in real time (DART) coupled to time-of-flight mass spectrometry (TOF-MS) combined with ion mobility spectrometry (IMS).

PubMed

Lian, Ru; Wu, Zhongping; Lv, Xiaobao; Rao, Yulan; Li, Haiyang; Li, Jinghua; Wang, Rong; Ni, Chunfang; Zhang, Yurong

2017-10-01

Increasing in cases involving drugs of abuse leads to heavy burden for law enforcement agencies, exacerbating demand for rapid screening technique. In this study, atmospheric pressure ionization technologies including direct analysis in real time (DART) ion source coupled to a time-of-flight mass spectrometer (DART-TOF-MS)as well asdopant-assisted positive photoionization ion mobility spectrometry (DAPP-IMS) without radioactivity were utilized together as the powerful analytical tool for the rapid screening and identification of 53 abused drugs.The limits of detection (LOD) were 0.05-2μg/mL when using DART-TOF-MS and 0.02-2μg when using DAPP-IMS which could satisfy the actual requirement in forensic science laboratory. The advantages of this method included fast response, high-throughput potential, high specificity, and minimal sample preparation. A screening library of reduced mobility (K 0 ), accurate mass of informative precursor ion ([M+H] + ) and fragment ions was established respectively by employing a bench-top DAPP-IMS and TOF-MS in-source collision induced dissociation (CID) mode. Then the standardized screening procedure was developed with criteria for the confirmation of positive result. A total of 50 seized drug samples provided by local forensic laboratory we reanalyzed to testify the utility of the method. This study suggests that a method combing DART-TOF-MS and DAPP-IMS is promising for the rapid screening and identification of abused drugs with minimal sample preparation and absence of chromatography. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of biogenic amines using corona discharge ion mobility spectrometry.

PubMed

Hashemian, Z; Mardihallaj, A; Khayamian, T

2010-05-15

A new method based on corona discharge ion mobility spectrometry (CD-IMS) was developed for the analysis of biogenic amines including spermidine, spermine, putrescine, and cadaverine. The ion mobility spectra of the compounds were obtained with and without n-Nonylamine used as the reagent gas. The high proton affinity of n-Nonylamine prevented ion formation from compounds with a proton affinity lower than that of n-Nonylamine and, therefore, enhanced its selectivity. It was also realized that the ion mobility spectrum of n-Nonylamine varied with its concentration. A sample injection port of a gas chromatograph was modified and used as the sample introduction system into the CD-IMS. The detection limits, dynamic ranges, and analytical parameters of the compounds with and without using the reagent gas were obtained. The detection limits and dynamic ranges of the compounds were about 2ng and 2 orders of magnitude, respectively. The wide dynamic range of CD-IMS originates from the high current of the corona discharge. The results revealed the high capability of the CD-IMS for the analysis of biogenic amines.

A strategy for identification and structural characterization of compounds from Gardenia jasminoides by integrating macroporous resin column chromatography and liquid chromatography-tandem mass spectrometry combined with ion-mobility spectrometry.

PubMed

Wang, Lu; Liu, Shu; Zhang, Xueju; Xing, Junpeng; Liu, Zhiqiang; Song, Fengrui

2016-06-24

In this paper, an analysis strategy integrating macroporous resin (AB-8) column chromatography and high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) combined with ion mobility spectrometry (IMS) was proposed and applied for identification and structural characterization of compounds from the fruits of Gardenia jasminoides. The extracts of G. jasminoides were separated by AB-8 resin column chromatography combined with reversed phase liquid chromatography (C18 column) and detected by electrospray ionization tandem mass spectrometry. Additionally, ion mobility spectrometry (IMS) was employed as a supplementary separation technique to discover previously undetected isomers from the fruits of G. jasminoides. A total of 71 compounds, including iridoids, flavonoids, triterpenes, monoterpenoids, carotenoids and phenolic acids were identified by the characteristic high resolution mass spectrometry and the ESI-MS/MS fragmentations. In conclusion, the IMS-MS technique achieved the separation of isomers in crocin-3 and crocin-4 according to their acquired mobility drift times differing from classical analysis by mass spectrometry. The proposed strategy can be used as a highly sensitive and efficient procedure for identification and separation isomeric components in extracts of herbal medicines. Copyright © 2016 Elsevier B.V. All rights reserved.

Broad Separation of Isomeric Lipids by High-Resolution Differential Ion Mobility Spectrometry with Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Bowman, Andrew P.; Abzalimov, Rinat R.; Shvartsburg, Alexandre A.

2017-08-01

Maturation of metabolomics has brought a deeper appreciation for the importance of isomeric identity of lipids to their biological role, mirroring that for proteoforms in proteomics. However, full characterization of the lipid isomerism has been thwarted by paucity of rapid and effective analytical tools. A novel approach is ion mobility spectrometry (IMS) and particularly differential or field asymmetric waveform IMS (FAIMS) at high electric fields, which is more orthogonal to mass spectrometry. Here we broadly explore the power of FAIMS to separate lipid isomers, and find a 75% success rate across the four major types of glycero- and phospho- lipids ( sn, chain length, double bond position, and cis/ trans). The resolved isomers were identified using standards, and (for the first two types) tandem mass spectrometry. These results demonstrate the general merit of incorporating high-resolution FAIMS into lipidomic analyses.

LC-IMS-MS Feature Finder

DOE Office of Scientific and Technical Information (OSTI.GOV)

2013-03-07

LC-IMS-MS Feature Finder is a command line software application which searches for possible molecular ion signatures in multidimensional liquid chromatography, ion mobility spectrometry, and mass spectrometry data by clustering deisotoped peaks with similar monoisotopic mass values, charge states, elution times, and drift times. The software application includes an algorithm for detecting multiple conformations and co-eluting species in the ion mobility dimension. LC-IMS-MS Feature Finder is designed to create an output file with detected features that includes associated information about the detected features.

Integrating ion mobility spectrometry into mass spectrometry-based exposome measurements: what can it add and how far can it go?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Metz, Thomas O.; Baker, Erin S.; Schymanski, Emma L.

Here, measuring the exposome remains a challenge due to the range and number of anthropogenic molecules that are encountered in our daily lives, as well as the complex systemic responses to these exposures. One option for improving the coverage, dynamic range and throughput of measurements is to incorporate ion mobility spectrometry (IMS) into current mass spectrometry (MS)-based analytical methods. In this perspective, we briefly review the state-of-the-art in measuring the exposome, and discuss the potential use for IMS-MS and the physico-chemical property of collisional cross section in both exposure assessment and molecular identification.

Integrating ion mobility spectrometry into mass spectrometry-based exposome measurements: what can it add and how far can it go?

DOE PAGES

Metz, Thomas O.; Baker, Erin S.; Schymanski, Emma L.; ...

2016-12-06

Here, measuring the exposome remains a challenge due to the range and number of anthropogenic molecules that are encountered in our daily lives, as well as the complex systemic responses to these exposures. One option for improving the coverage, dynamic range and throughput of measurements is to incorporate ion mobility spectrometry (IMS) into current mass spectrometry (MS)-based analytical methods. In this perspective, we briefly review the state-of-the-art in measuring the exposome, and discuss the potential use for IMS-MS and the physico-chemical property of collisional cross section in both exposure assessment and molecular identification.

Ion-neutral potential models in atmospheric pressure ion mobility time-of-flight mass spectrometry IM(tof)MS.

PubMed

Steiner, Wes E; English, William A; Hill, Herbert H

2006-02-09

The ion mobilities and their respective masses of several classes of amines (primary, secondary, and tertiary) were measured by electrospray ionization atmospheric pressure ion mobility time-of-flight mass spectrometry IM(tof)MS. The experimental data obtained were comparatively analyzed by the one-temperature kinetic theory of Chapman-Enskog. Several theoretical models were used to estimate the collision cross-sections; they include the rigid-sphere, polarization-limit, 12-6-4, and 12-4 potential models. These models were investigated to represent the interaction potentials contained within the collision integral that occurs between the polyatomic ions and the neutral drift gas molecules. The effectiveness of these collision cross-section models on predicting the mobility of these amine ions was explored. Moreover, the effects of drift gas selectivity on the reduced-mass term and in the collision cross-section term was examined. Use of a series of drift gases, namely, helium, neon, argon, nitrogen, and carbon dioxide, made it possible to distinguish between mass effects and polarizability effects. It was found that the modified 12-4 potential that compensates for the center of charge not being at the same location as the centers of mass showed improved agreement over the other collision cross-section models with respect to experimental data.

Identification of terpenes and essential oils by means of static headspace gas chromatography-ion mobility spectrometry.

PubMed

Rodríguez-Maecker, Roman; Vyhmeister, Eduardo; Meisen, Stefan; Rosales Martinez, Antonio; Kuklya, Andriy; Telgheder, Ursula

2017-11-01

Static headspace gas chromatography-ion mobility spectrometry (SHS GC-IMS) is a relatively new analytical technique that has considerable potential for analysis of volatile organic compounds (VOCs). In this study, SHS GC-IMS was used for the identification of the major terpene components of various essential oils (EOs). Based on the data obtained from 25 terpene standards and 50 EOs, a database for fingerprint identification of characteristic terpenes and EOs was generated utilizing SHS GC-IMS for authenticity testing of fragrances in foods, cosmetics, and personal care products. This database contains specific normalized IMS drift times and GC retention indices for 50 terpene components of EOs. Initially, the SHS GC-IMS parameters, e.g., drift gas and carrier gas flow rates, drift tube, and column temperatures, were evaluated to determine suitable operating conditions for terpene separation and identification. Gas chromatography-mass spectrometry (GC-MS) was used as a reference method for the identification of terpenes in EOs. The fingerprint pattern based on the normalized IMS drift times and retention indices of 50 terpenes is presented for 50 EOs. The applicability of the method was proven on examples of ten commercially available food, cosmetic, and personal care product samples. The results confirm the suitability of SHS GC-IMS as a powerful analytical technique for direct identification of terpene components in solid and liquid samples without any pretreatment. Graphical abstract Fingerprint pattern identification of terpenes and essential oils using static headspace gas chromatography-ion mobility spectrometry.

Toward artifact-free data in Hadamard transform-based double multiplexing of ion mobility-Orbitrap mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tummalacherla, Meghasyam; Garimella, Sandilya V. B.; Prost, Spencer A.

The integration of ion mobility spectrometry (IMS) with trap-based mass spectrometer (MS) such as Orbitrap using the dual gate approach suffers from low duty cycle. Efforts to improve the duty cycle involve the utilization of Hadamard transform based double multiplexing which significantly improve the signal to noise ratio and duty cycle of the ion mobility – Orbitrap mass spectrometry (IM – Orbitrap MS) platform. However, significant fluctuations in ion intensity and the temporal shifts in the encoded data give rise to artifacts and noise in the demultiplexed data which significantly reduce the data quality and negate the benefits of multiplexing.more » We propose a new approach that identifies the true IM peaks and helps in eliminating the artifacts in the demultiplexed data leading to a decrease in false positives in subsequent data processing. The algorithm takes an analytical approach to first identify the position of the IM peak in the temporal domain, and then demultiplex and identify the true data making it easier for subsequent data processing. After the application of the algorithm, the quality of the IM-Orbitrap MS measurements was greatly improved because of the reduction in artifacts.« less

Analysis of explosives using corona discharge ionization combined with ion mobility spectrometry-mass spectrometry.

PubMed

Lee, Jihyeon; Park, Sehwan; Cho, Soo Gyeong; Goh, Eun Mee; Lee, Sungman; Koh, Sung-Suk; Kim, Jeongkwon

2014-03-01

Corona discharge ionization combined with ion mobility spectrometry-mass spectrometry (IMS-MS) was utilized to investigate five common explosives: cyclonite (RDX), trinitrotoluene (TNT), pentaerythritol tetranitrate (PETN), cyclotetramethylenetetranitramine (HMX), and 2,4-dinitrotoluene (DNT). The MS scan and the selected ion IMS analyses confirmed the identities of the existing ion species and their drift times. The ions observed were RDX·NO3(-), TNT(-), PETN·NO3(-), HMX·NO3(-), and DNT(-), with average drift times of 6.93 ms, 10.20 ms, 9.15 ms, 12.24 ms, 11.30 ms, and 8.89 ms, respectively. The reduced ion mobility values, determined from a standard curve calculated by linear regression of (normalized drift times)(-1) versus literature K0 values, were 2.09, 1.38, 1.55, 1.15, 1.25, and 1.60 cm(2) V(-1) s(-1), respectively. The detection limits were found to be 0.1 ng for RDX, 10 ng for TNT, 0.5 ng for PETN, 5.0 ng for HMX, and 10 ng for DNT. Simplified chromatograms were observed when nitrogen, as opposed to air, was used as the drift gas, but the detection limits were approximately 10 times worse (i.e., less sensitivity of detection). © 2013 Elsevier B.V. All rights reserved.

Aerosol Vacuum-Assisted Plasma Ionization (Aero-VaPI) Coupled to Ion Mobility-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Blair, Sandra L.; Ng, Nga L.; Zambrzycki, Stephen C.; Li, Anyin; Fernández, Facundo M.

2018-02-01

In this communication, we report on the real-time analysis of organic aerosol particles by Vacuum-assisted Plasma Ionization-Mass Spectrometry (Aero-VaPI-MS) using a home-built VaPI ion source coupled to a Synapt G2-S HDMS ion mobility-mass spectrometry (IM-MS) system. Standards of organic molecules of interest in prebiotic chemistry were used to generate aerosols. Monocaprin and decanoic acid aerosol particles were successfully detected in both the positive and negative ion modes, respectively. A complex aerosol mixture of different sizes of polymers of L-malic acid was also examined through ion mobility (IM) separations, resulting in the detection of polymers of up to eight monomeric units. This noncommercial plasma ion source is proposed as a low cost alternative to other plasma ionization platforms used for aerosol analysis, and a higher-performance alternative to more traditional aerosol mass spectrometers. VaPI provides robust online ionization of organics in aerosols without extensive ion activation, with the coupling to IM-MS providing higher peak capacity and excellent mass accuracy. [Figure not available: see fulltext.

Enhancement in sample collection for the detection of MDMA using a novel planar SPME (PSPME) device coupled to ion mobility spectrometry (IMS).

PubMed

Gura, Sigalit; Guerra-Diaz, Patricia; Lai, Hanh; Almirall, José R

2009-07-01

Trace detection of illicit drugs challenges the scientific community to develop improved sensitivity and selectivity in sampling and detection techniques. Ion mobility spectrometry (IMS) is one of the prominent trace detectors for illicit drugs and explosives, mostly due to its portability, high sensitivity and fast analysis. Current sampling methods for IMS rely on wiping suspected surfaces or withdrawing air through filters to collect particulates. These methods depend greatly on the particulates being bound onto surfaces or having sufficient vapour pressure to be airborne. Many of these compounds are not readily available in the headspace due to their low vapour pressure. This research presents a novel SPME device for enhanced air sampling and shows the use of optimized IMS by genetic algorithms to target volatile markers and/or odour signatures of illicit substances. The sampling method was based on unique static samplers, planar substrates coated with sol-gel polydimethyl siloxane (PDMS) nanoparticles, also known as planar solid-phase microextraction (PSPME). Due to its surface chemistry, high surface area and capacity, PSPME provides significant increases in sensitivity over conventional fibre SPME. The results show a 50-400 times increase in the detection capacity for piperonal, the odour signature of 3,4-methylenedioxymethamphetamine (MDMA). The PSPME-IMS technique was able to detect 600 ng of piperonal in a 30 s extraction from a quart-sized can containing 5 MDMA tablets, while detection using fibre SPME-IMS was not attainable. In a blind study of six cases suspected to contain varying amounts of MDMA in the tablets, PSPME-IMS successfully detected five positive cases and also produced no false positives or false negatives. One positive case had minimal amounts of MDMA resulting in a false negative response for fibre SPME-IMS.

Cryogenic IR spectroscopy combined with ion mobility spectrometry for the analysis of human milk oligosaccharides.

PubMed

Khanal, Neelam; Masellis, Chiara; Kamrath, Michael Z; Clemmer, David E; Rizzo, Thomas R

2018-04-16

We report here our combination of cryogenic, messenger-tagging, infrared (IR) spectroscopy with ion mobility spectrometry (IMS) and mass spectrometry (MS) as a way to identify and analyze a set of human milk oligosaccharides (HMOs) ranging from trisaccharides to hexasaccharides. The added dimension of IR spectroscopy provides a diagnostic fingerprint in the OH and NH stretching region, which is crucial to identify these oligosaccharides, which are difficult to distinguish by IMS alone. These results extend our previous work in demonstrating the generality of this combined approach for distinguishing subtly different structural and regioisomers of glycans of biologically relevant size.

Cocaine abuse determination by ion mobility spectrometry using molecular imprinting.

PubMed

Sorribes-Soriano, A; Esteve-Turrillas, F A; Armenta, S; de la Guardia, M; Herrero-Martínez, J M

2017-01-20

A cocaine-based molecular imprinted polymer (MIP) has been produced by bulk polymerization and employed as selective solid-phase extraction support for the determination of cocaine in saliva samples by ion mobility spectrometry (IMS). The most appropriate conditions for washing and elution of cocaine from MIPs were studied and MIPs were characterized in terms of analyte binding capacity, reusability in water and saliva analysis, imprinting factor and selectivity were established and compared with non-imprinted polymers. The proposed MIP-IMS method provided a LOD of 18μgL -1 and quantitative recoveries for blank saliva samples spiked from 75 to 500μgL -1 cocaine. Oral fluid samples were collected from cocaine consumers and analysed by the proposed MIP-IMS methodology. Results, ranging from below the LOD to 51±2mgL -1 , were statistically comparable to those obtained by a confirmatory gas chromatography-mass spectrometry method. Moreover, results were compared to a qualitative lateral flow immunoassay procedure providing similar classification of the samples. Thus, MIP-IMS can be considered an useful alternative that provided fast, selective and sensitive results with a cost affordable instrumentation that does not require skilled operators. Copyright © 2016 Elsevier B.V. All rights reserved.

Separation and Classification of Lipids Using Differential Ion Mobility Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shvartsburg, Alexandre A.; Isaac, Georgis; Leveque, Nathalie

2011-04-12

Correlations between the dimensions of a 2-D separation create trend lines that normally depend on structural or functional characteristics of the compound class and thus facilitate classification of unknowns. This broadly applies to conventional ion mobility spectrometry (IMS)/mass spectrometry (MS), where the major biomolecular classes (e.g., lipids, peptides, nucleotides) occupy different trend line domains. However, strong correlation between the IMS and MS separations for ions of same charge has impeded finer distinctions. Differential IMS (or FAIMS) is generally much less correlated to MS and thus should better separate the trend lines and associated domains. We report the first observation ofmore » chemical class separation by trend lines using FAIMS, here for lipids. For all lipids, FAIMS is indeed more independent of MS than conventional IMS, and subclasses (such as phospho-, glycero-, or sphingolipids) form distinct, often non-overlapping domains. Even finer categories with different functional groups or degrees of unsaturation are often separated. As expected, resolution improves in He-rich gases: at ~70% He, glycerolipid isomers with different positions of fatty acid attachment can be resolved. These results open the door for lipidomics application of FAIMS, particularly shotgun lipidomics and targeted analyses of bioactive lipids.« less

Ion mobility spectrometry for the rapid analysis of over-the-counter drugs and beverages

PubMed Central

Fernández-Maestre, Roberto

2009-01-01

In the pharmaceutical industry, there are increasing requirements for analytical methods in quality assessment for the production of drugs. In this investigation, ion mobility spectrometry (IMS) was used for the rapid qualitative separation and identification of active ingredients in generic over-the-counter drugs and food additives in beverages. The active ingredients determined in drugs were acetaminophen, aspartame, bisacodyl, caffeine, dextromethorphan, diphenhydramine, famotidine, glucosamine, guaifenesin, loratadine, niacin, phenylephrine, pyridoxine, thiamin, and tetrahydrozoline. Aspartame and caffeine were determined in beverages. Fourteen over-the-counter drugs and beverages were analyzed. Analysis times below 10 s were obtained for IMS, and reduced mobilities were reported for the first time for 12 compounds. A quadrupole mass spectrometer coupled to a mobility spectrometer was used to assure a correct peak assignation. The combination of fast analysis, low cost, and inexpensive maintenance of IMS instruments makes IMS an attractive technique for the qualitative determination of the active ingredients in over-the-counter drugs and food additives in manufacture quality control and cleaning verification for the drug and food industries. PMID:20835390

Investigation of drift gas selectivity in high resolution ion mobility spectrometry with mass spectrometry detection.

PubMed

Matz, Laura M; Hill, Herbert H; Beegle, Luther W; Kanik, Isik

2002-04-01

Recent studies in electrospray ionization (ESI)/ion mobility spectrometry (IMS) have focussed on employing different drift gases to alter separation efficiency for some molecules. This study investigates four structurally similar classes of molecules (cocaine and metabolites, amphetamines, benzodiazepines, and small peptides) to determine the effect of structure on relative mobility changes in four drift gases (helium, nitrogen, argon, carbon dioxide). Collision cross sections were plotted against drift gas polarizability and a linear relationship was found for the nineteen compounds evaluated in the study. Based on the reduced mobility database, all nineteen compounds could be separated in one of the four drift gases, however, the drift gas that provided optimal separation was specific for the two compounds.

Enhancing glycan isomer separations with metal ions and positive and negative polarity ion mobility spectrometry-mass spectrometry analyses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Xueyun; Zhang, Xing; Schocker, Nathaniel S.

Glycomics has become an increasingly important field of research since glycans play critical roles in biology processes ranging from molecular recognition and signaling to cellular communication. Glycans often conjugate with other biomolecules such as proteins and lipids, and alter their properties and functions, so understanding the effect glycans have on cellular systems is essential. However the analysis of glycans is extremely difficult due to their complexity and structural diversity (i.e., the number and identity of monomer units, and configuration of their glycosidic linkages and connectivities). In this work, we coupled ion mobility spectrometry with mass spectrometry (IMS-MS) to characterize glycanmore » standards and biologically important isomers of synthetic αGal-containing O-glycans including glycotopes of the protozoan parasite Trypanosoma cruzi, which is the causative agent of Chagas disease. IMS-MS results showed significant differences for the glycan structural isomers when analyzed in positive and negative polarity and complexed with different metal cations. These results suggest specific metal ions or ion polarities could be used to target and baseline separate glycan isomers of interest with IMS-MS.« less

Ion Mobility-Mass Spectrometry Analysis of Serum N-linked Glycans from Esophageal Adenocarcinoma Phenotypes

PubMed Central

Gaye, M. M.; Valentine, S. J.; Hu, Y.; Mirjankar, N.; Hammoud, Z. T.; Mechref, Y.; Lavine, B. K.; Clemmer, D. E.

2012-01-01

Three disease phenotypes, Barrett’s esophagus (BE), high-grade dysplasia (HGD), esophageal adenocarcinoma (EAC), and a set of normal control (NC) serum samples are examined using a combination of ion mobility spectrometry (IMS), mass spectrometry (MS) and principal component analysis (PCA) techniques. Samples from a total of 136 individuals were examined, including: 7 characterized as BE, 12 as HGD, 56 as EAC and 61 as NC. In typical datasets it was possible to assign ~20 to 30 glycan ions based on MS measurements. Ion mobility distributions for these ions show multiple features. In some cases, such as the [S1H5N4+3Na]3+ and [S1F1H5N4+3Na]3+ glycan ions, the ratio of intensities of high-mobility features to low-mobility features vary significantly for different groups. The degree to which such variations in mobility profiles can be used to distinguish phenotypes is evaluated for eleven N-linked glycan ions. An outlier analysis on each sample class followed by an unsupervised PCA using a genetic algorithm for pattern recognition reveals that EAC samples are separated from NC samples based on 46 features originating from the 11-glycan composite IMS distribution. PMID:23126309

Environment applications for ion mobility spectrometry

NASA Technical Reports Server (NTRS)

Ritchie, Robert K.; Rudolph, Andreas

1995-01-01

The detection of environmentally important polychlorinated aromatics by ion mobility spectrometry (IMS) was investigated. Single polychlorinated biphenyl (PCB) isomers (congeners) having five or more chlorine atoms were reliably detected in isooctane solution at levels of 35 ng with a Barringer IONSCAN ion mobility spectrometer operating in negative mode; limits of detection (LOD) were extrapolated to be in the low ng region. Mixtures of up to four PCB congeners, showing characteristic multiple peaks, and complex commercial mixtures of PCBs (Aroclors) were also detected. Detection of Aroclors in transformer oil was suppressed by the presence of the antioxidant BHT (2,6-di-t-butyl4-methylphenol) in the oil. The wood preservative pentachlorophenol (PCP) was easily detected in recycled wood shavings at levels of 52 ppm with the IONSCAN; the LOD was extrapolated to be in the low ppm region.

Buffer Gas Modifiers Effect Resolution in Ion Mobility Spectrometry through Selective Ion-Molecule Clustering Reactions

PubMed Central

Fernández-Maestre, Roberto; Wu, Ching; Hill, Herbert H.

2013-01-01

RATIONALE When polar molecules (modifiers) are introduced into the buffer gas of an ion mobility spectrometer, most ion mobilities decrease due to the formation of ion-modifier clusters. METHODS We used ethyl lactate, nitrobenzene, 2-butanol, and tetrahydrofuran-2-carbonitrile as buffer gas modifiers and electrospray ionization ion mobility spectrometry (IMS) coupled to quadrupole mass spectrometry. Ethyl lactate, nitrobenzene, and tetrahydrofuran-2-carbonitrile had not been tested as buffer gas modifiers and 2-butanol had not been used with basic amino acids. RESULTS The ion mobilities of several diamines (arginine, histidine, lysine, and atenolol) were not affected or only slightly reduced when these modifiers were introduced into the buffer gas (3.4% average reduction in an analyte's mobility for the three modifiers). Intramolecular bridges caused limited change in the ion mobilities of diamines when modifiers were added to the buffer gas; these bridges hindered the attachment of modifier molecules to the positive charge of ions and delocalized the charge, which deterred clustering. There was also a tendency towards large changes in ion mobility when the mass of the analyte decreased; ethanolamine, the smallest compound tested, had the largest reduction in ion mobility with the introduction of modifiers into the buffer gas (61%). These differences in mobilities, together with the lack of shift in bridge-forming ions, were used to separate ions that overlapped in IMS, such as isoleucine and lysine, and arginine and phenylalanine, and made possible the prediction of separation or not of overlapping ions. CONCLUSIONS The introduction of modifiers into the buffer gas in IMS can selectively alter the mobilities of analytes to aid in compound identification and/or enable the separation of overlapping analyte peaks. PMID:22956312

Application of Ion Mobility Spectrometry (IMS) in forensic chemistry and toxicology with focus on biological matrices

NASA Technical Reports Server (NTRS)

Bernhard, Werner; Keller, Thomas; Regenscheit, Priska

1995-01-01

The IMS (Ion Mobility Spectroscopy) instrument 'Ionscan' takes advantage of the fact that trace quantities of illicit drugs are adsorbed on dust particles on clothes, in cars and on other items of evidence. The dust particles are collected on a membrane filter by a special attachment on a vacuum cleaner. The sample is then directly inserted into the spectrometer and can be analyzed immediately. We show casework applications of a forensic chemistry and toxicology laboratory. One new application of IMS in forensic chemistry is the detection of psilocybin in dried mushrooms without any further sample preparation.

Using gas chromatography with ion mobility spectrometry to resolve explosive compounds in the presence of interferents.

PubMed

Cook, Greg W; LaPuma, Peter T; Hook, Gary L; Eckenrode, Brian A

2010-11-01

Ion mobility spectrometry (IMS) is a valued field detection technology because of its speed and high sensitivity, but IMS cannot easily resolve analytes of interest within mixtures. Coupling gas chromatography (GC) to IMS adds a separation capability to resolve complex matrices. A GC-IONSCAN® operated in IMS and GC⁄ IMS modes was evaluated with combinations of five explosives and four interferents. In 100 explosive/interferent combinations, IMS yielded 21 false positives while GC⁄ IMS substantially reduced the occurrence of false positives to one. In addition, the results indicate that through redesign or modification of the preconcentrator there would be significant advantages to using GC⁄ IMS, such as enhancement of the linear dynamic range (LDR) in some situations. By balancing sensitivity with LDR, GC⁄ IMS could prove to be a very advantageous tool when addressing real world complex mixture situations.

Atmospheric Solid Analysis Probe Coupled to Ion Mobility Spectrometry-Mass Spectrometry, a Fast and Simple Method for Polyalphaolefin Characterization

NASA Astrophysics Data System (ADS)

Mendes Siqueira, Anna Luiza; Beaumesnil, Mathieu; Hubert-Roux, Marie; Loutelier-Bourhis, Corinne; Afonso, Carlos; Bai, Yang; Courtiade, Marion; Racaud, Amandine

2018-05-01

Polyalphaolefins (PAOs) are polymers produced from linear alpha olefins through catalytic oligomerization processes. The PAOs are known as synthetic high-performance base stock fluids used to improve the efficiency of many other synthetic products. In this study, we report the direct characterization of PAOs using atmospheric solid analysis probe (ASAP) coupled with ion mobility spectrometry-mass spectrometry (IMS-MS). We studied different PAOs grades exhibiting low- and high-viscosity index. Specific adjustments of the ASAP source parameters permitted the monitoring of ionization processes as three mechanisms could occur for these compounds: hydride abstraction, nitrogen addition, and/or the formation of [M-2H]+• ions. Several series of fragment ions were obtained, which allowed the identification of the alpha olefin used to synthesize the PAO. The use of the ion mobility separation dimension provides information on isomeric species. In addition, the drift time versus m/z plots permitted rapid comparison between PAO samples and to evidence their complexity. These 2D plots appear as fingerprints of PAO samples. To conclude, the resort to ASAP-IMS-MS provides a rapid characterization of the PAO samples in a direct analysis approach, without any sample preparation.

Analysis of Listeria using exogenous volatile organic compound metabolites and their detection by static headspace-multi-capillary column-gas chromatography-ion mobility spectrometry (SHS-MCC-GC-IMS).

PubMed

Taylor, Carl; Lough, Fraser; Stanforth, Stephen P; Schwalbe, Edward C; Fowlis, Ian A; Dean, John R

2017-07-01

Listeria monocytogenes is a Gram-positive bacterium and an opportunistic food-borne pathogen which poses significant risk to the immune-compromised and pregnant due to the increased likelihood of acquiring infection and potential transmission of infection to the unborn child. Conventional methods of analysis suffer from either long turn-around times or lack the ability to discriminate between Listeria spp. reliably. This paper investigates an alternative method of detecting Listeria spp. using two novel enzyme substrates that liberate exogenous volatile organic compounds in the presence of α-mannosidase and D-alanyl aminopeptidase. The discriminating capabilities of this approach for identifying L. monocytogenes from other species of Listeria are investigated. The liberated volatile organic compounds (VOCs) are detected using an automated analytical technique based on static headspace-multi-capillary column-gas chromatography-ion mobility spectrometry (SHS-MCC-GC-IMS). The results obtained by SHS-MCC-GC-IMS are compared with those obtained by the more conventional analytical technique of headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results found that it was possible to differentiate between L. monocytogenes and L. ivanovii, based on their VOC response from α-mannosidase activity.

Ion mobility-mass spectrometry of complex carbohydrates: collision cross sections of sodiated N-linked glycans.

PubMed

Pagel, Kevin; Harvey, David J

2013-05-21

Currently, the vast majority of complex carbohydrates are characterized using mass spectrometry (MS)-based techniques. Measuring the molecular mass of a sugar, however, immediately poses a fundamental problem: entire classes of the constituting monosaccharide building blocks exhibit an identical atomic composition and, consequently, also an identical mass. Therefore, carbohydrate MS data can be highly ambiguous and often it is simply not possible to clearly assign a particular molecular structure. A promising approach to overcome the above-mentioned limitation is to implement an additional gas-phase separation dimension using ion mobility spectrometry (IMS), which is a method in which molecules of identical mass and structure but different structure can be separated according to their shape and collision cross section (CCS). With the emergence of commercially available hybrid ion mobility-mass spectrometry (IM-MS) instruments in 2006, IMS technology became readily available. Because of the nonhomogeneous, traveling wave (TW) field utilized in these instruments, however, CCS values currently cannot be determined directly from the drift times measured. Instead, an external calibration using compounds of known CCS and similar molecular identity is required. Here, we report a calibration protocol for TW IMS instruments using a series of sodiated N-glycans that were released from commercially available glycoproteins using an easy-to-follow protocol. The underlying CCS values were determined using a modified Synapt HDMS instrument with a linear drift tube, which was described in detail previously. Our data indicate that, under in-source fragmentation conditions, only a few glycans are required to obtain a TW IMS calibration of sufficient quality. In this context, however, the type of glycan was shown to be of tremendous importance. Furthermore, our data clearly demonstrate that carbohydrate isomers with identical mass but different conformation can be distinguished based

Applicability of ion mobility spectrometry for detection of quarantine pests in wood

NASA Astrophysics Data System (ADS)

Ewing, K. J.; Sanghera, J.; Myers, S. W.; Ervin, A. M.; Carey, C.; Gleason, G.; Mosser, L.; Levy, L.; Hennessey, M. K.; Bulluck, R.

2016-05-01

Visual inspection is the most commonly used method for detecting quarantine pests in agricultural cargo items at ports. For example, solid wood packing material (SWPM) at ports may be a pathway for wood pests and is a frequent item of inspection at ports. The inspection process includes examination of the external surface of the item and often destructive sampling to detect internal pest targets. There are few tools available to inspectors to increase the efficiency of inspection and reduce the labor involved. Ion mobility spectrometry (IMS) has promise as an aid for inspection. Because pests emit volatile organic compounds (VOCs) such as hormone like substances, Ion Mobility Spectrometry (IMS) was investigated for possible utility for detecting pests during inspection. SWPM is a major pest pathway in trade, and fumigation of many kinds of wood, including SWPM, with methyl bromide (MeBr) following a published schedule1 is regularly conducted for phytosanitary reasons prior to shipment to the United States. However, the question remains as to how long the methyl bromide remains in the wood samples after fumigation such that it could act as an interferent to the detection of pest related VOC emissions. This work investigates the capability of ion mobility spectrometry to detect the presence of residual methyl bromide in fumigated maple and poplar wood samples at different times post fumigation up to 118 days after fumigation. Data show that MeBr can be detected in the less dense poplar wood up to 118 days after fumigation while MeBr can be detected in the denser maple wood 55 days after fumigation.

Multi-Capillary Column-Ion Mobility Spectrometry of Volatile Metabolites Emitted by Saccharomyces Cerevisiae

PubMed Central

Halbfeld, Christoph; Ebert, Birgitta E.; Blank, Lars M.

2014-01-01

Volatile organic compounds (VOCs) produced during microbial fermentations determine the flavor of fermented food and are of interest for the production of fragrances or food additives. However, the microbial synthesis of these compounds from simple carbon sources has not been well investigated so far. Here, we analyzed the headspace over glucose minimal salt medium cultures of Saccharomyces cerevisiae using multi-capillary column-ion mobility spectrometry (MCC-IMS). The high sensitivity and fast data acquisition of the MCC-IMS enabled online analysis of the fermentation off-gas and 19 specific signals were determined. To four of these volatile compounds, we could assign the metabolites ethanol, 2-pentanone, isobutyric acid, and 2,3-hexanedione by MCC-IMS measurements of pure standards and cross validation with thermal desorption–gas chromatography-mass spectrometry measurements. Despite the huge biochemical knowledge of the biochemistry of the model organism S. cerevisiae, only the biosynthetic pathways for ethanol and isobutyric acid are fully understood, demonstrating the considerable lack of research of volatile metabolites. As monitoring of VOCs produced during microbial fermentations can give valuable insight into the metabolic state of the organism, fast and non-invasive MCC-IMS analyses provide valuable data for process control. PMID:25197771

Hooked differential mobility spectrometry apparatus and method therefore

DOEpatents

Shvartsburg, Alexandre A [Richland, WA; Tang, Keqi [Richland, WA; Ibrahim, Yehia M [Richland, WA; Smith, Richard D [Richland, WA

2009-02-17

Disclosed are a device and method for improved interfacing of differential mobility spectrometry (DMS) or field asymmetric waveform ion mobility spectrometry (FAIMS) analyzers of substantially planar geometry to subsequent or preceding instrument stages. Interfacing is achieved using curved DMS elements, where a thick ion beam emitted by planar DMS analyzers or injected into them for ion filtering is compressed to the gap median by DMS ion focusing effect in a spatially inhomogeneous electric field. Resulting thinner beams are more effectively transmitted through necessarily constrained conductance limit apertures to subsequent instrument stages operated at a pressure lower than DMS, and/or more effectively injected into planar DMS analyzers. The technology is synergetic with slit apertures, slit aperture/ion funnels, and high-pressure ion funnel interfaces known in the art which allow for increasing cross-sectional area of MS inlets. The invention may be used in integrated analytical platforms, including, e.g., DMS/MS, LC/DMS/MS, and DMS/IMS/MS that could replace and/or enhance current LC/MS methods, e.g., for proteomics research.

Mass Spectrometry and Ion Mobility Characterization of Bioactive Peptide-Synthetic Polymer Conjugates.

PubMed

Alalwiat, Ahlam; Tang, Wen; Gerişlioğlu, Selim; Becker, Matthew L; Wesdemiotis, Chrys

2017-01-17

The bioconjugate BMP2-(PEO-HA) 2 , composed of a dendron with two monodisperse poly(ethylene oxide) (PEO) branches terminated by a hydroxyapatite binding peptide (HA), and a focal point substituted with a bone growth stimulating peptide (BMP2), has been comprehensively characterized by mass spectrometry (MS) methods, encompassing matrix-assisted laser desorption ionization (MALDI), electrospray ionization (ESI), tandem mass spectrometry (MS 2 ), and ion mobility mass spectrometry (IM-MS). MS 2 experiments using different ion activation techniques validated the sequences of the synthetic, bioactive peptides HA and BMP2, which contained highly basic amino acid residues either at the N-terminus (BMP2) or C-terminus (HA). Application of MALDI-MS, ESI-MS, and IM-MS to the polymer-peptide biomaterial confirmed its composition. Collision cross-section measurements and molecular modeling indicated that BMP2-(PEO-HA) 2 exists in several folded and extended conformations, depending on the degree of protonation. Protonation of all basic sites of the hybrid material nearly doubles its conformational space and accessible surface area.

Miniature GC-Minicell Ion Mobility Spectrometer (IMS) for In Situ Measurements in Astrobiology Planetary Missions

NASA Technical Reports Server (NTRS)

Kojiro, Daniel R.; Stimac, Robert M.; Kaye, William J.; Holland, Paul M.; Takeuchi, Norishige

2006-01-01

Astrobiology flight experiments require highly sensitive instrumentation for in situ analysis of volatile chemical species and minerals present in the atmospheres and surfaces of planets, moons, and asteroids. The complex mixtures encountered place a heavy burden on the analytical instrumentation to detect and identify all species present. The use of land rovers and balloon aero-rovers place additional emphasis on miniaturization of the analytical instrumentation. In addition, smaller instruments, using tiny amounts of consumables, allow the use of more instrumentation and/or ionger mission life for stationary landers/laboratories. The miniCometary Ice and Dust Experiment (miniCIDEX), which combined Gas Chromatography (GC) with helium Ion Mobility Spectrometry (IMS), was capable of providing the wide range of analytical information required for Astrobiology missions. The IMS used here was based on the PCP model 111 IMS. A similar system, the Titan Ice and Dust Experiment (TIDE), was proposed as part of the Titan Orbiter Aerorover Mission (TOAM). Newer GC systems employing Micro Electro- Mechanical System (MEMS) based technology have greatly reduced both the size and resource requirements for space GCs. These smaller GCs, as well as the continuing miniaturization of Astrobiology analytical instruments in general, has highlighted the need for smaller, dry helium IMS systems. We describe here the development of a miniature, MEMS GC-IMS system (MEMS GC developed by Thorleaf Research Inc.), employing the MiniCell Ion Mobility Spectrometer (IMS), from Ion Applications Inc., developed through NASA's Astrobiology Science and Technology Instrument Development (ASTID) Program and NASA s Small Business Innovative Research (SBIR) Program.

A Novel Microwave-Induced Plasma Ionization Source for Ion Mobility Spectrometry

NASA Astrophysics Data System (ADS)

Dai, Jianxiong; Zhao, Zhongjun; Liang, Gaoling; Duan, Yixiang

2017-03-01

This work demonstrates the application of a novel microwave induced plasma ionization (MIPI) source to ion mobility spectrometry (IMS). The MIPI source, called Surfatron, is composed of a copper cavity and a hollow quartz discharge tube. The ion mobility spectrum of synthetics air has a main peak with reduced mobility of 2.14 cm2V-1s-1 for positive ion mode and 2.29 cm2V-1s-1 for negative ion mode. The relative standard deviations (RSD) are 0.7% and 1.2% for positive and negative ion mode, respectively. The total ion current measured was more than 3.5 nA, which is much higher than that of the conventional 63Ni source. This indicates that a better signal-to-noise ratio (SNR) can be acquired from the MIPI source. The SNR was 110 in the analysis of 500 pptv methyl tert-butyl ether (MTBE), resulting in the limit of detection (SNR = 3) of 14 pptv. The linear range covers close to 2.5 orders of magnitude in the detection of triethylamine with a concentration range from 500 pptv to 80 ppbv. Finally, this new MIPI-IMS was used to detect some volatile organic compounds, which demonstrated that the MIPI-IMS has great potential in monitoring pollutants in air.

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry*

PubMed Central

Burnum-Johnson, Kristin E.; Nie, Song; Casey, Cameron P.; Monroe, Matthew E.; Orton, Daniel J.; Ibrahim, Yehia M.; Gritsenko, Marina A.; Clauss, Therese R. W.; Shukla, Anil K.; Moore, Ronald J.; Purvine, Samuel O.; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S.; Smith, Richard D.

2016-01-01

Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. PMID:27670688

Correlation of mass spectrometry identified bacterial biomarkers from a fielded pyrolysis-gas chromatography-ion mobility spectrometry biodetector with the microbiological gram stain classification scheme.

PubMed

Snyder, A Peter; Dworzanski, Jacek P; Tripathi, Ashish; Maswadeh, Waleed M; Wick, Charles H

2004-11-01

A pyrolysis-gas chromatography-ion mobility spectrometry (Py-GC-IMS) briefcase system has been shown to detect and classify deliberately released bioaerosols in outdoor field scenarios. The bioaerosols included Gram-positive and Gram-negative bacteria, MS-2 coliphage virus, and ovalbumin protein species. However, the origin and structural identities of the pyrolysate peaks in the GC-IMS data space, their microbiological information content, and taxonomic importance with respect to biodetection have not been determined. The present work interrogates the identities of the peaks by inserting a time-of-flight mass spectrometry system in parallel with the IMS detector through a Tee connection in the GC module. Biological substances producing ion mobility peaks from the pyrolysis of microorganisms were identified by their GC retention time, matching of their electron ionization mass spectra with authentic standards, and the National Institutes for Standards and Technology mass spectral database. Strong signals from 2-pyridinecarboxamide were identified in Bacillus samples including Bacillus anthracis, and its origin was traced to the cell wall peptidoglycan macromolecule. 3-Hydroxymyristic acid is a component of lipopolysaccharides in the cell walls of Gram-negative organisms. The Gram-negative Escherichia coli organism showed significant amounts of 3-hydroxymyristic acid derivatives and degradation products in Py-GC-MS analyses. Some of the fatty acid derivatives were observed in very low abundance in the ion mobility spectra, and the higher boiling lipid species were absent. Evidence is presented that the Py-GC-ambient temperature and pressure-IMS system generates and detects bacterial biochemical information that can serve as components of a biological classification scheme directly correlated to the Gram stain reaction in microorganism taxonomy.

Corona discharge ion mobility spectrometry with orthogonal acceleration time of flight mass spectrometry for monitoring of volatile organic compounds.

PubMed

Sabo, Martin; Matejčík, Štefan

2012-06-19

We demonstrate the application of corona discharge ion mobility spectrometry with orthogonal acceleration time of flight mass spectrometry (CD IMS-oaTOF) for volatile organic compounds (VOCs) monitoring. Two-dimensional (2D) IMS-oaTOF spectra of VOCs were recorded in nearly real time. The corona discharge atmospheric pressure chemical ionization (APCI) source was operated in positive mode in nitrogen and air. The CD ion source generates in air H(3)O(+)(H(2)O)(n) and NO(+). The NO(+) offers additional possibility for selective ionization and for an increase of the sensitivity of monoaromatic compounds. In addition to H(3)O(+)(H(2)O)(n) and NO(+), we have carried out ionization of VOCs using acetone as dopant gas ((CH(3))(2)COH(+)). Sixteen model VOCs (tetrahydrofuran, butanol, n-propanol, iso-propano, acetone, methanol, ethanol, toluene, benzene, amomnia, dioxan, triethylamine, acetonitrile, formaldehyde, m-xylene, 2,2,2-trifluoroethylamine) were tested using these ionization techniques.

Development of a plug-type IMS-MS instrument and its applications in resolving problems existing in in-situ detection of illicit drugs and explosives by IMS.

PubMed

Du, Zhenxia; Sun, Tangqiang; Zhao, Jianan; Wang, Di; Zhang, Zhongxia; Yu, Wenlian

2018-07-01

Ion mobility spectrometry (IMS) which acts as a rapid analysis technique is widely used in the field detection of illicit drugs and explosives. Due to limited separation abilities of the pint-sized IMS challenges and problems still exist regarding high false positive and false negative responses due to the interference of the matrix. In addition, the gas-phase ion chemistry and special phenomena in the IMS spectra, such one substance showing two peaks, were not identified unambiguously. In order to explain or resolve these questions, in this paper, an ion mobility spectrometry was coupled to a mass spectrometry (IMS-MS). A commercial IMS is embedded in a custom-built ion chamber shell was attached to the mass spectrometer. The faraday plate of IMS was fabricated with a hole for the ions to passing through to the mass spectrometer. The ion transmission efficiency of IMS-MS was optimized by optimizing the various parameters, especially the distance between the faraday plate and the cone of mass spectrum. This design keeps the integrity of the two original instruments and the mass spectrometry still works with multimode ionization source (i.e., IMS-MS, ESI-MS, APCI-MS modes). The illicit drugs and explosive samples were analyzed by the IMS-MS with 63 Ni source. The results showed that the IMS-MS is of high sensitivity. The ionization mechanism of the illicit drug and explosive samples with 63 Ni source were systematically studied. In addition, the interferent which interfered the detection of cocaine was identified as dibutyl phthalate (DBP) by this platform. The reason why the acetone solution of amphetamine showed two peaks was explained. Copyright © 2018 Elsevier B.V. All rights reserved.

Profiling the indole alkaloids in yohimbe bark with ultra-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry.

PubMed

Sun, Jianghao; Baker, Andrew; Chen, Pei

2011-09-30

An ultra-performance liquid chromatography/ion mobility quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) method was developed for profiling the indole alkaloids in yohimbe bark. Many indole alkaloids with the yohimbine or ajmalicine core structure, plus methylated, oxidized and reduced species, were characterized. Common fragments and mass differences are described. It was shown that the use of IMS could provide another molecular descriptor, i.e. molecular shape by rotationally averaged collision cross-section; this is of great value for identification of constituents when reference materials are usually not available. Using the combination of high resolution (~40000) accurate mass measurement with time-aligned parallel (TAP) fragmentation, MS(E) (where E represents collision energy), ion mobility mass spectrometry (IMS) and UPLC chromatography, a total 55 indole alkaloids were characterized and a few new indole alkaloids are reported for the first time. Published in 2011 by John Wiley & Sons, Ltd.

Ion Mobility Spectrometry-Mass Spectrometry Coupled with Gas-Phase Hydrogen/Deuterium Exchange for Metabolomics Analyses

NASA Astrophysics Data System (ADS)

Maleki, Hossein; Karanji, Ahmad K.; Majuta, Sandra; Maurer, Megan M.; Valentine, Stephen J.

2018-02-01

Ion mobility spectrometry-mass spectrometry (IMS-MS) in combination with gas-phase hydrogen/deuterium exchange (HDX) and collision-induced dissociation (CID) is evaluated as an analytical method for small-molecule standard and mixture characterization. Experiments show that compound ions exhibit unique HDX reactivities that can be used to distinguish different species. Additionally, it is shown that gas-phase HDX kinetics can be exploited to provide even further distinguishing capabilities by using different partial pressures of reagent gas. The relative HDX reactivity of a wide variety of molecules is discussed in light of the various molecular structures. Additionally, hydrogen accessibility scoring (HAS) and HDX kinetics modeling of candidate ( in silico) ion structures is utilized to estimate the relative ion conformer populations giving rise to specific HDX behavior. These data interpretation methods are discussed with a focus on developing predictive tools for HDX behavior. Finally, an example is provided in which ion mobility information is supplemented with HDX reactivity data to aid identification efforts of compounds in a metabolite extract.

Utilizing ion mobility spectrometry and mass spectrometry for the analysis of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polybrominated diphenyl ethers and their metabolites

DOE PAGES

Zheng, Xueyun; Dupuis, Kevin T.; Aly, Noor A.; ...

2018-03-02

Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants originating from incomplete combustion of organic materials and synthetic sources. PAHs, PCBs, and PBDEs have all been shown to have a significant effect on human health with correlations to cancer and other diseases. Therefore, measuring the presence of these xenobiotics in the environment and human body is imperative for assessing their health risks. To date, their analyses require both gas chromatography and liquid chromatography separations in conjunction with mass spectrometry measurements for detection of both the parent molecules and their hydroxylated metabolites, making theirmore » studies extremely time consuming. Here in this work, we characterized PAHs, PCBs, PBDEs and their hydroxylated metabolites using ion mobility spectrometry coupled with mass spectrometry (IMS-MS) and in combination with different ionization methods including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI). Finally, the collision cross section and m/z trend lines derived from the IMS-MS analyses displayed distinct trends for each molecule type. Additionally, the rapid isomeric and molecular separations possible with IMS-MS showed great promise for quickly distinguishing the parent and metabolized PAH, PCB, and PDBE molecules in complex environmental and biological samples.« less

Utilizing ion mobility spectrometry and mass spectrometry for the analysis of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polybrominated diphenyl ethers and their metabolites

DOE PAGES

Zheng, Xueyun; Dupuis, Kevin T.; Aly, Noor A.; ...

2018-03-02

Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants originating from incomplete combustion of organic materials and synthetic sources. PAHs, PCBs, and PBDEs have all been shown to have a significant effect on human health with correlations to cancer and other diseases. Therefore, measuring the presence of these xenobiotics in the environment and human body is imperative for assessing their health risks. To date, their analyses require both gas chromatography and liquid chromatography separations in conjunction with mass spectrometry measurements for detection of both the parent molecules and their hydroxylated metabolites, making theirmore » studies extremely time consuming. Here in this work, we characterized PAHs, PCBs, PBDEs and their hydroxylated metabolites using ion mobility spectrometry coupled with mass spectrometry (IMS-MS) and in combination with different ionization methods including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI). In conclusion, the collision cross section and m/z trend lines derived from the IMS-MS analyses displayed distinct trends for each molecule type. Additionally, the rapid isomeric and molecular separations possible with IMS-MS showed great promise for quickly distinguishing the parent and metabolized PAH, PCB, and PDBE molecules in complex environmental and biological samples.« less

Utilizing ion mobility spectrometry and mass spectrometry for the analysis of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polybrominated diphenyl ethers and their metabolites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Xueyun; Dupuis, Kevin T.; Aly, Noor A.

Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants originating from incomplete combustion of organic materials and synthetic sources. PAHs, PCBs, and PBDEs have all been shown to have a significant effect on human health with correlations to cancer and other diseases. Therefore, measuring the presence of these xenobiotics in the environment and human body is imperative for assessing their health risks. To date, their analyses require both gas chromatography and liquid chromatography separations in conjunction with mass spectrometry measurements for detection of both the parent molecules and their hydroxylated metabolites, making theirmore » studies extremely time consuming. Here in this work, we characterized PAHs, PCBs, PBDEs and their hydroxylated metabolites using ion mobility spectrometry coupled with mass spectrometry (IMS-MS) and in combination with different ionization methods including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI). In conclusion, the collision cross section and m/z trend lines derived from the IMS-MS analyses displayed distinct trends for each molecule type. Additionally, the rapid isomeric and molecular separations possible with IMS-MS showed great promise for quickly distinguishing the parent and metabolized PAH, PCB, and PDBE molecules in complex environmental and biological samples.« less

Rapid, in situ detection of cocaine residues based on paper spray ionization coupled with ion mobility spectrometry.

PubMed

Li, Ming; Zhang, Jingjing; Jiang, Jie; Zhang, Jing; Gao, Jing; Qiao, Xiaolin

2014-04-07

In this paper, a novel approach based on paper spray ionization coupled with ion mobility spectrometry (PSI-IMS) was developed for rapid, in situ detection of cocaine residues in liquid samples and on various surfaces (e.g. glass, marble, skin, wood, fingernails), without tedious sample pretreatment. The obvious advantages of PSI are its low cost, easy operation and simple configuration without using nebulizing gas or discharge gas. Compared with mass spectrometry, ion mobility spectrometry (IMS) takes advantage of its low cost, easy operation, and simple configuration without requiring a vacuum system. Therefore, IMS is a more congruous detection method for PSI in the case of rapid, in situ analysis. For the analysis of cocaine residues in liquid samples, dynamic responses from 5 μg mL(-1) to 200 μg mL(-1) with a linear coefficient (R(2)) of 0.992 were obtained. In this case, the limit of detection (LOD) was calculated to be 2 μg mL(-1) as signal to noise (S/N) was 3 with a relative standard deviation (RSD) of 6.5% for 11 measurements (n = 11). Cocaine residues on various surfaces such as metal, glass, marble, wood, skin, and fingernails were also directly analyzed before wiping the surfaces with a piece of paper. The LOD was calculated to be as low as 5 ng (S/N = 3, RSD = 6.3%, n = 11). This demonstrates the capability of the PSI-IMS method for direct detection of cocaine residues at scenes of cocaine administration. Our results show that PSI-IMS is a simple, sensitive, rapid and economical method for in situ detection of this illicit drug, which could help governments to combat drug abuse.

Pseudo-Random Sequence Modifications for Ion Mobility Orthogonal Time of Flight Mass Spectrometry

PubMed Central

Clowers, Brian H.; Belov, Mikhail E.; Prior, David C.; Danielson, William F.; Ibrahim, Yehia; Smith, Richard D.

2008-01-01

Due to the inherently low duty cycle of ion mobility spectrometry (IMS) experiments that sample from continuous ion sources, a range of experimental advances have been developed to maximize ion utilization efficiency. The use of ion trapping mechanisms prior to the ion mobility drift tube has demonstrated significant gains over discrete sampling from continuous sources; however, these technologies have traditionally relied upon a signal averaging to attain analytically relevant signal-to-noise ratios (SNR). Multiplexed (MP) techniques based upon the Hadamard transform offer an alternative experimental approach by which ion utilization efficiency can be elevated to ∼ 50 %. Recently, our research group demonstrated a unique multiplexed ion mobility time-of-flight (MP-IMS-TOF) approach that incorporates ion trapping and can extend ion utilization efficiency beyond 50 %. However, the spectral reconstruction of the multiplexed signal using this experiment approach requires the use of sample-specific weighing designs. Though general weighing designs have been shown to significantly enhance ion utilization efficiency using this MP technique, such weighing designs cannot be applied to all samples. By modifying both the ion funnel trap and the pseudo random sequence (PRS) used for the MP experiment we have eliminated the need for complex weighing matrices. For both simple and complex mixtures SNR enhancements of up to 13 were routinely observed as compared to the SA-IMS-TOF experiment. In addition, this new class of PRS provides a two fold enhancement in ion throughput compared to the traditional HT-IMS experiment. PMID:18311942

Online Ozonolysis Combined with Ion Mobility-Mass Spectrometry Provides a New Platform for Lipid Isomer Analyses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poad, Berwyck L. J.; Zheng, Xueyun; Mitchell, Todd W.

One of the most significant challenges in contemporary lipidomics lies in the separation and identification of lipid isomers that differ only in site(s) of unsaturation or geometric configuration of the carbon-carbon double bonds. While analytical separation techniques including ion mobility spectrometry (IMS) and liquid chromatography (LC) can separate isomeric lipids under appropriate conditions, conventional tandem mass spectrometry cannot provide unequivocal identification. To address this challenge, we have implemented ozone-induced dissociation (OzID) in-line with LC, IMS and high resolution mass spectrometry. Modification of an IMS- capable quadrupole time-of-flight mass spectrometer was undertaken to allow the introduction of ozone into the high-pressuremore » trapping ion funnel region preceding the IMS cell. This enabled the novel LC-OzID-IMS-MS configuration where ozonolysis of ionized lipids occurred rapidly (10 ms) without prior mass-selection. LC-elution time alignment combined with accurate mass and arrival time extraction of ozonolysis products facilitated correlation of precursor and product ions without mass-selection (and associated reductions in duty cycle). Unsaturated lipids across 11 classes were examined using this workflow in both positive and negative ion modalities and in all cases the positions of carbon-carbon double bonds were unequivocally assigned based on predictable OzID transitions. Under these conditions geometric isomers exhibited different IMS arrival time distributions and distinct OzID product ion ratios providing a means for discrimination of cis/trans double bonds in complex lipids. The combination of OzID with multidimensional separations shows significant promise for facile profiling of unsaturation patterns within complex lipidomes.« less

Ion mobility spectrometry fingerprints: A rapid detection technology for adulteration of sesame oil.

PubMed

Zhang, Liangxiao; Shuai, Qian; Li, Peiwu; Zhang, Qi; Ma, Fei; Zhang, Wen; Ding, Xiaoxia

2016-02-01

A simple and rapid detection technology was proposed based on ion mobility spectrometry (IMS) fingerprints to determine potential adulteration of sesame oil. Oil samples were diluted by n-hexane and analyzed by IMS for 20s. Then, chemometric methods were employed to establish discriminant models for sesame oils and four other edible oils, pure and adulterated sesame oils, and pure and counterfeit sesame oils, respectively. Finally, Random Forests (RF) classification model could correctly classify all five types of edible oils. The detection results indicated that the discriminant models built by recursive support vector machine (R-SVM) method could identify adulterated sesame oil samples (⩾ 10%) with an accuracy value of 94.2%. Therefore, IMS was shown to be an effective method to detect the adulterated sesame oils. Meanwhile, IMS fingerprints work well to detect the counterfeit sesame oils produced by adding sesame oil essence into cheaper edible oils. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry.

PubMed

Burnum-Johnson, Kristin E; Nie, Song; Casey, Cameron P; Monroe, Matthew E; Orton, Daniel J; Ibrahim, Yehia M; Gritsenko, Marina A; Clauss, Therese R W; Shukla, Anil K; Moore, Ronald J; Purvine, Samuel O; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S; Smith, Richard D

2016-12-01

Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Lipid and glycolipid isomer analyses using ultra-high resolution ion mobility spectrometry separations

DOE PAGES

Wojcik, Roza; Webb, Ian K.; Deng, Liulin; ...

2017-01-18

Understanding the biological mechanisms related to lipids and glycolipids is challenging due to the vast number of possible isomers. Mass spectrometry (MS) measurements are currently the dominant approach for studying and providing detailed information on lipid and glycolipid structures. However, difficulties in distinguishing many structural isomers (e.g. distinct acyl chain positions, double bond locations, as well as glycan isomers) inhibit the understanding of their biological roles. Here we utilized ultra-high resolution ion mobility spectrometry (IMS) separations based upon the use of traveling waves in a serpentine long path length multi-pass Structures for Lossless Manipulations (SLIM) to enhance isomer resolution. Themore » multi-pass arrangement allowed separations ranging from ~16 m (1 pass) to ~470 m (32 passes) to be investigated for the distinction of lipids and glycolipids with extremely small structural differences. Lastly, these ultra-high resolution SLIM IMS-MS analyses provide a foundation for exploring and better understanding isomer specific biological and disease processes.« less

An online peak extraction algorithm for ion mobility spectrometry data.

PubMed

Kopczynski, Dominik; Rahmann, Sven

2015-01-01

Ion mobility (IM) spectrometry (IMS), coupled with multi-capillary columns (MCCs), has been gaining importance for biotechnological and medical applications because of its ability to detect and quantify volatile organic compounds (VOC) at low concentrations in the air or in exhaled breath at ambient pressure and temperature. Ongoing miniaturization of spectrometers creates the need for reliable data analysis on-the-fly in small embedded low-power devices. We present the first fully automated online peak extraction method for MCC/IMS measurements consisting of several thousand individual spectra. Each individual spectrum is processed as it arrives, removing the need to store the measurement before starting the analysis, as is currently the state of the art. Thus the analysis device can be an inexpensive low-power system such as the Raspberry Pi. The key idea is to extract one-dimensional peak models (with four parameters) from each spectrum and then merge these into peak chains and finally two-dimensional peak models. We describe the different algorithmic steps in detail and evaluate the online method against state-of-the-art peak extraction methods.

Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 2. Assessing Charge Site Location and Isotope Scrambling

NASA Astrophysics Data System (ADS)

Khakinejad, Mahdiar; Ghassabi Kondalaji, Samaneh; Donohoe, Gregory C.; Valentine, Stephen J.

2016-03-01

Ion mobility spectrometry (IMS) coupled with gas-phase hydrogen deuterium exchange (HDX)-mass spectrometry (MS) and molecular dynamic simulations (MDS) has been used for structural investigation of anions produced by electrospraying a sample containing a synthetic peptide having the sequence KKDDDDDIIKIIK. In these experiments the potential of the analytical method for locating charge sites on ions as well as for utilizing collision-induced dissociation (CID) to reveal the degree of deuterium uptake within specific amino acid residues has been assessed. For diffuse (i.e., more elongated) [M - 2H]2- ions, decreased deuterium content along with MDS data suggest that the D4 and D6 residues are charge sites, whereas for the more diffuse [M - 3H]3- ions, the data suggest that the D4, D7, and the C-terminus are deprotonated. Fragmentation of mobility-selected, diffuse [M - 2H]2- ions to determine deuterium uptake at individual amino acid residues reveals a degree of deuterium retention at incorporation sites. Although the diffuse [M - 3H]3- ions may show more HD scrambling, it is not possible to clearly distinguish HD scrambling from the expected deuterium uptake based on a hydrogen accessibility model. The capability of the IMS-HDX-MS/MS approach to provide relevant details about ion structure is discussed. Additionally, the ability to extend the approach for locating protonation sites on positively-charged ions is presented.

Selectivity improvement of positive photoionization ion mobility spectrometry for rapid detection of organophosphorus pesticides by switching dopant concentration.

PubMed

Zhou, Qinghua; Li, Jia; Wang, Bin; Wang, Shuang; Li, Haiyang; Chen, Jinyuan

2018-01-01

Ion mobility spectrometry (IMS) opened a potential avenue for the rapid detection of organophosphorus pesticides (OPPs), though an improved selectivity of stand-alone IMS was still in high demand. In this study, a stand-alone positive photoionization ion mobility spectrometry (PP-IMS) apparatus was constructed for the rapid detection of OPPs with acetone as dopant. The photoionization of acetone molecules was induced by the ultraviolet irradiation to produce the reactant ions (Ac) 2 H + , which were employed to ionize the OPPs including fenthion, imidan, phosphamidon, dursban, dimethoate and isocarbophos via the proton transfer reaction. Due to the difference in proton affinity, the tested OPPs exhibited the different dopant-dependent manners. Based on this observation, the switching of dopant concentration was implemented to improve the selectivity of PP-IMS for OPPs detection. For instance, a mixture of fenthion, dursban and dimethoate was tested. By switching the concentration of doped acetone from 0.07 to 2.33 to 19.94mgL -1 , the ion peaks of fenthion and dursban were inhibited in succession, achieving the selective detection of dimethoate at last. In addition, another mixture of imidan and phosphamidon was initially detected by PP-IMS with a dose of 0.07mgL -1 acetone, indicating that their ion peaks were severely overlapped; when the concentration of doped acetone was switched to 19.94mgL -1 , the inhibition of imidan signals promised the accurate identification of phosphamidon in mixture. Finally, the PP-IMS in combination of switching dopant concentration was applied to detect the mixed fenthion, dursban and dimethoate in Chinese cabbage, demonstrating the applicability of proposed method to real samples. Copyright © 2017. Published by Elsevier B.V.

Design for gas chromatography-corona discharge-ion mobility spectrometry.

PubMed

Jafari, Mohammad T; Saraji, Mohammad; Sherafatmand, Hossein

2012-11-20

A corona discharge ionization-ion mobility spectrometry (CD-IMS) with a novel sample inlet system was designed and constructed as a detector for capillary gas chromatography. In this design, a hollow needle was used instead of a solid needle which is commonly used for corona discharge creation, helping us to have direct axial interfacing for GC-IMS. The capillary column was passed through the needle, resulting in a reaction of effluents with reactant ions on the upstream side of the corona discharge ionization source. Using this sample introduction design, higher ionization efficiency was achieved relative to the entrance direction through the side of the drift tube. In addition, the volume of the ionization region was reduced to minimize the resistance time of compounds in the ionization source, increasing chromatographic resolution of the instrument. The effects of various parameters such as drift gas flow, makeup gas flow, and column tip position inside the needle were investigated. The designed instrument was exhaustively validated in terms of sensitivity, resolution, and reproducibility by analyzing the standard solutions of methyl isobutyl ketone, heptanone, nonanone, and acetophenone as the test compounds. The results obtained by CD-IMS detector were compared with those of the flame ionization detector, which revealed the capability of the proposed GC-IMS for two-dimensional separation (based on the retention time and drift time information) and identification of an analyte in complex matrixes.

Analysis of ecstasy in oral fluid by ion mobility spectrometry and infrared spectroscopy after liquid-liquid extraction.

PubMed

Armenta, Sergio; Garrigues, Salvador; de la Guardia, Miguel; Brassier, Judit; Alcalà, Manel; Blanco, Marcelo

2015-03-06

We developed and evaluated two different strategies for determining abuse drugs based on (i) the analysis of saliva by ion mobility spectrometry (IMS) after thermal desorption and (ii) the joint use of IMS and infrared (IR) spectroscopy after liquid-liquid microextraction (LLME) to enable the sensitivity-enhanced detection and double confirmation of ecstasy (MDMA) abuse. Both strategies proved effective for the intended purpose. Analysing saliva by IMS after thermal desorption, which provides a limit of detection (LOD) of 160μgL(-1), requires adding 0.2M acetic acid to the sample and using the truncated negative second derivative of the ion mobility spectrum. The joint use of IMS and IR spectroscopy after LLME provides an LOD of 11μgL(-1) with the former technique and 800μgL(-1) with the latter, in addition to a limit of confirmation (LOC) of 1.5mgL(-1). Using IMS after thermal desorption simplifies the operational procedure, and using it jointly with IR spectroscopy after LLME allows double confirmation of MDMA abuse with two techniques based on different principles (viz., IMS drift times and IR spectra). Also, it affords on-site analyses, albeit at a lower throughput. Copyright © 2015 Elsevier B.V. All rights reserved.

Integrating ion mobility spectrometry into mass spectrometry-based exposome measurements: what can it add and how far can it go?

PubMed

Metz, Thomas O; Baker, Erin S; Schymanski, Emma L; Renslow, Ryan S; Thomas, Dennis G; Causon, Tim J; Webb, Ian K; Hann, Stephan; Smith, Richard D; Teeguarden, Justin G

2017-01-01

Measuring the exposome remains a challenge due to the range and number of anthropogenic molecules that are encountered in our daily lives, as well as the complex systemic responses to these exposures. One option for improving the coverage, dynamic range and throughput of measurements is to incorporate ion mobility spectrometry (IMS) into current MS-based analytical methods. The implementation of IMS in exposomics studies will lead to more frequent observations of previously undetected chemicals and metabolites. LC-IMS-MS will provide increased overall measurement dynamic range, resulting in detections of lower abundance molecules. Alternatively, the throughput of IMS-MS alone will provide the opportunity to analyze many thousands of longitudinal samples over lifetimes of exposure, capturing evidence of transitory accumulations of chemicals or metabolites. The volume of data corresponding to these new chemical observations will almost certainly outpace the generation of reference data to enable their confident identification. In this perspective, we briefly review the state-of-the-art in measuring the exposome, and discuss the potential use for IMS-MS and the physico-chemical property of collisional cross section in both exposure assessment and molecular identification.

Integrating ion mobility spectrometry into mass spectrometry-based exposome measurements: what can it add and how far can it go?

PubMed Central

Metz, Thomas O; Baker, Erin S; Schymanski, Emma L; Renslow, Ryan S; Thomas, Dennis G; Causon, Tim J; Webb, Ian K; Hann, Stephan; Smith, Richard D; Teeguarden, Justin G

2017-01-01

Measuring the exposome remains a challenge due to the range and number of anthropogenic molecules that are encountered in our daily lives, as well as the complex systemic responses to these exposures. One option for improving the coverage, dynamic range and throughput of measurements is to incorporate ion mobility spectrometry (IMS) into current MS-based analytical methods. The implementation of IMS in exposomics studies will lead to more frequent observations of previously undetected chemicals and metabolites. LC-IMS-MS will provide increased overall measurement dynamic range, resulting in detections of lower abundance molecules. Alternatively, the throughput of IMS-MS alone will provide the opportunity to analyze many thousands of longitudinal samples over lifetimes of exposure, capturing evidence of transitory accumulations of chemicals or metabolites. The volume of data corresponding to these new chemical observations will almost certainly outpace the generation of reference data to enable their confident identification. In this perspective, we briefly review the state-of-the-art in measuring the exposome, and discuss the potential use for IMS-MS and the physico-chemical property of collisional cross section in both exposure assessment and molecular identification. PMID:27921453

Data collection in IMS: It's not as easy as it looks

NASA Technical Reports Server (NTRS)

Davis, Dennis M.; Maswadeh, Waleed; Shoff, Donald B.; Harden, Charles S.; Snyder, A. Peter

1995-01-01

Data collection in Ion Mobility Spectrometry (IMS) is not as easy an endeavor as it appears. Despite the advent of high speed personal computers and fast analog-to-digital converters (ADC's), care must be taken to ensure that reliable data are obtained in a timely fashion. This is especially true in hyphenated techniques, e.g. GC-IMS, where the amount of data increases dramatically when gas chromatography-ion mobility spectrometry (GC-IMS) data is being collected. Using the Graseby GC-IMS, with a gate repetition rate of 33 Hz, it is theoretically possible to collect 33 spectra per second. This collection rate is not realistically obtained due to a number of factors. Among these factors are inaccuracy of the timing signal from the IMS, the necessity to store the data, disk input/output limitations, disk operating system limitations, and program overhead. Taking these factors into account, we have achieved a data collection rate of 20 spectra per second. This paper will describe these problems, demonstrate the practical effects these problems present, and present methods for minimizing these effects.

Fast Orthogonal Separation by Superposition of Time of Flight and Field Asymmetric Ion Mobility Spectrometry.

PubMed

Bohnhorst, Alexander; Kirk, Ansgar T; Berger, Marc; Zimmermann, Stefan

2018-01-16

Ion mobility spectrometry is a powerful and low-cost technique for the identification of chemical warfare agents, toxic chemicals, or explosives in air. Drift tube ion mobility spectrometers (DT-IMS) separate ions by the absolute value of their low field ion mobility, while field asymmetric ion mobility spectrometers (FAIMS) separate them by the change of their ion mobility at high fields. However, using one of these devices alone, some common and harmless substances show the same response as the hazardous target substances. In order to increase the selectivity, orthogonal data are required. Thus, in this work, we present for the first time an ambient pressure ion mobility spectrometer which is able to separate ions both by their differential and low field mobility, providing additional information for selectivity enhancement. This novel field asymmetric time of flight ion mobility spectrometer (FAT-IMS) allows high repetition rates and reaches limits of detection in the low ppb range common for DT-IMS. The device consists of a compact 44 mm drift tube with a tritium ionization source and a resolving power of 70. An increased separation of four substances with similar low field ion mobility is shown: phosgene (K 0 = 2.33 cm 2 /(V s)), 1,1,2-trichlorethane (K 0 = 2.31 cm 2 /(V s)), chlorine (K 0 = 2.24 cm 2 /(V s)), and nitrogen dioxide (K 0 = 2.25 cm 2 /(V s)). Furthermore, the behavior and limits of detection for acetonitrile, dimethyl methylphosphonate, diisopropyl methyl phosphonate in positive polarity and carbon dioxide, sulfur dioxide, hydrochloric acid, cyanogen chloride, and hydrogen cyanide in negative polarity are investigated.

Structural Elucidation of Enzymatically Synthesized Galacto-oligosaccharides Using Ion-Mobility Spectrometry-Tandem Mass Spectrometry.

PubMed

Carević, Milica; Bezbradica, Dejan; Banjanac, Katarina; Milivojević, Ana; Fanuel, Mathieu; Rogniaux, Hélène; Ropartz, David; Veličković, Dušan

2016-05-11

Galacto-oligosaccharides (GOS) represent a diverse group of well-characterized prebiotic ingredients derived from lactose in a reaction catalyzed with β-galactosidases. Enzymatic transgalactosylation results in a mixture of compounds of various degrees of polymerization and types of linkages. Because structure plays an important role in terms of prebiotic activity, it is of crucial importance to provide an insight into the mechanism of transgalactosylation reaction and occurrence of different types of β-linkages during GOS synthesis. Our study proved that a novel one-step method, based on ion-mobility spectrometry-tandem mass spectrometry (IMS-MS/MS), enables complete elucidation of GOS structure. It has been shown that β-galactosidase from Aspergillus oryzae has the highest affinity toward formation of β-(1→3) or β-(1→6) linkages. Additionally, it was observed that the occurrence of different linkages varies during the reaction course, indicating that tailoring favorable GOS structures with improved prebiotic activity can be achieved by adequate control of enzymatic synthesis.

Distinguishing d - and l -aspartic and isoaspartic acids in amyloid β peptides with ultrahigh resolution ion mobility spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Xueyun; Deng, Liulin; Baker, Erin S.

2017-01-01

Ion mobility spectrometry (IMS) was utilized to separate Aβ peptide variants containing isomeric asparic and isoaspartic acid residues with either al- ord-form. The abundance of each variant is of great interest in Alzheimer's disease studies and also to evaluate how often these modifications are occurring in other environmental and biological samples.

On-site Rapid Detection of Trace Non-volatile Inorganic Explosives by Stand-alone Ion Mobility Spectrometry via Acid-enhanced Evaporization

PubMed Central

Peng, Liying; Hua, Lei; Wang, Weiguo; Zhou, Qinghua; Li, Haiyang

2014-01-01

New techniques for the field detection of inorganic improvised explosive devices (IEDs) are urgently developed. Although ion mobility spectrometry (IMS) has been proved to be the most effective method for screening organic explosives, it still faces a major challenge to detect inorganic explosives owing to their low volatilities. Herein, we proposed a strategy for detecting trace inorganic explosives by thermal desorption ion mobility spectrometry (TD-IMS) with sample-to-sample analysis time less than 5 s based on in-situ acidification on the sampling swabs. The responses for typical oxidizers in inorganic explosives, such as KNO3, KClO3 and KClO4 were at least enhanced by a factor of 3000 and their limits of detection were found to be subnanogram. The common organic explosives and their mixtures with inorganic oxidizers were detected, indicating that the acidification process did not affect the detection of organic explosives. Moreover, the typical inorganic explosives such as black powders, firecrackers and match head could be sensitively detected as well. These results demonstrated that this method could be easily employed in the current deployed IMS for on-site sensitive detection of either inorganic explosives or organic ones. PMID:25318960

Separation and characterization of metallosupramolecular libraries by ion mobility mass spectrometry.

PubMed

Li, Xiaopeng; Chan, Yi-Tsu; Casiano-Maldonado, Madalis; Yu, Jing; Carri, Gustavo A; Newkome, George R; Wesdemiotis, Chrys

2011-09-01

The self-assembly of Zn(II) ions and bis(terpyridine) (tpy) ligands carrying 120° or 180° angles between their metal binding sites was utilized to prepare metallosupramolecular libraries with the connectivity. These combinatorial libraries were separated and characterized by ion mobility mass spectrometry (IM MS) and tandem mass spectrometry (MS(2)). The 180°-angle building blocks generate exclusively linear complexes, which were used as standards to determine the architectures of the assemblies resulting from the 120°-angle ligands. The latter ligand geometry promotes the formation of macrocyclic hexamers, but other n-mers with smaller (n = 5) or larger ring sizes (n = 7-9) were identified as minor products, indicating that the angles in the bis(terpyridine) ligand and within the coordinative tpy-Zn(II)-tpy bonds are not as rigid, as previously believed. Macrocyclic and linear isomers were detected in penta- and heptameric assemblies; in the larger octa- and nonameric assemblies, ring-opened conformers with compact and folded geometries were observed in addition to linear extended and cyclic architectures. IM MS(2) experiments provided strong evidence that the macrocycles present in the libraries were already formed in solution, during the self-assembly process, not by dissociation of larger complexes in the gas phase. The IM MS/MS(2) methods provide a means to analyze, based on size and shape (architecture), supramolecular libraries that are not amenable to liquid chromatography, LC-MS, NMR, and/or X-ray techniques.

Sensitive detection of trimethylamine based on dopant-assisted positive photoionization ion mobility spectrometry.

PubMed

Cheng, Shasha; Li, Haitao; Jiang, Dandan; Chen, Chuang; Zhang, Tan; Li, Yong; Wang, Haitao; Zhou, Qinghua; Li, Haiyang; Tan, Mingqian

2017-01-01

Biogenic amines are degradation products generated through enzymatic and microbial processes during food spoilage, which may pose a health hazard to consumers at elevated levels. Trimethylamine (TMA) is a good target for the detection of biogenic amines due to its volatility and fishy odor. In this study, we developed a stand-alone dopant-assisted positive photoionization ion mobility spectrometry (DAPP-IMS) for rapid and sensitive detection of TMA. Response of TMA was enhanced by the addition of dopants and characteristic product ions with reduced mobility 2.26cm 2 V -1 s -1 were formed. 2-Butaone was chosen as the dopant for better separation between reagent ion peak and TMA product ion peak as well as higher sensitivity and the limit of detections (LODs) for TMA standard sample was 1ppb. The potential application of DAAP-IMS was evaluated by the detection of TMA generated by oyster and shrimp during 4°C storage. Analysis of two kinds of seafood showed the same characteristic peak to TMA standard sample, and the intensity of TMA increased over the storage time. The results of this study testify to the potential of DAPP-IMS for qualitative and quantitative determination of TMA in real food samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Profiling the indole alkaloids in yohimbe bark with ultra-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry

USDA-ARS?s Scientific Manuscript database

An ultra-high performance liquid chromatography-ion mobility- quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF-MS) method was developed for profiling the indole alkaloids in yohimbe bark. Many indole alkaloids with the yohimbine core structure, plus methylated, oxidized, and reduced speci...

Determination and identification of malathion, ethion and dichlorovos using ion mobility spectrometry.

PubMed

Jafari, Mohammad T

2006-07-15

Positive ion mobility spectra of different organophosphorus pesticides such as malathion (s-(1,2-dicarb-ethoxyethyl) o,o-dimethyl dithiophosphate), ethion (o,o,o',o'-tetraethyl s,s'-methylene bis(phosphorodithioate)) and dichlorovos (2,2-dichlorovinyl dimethyl phosphate) have been studied in air at ambient pressure using ion mobility spectrometry method with (63)Ni ionization source. The limits of quantification (LOQs) were 1.0 x 10(-9), 1.0 x 10(-9) and 5.0 x 10(-9)g for malathion, ethion and dichlorovos, respectively. The working range of these compounds was about three orders of magnitude and the relative standard deviation (R.S.D.) of repeatability at the 5 microg ml(-1) level were all below 15%. Furthermore, in this study, the influences of IMS cell temperature on the ion mobility spectra of these compounds were investigated.

Gas chromatography/ion mobility spectrometry as a hyphenated technique for improved explosives detection and analysis

NASA Technical Reports Server (NTRS)

Mercado, AL; Marsden, Paul

1995-01-01

Ion Mobility Spectrometry (IMS) is currently being successfully applied to the problem of on-line trace detection of plastic and other explosives in airports and other facilities. The methods of sample retrieval primarily consist of batch sampling for particulate residue on a filter card for introduction into the IMS. The sample is desorbed into the IMS using air as the carrier and negative ions of the explosives are detected, some as an adduct with a reagent ion such as Cl(-). Based on studies and tests conducted by different airport authorities, this method seems to work well for low vapor pressure explosives such as RDX and PETN, as well as TNT that are highly adsorptive and can be found in nanogram quantities on contaminated surfaces. Recently, the changing terrorist threat and the adoption of new marking agents for plastic explosives has meant that the sample introduction and analysis capabilities of the IMS must be enhanced in order to keep up with other detector developments. The IMS has sufficient analytical resolution for a few threat compounds but the IMS Plasmogram becomes increasingly more difficult to interpret when the sample mixture gets more complex.

IMS applications analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

RODACY,PHILIP J.; REBER,STEPHEN D.; SIMONSON,ROBERT J.

This report examines the market potential of a miniature, hand-held Ion Mobility Spectrometer. Military and civilian markets are discussed, as well as applications in a variety of diverse fields. The strengths and weaknesses of competing technologies are discussed. An extensive Ion Mobility Spectrometry (IMS) bibliography is included. The conclusions drawn from this study are: (1) There are a number of competing technologies that are capable of detecting explosives, drugs, biological, or chemical agents. The IMS system currently represents the best available compromise regarding sensitivity, specificity, and portability. (2) The military market is not as large as the commercial market, butmore » the military services are more likely to invest R and D funds in the system. (3) Military applications should be addressed before commercial applications are addressed. (4) There is potentially a large commercial market for rugged, hand-held Ion Mobility Spectrometer systems. Commercial users typically do not invest R and D funds in this type of equipment rather, they wait for off-the-shelf availability.« less

Optimization of curved drift tubes for ultraviolet-ion mobility spectrometry

NASA Astrophysics Data System (ADS)

Ni, Kai; Ou, Guangli; Zhang, Xiaoguo; Yu, Zhou; Yu, Quan; Qian, Xiang; Wang, Xiaohao

2015-08-01

Ion mobility spectrometry (IMS) is a key trace detection technique for toxic pollutants and explosives in the atmosphere. Ultraviolet radiation photoionization source is widely used as an ionization source for IMS due to its advantages of high selectivity and non-radioactivity. However, UV-IMS bring problems that UV rays will be launched into the drift tube which will cause secondary ionization and lead to the photoelectric effect of the Faraday disk. So air is often used as working gas to reduce the effective distance of UV rays, but it will limit the application areas of UV-IMS. In this paper, we propose a new structure of curved drift tube, which can avoid abnormally incident UV rays. Furthermore, using curved drift tube may increase the length of drift tube and then improve the resolution of UV-IMS according to previous research. We studied the homogeneity of electric field in the curved drift tube, which determined the performance of UV-IMS. Numerical simulation of electric field in curved drift tube was conducted by SIMION in our study. In addition, modeling method and homogeneity standard for electric field were also presented. The influences of key parameters include radius of gyration, gap between electrode as well as inner diameter of curved drift tube, on the homogeneity of electric field were researched and some useful laws were summarized. Finally, an optimized curved drift tube is designed to achieve homogenous drift electric field. There is more than 98.75% of the region inside the curved drift tube where the fluctuation of the electric field strength along the radial direction is less than 0.2% of that along the axial direction.

Structural Elucidation of cis / trans Dicaffeoylquinic Acid Photoisomerization Using Ion Mobility Spectrometry-Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Xueyun; Renslow, Ryan S.; Makola, Mpho M.

Due to the recently uncovered health benefits and anti-HIV activities of dicaffeoylquinic acids (diCQAs), understanding their structures and functions is of great interest for drug discovery efforts. DiCQAs are analytically challenging to identify and quantify since they commonly exist as a diverse mixture of positional and geometric (cis/trans) isomers. In this work, we utilized ion mobility spectrometry coupled with mass spectrometry to separate the various isomers before and after UV irradiation. The experimental collision cross sections were then compared with theoretical structures to differentiate and identify the diCQA isomers. Our analyses found that naturally the diCQAs existed predominantly as trans/transmore » isomers, but after 3 h of UV irradiation, cis/cis, cis/trans, trans/cis, and trans/trans isomers were all present in the mixture. This is the first report of successful differentiation of cis/trans diCQA isomers individually, which shows the great promise of IMS coupled with theoretical calculations for determining the structure and activity relationships of different isomers in drug discovery studies.« less

Mass spectrometry methods for the analysis of biodegradable hybrid materials

NASA Astrophysics Data System (ADS)

Alalwiat, Ahlam

This dissertation focuses on the characterization of hybrid materials and surfactant blends by using mass spectrometry (MS), tandem mass spectrometry (MS/MS), liquid chromatography (LC), and ion mobility (IM) spectrometry combined with measurement and simulation of molecular collision cross sections. Chapter II describes the principles and the history of mass spectrometry (MS) and liquid chromatography (LC). Chapter III introduces the materials and instrumentation used to complete this dissertation. In chapter IV, two hybrid materials containing poly(t-butyl acrylate) (PtBA) or poly(acrylic acid) (PAA) blocks attached to a hydrophobic peptide rich in valine and glycine (VG2), as well as the poly(acrylic acid) (PAA) and VG2 peptide precursor materials, are characterized by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), electrospray ionization mass spectrometry (ESI-MS) and ion mobility mass spectrometry (IM-MS). Collision cross-sections and molecular modeling have been used to determine the final architecture of both hybrid materials. Chapter V investigates a different hybrid material, [BMP-2(HA)2 ], comprised of a dendron with two polyethylene glycol (PEG) branches terminated by a hydroxyapatite binding peptide (HA), and a focal point substituted with a bone morphogenic protein mimicking peptide (BMP-2). MALDI-MS, ESI-MS and IM-MS have been used to characterize the HA and BMP-2 peptides. Collisionally activated dissociation (CAD) and electron transfer dissociation (ETD) have been employed in double stage (i.e. tandem) mass spectrometry (MS/MS) experiments to confirm the sequences of the two peptides HA and BMP-2. The MALDI-MS, ESI-MS and IM-MS methods were also applied to characterize the [BMP-2(HA)2] hybrid material. Collision cross-section measurements and molecular modeling indicated that [BMP-2(HA)2] can attain folded or extended conformation, depending on its degree of protonation (charge state). Chapter VI focuses on the analysis of

Distinguishing d- and l-aspartic and isoaspartic acids in amyloid β peptides with ultrahigh resolution ion mobility spectrometry.

PubMed

Zheng, Xueyun; Deng, Liulin; Baker, Erin S; Ibrahim, Yehia M; Petyuk, Vladislav A; Smith, Richard D

2017-07-11

While α-linked amino acids in the l-form are exclusively utilized in mammalian protein building, β-linked and d-form amino acids also have important biological roles. Unfortunately, the structural elucidation and separation of these different amino acid types in peptides has been analytically challenging to date due to the numerous isomers present, limiting our knowledge about their existence and biological roles. Here, we utilized an ultrahigh resolution ion mobility spectrometry platform coupled with mass spectrometry (IMS-MS) to separate amyloid β (Aβ) peptides containing l-aspartic acid, d-aspartic acid, l-isoaspartic acid, and d-isoaspartic acid residues which span α- and β-linked amino acids in both d- and l-forms. The results illustrate how IMS-MS could be used to better understand age-related diseases or protein folding disorders resulting from amino acid modifications.

Atmospheric Pressure Chemical Ionization Sources Used in The Detection of Explosives by Ion Mobility Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waltman, Melanie J.

2010-05-01

Explosives detection is a necessary and wide spread field of research. From large shipping containers to airline luggage, numerous items are tested for explosives every day. In the area of trace explosives detection, ion mobility spectrometry (IMS) is the technique employed most often because it is a quick, simple, and accurate way to test many items in a short amount of time. Detection by IMS is based on the difference in drift times of product ions through the drift region of an IMS instrument. The product ions are created when the explosive compounds, introduced to the instrument, are chemically ionizedmore » through interactions with the reactant ions. The identity of the reactant ions determines the outcomes of the ionization process. This research investigated the reactant ions created by various ionization sources and looked into ways to manipulate the chemistry occurring in the sources.« less

Comprehensive lipidomic analysis of human plasma using multidimensional liquid- and gas-phase separations: Two-dimensional liquid chromatography-mass spectrometry vs. liquid chromatography-trapped-ion-mobility-mass spectrometry.

PubMed

Baglai, Anna; Gargano, Andrea F G; Jordens, Jan; Mengerink, Ynze; Honing, Maarten; van der Wal, Sjoerd; Schoenmakers, Peter J

2017-12-29

Recent advancements in separation science have resulted in the commercialization of multidimensional separation systems that provide higher peak capacities and, hence, enable a more-detailed characterization of complex mixtures. In particular, two powerful analytical tools are increasingly used by analytical scientists, namely online comprehensive two-dimensional liquid chromatography (LC×LC, having a second-dimension separation in the liquid phase) and liquid chromatography-ion mobility-spectrometry (LC-IMS, second dimension separation in the gas phase). The goal of the current study was a general assessment of the liquid-chromatography-trapped-ion-mobility-mass spectrometry (LC-TIMS-MS) and comprehensive two-dimensional liquid chromatography-mass spectrometry (LC×LC-MS) platforms for untargeted lipid mapping in human plasma. For the first time trapped-ion-mobility spectrometry (TIMS) was employed for the separation of the major lipid classes and ion-mobility-derived collision-cross-section values were determined for a number of lipid standards. The general effects of a number of influencing parameters have been inspected and possible directions for improvements are discussed. We aimed to provide a general indication and practical guidelines for the analyst to choose an efficient multidimensional separation platform according to the particular requirements of the application. Analysis time, orthogonality, peak capacity, and an indicative measure for the resolving power are discussed as main characteristics for multidimensional separation systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlating Resolving Power, Resolution, and Collision Cross Section: Unifying Cross-Platform Assessment of Separation Efficiency in Ion Mobility Spectrometry.

PubMed

Dodds, James N; May, Jody C; McLean, John A

2017-11-21

Here we examine the relationship among resolving power (R p ), resolution (R pp ), and collision cross section (CCS) for compounds analyzed in previous ion mobility (IM) experiments representing a wide variety of instrument platforms and IM techniques. Our previous work indicated these three variables effectively describe and predict separation efficiency for drift tube ion mobility spectrometry experiments. In this work, we seek to determine if our previous findings are a general reflection of IM behavior that can be applied to various instrument platforms and mobility techniques. Results suggest IM distributions are well characterized by a Gaussian model and separation efficiency can be predicted on the basis of the empirical difference in the gas-phase CCS and a CCS-based resolving power definition (CCS/ΔCCS). Notably traveling wave (TWIMS) was found to operate at resolutions substantially higher than a single-peak resolving power suggested. When a CCS-based R p definition was utilized, TWIMS was found to operate at a resolving power between 40 and 50, confirming the previous observations by Giles and co-workers. After the separation axis (and corresponding resolving power) is converted to cross section space, it is possible to effectively predict separation behavior for all mobility techniques evaluated (i.e., uniform field, trapped ion mobility, traveling wave, cyclic, and overtone instruments) using the equations described in this work. Finally, we are able to establish for the first time that the current state-of-the-art ion mobility separations benchmark at a CCS-based resolving power of >300 that is sufficient to differentiate analyte ions with CCS differences as small as 0.5%.

Assessment of altered lipid homeostasis by HILIC-ion mobility-mass spectrometry-based lipidomics[S

PubMed Central

Hines, Kelly M.; Herron, Josi; Xu, Libin

2017-01-01

Ion mobility-mass spectrometry (IM-MS) has proven to be a highly informative technique for the characterization of lipids from cells and tissues. We report the combination of hydrophilic-interaction liquid chromatography (HILIC) with traveling-wave IM-MS (TWIM-MS) for comprehensive lipidomics analysis. Main lipid categories such as glycerolipids, sphingolipids, and glycerophospholipids are separated on the basis of their lipid backbones in the IM dimension, whereas subclasses of each category are mostly separated on the basis of their headgroups in the HILIC dimension, demonstrating the orthogonality of HILIC and IM separations. Using our previously established lipid calibrants for collision cross-section (CCS) measurements in TWIM, we measured over 250 CCS values covering 12 lipid classes in positive and negative modes. The coverage of the HILIC-IM-MS method is demonstrated in the analysis of Neuro2a neuroblastoma cells exposed to benzalkonium chlorides (BACs) with C10 or C16 alkyl chains, which we have previously shown to affect gene expression related to cholesterol and lipid homeostasis. We found that BAC exposure resulted in significant changes to several lipid classes, including glycerides, sphingomyelins, phosphatidylcholines, and phosphatidylethanolamines. Our results indicate that BAC exposure modifies lipid homeostasis in a manner that is dependent upon the length of the BAC alkyl chain. PMID:28167702

Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 1. Peptides to Proteins

NASA Astrophysics Data System (ADS)

Donohoe, Gregory C.; Khakinejad, Mahdiar; Valentine, Stephen J.

2015-04-01

Ion mobility spectrometry (IMS) coupled with hydrogen deuterium exchange (HDX)-mass spectrometry (MS) has been used to study the conformations of negatively-charged peptide and protein ions. Results are presented for ion conformers of angiotensin 1, a synthetic peptide (SP), bovine insulin, ubiquitin, and equine cytochrome c. In general, the SP ion conformers demonstrate a greater level of HDX efficiency as a greater proportion of the sites undergo HDX. Additionally, these ions exhibit the fastest rates of exchange. Comparatively, the angiotensin 1 ions exhibit a lower rate of exchange and HDX level presumably because of decreased accessibility of exchange sites by charge sites. The latter are likely confined to the peptide termini. Insulin ions show dramatically reduced HDX levels and exchange rates, which can be attributed to decreased conformational flexibility resulting from the disulfide bonds. For the larger ubiquitin and protein ions, increased HDX is observed for larger ions of higher charge state. For ubiquitin, a conformational transition from compact to more elongated species (from lower to higher charge states) is reflected by an increase in HDX levels. These results can be explained by a combination of interior site protection by compact conformers as well as decreased access by charge sites. The elongated cytochrome c ions provide the largest HDX levels where higher values correlate with charge state. These results are consistent with increased exchange site accessibility by additional charge sites. The data from these enhanced IMS-HDX experiments are described in terms of charge site location, conformer rigidity, and interior site protection.

The use of dopants in high field asymmetric waveform spectrometry.

PubMed

Ross, Stuart K; McDonald, Gwenda; Marchant, Sarah

2008-05-01

Ion mobility spectrometry (IMS) is proven core technology for the gas-phase detection of chemical warfare (CW) agents. One disadvantage of IMS technology is that ions of similar mobility cannot readily be resolved, resulting in false alarm responses and a loss of user confidence. High field asymmetric waveform spectrometry (HiFAWS) is an emerging technology for the gas-phase detection of CW agents. Of particular interest is the potential of a HiFAWS-based platform to reduce the number of false alarms by resolving ions that cannot be discriminated using IMS. It has been demonstrated that a water clustering/declustering mechanism can be a dominant process in HiFAWS. Ions that cannot be discriminated in IMS because they possess the same low field mobility value can be resolved using HiFAWS due to differences in the extent of low field ion solvation and high field ion desolvation. When operating in complex environments such as those potentially experienced in military and security arenas, IMS systems commonly employ internal dopants to reduce the number of background responses. It is possible that HiFAWS systems may also require the use of internal dopants for the same reason. It has been demonstrated that dopants employed for use in IMS may not be suitable for use in HiFAWS.

Improved Quantitative Analysis of Ion Mobility Spectrometry by Chemometric Multivariate Calibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraga, Carlos G.; Kerr, Dayle; Atkinson, David A.

2009-09-01

Traditional peak-area calibration and the multivariate calibration methods of principle component regression (PCR) and partial least squares (PLS), including unfolded PLS (U-PLS) and multi-way PLS (N-PLS), were evaluated for the quantification of 2,4,6-trinitrotoluene (TNT) and cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX) in Composition B samples analyzed by temperature step desorption ion mobility spectrometry (TSD-IMS). The true TNT and RDX concentrations of eight Composition B samples were determined by high performance liquid chromatography with UV absorbance detection. Most of the Composition B samples were found to have distinct TNT and RDX concentrations. Applying PCR and PLS on the exact same IMS spectra used for themore » peak-area study improved quantitative accuracy and precision approximately 3 to 5 fold and 2 to 4 fold, respectively. This in turn improved the probability of correctly identifying Composition B samples based upon the estimated RDX and TNT concentrations from 11% with peak area to 44% and 89% with PLS. This improvement increases the potential of obtaining forensic information from IMS analyzers by providing some ability to differentiate or match Composition B samples based on their TNT and RDX concentrations.« less

Dopant titrating ion mobility spectrometry for trace exhaled nitric oxide detection.

PubMed

Peng, Liying; Hua, Lei; Li, Enyou; Wang, Weiguo; Zhou, Qinghua; Wang, Xin; Wang, Changsong; Li, Jinghua; Li, Haiyang

2015-01-05

Ion mobility spectrometry (IMS) is a promising non-invasive tool for the analysis of exhaled gas and exhaled nitric oxide (NO), a biomarker for diagnosis of respiratory diseases. However, the high moisture in exhaled gas always brings about extra overlapping ion peaks and results in poor identification ability. In this paper, p-benzoquinone (PBQ) was introduced into IMS to eliminate the interference of overlapping ion peaks and realize the selective identification of NO. The overlapping ions caused by moisture were titrated by PBQ and then converted to hydrated PBQ anions (C6H4[Formula: see text](H2O)n). The NO concentration could be determined by quantifying gas phase hydrated nitrite anions (N[Formula: see text](H2O)n), product ions of NO. Under optimized conditions, a limit of detection (LOD) of about 1.4 ppbv and a linear range of 10-200 ppbv were obtained for NO even in 100% relative humidity (RH) purified air. Furthermore, this established method was applied to measure hourly the exhaled NO of eight healthy volunteers, and real-time monitoring the exhaled NO of an esophageal carcinoma patient during radical surgery. These results revealed the potential of the current dopant titrating IMS method in the measurement of exhaled NO for medical disease diagnosis.

Effects of drift gas on collision cross sections of a protein standard in linear drift tube and traveling wave ion mobility mass spectrometry.

PubMed

Jurneczko, Ewa; Kalapothakis, Jason; Campuzano, Iain D G; Morris, Michael; Barran, Perdita E

2012-10-16

There has been a significant increase in the use of ion mobility mass spectrometry (IM-MS) to investigate conformations of proteins and protein complexes following electrospray ionization. Investigations which employ traveling wave ion mobility mass spectrometry (TW IM-MS) instrumentation rely on the use of calibrants to convert the arrival times of ions to collision cross sections (CCS) providing "hard numbers" of use to structural biology. It is common to use nitrogen as the buffer gas in TW IM-MS instruments and to calibrate by extrapolating from CCS measured in helium via drift tube (DT) IM-MS. In this work, both DT and TW IM-MS instruments are used to investigate the effects of different drift gases (helium, neon, nitrogen, and argon) on the transport of multiply charged ions of the protein myoglobin, frequently used as a standard in TW IM-MS studies. Irrespective of the drift gas used, recorded mass spectra are found to be highly similar. In contrast, the recorded arrival time distributions and the derived CCS differ greatly. At low charge states (7 ≤ z ≤ 11) where the protein is compact, the CCS scale with the polarizability of the gas; this is also the case for higher charge states (12 ≤ z ≤ 22) where the protein is more unfolded for the heavy gases (neon, argon, and nitrogen) but not the case for helium. This is here interpreted as a different conformational landscape being sampled by the lighter gas and potentially attributable to increased field heating by helium. Under nanoelectrospray ionization (nESI) conditions, where myoglobin is sprayed from an aqueous solution buffered to pH 6.8 with 20 mM ammonium acetate, in the DT IM-MS instrument, each buffer gas can yield a different arrival time distribution (ATD) for any given charge state.

Magnetic molecularly imprinted polymers for the selective determination of cocaine by ion mobility spectrometry.

PubMed

Sorribes-Soriano, Aitor; Esteve-Turrillas, Francesc Albert; Armenta, Sergio; Montoya, Ana; Herrero-Martínez, José Manuel; de la Guardia, Miguel

2018-04-13

Magnetic molecularly imprinted polymers (MMIPs) were prepared for cocaine recognition by bulk polymerization in the presence of magnetic nanoparticles (MNPs). Two reagents (polyethylene glycol (PEG) and 3-(trimethoxysilyl)propyl methacrylate (V)) were used for MNPs modification. MMIPs were characterized and compared in terms of loading capacity, reusability, accuracy and precision for the extraction of cocaine from saliva samples. It was observed that V-MMIPs gave higher physical stability than PEG-MMIPs. Thus, V-MMIP were used for the analysis of cocaine users saliva. The developed procedure based on ion mobility spectrometry (IMS) provided limits of detection and quantification of 4 and 14 μg L -1 , respectively, and recoveries in cocaine free saliva samples spiked at 80, 270 and 560 μg L -1 ranging from 80 to 99%. Results found by the proposed method were statistically comparable to those obtained by two reference procedures; a lateral flow immunoassay and an ultra-high performance liquid chromatography coupled with tandem mass spectrometry. Therefore, MMIP-IMS can be considered as a fast, selective and sensitive alternative to reference methods with affordable cost avoiding the requirement of skilled operator. Copyright © 2018 Elsevier B.V. All rights reserved.

In-Source Reduction of Disulfide-Bonded Peptides Monitored by Ion Mobility Mass Spectrometry

NASA Astrophysics Data System (ADS)

Stocks, Bradley B.; Melanson, Jeremy E.

2018-02-01

Many peptides with antimicrobial activity and/or therapeutic potential contain disulfide bonds as a means to enhance stability, and their quantitation is often performed using electrospray ionization mass spectrometry (ESI-MS). Disulfides can be reduced during ESI under commonly used instrument conditions, which has the potential to hinder accurate peptide quantitation. We demonstrate that this in-source reduction (ISR) is predominantly observed for peptides infused from acidic solutions and subjected to elevated ESI voltages (3-4 kV). ISR is readily apparent in the mass spectrum of oxytocin—a small, single disulfide-containing peptide. However, subtle m/z shifts due to partial ISR of highly charged (z ≥ 3) peptides with multiple disulfide linkages may proceed unnoticed. Ion mobility (IM)-MS separates ions on the basis of charge and shape in the gas phase, and using insulin as a model system, we show that IM-MS arrival time distributions (ATDs) are particularly sensitive to partial ISR of large peptides. Isotope modeling allows for the relative quantitation of disulfide-intact and partially reduced states of the mobility-separated peptide conformers. Interestingly, hepcidin peptides ionized from acidic solutions at elevated ESI voltages undergo gas-phase compaction, ostensibly due to partial disulfide ISR. Our IM-MS results lead us to propose that residual acid is the likely cause of disparate ATDs recently measured for hepcidin from different suppliers [Anal. Bioanal. Chem. 409, 2559-2567 (2017)]. Overall, our results demonstrate the utility of IM-MS to detect partial ISR of disulfide-bonded peptides and reinforce the notion that peptide/protein measurements should be carried out using minimally activating instrument conditions. [Figure not available: see fulltext.

Measurement of drug facilitated sexual assault agents in simulated sweat by ion mobility spectrometry.

PubMed

Demoranville, Leonard T; Verkouteren, Jennifer R

2013-03-15

Ion mobility spectrometry has found widespread use for the detection of explosives and illicit drugs. The technique offers rapid results with high sensitivity and little sample preparation. As such, it is well suited for field deployed screening settings. Here the response of ion mobility spectrometers for three drug-facilitated sexual assault (DFSA) agents - flunitrazepam, ketamine, and MDMA - and related metabolites has been studied in the presence of a simulated sweat. While all three DFSA agents present certain challenges for qualitative identification, IMS can provide useful information to guide the early treatment and investigation of sexual assault cases. Used as a presumptive test, the identification of DFSA agents would later require confirmatory analysis by other techniques. Published by Elsevier B.V.

Multiple Gas-Phase Conformations of a Synthetic Linear Poly(acrylamide) Polymer Observed Using Ion Mobility-Mass Spectrometry.

PubMed

Haler, Jean R N; Far, Johann; Aqil, Abdelhafid; Claereboudt, Jan; Tomczyk, Nick; Giles, Kevin; Jérôme, Christine; De Pauw, Edwin

2017-11-01

Ion mobility-mass spectrometry (IM-MS) has emerged as a powerful separation and identification tool to characterize synthetic polymer mixtures and topologies (linear, cyclic, star-shaped,…). Electrospray coupled to IM-MS already revealed the coexistence of several charge state-dependent conformations for a single charge state of biomolecules with strong intramolecular interactions, even when limited resolving power IM-MS instruments were used. For synthetic polymers, the sample's polydispersity allows the observation of several chain lengths. A unique collision cross-section (CCS) trend is usually observed when increasing the degree of polymerization (DP) at constant charge state, allowing the deciphering of different polymer topologies. In this paper, we report multiple coexisting CCS trends when increasing the DP at constant charge state for linear poly(acrylamide) PAAm in the gas phase. This is similar to observations on peptides and proteins. Biomolecules show in addition population changes when collisionally heating the ions. In the case of synthetic PAAm, fragmentation occurred before reaching the energy for conformation conversion. These observations, which were made on two different IM-MS instruments (SYNAPT G2 HDMS and high resolution multi-pass cyclic T-Wave prototype from Waters), limit the use of ion mobility for synthetic polymer topology interpretations to polymers where unique CCS values are observed for each DP at constant charge state. Graphical Abstract ᅟ.

Multiple Gas-Phase Conformations of a Synthetic Linear Poly(acrylamide) Polymer Observed Using Ion Mobility-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Haler, Jean R. N.; Far, Johann; Aqil, Abdelhafid; Claereboudt, Jan; Tomczyk, Nick; Giles, Kevin; Jérôme, Christine; De Pauw, Edwin

2017-08-01

Ion mobility-mass spectrometry (IM-MS) has emerged as a powerful separation and identification tool to characterize synthetic polymer mixtures and topologies (linear, cyclic, star-shaped,…). Electrospray coupled to IM-MS already revealed the coexistence of several charge state-dependent conformations for a single charge state of biomolecules with strong intramolecular interactions, even when limited resolving power IM-MS instruments were used. For synthetic polymers, the sample's polydispersity allows the observation of several chain lengths. A unique collision cross-section (CCS) trend is usually observed when increasing the degree of polymerization (DP) at constant charge state, allowing the deciphering of different polymer topologies. In this paper, we report multiple coexisting CCS trends when increasing the DP at constant charge state for linear poly(acrylamide) PAAm in the gas phase. This is similar to observations on peptides and proteins. Biomolecules show in addition population changes when collisionally heating the ions. In the case of synthetic PAAm, fragmentation occurred before reaching the energy for conformation conversion. These observations, which were made on two different IM-MS instruments (SYNAPT G2 HDMS and high resolution multi-pass cyclic T-Wave prototype from Waters), limit the use of ion mobility for synthetic polymer topology interpretations to polymers where unique CCS values are observed for each DP at constant charge state. [Figure not available: see fulltext.

Correlation ion mobility spectroscopy

DOEpatents

Pfeifer, Kent B [Los Lunas, NM; Rohde, Steven B [Corrales, NM

2008-08-26

Correlation ion mobility spectrometry (CIMS) uses gating modulation and correlation signal processing to improve IMS instrument performance. Closely spaced ion peaks can be resolved by adding discriminating codes to the gate and matched filtering for the received ion current signal, thereby improving sensitivity and resolution of an ion mobility spectrometer. CIMS can be used to improve the signal-to-noise ratio even for transient chemical samples. CIMS is especially advantageous for small geometry IMS drift tubes that can otherwise have poor resolution due to their small size.

Experimental and Theoretical Investigation of Sodiated Multimers of Steroid Epimers with Ion Mobility-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Chouinard, Christopher D.; Cruzeiro, Vinícius Wilian D.; Roitberg, Adrian E.; Yost, Richard A.

2017-02-01

Ion mobility-mass spectrometry (IM-MS) has recently seen increased use in the analysis of small molecules, especially in the field of metabolomics, for increased breadth of information and improved separation of isomers. In this study, steroid epimers androsterone and trans-androsterone were analyzed with IM-MS to investigate differences in their relative mobilities. Although sodiated monomers exhibited very similar collision cross-sections (CCS), baseline separation was observed for the sodiated dimer species (RS = 1.81), with measured CCS of 242.6 and 256.3 Å2, respectively. Theoretical modeling was performed to determine the most energetically stable structures of solution-phase and gas-phase monomer and dimer structures. It was revealed that these epimers differ in their preferred dimer binding mode in solution phase: androsterone adopts a R=O - Na+ - OH—R' configuration, whereas trans-androsterone adopts a R=O - Na+ - O=R' configuration. This difference contributes to a significant structural variation, and subsequent CCS calculations based on these structures relaxed in the gas phase were in agreement with experimentally measured values (ΔCCS 5%). Additionally, these calculations accurately predicted the relative difference in mobility between the epimers. This study illustrates the power of combining experimental and theoretical results to better elucidate gas-phase structures.

Evaluation of Gas Chromatography/Mini-IMS to Detect VOCs

NASA Technical Reports Server (NTRS)

Limero, Thomas; Reese, Eric; Peters, Randy; James, John T.; Billica, Roger (Technical Monitor)

1999-01-01

The Toxicology Laboratory at Johnson Space Center (JSC) has pioneered the use of gas chromatography-ion mobility spectrometry (GC/IMS) for measuring target volatile organic compounds (VOCs) aboard spacecraft. Graseby Dynamics, under contract to NASA/Wyle, has built several volatile organic analyzers (VOA) based on GC/IMS. Foremost among these have been the volatile organic analyzer-risk mitigation unit and the two flight VOA units for International Space Station (ISS). The development and evaluation of these instruments has been chronicled through presentations at the International Conference on Ion Mobility Spectrometry over the past three years. As the flight VOA from Graseby is prepared for operation on ISS at JSC, it is time to begin evaluations of technologies for the next generation VOA, Although the desired instrument characteristics for the next generation unit are the same as the current unit, the requirements are much more stringent. As NASA looks toward future missions beyond Earth environs, a premium will be placed upon small, light, reliable, autonomous hardware. It is with these visions in mind that the JSC Toxicology Laboratory began a search for the next generation VOA. One technology that is a candidate for the next generation VOA is GC/IMS. The recent miniaturization of IMS technology permits it to compete with other, inherently small, technologies such as chip-sized sensor arrays. This paper will discuss the lessons learned from the VOA experience and how that has shaped the design of a potential second generation VOA based upon GC/IMS technology. Data will be presented from preliminary evaluations of GC technology and the mini-IMS when exposed to VOCs likely to be detected aboard spacecraft. Results from the evaluation of an integrated GC/mini-IMS system will be shown if available.

A novel approach to increasing cocaine detection confidence utilizing ion mobility spectrometry

NASA Technical Reports Server (NTRS)

Jadamec, J. Richard; Su, Chih-Wu; Rigdon, Stephen; Norwood, Lavan

1995-01-01

When a positive detection of a narcotic occurs during the search of a vessel, a decision has to be made whether further intensive search is warranted. In terms of unwarranted delays of vessels and possible property damage, the accuracy of the analytical determination is very important. Analytical accuracy becomes critical when the data may be used in court actions as evidence. For this purpose, the U.S. Coast Guard has been investigating several confirmatory ion mobility spectrometry (IMS) field methods for the detection and identification of cocaine. This paper presents the findings of our investigations on the use of catalytic pyrolysis and base hydrolysis as confirmatory methods. The catalytic effects of various metals on the pyrolysis reaction are reported. In addition, the effects of several different ion mobility spectrometer sample transfer mediums and varying laboratory conditions on the base hydrolysis of the cocaine molecule are also be reported.

Gas-Phase Dopant-Induced Conformational Changes Monitored with Transversal Modulation Ion Mobility Spectrometry.

PubMed

Meyer, Nicole Andrea; Root, Katharina; Zenobi, Renato; Vidal-de-Miguel, Guillermo

2016-02-16

The potential of a Transversal Modulation Ion Mobility Spectrometry (TMIMS) instrument for protein analysis applications has been evaluated. The Collision Cross Section (CCS) of cytochrome c measured with the TMIMS is in agreement with values reported in the literature. Additionally, it enables tandem IMS-IMS prefiltration in dry gas and in vapor doped gas. The chemical specificity of the different dopants enables interesting studies on the structure of proteins as CCS changed strongly depending on the specific dopant. Hexane produced an unexpectedly high CCS shift, which can be utilized to evaluate the exposure of hydrophobic parts of the protein. Alcohols produced higher shifts with a dual behavior: an increase in CCS due to vapor uptake at specific absorption sites, followed by a linear shift typical for unspecific and unstable vapor uptake. The molten globule +8 shows a very specific transition. Initially, its CCS follows the trend of the compact folded states, and then it rapidly increases to the levels of the unfolded states. This strong variation suggests that the +8 charge state undergoes a dopant-induced conformational change. Interestingly, more sterically demanding alcohols seem to unfold the protein more effectively also in the gas phase. This study shows the capabilities of the TMIMS device for protein analysis and how tandem IMS-IMS with dopants could provide better understanding of the conformational changes of proteins.

An IMS-Based Middleware Solution for Energy-Efficient and Cost-Effective Mobile Multimedia Services

NASA Astrophysics Data System (ADS)

Bellavista, Paolo; Corradi, Antonio; Foschini, Luca

Mobile multimedia services have recently become of extreme industrial relevance due to the advances in both wireless client devices and multimedia communications. That has motivated important standardization efforts, such as the IP Multimedia Subsystem (IMS) to support session control, mobility, and interoperability in all-IP next generation networks. Notwithstanding the central role of IMS in novel mobile multimedia, the potential of IMS-based service composition for the development of new classes of ready-to-use, energy-efficient, and cost-effective services is still widely unexplored. The paper proposes an original solution for the dynamic and standard-compliant redirection of incoming voice calls towards WiFi-equipped smart phones. The primary design guideline is to reduce energy consumption and service costs for the final user by automatically switching from the 3G to the WiFi infrastructure whenever possible. The proposal is fully compliant with the IMS standard and exploits the recently released IMS presence service to update device location and current communication opportunities. The reported experimental results point out that our solution, in a simple way and with full compliance with state-of-the-art industrially-accepted standards, can significantly increase battery lifetime without negative effects on call initiation delay.

Ion mobility spectrometry as a detector for molecular imprinted polymer separation and metronidazole determination in pharmaceutical and human serum samples.

PubMed

Jafari, M T; Rezaei, B; Zaker, B

2009-05-01

Application of ion mobility spectrometry (IMS) as the detection technique for a separation method based on molecular imprinted polymer (MIP) was investigated and evaluated for the first time. On the basis of the results obtained in this work, the MIP-IMS system can be used as a powerful technique for separation, preconcentration, and detection of the metronidazole drug in pharmaceutical and human serum samples. The method is exhaustively validated in terms of sensitivity, selectivity, recovery, reproducibility, and column capacity. The linear dynamic range of 0.05-70.00 microg/mL was obtained for the determination of metronidazole with IMS. The recovery of analyzed drug was calculated to be above 89%, and the relative standard deviation (RSD) was lower than 6% for all experiments. Various real samples were analyzed with the coupled techniques, and the results obtained revealed the efficient cleanup of the samples using MIP separation before the analysis by IMS as a detection technique.

A critical review of ion mobility spectrometry for the detection of explosives and explosive related compounds.

PubMed

Ewing, R G; Atkinson, D A; Eiceman, G A; Ewing, G J

2001-05-10

Ion mobility spectrometry has become the most successful and widely used technology for the detection of trace levels of nitro-organic explosives on handbags and carry on-luggage in airports throughout the US. The low detection limits are provided by the efficient ionization process, namely, atmospheric pressure chemical ionization (APCI) reactions in negative polarity. An additional level of confidence in a measurement is imparted by characterization of ions for mobilities in weak electric fields of a drift tube at ambient pressure. Findings from over 30 years of investigations into IMS response to these explosives have been collected and assessed to allow a comprehensive view of the APCI reactions characteristic of nitro-organic explosives. Also, the drift tube conditions needed to obtain particular mobility spectra have been summarized. During the past decade, improvements have occurred in IMS on the understanding of reagent gas chemistries, the influence of temperature on ion stability, and sampling methods. In addition, commercial instruments have been refined to provide fast and reliable measurements for on-site detection of explosives. The gas phase ion chemistry of most explosives is mediated by the fragile CONO(2) bonds or the acidity of protons. Thus, M(-) or M.Cl(-) species are found with only a few explosives and loss of NO(2), NO(3) and proton abstraction reactions are common and complicating pathways. However, once ions are formed, they appear to have stabilities on time scales equal to or longer than ion drift times from 5-20 ms. As such, peak shapes in IMS are suitable for high selectivity and sensitivity.

Effect of charge on the conformation of highly basic peptides including the tail regions of histone proteins by ion mobility mass spectrometry.

PubMed

Akashi, Satoko; Downard, Kevin M

2016-09-01

The first systematic and comprehensive study of the charging behaviour and effect of charge on the conformation of specifically constructed arginine-rich peptides and its significance to the N- and C-terminal basic tail regions of histone proteins was conducted using ion mobility mass spectrometry (IM-MS). Among the basic amino acids, arginine has the greatest impact on the charging behaviour and structures of gas phase ions by virtue of its high proton affinity. A close linear correlation was found between either the maximum charge, or most abundant charge state, that the peptides support and their average collision cross section (CCS) values measured by ion mobility mass spectrometry. The calculated collision cross sections for the lowest energy solution state models predicted by the PEP-FOLD algorithm using a modified MOBCAL trajectory method were found to best correlate with the values measured by IM-MS. In the case of the histone peptides, more compact folded structures, supporting less than the maximum number of charges, were observed. These results are consistent with those previously reported for histone dimers where neutralization of the charge at the basic residues of the tail regions did not affect their CCS values.

Feasibility of corona discharge ion mobility spectrometry for direct analysis of samples extracted by dispersive liquid-liquid microextraction.

PubMed

Jafari, Mohammad T; Riahi, Farhad

2014-05-23

The capability of corona discharge ionization ion mobility spectrometry (CD-IMS) for direct analysis of the samples extracted by dispersive liquid-liquid microextraction (DLLME) was investigated and evaluated, for the first time. To that end, an appropriate new injection port was designed and constructed, resulting in possibility of direct injection of the known sample volume, without tedious sample preparation steps (e.g. derivatization, solvent evaporation, and re-solving in another solvent…). Malathion as a test compound was extracted from different matrices by a rapid and convenient DLLME method. The positive ion mobility spectra of the extracted malathion were obtained after direct injection of carbon tetrachloride or methanol solutions. The analyte responses were compared and the statistical results revealed the feasibility of direct analysis of the extracted samples in carbon tetrachloride, resulting in a convenient methodology. The coupled method of DLLME-CD-IMS was exhaustively validated in terms of sensitivity, dynamic range, recovery, and enrichment factor. Finally, various real samples of apple, river and underground water were analyzed, all verifying the feasibility and success of the proposed method for the easy extraction of the analyte using DLLME separation before the direct analysis by CD-IMS. Copyright © 2014 Elsevier B.V. All rights reserved.

Direct antigen detection from immunoprecipitated beads using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; a new method for immunobeads-mass spectrometry (iMS).

PubMed

Shimada, Takashi; Toyama, Atsuhiko; Aoki, Chikage; Aoki, Yutaka; Tanaka, Koichi; Sato, Taka-Aki

2011-12-15

One-step detection of biological molecules is one of the principal techniques for clinical diagnosis, and the potential of mass spectrometry for biomarker detection has been a promising new approach in the field of medical sciences. We demonstrate here a new and high-sensitivity method that we termed immunobeads-mass spectrometry (iMS), which combines conventional immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The key feature of iMS is the MS-compatible condition of immunoprecipitation using detergents with a monosaccaride-C8 alkyl chain or a disaccharide-C10 alkyl chain, and the minimized number of steps required for high-sensitivity detection of target peptides in serum or biological fluid. This was achieved by optimizing the wash buffer and subjecting the immunobeads directly to MALDI-TOF MS analysis. Using this method, we showed that 1 fmol of amyloid beta peptide spiked in serum was readily detectable, demonstrating the powerful tool of iMS as a biomarker detection method. Copyright © 2011 John Wiley & Sons, Ltd.

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burnum-Johnson, Kristin E.; Nie, Song; Casey, Cameron P.

Current proteomics approaches are comprised of both broad discovery measurements as well as more quantitative targeted measurements. These two different measurement types are used to initially identify potentially important proteins (e.g., candidate biomarkers) and then enable improved quantification for a limited number of selected proteins. However, both approaches suffer from limitations, particularly the lower sensitivity, accuracy, and quantitation precision for discovery approaches compared to targeted approaches, and the limited proteome coverage provided by targeted approaches. Herein, we describe a new proteomics approach that allows both discovery and targeted monitoring (DTM) in a single analysis using liquid chromatography, ion mobility spectrometrymore » and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled peptides for target ions are spiked into tryptic digests and both the labeled and unlabeled peptides are broadly detected using LC-IMS-MS instrumentation, allowing the benefits of discovery and targeted approaches. To understand the possible improvement of the DTM approach, it was compared to LC-MS broad measurements using an accurate mass and time tag database and selected reaction monitoring (SRM) targeted measurements. The DTM results yielded greater peptide/protein coverage and a significant improvement in the detection of lower abundance species compared to LC-MS discovery measurements. DTM was also observed to have similar detection limits as SRM for the targeted measurements indicating its potential for combining the discovery and targeted approaches.« less

Feasibility of Higher-Order Differential Ion Mobility Separations Using New Asymmetric Waveforms

PubMed Central

Shvartsburg, Alexandre A.; Mashkevich, Stefan V.; Smith, Richard D.

2011-01-01

Technologies for separating and characterizing ions based on their transport properties in gases have been around for three decades. The early method of ion mobility spectrometry (IMS) distinguished ions by absolute mobility that depends on the collision cross section with buffer gas atoms. The more recent technique of field asymmetric waveform IMS (FAIMS) measures the difference between mobilities at high and low electric fields. Coupling IMS and FAIMS to soft ionization sources and mass spectrometry (MS) has greatly expanded their utility, enabling new applications in biomedical and nanomaterials research. Here, we show that time-dependent electric fields comprising more than two intensity levels could, in principle, effect an infinite number of distinct differential separations based on the higher-order terms of expression for ion mobility. These analyses could employ the hardware and operational procedures similar to those utilized in FAIMS. Methods up to the 4th or 5th order (where conventional IMS is 1st order and FAIMS is 2nd order) should be practical at field intensities accessible in ambient air, with still higher orders potentially achievable in insulating gases. Available experimental data suggest that higher-order separations should be largely orthogonal to each other and to FAIMS, IMS, and MS. PMID:16494377

Determination of ion mobility collision cross sections for unresolved isomeric mixtures using tandem mass spectrometry and chemometric deconvolution.

PubMed

Harper, Brett; Neumann, Elizabeth K; Stow, Sarah M; May, Jody C; McLean, John A; Solouki, Touradj

2016-10-05

Ion mobility (IM) is an important analytical technique for determining ion collision cross section (CCS) values in the gas-phase and gaining insight into molecular structures and conformations. However, limited instrument resolving powers for IM may restrict adequate characterization of conformationally similar ions, such as structural isomers, and reduce the accuracy of IM-based CCS calculations. Recently, we introduced an automated technique for extracting "pure" IM and collision-induced dissociation (CID) mass spectra of IM overlapping species using chemometric deconvolution of post-IM/CID mass spectrometry (MS) data [J. Am. Soc. Mass Spectrom., 2014, 25, 1810-1819]. Here we extend those capabilities to demonstrate how extracted IM profiles can be used to calculate accurate CCS values of peptide isomer ions which are not fully resolved by IM. We show that CCS values obtained from deconvoluted IM spectra match with CCS values measured from the individually analyzed corresponding peptides on uniform field IM instrumentation. We introduce an approach that utilizes experimentally determined IM arrival time (AT) "shift factors" to compensate for ion acceleration variations during post-IM/CID and significantly improve the accuracy of the calculated CCS values. Also, we discuss details of this IM deconvolution approach and compare empirical CCS values from traveling wave (TW)IM-MS and drift tube (DT)IM-MS with theoretically calculated CCS values using the projected superposition approximation (PSA). For example, experimentally measured deconvoluted TWIM-MS mean CCS values for doubly-protonated RYGGFM, RMFGYG, MFRYGG, and FRMYGG peptide isomers were 288.8 Å(2), 295.1 Å(2), 296.8 Å(2), and 300.1 Å(2); all four of these CCS values were within 1.5% of independently measured DTIM-MS values. Copyright © 2016 Elsevier B.V. All rights reserved.

Identity confirmation of drugs and explosives in ion mobility spectrometry using a secondary drift gas.

PubMed

Kanu, Abu B; Hill, Herbert H

2007-10-15

This work demonstrated the potential of using a secondary drift gas of differing polarizability from the primary drift gas for confirmation of a positive response for drugs or explosives by ion mobility spectrometry (IMS). The gas phase mobilities of response ions for selected drugs and explosives were measured in four drift gases. The drift gases chosen for this study were air, nitrogen, carbon dioxide and nitrous oxide providing a range of polarizability and molecular weights. Four other drift gases (helium, neon, argon and sulfur hexafluoride) were also investigated but design limitations of the commercial instrument prevented their use for this application. When ion mobility was plotted against drift gas polarizability, the resulting slopes were often unique for individual ions, indicating that selectivity factors between any two analytes varied with the choice of drift gas. In some cases, drugs like THC and heroin, which are unresolved in air or nitrogen, were well resolved in carbon dioxide or nitrous oxide.

Rapid screening of 35 new psychoactive substances by ion mobility spectrometry (IMS) and direct analysis in real time (DART) coupled to quadrupole time-of-flight mass spectrometry (QTOF-MS).

PubMed

Gwak, Seongshin; Almirall, Jose R

2015-10-01

The recent propagation of new psychoactive substances (NPS) has led to the development of new techniques for the rapid characterization of controlled substances in this category. A commercial bench-top ion mobility spectrometer (IMS) with a (63) Ni ionization source and a direct analysis in real time (DART) coupled to quadrupole time-of-flight (QTOF) were used for the rapid characterization of 35 NPS. The advantages of these techniques are fast response, ease of operation, and minimal sample preparation. The characteristic reduced mobilities of each substance are reported as are the mass spectra of the 35 compounds. The acquired product ion scan mass spectra were also compared to a library database constructed by QTOF with a electrospray ionization (ESI) source and showed a consistent relative abundance for each peak over time. A total of four seized drug samples provided by the local forensic laboratory were analyzed in order to demonstrate the utility of this approach. The results of this study suggest that both IMS and DART-QTOF are promising alternatives for the rapid screening and characterization of these new psychoactive substances. Copyright © 2015 John Wiley & Sons, Ltd.

Mitigation of solvent interference using a short packed column prior to ion mobility spectrometry.

PubMed

Jafari, Mohammad T; Saraji, Mohammad; Mossaddegh, Mehdi

2017-05-15

This paper introduces a novel approach to overcome the solvent interference in corona discharge-ion mobility spectrometry (CD-IMS) based on the time-resolved signals of the solvent and the analyte. To that end, a short Teflon tube was filled with a low amount of squalene or OV-1, which was prepared and located between the injection port and the entrance of the CD-IMS cell. Through this procedure, a sufficient delay (~5s) was obtained between the introduction of the solvent and the analyte into the reaction region of IMS. This resulted in removing the proton by solvent molecules, as well as increasing the effective collision during the analyte ionization, thereby providing an analysis with more sensitivity, accuracy, and precision. To show the column efficiency, ethion and diazinon (organophosphorus pesticides) were selected as the test compounds and their solutions were analyzed by the proposed method. The amount of sorbent, carrier gas flow rate, and the sorbent temperature affecting the sorbent efficiency were optimized by employing the response surface methodology and the central composite design. The proposed method was exhaustively validated in terms of sensitivity, linearity, and repeatability. In particular, the feasibility of direct injection was successfully verified by the satisfactory results, as compared with those achieved without the prior column. The methodology used in this study is very simple and inexpensive, which can overcome the solvent interference when a solution is directly injected into the CD-IMS. Copyright © 2017 Elsevier B.V. All rights reserved.

Coming to Grips with Ambiguity: Ion Mobility-Mass Spectrometry for Protein Quaternary Structure Assignment

NASA Astrophysics Data System (ADS)

Eschweiler, Joseph D.; Frank, Aaron T.; Ruotolo, Brandon T.

2017-10-01

Multiprotein complexes are central to our understanding of cellular biology, as they play critical roles in nearly every biological process. Despite many impressive advances associated with structural characterization techniques, large and highly-dynamic protein complexes are too often refractory to analysis by conventional, high-resolution approaches. To fill this gap, ion mobility-mass spectrometry (IM-MS) methods have emerged as a promising approach for characterizing the structures of challenging assemblies due in large part to the ability of these methods to characterize the composition, connectivity, and topology of large, labile complexes. In this Critical Insight, we present a series of bioinformatics studies aimed at assessing the information content of IM-MS datasets for building models of multiprotein structure. Our computational data highlights the limits of current coarse-graining approaches, and compelled us to develop an improved workflow for multiprotein topology modeling, which we benchmark against a subset of the multiprotein complexes within the PDB. This improved workflow has allowed us to ascertain both the minimal experimental restraint sets required for generation of high-confidence multiprotein topologies, and quantify the ambiguity in models where insufficient IM-MS information is available. We conclude by projecting the future of IM-MS in the context of protein quaternary structure assignment, where we predict that a more complete knowledge of the ultimate information content and ambiguity within such models will undoubtedly lead to applications for a broader array of challenging biomolecular assemblies. [Figure not available: see fulltext.

Demonstrated Potential of Ion Mobility Spectrometry for Detection of Adulterated Perfumes and Plant Speciation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, Jared Matthew; Daum, Keith Alvin; Kalival, J. H.

2003-01-01

This initial study evaluates the use of ion mobility spectrometry (IMS) as a rapid test procedure for potential detection of adulterated perfumes and speciation of plant life. Sample types measured consist of five genuine perfumes, two species of sagebrush, and four species of flowers. Each sample type is treated as a separate classification problem. It is shown that discrimination using principal component analysis with K-nearest neighbors can distinguish one class from another. Discriminatory models generated using principal component regressions are not as effective. Results from this examination are encouraging and represent an initial phase demonstrating that perfumes and plants possessmore » characteristic chemical signatures that can be used for reliable identification.« less

Laser desorption with corona discharge ion mobility spectrometry for direct surface detection of explosives.

PubMed

Sabo, M; Malásková, M; Matejčík, S

2014-10-21

We present a new highly sensitive technique for the detection of explosives directly from the surface using laser desorption-corona discharge-ion mobility spectrometry (LD-CD-IMS). We have developed LD based on laser diode modules (LDM) and the technique was tested using three different LDM (445, 532 and 665 nm). The explosives were detected directly from the surface without any further preparation. We discuss the mechanism of the LD and the limitations of this technique such as desorption time, transport time and desorption area. After the evaluation of experimental data, we estimated the potential limits of detection of this method to be 0.6 pg for TNT, 2.8 pg for RDX and 8.4 pg for PETN.

Ion mobility-mass spectrometry reveals conformational flexibility in the deubiquitinating enzyme USP5.

PubMed

Scott, Daniel; Layfield, Robert; Oldham, Neil J

2015-08-01

Many proteins exhibit conformation flexibility as part of their biological function, whether through the presence of a series of well-defined states or by the existence of intrinsic disorder. Ion mobility spectrometry, in combination with MS (IM-MS), offers a rapid and sensitive means of probing ensembles of protein structures through measurement of gas-phase collisional cross sections. We have applied IM-MS analysis to the multidomain deubiquitinating enzyme ubiquitin specific protease 5 (USP5), which is believed to exhibit significant conformational flexibility. Native ESI-MS measurement of the 94-kDa USP5 revealed two distinct charge-state distributions: [M + 17H](+) to [M + 21H](+) and [M + 24H](+) to [M + 29H](+). The collisional cross sections of these ions revealed clear groupings of 52 ± 4 nm(2) for the lower charges and 66 ± 6 nm(2) for the higher charges. Molecular dynamics simulation of a compact form of USP5, based on a crystal structure, produced structures of 53-54 nm(2) following 2 ns in the gas phase, while simulation of an extended form (based on small-angle X-ray scattering data) led to structures of 64 nm(2). These data demonstrate that IM-MS is a valuable tool in studying proteins with different discrete conformational states. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of Different Ion Mobility Setups Using Poly (Ethylene Oxide) PEO Polymers: Drift Tube, TIMS, and T-Wave

NASA Astrophysics Data System (ADS)

Haler, Jean R. N.; Massonnet, Philippe; Chirot, Fabien; Kune, Christopher; Comby-Zerbino, Clothilde; Jordens, Jan; Honing, Maarten; Mengerink, Ynze; Far, Johann; Dugourd, Philippe; De Pauw, Edwin

2018-01-01

Over the years, polymer analyses using ion mobility-mass spectrometry (IM-MS) measurements have been performed on different ion mobility spectrometry (IMS) setups. In order to be able to compare literature data taken on different IM(-MS) instruments, ion heating and ion temperature evaluations have already been explored. Nevertheless, extrapolations to other analytes are difficult and thus straightforward same-sample instrument comparisons seem to be the only reliable way to make sure that the different IM(-MS) setups do not greatly change the gas-phase behavior. We used a large range of degrees of polymerization (DP) of poly(ethylene oxide) PEO homopolymers to measure IMS drift times on three different IM-MS setups: a homemade drift tube (DT), a trapped (TIMS), and a traveling wave (T-Wave) IMS setup. The drift time evolutions were followed for increasing polymer DPs (masses) and charge states, and they are found to be comparable and reproducible on the three instruments. [Figure not available: see fulltext.

Immobilized aptamer paper spray ionization source for ion mobility spectrometry.

PubMed

Zargar, Tahereh; Khayamian, Taghi; Jafari, Mohammad T

2017-01-05

A selective thin-film microextraction based on aptamer immobilized on cellulose paper was used as a paper spray ionization source for ion mobility spectrometry (PSI-IMS), for the first time. In this method, the paper is not only used as an ionization source but also it is utilized for the selective extraction of analyte, based on immobilized aptamer. This combination integrates both sample preparation and analyte ionization in a Whatman paper. To that end, an appropriate sample introduction system with a novel design was constructed for the paper spray ionization source. Using this system, a continuous solvent flow works as an elution and spray solvent simultaneously. In this method, analyte is adsorbed on a triangular paper with immobilized aptamer and then it is desorbed and ionized by elution solvent and applied high voltage on paper, respectively. The effects of different experimental parameters such as applied voltage, angle of paper tip, distance between paper tip and counter electrode, elution solvent type, and solvent flow rate were optimized. The proposed method was exhaustively validated in terms of sensitivity and reproducibility by analyzing the standard solutions of codeine and acetamiprid. The analytical results obtained are promising enough to ensure the use of immobilized aptamer paper-spray as both the extraction and ionization techniques in IMS for direct analysis of biomedicine. Copyright © 2016 Elsevier B.V. All rights reserved.

Negative corona discharge-ion mobility spectrometry as a detection system for low density extraction solvent-based dispersive liquid-liquid microextraction.

PubMed

Ebrahimi, Amir; Jafari, Mohammad T

2015-03-01

This paper deals with a method based on negative corona discharge ionization ion mobility spectrometry (NCD-IMS) for the analysis of ethion (as an organophosphorus pesticide). The negative ions such as O2(-) and NO(x)(-) were eliminated from the background spectrum to increase the instrument sensitivity. The method was used to specify the sample extracted via dispersive liquid-liquid microextraction (DLLME) based on low density extraction solvent. The ion mobility spectrum of ethion in the negative mode and the reduced mobility value for its ion peak are firstly reported and compared with those of the positive mode. In order to combine the low density solvent DLLME directly with NCD-IMS, cyclohexane was selected as the extraction solvent, helping us to have a direct injection up to 20 µL solution, without any signal interference. The method was exhaustively validated in terms of sensitivity, enrichment factor, relative recovery, and repeatability. The linear dynamic range of 0.2-100.0 µg L(-1), detection limit of 0.075 µg L(-1), and the relative standard deviation (RSD) of about 5% were obtained for the analysis of ethion through this method. The average recoveries were calculated about 68% and 92% for the grape juice and underground water, respectively. Finally, some real samples were analyzed and the feasibility of the proposed method was successfully verified by the efficient extraction of the analyte using DLLME before the analysis by NCD-IMS. Copyright © 2014 Elsevier B.V. All rights reserved.

Application of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Imaging Mass Spectrometry (MALDI-TOF IMS) for Premalignant Gastrointestinal Lesions

PubMed Central

Ko, Kwang Hyun; Kwon, Chang Il; Park, So Hye; Han, Na Young; Lee, Hoo Keun; Kim, Eun Hee

2013-01-01

Imaging mass spectrometry (IMS) is currently receiving large attention from the mass spectrometric community, although its use is not yet well known in the clinic. As matrix-assisted laser desorption/ionization time-of-flight (MALDI)-IMS can show the biomolecular changes in cells as well as tissues, it can be an ideal tool for biomedical diagnostics as well as the molecular diagnosis of clinical specimens, especially aimed at the prompt detection of premalignant lesions much earlier before overt mass formation, or for obtaining histologic clues from endoscopic biopsy. Besides its use for pathologic diagnosis, MALDI-IMS is also a powerful tool for the detection and localization of drugs, proteins, and lipids in tissue. Measurement of parameters that define and control the implications, challenges, and opportunities associated with the application of IMS to biomedical tissue studies might be feasible through a deep understanding of mass spectrometry. In this focused review series, new insights into the molecular processes relevant to IMS as well as other field applications are introduced. PMID:24340253

Lifetimes and stabilities of familiar explosives molecular adduct complexes during ion mobility measurements

PubMed Central

McKenzie, Alan; DeBord, John Daniel; Ridgeway, Mark; Park, Melvin; Eiceman, Gary; Fernandez-Lima, Francisco

2015-01-01

Trapped ion mobility spectrometry coupled to mass spectrometry (TIMS-MS) was utilized for the separation and identification of familiar explosives in complex mixtures. For the first time, molecular adduct complex lifetimes, relative stability, binding energies and candidate structures are reported for familiar explosives. Experimental and theoretical results showed that the adduct size and reactivity, complex binding energy and the explosive structure tailors the stability of the molecular adduct complex. TIMS flexibility to adapt the mobility separation as a function of the molecular adduct complex stability (i.e., short or long IMS experiments / low or high IMS resolution) permits targeted measurements of explosives in complex mixtures with higher confidence levels. PMID:26153567

MALDI Imaging Mass Spectrometry (MALDI-IMS)-application of spatial proteomics for ovarian cancer classification and diagnosis.

PubMed

Gustafsson, Johan O R; Oehler, Martin K; Ruszkiewicz, Andrew; McColl, Shaun R; Hoffmann, Peter

2011-01-21

MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment where relative spatial abundance for potentially hundreds of analytes across virtually any tissue section can be measured. Crucially, imaging can be achieved without prior knowledge of tissue composition and without the use of antibodies. In effect MALDI-IMS allows generation of molecular data which complement and expand upon the information provided by histology including immuno-histochemistry, making its application valuable to both cancer biomarker research and diagnostics. The current state of MALDI-IMS, key biological applications to ovarian cancer research and practical considerations for analysis of peptides and proteins on ovarian tissue are presented in this review.

MALDI (matrix assisted laser desorption ionization) Imaging Mass Spectrometry (IMS) of skin: Aspects of sample preparation.

PubMed

de Macedo, Cristiana Santos; Anderson, David M; Schey, Kevin L

2017-11-01

MALDI (matrix assisted laser desorption ionization) Imaging Mass Spectrometry (IMS) allows molecular analysis of biological materials making possible the identification and localization of molecules in tissues, and has been applied to address many questions on skin pathophysiology, as well as on studies about drug absorption and metabolism. Sample preparation for MALDI IMS is the most important part of the workflow, comprising specimen collection and preservation, tissue embedding, cryosectioning, washing, and matrix application. These steps must be carefully optimized for specific analytes of interest (lipids, proteins, drugs, etc.), representing a challenge for skin analysis. In this review, critical parameters for MALDI IMS sample preparation of skin samples will be described. In addition, specific applications of MALDI IMS of skin samples will be presented including wound healing, neoplasia, and infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Towards metals analysis using corona discharge ionization ion mobility spectrometry.

PubMed

Jafari, Mohammad T; Saraji, Mohammad; Sherafatmand, Hossein

2016-02-25

For the first time, the capability of corona discharge ionization ion mobility spectrometry (CD-IMS) in the determination of metal complex was evaluated. The extreme simplicity of dispersive liquid-liquid microextraction (DLLME) coupled to the high sensitivity of CD-IMS measurement could make this combination really useful for simple, rapid, and sensitive determination of metals in different samples. In this regard, mercury, as a model metal, was complexed with diethyldithiocarbamate (DEDTC), and then extracted into the carbon tetrachloride using DLLME. Some parameters affecting the extraction efficiency, including the type and volume of the extraction solvent, the type and volume of the disperser solvent, the concentration of the chelating agent, salt addition and, pH were exhaustively investigated. Under the optimized condition, the enrichment factor was obtained to be 142. The linear range of 0.035-10.0 μg mL(-1) with r(2) = 0.997 and the detection limit of 0.010 μg mL(-1) were obtained. The relative standard deviation values were calculated to be lower than 4% and 8% for intra-day and inter-day, respectively. Finally, the developed method was successfully applied for the extraction and determination of mercury in various real samples. The satisfactory results revealed the capability of the proposed method in trace analysis without tedious derivatization or hydride generation. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection of aqueous phase chemical warfare agent degradation products by negative mode ion mobility time-of-flight mass spectrometry [IM(tof)MS].

PubMed

Steiner, Wes E; Harden, Charles S; Hong, Feng; Klopsch, Steve J; Hill, Herbert H; McHugh, Vincent M

2006-02-01

The use of negative ion monitoring mode with an atmospheric pressure ion mobility orthogonal reflector time-of-flight mass spectrometer [IM(tof)MS] to detect chemical warfare agent (CWA) degradation products from aqueous phase samples has been determined. Aqueous phase sampling used a traditional electrospray ionization (ESI) source for sample introduction and ionization. Certified reference materials (CRM) of CWA degradation products for the detection of Schedule 1, 2, or 3 toxic chemicals or their precursors as defined by the chemical warfare convention (CWC) treaty verification were used in this study. A mixture of six G-series nerve related CWA degradation products (EMPA, IMPA, EHEP, IHEP, CHMPA, and PMPA) and their related collision induced dissociation (CID) fragment ions (MPA and EPA) were found in each case to be clearly resolved and detected using the IM(tof)MS instrument in negative ion monitoring mode. Corresponding ions, masses, drift times, K(o) values, and signal intensities for each of the CWA degradation products are reported.

Contaminant screening of wastewater with HPLC-IM-qTOF-MS and LC+LC-IM-qTOF-MS using a CCS database.

PubMed

Stephan, Susanne; Hippler, Joerg; Köhler, Timo; Deeb, Ahmad A; Schmidt, Torsten C; Schmitz, Oliver J

2016-09-01

Non-target analysis has become an important tool in the field of water analysis since a broad variety of pollutants from different sources are released to the water cycle. For identification of compounds in such complex samples, liquid chromatography coupled to high resolution mass spectrometry are often used. The introduction of ion mobility spectrometry provides an additional separation dimension and allows determining collision cross sections (CCS) of the analytes as a further physicochemical constant supporting the identification. A CCS database with more than 500 standard substances including drug-like compounds and pesticides was used for CCS data base search in this work. A non-target analysis of a wastewater sample was initially performed with high performance liquid chromatography (HPLC) coupled to an ion mobility-quadrupole-time of flight mass spectrometer (IM-qTOF-MS). A database search including exact mass (±5 ppm) and CCS (±1 %) delivered 22 different compounds. Furthermore, the same sample was analyzed with a two-dimensional LC method, called LC+LC, developed in our group for the coupling to IM-qTOF-MS. This four dimensional separation platform revealed 53 different compounds, identified over exact mass and CCS, in the examined wastewater sample. It is demonstrated that the CCS database can also help to distinguish between isobaric structures exemplified for cyclophosphamide and ifosfamide. Graphical Abstract Scheme of sample analysis and database screening.

MALDI Imaging Mass Spectrometry (MALDI-IMS)—Application of Spatial Proteomics for Ovarian Cancer Classification and Diagnosis

PubMed Central

Gustafsson, Johan O. R.; Oehler, Martin K.; Ruszkiewicz, Andrew; McColl, Shaun R.; Hoffmann, Peter

2011-01-01

MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment where relative spatial abundance for potentially hundreds of analytes across virtually any tissue section can be measured. Crucially, imaging can be achieved without prior knowledge of tissue composition and without the use of antibodies. In effect MALDI-IMS allows generation of molecular data which complement and expand upon the information provided by histology including immuno-histochemistry, making its application valuable to both cancer biomarker research and diagnostics. The current state of MALDI-IMS, key biological applications to ovarian cancer research and practical considerations for analysis of peptides and proteins on ovarian tissue are presented in this review. PMID:21340013

Analysis of model Titan atmospheric components using ion mobility spectrometry

NASA Technical Reports Server (NTRS)

Kojiro, D. R.; Cohen, M. J.; Wernlund, R. F.; Stimac, R. M.; Humphry, D. E.; Takeuchi, N.

1991-01-01

The Gas Chromatograph-Ion Mobility Spectrometer (GC-IMS) was proposed as an analytical technique for the analysis of Titan's atmosphere during the Cassini Mission. The IMS is an atmospheric pressure, chemical detector that produces an identifying spectrum of each chemical species measured. When the IMS is combined with a GC as a GC-IMS, the GC is used to separate the sample into its individual components, or perhaps small groups of components. The IMS is then used to detect, quantify, and identify each sample component. Conventional IMS detection and identification of sample components depends upon a source of energetic radiation, such as beta radiation, which ionizes the atmospheric pressure host gas. This primary ionization initiates a sequence of ion-molecule reactions leading to the formation of sufficiently energetic positive or negative ions, which in turn ionize most constituents in the sample. In conventional IMS, this reaction sequence is dominated by the water cluster ion. However, many of the light hydrocarbons expected in Titan's atmosphere cannot be analyzed by IMS using this mechanism at the concentrations expected. Research at NASA Ames and PCP Inc., has demonstrated IMS analysis of expected Titan atmospheric components, including saturated aliphatic hydrocarbons, using two alternate sample ionizations mechanisms. The sensitivity of the IMS to hydrocarbons such as propane and butane was increased by several orders of magnitude. Both ultra dry (waterless) IMS sample ionization and metastable ionization were successfully used to analyze a model Titan atmospheric gas mixture.

Direct analysis of organic priority pollutants by IMS

NASA Technical Reports Server (NTRS)

Giam, C. S.; Reed, G. E.; Holliday, T. L.; Chang, L.; Rhodes, B. J.

1995-01-01

Many routine methods for monitoring of trace amounts of atmospheric organic pollutants consist of several steps. Typical steps are: (1) collection of the air sample; (2) trapping of organics from the sample; (3) extraction of the trapped organics; and (4) identification of the organics in the extract by GC (gas chromatography), HPLC (High Performance Liquid Chromatography), or MS (Mass Spectrometry). These methods are often cumbersome and time consuming. A simple and fast method for monitoring atmospheric organics using an IMS (Ion Mobility Spectrometer) is proposed. This method has a short sampling time and does not require extraction of the organics since the sample is placed directly in the IMS. The purpose of this study was to determine the responses in the IMS to organic 'priority pollutants'. Priority pollutants including representative polycyclic aromatic hydrocarbons (PAHs), phthalates, phenols, chlorinated pesticides, and polychlorinated biphenyls (PCB's) were analyzed in both the positive and negative detection mode at ambient atmospheric pressure. Detection mode and amount detected are presented.

Mass spectrometric characterization of a high-field asymmetric waveform ion mobility spectrometer

NASA Astrophysics Data System (ADS)

Purves, Randy W.; Guevremont, Roger; Day, Stephen; Pipich, Charles W.; Matyjaszczyk, Matthew S.

1998-12-01

Ion mobility spectrometry (IMS) has become an important method for the detection of many compounds because of its high sensitivity and amenability to miniaturization for field-portable monitoring; applications include detection of narcotics, explosives, and chemical warfare agents. High-field asymmetric waveform ion mobility spectrometry (FAIMS) differs from IMS in that the electric fields are applied using a high-frequency periodic asymmetric waveform, rather than a dc voltage. Furthermore, in FAIMS the compounds are separated by the difference in the mobility of ions at high electric field relative to low field, rather than by compound to compound differences in mobility at low electric field (IMS). We report here the first cylindrical-geometry-FAIMS interface with mass spectrometry (FAIMS-MS) and the MS identification of the peaks observed in a FAIMS compensation voltage (CV) spectrum. Using both an electrometer-based-FAIMS (FAIMS-E) and FAIMS-MS, several variables that affect the sensitivity of ion detection were examined for two (polarity reversed) asymmetric waveforms (modes 1 and 2) each of which yields a unique spectrum. An increase in the dispersion voltage (DV) was found to improve the sensitivity and separation observed in the FAIMS CV spectrum. This increase in sensitivity and the unexpected dissimilarity in modes 1 and 2 suggest that atmospheric pressure ion focusing is occurring in the FAIMS analyzer. The sensitivity and peak locations in the CV spectra were affected by temperature, gas flow rates, operating pressure, and analyte concentration.

Im/mobilities and dis/connectivities in medical globalisation: How global is Global Health?

PubMed

Dilger, Hansjörg; Mattes, Dominik

2018-03-01

The interdisciplinary, politically contested field of Global Health has often been described as a consequence of, and response to, an intensification of the mobilities of, and connectivities between, people, pathogens, ideas, and infrastructure across national borders and large distances. However, such global mobilities and connectivities are not as omnidirectional and unpatterned as the rhetoric of many Global Health actors suggests. Instead, we argue that they are suffused by a plethora of institutional, national, and global political agendas, and substantially shaped by transnational and postcolonial power relations. Furthermore, the configurations that are typically subsumed under the category of Global Health represent only a minor part of the range of im/mobilities and dis/connectivities that are essential for understanding transformations of epidemiological patterns, health care infrastructures, and the responses to health-related challenges in a globalising world. In order to broaden such a limiting analytical perspective, we propose to expand the analytical focus in studying Global Health phenomena by paying close attention to the myriad ways in which particular im/mobilities and dis/connectivities constitute medicine and well-being in global and transnational settings. Pursuing a conceptual shift from studies of 'Global Health' to studying 'medical globalization' may carve out new analytical ground for such an endeavour.

Spatially resolved chemical analysis of cicada wings using laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS).

PubMed

Román, Jessica K; Walsh, Callee M; Oh, Junho; Dana, Catherine E; Hong, Sungmin; Jo, Kyoo D; Alleyne, Marianne; Miljkovic, Nenad; Cropek, Donald M

2018-03-01

Laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS) is an emerging bioanalytical tool for direct imaging and analysis of biological tissues. Performing ionization in an ambient environment, this technique requires little sample preparation and no additional matrix, and can be performed on natural, uneven surfaces. When combined with optical microscopy, the investigation of biological samples by LAESI allows for spatially resolved compositional analysis. We demonstrate here the applicability of LAESI-IMS for the chemical analysis of thin, desiccated biological samples, specifically Neotibicen pruinosus cicada wings. Positive-ion LAESI-IMS accurate ion-map data was acquired from several wing cells and superimposed onto optical images allowing for compositional comparisons across areas of the wing. Various putative chemical identifications were made indicating the presence of hydrocarbons, lipids/esters, amines/amides, and sulfonated/phosphorylated compounds. With the spatial resolution capability, surprising chemical distribution patterns were observed across the cicada wing, which may assist in correlating trends in surface properties with chemical distribution. Observed ions were either (1) equally dispersed across the wing, (2) more concentrated closer to the body of the insect (proximal end), or (3) more concentrated toward the tip of the wing (distal end). These findings demonstrate LAESI-IMS as a tool for the acquisition of spatially resolved chemical information from fragile, dried insect wings. This LAESI-IMS technique has important implications for the study of functional biomaterials, where understanding the correlation between chemical composition, physical structure, and biological function is critical. Graphical abstract Positive-ion laser-ablation electrospray ionization mass spectrometry coupled with optical imaging provides a powerful tool for the spatially resolved chemical analysis of cicada wings.

Chemometric Data Analysis for Deconvolution of Overlapped Ion Mobility Profiles

NASA Astrophysics Data System (ADS)

Zekavat, Behrooz; Solouki, Touradj

2012-11-01

We present the details of a data analysis approach for deconvolution of the ion mobility (IM) overlapped or unresolved species. This approach takes advantage of the ion fragmentation variations as a function of the IM arrival time. The data analysis involves the use of an in-house developed data preprocessing platform for the conversion of the original post-IM/collision-induced dissociation mass spectrometry (post-IM/CID MS) data to a Matlab compatible format for chemometric analysis. We show that principle component analysis (PCA) can be used to examine the post-IM/CID MS profiles for the presence of mobility-overlapped species. Subsequently, using an interactive self-modeling mixture analysis technique, we show how to calculate the total IM spectrum (TIMS) and CID mass spectrum for each component of the IM overlapped mixtures. Moreover, we show that PCA and IM deconvolution techniques provide complementary results to evaluate the validity of the calculated TIMS profiles. We use two binary mixtures with overlapping IM profiles, including (1) a mixture of two non-isobaric peptides (neurotensin (RRPYIL) and a hexapeptide (WHWLQL)), and (2) an isobaric sugar isomer mixture of raffinose and maltotriose, to demonstrate the applicability of the IM deconvolution.

Size, weight and position: ion mobility spectrometry and imaging MS combined.

PubMed

Kiss, András; Heeren, Ron M A

2011-03-01

Size, weight and position are three of the most important parameters that describe a molecule in a biological system. Ion mobility spectrometry is capable of separating molecules on the basis of their size or shape, whereas imaging mass spectrometry is an effective tool to measure the molecular weight and spatial distribution of molecules. Recent developments in both fields enabled the combination of the two technologies. As a result, ion-mobility-based imaging mass spectrometry is gaining more and more popularity as a (bio-)analytical tool enabling the determination of the size, weight and position of several molecules simultaneously on biological surfaces. This paper reviews the evolution of ion-mobility-based imaging mass spectrometry and provides examples of its application in analytical studies of biological surfaces.

Monitoring of selected skin- and breath-borne volatile organic compounds emitted from the human body using gas chromatography ion mobility spectrometry (GC-IMS).

PubMed

Mochalski, Paweł; Wiesenhofer, Helmut; Allers, Maria; Zimmermann, Stefan; Güntner, Andreas T; Pineau, Nicolay J; Lederer, Wolfgang; Agapiou, Agapios; Mayhew, Christopher A; Ruzsanyi, Veronika

2018-02-15

Human smuggling and associated cross-border crimes have evolved as a major challenge for the European Union in recent years. Of particular concern is the increasing trend of smuggling migrants hidden inside shipping containers or trucks. Therefore, there is a growing demand for portable security devices for the non-intrusive and rapid monitoring of containers to detect people hiding inside. In this context, chemical analysis of volatiles organic compounds (VOCs) emitted from the human body is proposed as a locating tool. In the present study, an in-house made ion mobility spectrometer coupled with gas chromatography (GC-IMS) was used to monitor the volatile moieties released from the human body under conditions that mimic entrapment. A total of 17 omnipresent volatile compounds were identified and quantified from 35 ion mobility peaks corresponding to human presence. These are 7 aldehydes (acrolein, 2-methylpropanal, 3-methylbutanal, 2-ethacrolein, n-hexanal, n-heptanal, benzaldehyde), 3 ketones (acetone, 2-pentanone, 4-methyl-2-pentanone), 5 esters (ethyl formate, ethyl propionate, vinyl butyrate, butyl acetate, ethyl isovalerate), one alcohol (2-methyl-1-propanol) and one organic acid (acetic acid). The limits of detection (0.05-7.2 ppb) and relative standard deviations (0.6-11%) should be sufficient for detecting these markers of human presence in field conditions. This study shows that GC-IMS can be used as a portable field detector of hidden or entrapped people. Copyright © 2018 Elsevier B.V. All rights reserved.

Desorption electrospray ionization (DESI) with atmospheric pressure ion mobility spectrometry for drug detection.

PubMed

Roscioli, Kristyn M; Tufariello, Jessica A; Zhang, Xing; Li, Shelly X; Goetz, Gilles H; Cheng, Guilong; Siems, William F; Hill, Herbert H

2014-04-07

Desorption electrospray ionization (DESI) was coupled to an ambient pressure drift tube ion mobility time-of-flight mass spectrometer (IM-TOFMS) for the direct analysis of active ingredients in pharmaceutical samples. The DESI source was also coupled with a standalone IMS demonstrating potential of portable and inexpensive drug-quality testing platforms. The DESI-IMS required no sample pretreatment as ions were generated directly from tablets and cream formulations. The analysis of a range of over-the-counter and prescription tablet formations was demonstrated for amphetamine (methylphenidate), antidepressant (venlafaxine), barbiturate (Barbituric acid), depressant (alprazolam), narcotic (3-methylmorphine) and sympatholytic (propranolol) drugs. Active ingredients from soft and liquid formulations, such as Icy Hot cream (methyl salicylate) and Nyquil cold medicine (acetaminophen, dextromethorphan, doxylamine) were also detected. Increased sensitivity for selective drug responses was demonstrated through the formation of sodiated adduct ions by introducing small quantities of NaCl into the DESI solvent. Of the drugs and pharmaceuticals tested in this study, 68% (22 total samples) provided a clear ion mobility response at characteristic mobilities either as (M + H)(+), (M - H)(-), or (M + Na)(+) ions.

Dopant-assisted negative photoionization Ion mobility spectrometry coupled with on-line cooling inlet for real-time monitoring H2S concentration in sewer gas.

PubMed

Peng, Liying; Jiang, Dandan; Wang, Zhenxin; Hua, Lei; Li, Haiyang

2016-06-01

Malodorous hydrogen sulfide (H2S) gas often exists in the sewer system and associates with the problems of releasing the dangerous odor to the atmosphere and causing sewer pipe to be corroded. A simple method is in demand for real-time measuring H2S level in the sewer gas. In this paper, an innovated method based on dopant-assisted negative photoionization ion mobility spectrometry (DANP-IMS) with on-line semiconductor cooling inlet was put forward and successfully applied for the real-time measurement of H2S in sewer gas. The influence of moisture was effectively reduced via an on-line cooling method and a non-equilibrium dilution with drift gas. The limits of quantitation for the H2S in ≥60% relative humidity air could be obtained at ≤79.0ng L(-1) with linear ranges of 129-2064ng L(-1). The H2S concentration in a sewer manhole was successfully determined while its product ions were identified by an ion-mobility time-of-fight mass spectrometry. Finally, the correlation between sewer H2S concentration and the daily routines and habits of residents was investigated through hourly or real-time monitoring the variation of sewer H2S in manholes, indicating the power of this DANP-IMS method in assessing the H2S concentration in sewer system. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection and characterization of smokeless powders with ion mobility spectrometry

NASA Astrophysics Data System (ADS)

Hernandez, Neiza M.; Rosario, Santa V.; Hernandez, Samuel P.; Mina, Nairmen

2005-05-01

Smokeless Powders are a class of propellants that were developed in the late 19th century to replace black powder; it has been used as an explosive in shotguns, rifles, firearms and many other larger caliber weapons. These propellants can be placed into one of three different classes according to the chemical composition of their primary energetic ingredients. Advance equipment have been designed and used for the detection of explosives devices and compounds potentially energetic. In this research we are developing an analytical methodology to detect different formulation of smokeless powders: Alliant-American Select, Alliant-Bullseye, and Alliant-Red Dot using the ion mobility spectrometry (IMS) technique. We used different surfaces like computer diskettes, CD"s, book covers and plastics to study their adsorption/desorption process. Using micropipettes, we delivered solutions with different amounts of Smokeless Powders from a 1000 ppm solution and deposit it on various types of filters to make a calibration curve. Several amounts of Smokeless Powder were deposited to the different surfaces and collected with filter paper. The samples were desorbed directly from the filter to the instrument inlet port. Subsequently, the percentage of explosive recovered was calculated.

Comparison of reactant and analyte ions for ⁶³Nickel, corona discharge, and secondary electrospray ionization sources with ion mobility-mass spectrometry.

PubMed

Crawford, C L; Hill, H H

2013-03-30

(63)Nickel radioactive ionization ((63)Ni) is the most common and widely used ion source for ion mobility spectrometry (IMS). Regulatory, financial, and operational concerns with this source have promoted recent development of non-radioactive sources, such as corona discharge ionization (CD), for stand-alone IMS systems. However, there has been no comparison of the negative ion species produced by all three sources in the literature. This study compares the negative reactant and analyte ions produced by three sources on an ion mobility-mass spectrometer: conventional (63)Ni, CD, and secondary electrospray ionization (SESI). Results showed that (63)Ni and SESI produced the same reactant ion species while CD produced only the nitrate monomer and dimer ions. The analyte ions produced by each ion source were the same except for the CD source which produced a different ion species for the explosive RDX than either the (63)Ni or SESI source. Accurate and reproducible reduced mobility (K0) values, including several values reported here for the first time, were found for each explosive with each ion source. Overall, the SESI source most closely reproduced the reactant ion species and analyte ion species profiles for (63)Ni. This source may serve as a non-radioactive, robust, and flexible alternative for (63)Ni. Copyright © 2013 Elsevier B.V. All rights reserved.

Mobility-Resolved Ion Selection in Uniform Drift Field Ion Mobility Spectrometry/Mass Spectrometry: Dynamic Switching in Structures for Lossless Ion Manipulations

DOE PAGES

Webb, Ian K.; Garimella, Sandilya V. B.; Tolmachev, Aleksey V.; ...

2014-09-15

A Structures for Lossless Ion Manipulations (SLIM) module that allows ion mobility separations and the switching of ions between alternative drift paths is described. The SLIM switch component has a “Tee” configuration and allows switching of ions between a linear path and a 90-degree bend. By controlling switching times, ions can be deflected to an alternative channel as a function of their mobilities. In the initial evaluation the switch is used in a static mode and shown compatible with high performance ion mobility separations at 4 torr. In the “dynamic mode” we show that mobility-selected ions can be switched intomore » the alternative channel, and that various ion species can be independently selected based on their mobilities for time-of-flight mass spectrometer (TOF MS) IMS detection and mass analysis. Ultimately, this development also provides the basis for e.g. the selection of specific mobilities for storage and accumulation, and key modules for the assembly of SLIM devices enabling much more complex sequences of ion manipulations.« less

Supervised Semi-Automated Data Analysis Software for Gas Chromatography / Differential Mobility Spectrometry (GC/DMS) Metabolomics Applications.

PubMed

Peirano, Daniel J; Pasamontes, Alberto; Davis, Cristina E

2016-09-01

Modern differential mobility spectrometers (DMS) produce complex and multi-dimensional data streams that allow for near-real-time or post-hoc chemical detection for a variety of applications. An active area of interest for this technology is metabolite monitoring for biological applications, and these data sets regularly have unique technical and data analysis end user requirements. While there are initial publications on how investigators have individually processed and analyzed their DMS metabolomic data, there are no user-ready commercial or open source software packages that are easily used for this purpose. We have created custom software uniquely suited to analyze gas chromatograph / differential mobility spectrometry (GC/DMS) data from biological sources. Here we explain the implementation of the software, describe the user features that are available, and provide an example of how this software functions using a previously-published data set. The software is compatible with many commercial or home-made DMS systems. Because the software is versatile, it can also potentially be used for other similarly structured data sets, such as GC/GC and other IMS modalities.

Development of an ion mobility spectrometer with UV ionization source to detect ketones and BTX

NASA Astrophysics Data System (ADS)

Ni, Kai; Guo, Jingran; Ou, Guangli; Lei, Yu; Wang, Xiaohao

2014-11-01

Ion mobility spectrometry (IMS) is an attractive material analysis technology for developing a miniaturized volatile organic compounds (VOCs) on-site monitoring sensor. Having simple instrumentation, IMS is especially suitable when portability and sensitivity are required. In this work, we designed an ion mobility spectrometer with UV ionization. The geometric parameters of the UV-IMS were optimized based on a numerical simulation. The simulation results demonstrated that the drift electric field in the drift region was approximately homogenous and in the reaction region had an ion focusing effect, which could improve the sensitivity and resolving power of the IMS. The UV-IMS has been constructed and used to detect VOCs, such as acetone, benzene, toluene and m-xylene (BTX). The resolution of these substance measured from the UV-IMS in the atmospheric conditions are about 30 and the limit of detection (LOD) is low to ppmv. The ion mobility module and electric circuit are integrated in a main PCB, which can facilitate mass production and miniaturization. The present UV-IMS is expected to become a tool of choice for the on-site monitoring for VOCs.

Broadband ion mobility deconvolution for rapid analysis of complex mixtures.

PubMed

Pettit, Michael E; Brantley, Matthew R; Donnarumma, Fabrizio; Murray, Kermit K; Solouki, Touradj

2018-05-04

High resolving power ion mobility (IM) allows for accurate characterization of complex mixtures in high-throughput IM mass spectrometry (IM-MS) experiments. We previously demonstrated that pure component IM-MS data can be extracted from IM unresolved post-IM/collision-induced dissociation (CID) MS data using automated ion mobility deconvolution (AIMD) software [Matthew Brantley, Behrooz Zekavat, Brett Harper, Rachel Mason, and Touradj Solouki, J. Am. Soc. Mass Spectrom., 2014, 25, 1810-1819]. In our previous reports, we utilized a quadrupole ion filter for m/z-isolation of IM unresolved monoisotopic species prior to post-IM/CID MS. Here, we utilize a broadband IM-MS deconvolution strategy to remove the m/z-isolation requirement for successful deconvolution of IM unresolved peaks. Broadband data collection has throughput and multiplexing advantages; hence, elimination of the ion isolation step reduces experimental run times and thus expands the applicability of AIMD to high-throughput bottom-up proteomics. We demonstrate broadband IM-MS deconvolution of two separate and unrelated pairs of IM unresolved isomers (viz., a pair of isomeric hexapeptides and a pair of isomeric trisaccharides) in a simulated complex mixture. Moreover, we show that broadband IM-MS deconvolution improves high-throughput bottom-up characterization of a proteolytic digest of rat brain tissue. To our knowledge, this manuscript is the first to report successful deconvolution of pure component IM and MS data from an IM-assisted data-independent analysis (DIA) or HDMSE dataset.

Optimum Waveforms for Differential Ion Mobility Spectrometry (FAIMS)

PubMed Central

Shvartsburg, Alexandre A.; Smith, Richard D.

2009-01-01

Differential mobility spectrometry or field asymmetric waveform ion mobility spectrometry (FAIMS) is a new tool for separation and identification of gas-phase ions, particularly in conjunction with mass-spectrometry. In FAIMS, ions are filtered by the difference between mobilities in gases (K) at high and low electric field intensity (E) using asymmetric waveforms. An infinite number of possible waveform profiles make maximizing the performance within engineering constraints a major issue for FAIMS technology refinement. Earlier optimizations assumed the non-constant component of mobility to scale as E2, producing the same result for all ions. Here we show that the optimum profiles are defined by the full series expansion of K(E) that includes terms beyond the 1st that is proportional to E2. For many ion/gas pairs, the first two terms have different signs, and the optimum profiles at sufficiently high E in FAIMS may differ substantially from those previously reported, improving the resolving power by up to 2.2 times. This situation arises for some ions in all FAIMS systems, but becomes more common in recent miniaturized devices that employ higher E. With realistic K(E) dependences, the maximum waveform amplitude is not necessarily optimum and reducing it by up to ∼20 – 30% is beneficial in some cases. The present findings are particularly relevant to targeted analyses where separation depends on the difference between K(E) functions for specific ions. PMID:18585054

Evaluation of SDS depletion using an affinity spin column and IMS-MS detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hengel, Shawna M.; Floyd, Erica A.; Baker, Erin Shammel

2012-11-01

While the use of detergents is necessary for a variety of protein isolation preparation protocols, often prior to mass spectral (MS) analysis, they are not compatible with MS analysis due to ion suppression and adduct formation. This manuscript describes optimization of detergent removal, using commercially available SDS depletion spin columns containing an affinity resin, providing for both increased protein recovery and thorough SDS removal. Ion mobility spectrometry coupled with mass spectrometry (IMS-MS) allowed for a concurrent analysis of both analyte and detergent. In the case of both proteins and peptides, higher detergent concentrations than previously reported provided an increase ofmore » sample recovery; however there was a limit as SDS was detected by IMS-MS at higher levels of SDS indicating incomplete detergent depletion. The results also suggest optimal conditions for SDS removal are dependent on the sample concentration. Overall, this study provides a useful guide for proteomic studies where SDS is required for efficient sample preparation.« less

Signatures of Mechanically Interlocked Topology of Lasso Peptides by Ion Mobility-Mass Spectrometry: Lessons from a Collection of Representatives

NASA Astrophysics Data System (ADS)

Fouque, Kevin Jeanne Dit; Lavanant, Hélène; Zirah, Séverine; Hegemann, Julian D.; Zimmermann, Marcel; Marahiel, Mohamed A.; Rebuffat, Sylvie; Afonso, Carlos

2017-02-01

Lasso peptides are characterized by a mechanically interlocked structure, where the C-terminal tail of the peptide is threaded and trapped within an N-terminal macrolactam ring. Their compact and stable structures have a significant impact on their biological and physical properties and make them highly interesting for drug development. Ion mobility - mass spectrometry (IM-MS) has shown to be effective to discriminate the lasso topology from their corresponding branched-cyclic topoisomers in which the C-terminal tail is unthreaded. In fact, previous comparison of the IM-MS data of the two topologies has yielded three trends that allow differentiation of the lasso fold from the branched-cyclic structure: (1) the low abundance of highly charged ions, (2) the low change in collision cross sections (CCS) with increasing charge state and (3) a narrow ion mobility peak width. In this study, a three-dimensional plot was generated using three indicators based on these three trends: (1) mean charge divided by mass (ζ), (2) relative range of CCS covered by all protonated molecules (ΔΩ/Ω) and (3) mean ion mobility peak width (δΩ). The data were first collected on a set of twenty one lasso peptides and eight branched-cyclic peptides. The indicators were obtained also for eight variants of the well-known lasso peptide MccJ25 obtained by site-directed mutagenesis and further extended to five linear peptides, two macrocyclic peptides and one disulfide constrained peptide. In all cases, a clear clustering was observed between constrained and unconstrained structures, thus providing a new strategy to discriminate mechanically interlocked topologies.

High-field asymmetric waveform ion mobility spectrometry for mass spectrometry-based proteomics.

PubMed

Swearingen, Kristian E; Moritz, Robert L

2012-10-01

High-field asymmetric waveform ion mobility spectrometry (FAIMS) is an atmospheric pressure ion mobility technique that separates gas-phase ions by their behavior in strong and weak electric fields. FAIMS is easily interfaced with electrospray ionization and has been implemented as an additional separation mode between liquid chromatography (LC) and mass spectrometry (MS) in proteomic studies. FAIMS separation is orthogonal to both LC and MS and is used as a means of on-line fractionation to improve the detection of peptides in complex samples. FAIMS improves dynamic range and concomitantly the detection limits of ions by filtering out chemical noise. FAIMS can also be used to remove interfering ion species and to select peptide charge states optimal for identification by tandem MS. Here, the authors review recent developments in LC-FAIMS-MS and its application to MS-based proteomics.

Evaluation of Ion Mobility-Mass Spectrometry for Comparative Analysis of Monoclonal Antibodies

NASA Astrophysics Data System (ADS)

Ferguson, Carly N.; Gucinski-Ruth, Ashley C.

2016-05-01

Analytical techniques capable of detecting changes in structure are necessary to monitor the quality of monoclonal antibody drug products. Ion mobility mass spectrometry offers an advanced mode of characterization of protein higher order structure. In this work, we evaluated the reproducibility of ion mobility mass spectrometry measurements and mobiligrams, as well as the suitability of this approach to differentiate between and/or characterize different monoclonal antibody drug products. Four mobiligram-derived metrics were identified to be reproducible across a multi-day window of analysis. These metrics were further applied to comparative studies of monoclonal antibody drug products representing different IgG subclasses, manufacturers, and lots. These comparisons resulted in some differences, based on the four metrics derived from ion mobility mass spectrometry mobiligrams. The use of collision-induced unfolding resulted in more observed differences. Use of summed charge state datasets and the analysis of metrics beyond drift time allowed for a more comprehensive comparative study between different monoclonal antibody drug products. Ion mobility mass spectrometry enabled detection of differences between monoclonal antibodies with the same target protein but different production techniques, as well as products with different targets. These differences were not always detectable by traditional collision cross section studies. Ion mobility mass spectrometry, and the added separation capability of collision-induced unfolding, was highly reproducible and remains a promising technique for advanced analytical characterization of protein therapeutics.

A chemometric approach for characterization of serum transthyretin in familial amyloidotic polyneuropathy type I (FAP-I) by electrospray ionization-ion mobility mass spectrometry.

PubMed

Pont, Laura; Sanz-Nebot, Victoria; Vilaseca, Marta; Jaumot, Joaquim; Tauler, Roma; Benavente, Fernando

2018-05-01

In this study, we describe a chemometric data analysis approach to assist in the interpretation of the complex datasets from the analysis of high-molecular mass oligomeric proteins by ion mobility mass spectrometry (IM-MS). The homotetrameric protein transthyretin (TTR) is involved in familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR(Met30)) that can be easily detected analyzing the monomeric forms of the mutant protein. However, the mechanism of protein misfolding and aggregation onset, which could be triggered by structural changes in the native tetrameric protein, remains under investigation. Serum TTR from healthy controls and FAP-I patients was purified under non-denaturing conditions by conventional immunoprecipitation in solution and analyzed by IM-MS. IM-MS allowed separation and characterization of several tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time. After an appropriate data pre-processing, multivariate curve resolution alternating least squares (MCR-ALS) was applied to the complex datasets. A group of seven independent components being characterized by their ion mobility profiles and mass spectra were resolved to explain the observed data variance in control and patient samples. Then, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were considered for exploration and classification. Only four out of the seven resolved components were enough for an accurate differentiation. Furthermore, the specific TTR ions identified in the mass spectra of these components and the resolved ion mobility profiles provided a straightforward insight into the most relevant oligomeric TTR proteoforms for the disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Distance geometry protocol to generate conformations of natural products to structurally interpret ion mobility-mass spectrometry collision cross sections.

PubMed

Stow, Sarah M; Goodwin, Cody R; Kliman, Michal; Bachmann, Brian O; McLean, John A; Lybrand, Terry P

2014-12-04

Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data.

Distance Geometry Protocol to Generate Conformations of Natural Products to Structurally Interpret Ion Mobility-Mass Spectrometry Collision Cross Sections

PubMed Central

2015-01-01

Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data. PMID:25360896

The role of ion optics modeling in the design and development of ion mobility spectrometers

NASA Astrophysics Data System (ADS)

Griffin, Matthew T.

2005-05-01

Detection of trace gases by ion mobility spectroscopy (IMS) has become common in recent years. In fact, IMS devices are the most commonly deployed military devices for the detection of classical chemical warfare agents (CWA). IMS devices are protecting the homeland by aiding first responders in the identification of toxic industrial chemicals (TICs) and providing explosive and narcotic screening systems. Spurred by the asymmetric threat posed by new threat agents and the ever expanding list of toxic chemicals, research in the development, improvement, and optimization of IMS systems has increased. Much of the research is focused on increasing the sensitivity and selectivity of IMS systems. Ion optics is a large area of study in the field of mass spectrometry, but has been mostly overlooked in the design and development of IMS systems. Ion optics provides insight into particle trajectories, duty cycle, and efficiency of these systems. This paper will outline the role that ion optics can have in the development of IMS systems and introduce the trade space for traditional IMS as well as differential mobility spectroscopy.

The Characterization of Laser Ablation Patterns and a New Definition of Resolution in Matrix Assisted Laser Desorption Ionization Imaging Mass Spectrometry (MALDI-IMS).

PubMed

O'Rourke, Matthew B; Raymond, Benjamin B A; Padula, Matthew P

2017-05-01

Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) is a technique that has seen a sharp rise in both use and development. Despite this rapid adoption, there have been few thorough investigations into the actual physical mechanisms that underlie the acquisition of IMS images. We therefore set out to characterize the effect of IMS laser ablation patterns on the surface of a sample. We also concluded that the governing factors that control spatial resolution have not been correctly defined and therefore propose a new definition of resolution. Graphical Abstract ᅟ.

Mobility-Selected Ion Trapping and Enrichment Using Structures for Lossless Ion Manipulations

DOE PAGES

Chen, Tsung-Chi; Ibrahim, Yehia M.; Webb, Ian K.; ...

2016-01-11

The integration of ion mobility spectrometry (IMS) with mass spectrometry (MS) and the ability to trap ions in IMS-MS measurements is of great importance for performing reactions, accumulating ions, and increasing analytical measurement sensitivity. The development of Structures for Lossless Ion Manipulations (SLIM) offers the potential for ion manipulations in a more reliable and cost-effective manner, while opening opportunities for much more complex sequences of manipulations. Here, we demonstrate an ion separation and trapping module and a method based upon SLIM that consists of a linear mobility ion drift region, a switch/tee and a trapping region that allows the isolationmore » and accumulation of mobility-separated species. The operation and optimization of the SLIM switch/tee and trap are described and demonstrated for the enrichment of the low abundance ions. Lastly, we observed a linear increase in ion intensity with the number of trapping/accumulation events using the SLIM trap, illustrating its potential for enhancing the sensitivity of low abundance or targeted species.« less

Determining the Effect of Catechins on SOD1 Conformation and Aggregation by Ion Mobility Mass Spectrometry Combined with Optical Spectroscopy

NASA Astrophysics Data System (ADS)

Zhao, Bing; Zhuang, Xiaoyu; Pi, Zifeng; Liu, Shu; Liu, Zhiqiang; Song, Fengrui

2018-02-01

The aggregation of Cu,Zn-superoxide dismutase (SOD1) plays an important role in the etiology of amyotrophic lateral sclerosis (ALS). For the disruption of ALS progression, discovering new drugs or compounds that can prevent SOD1 aggregation is important. In this study, ESI-MS was used to investigate the interaction of catechins and SOD1. The noncovalent complex of catechins that interact with SOD1 was found and retained in the gas phase under native ESI-MS condition. The conformation changes of SOD1 after binding with catechins were also explored via traveling wave ion mobility (IM) spectrometry. Epigallocatechin gallate (EGCG) can stabilize SOD1 conformation against unfolding in three catechins. To further evaluate the efficacy of EGCG, we monitored the fluorescence changes of dimer E2,E2,-SOD1(apo-SOD1, E:empty) with and without ligands under denaturation conditions, and found that EGCG can inhibit apo-SOD1 aggregation. In addition, the circular dichroism spectra of the samples showed that EGCG can decrease the β-sheet content of SOD1, which can produce aggregates. These results indicated that orthogonal separation dimension in the gas-phase IM coupled with ESI-MS (ESI-IM-MS) can potentially provide insight into the interaction between SOD1 and small molecules. The advantage is that it dramatically decreases the analysis time. Meantime, optical spectroscopy techniques can be used to confirm ESI-IM-MS results. [Figure not available: see fulltext.

Discrimination of epimeric glycans and glycopeptides using IM-MS and its potential for carbohydrate sequencing

NASA Astrophysics Data System (ADS)

Both, P.; Green, A. P.; Gray, C. J.; Šardzík, R.; Voglmeir, J.; Fontana, C.; Austeri, M.; Rejzek, M.; Richardson, D.; Field, R. A.; Widmalm, G.; Flitsch, S. L.; Eyers, C. E.

2014-01-01

Mass spectrometry is the primary analytical technique used to characterize the complex oligosaccharides that decorate cell surfaces. Monosaccharide building blocks are often simple epimers, which when combined produce diastereomeric glycoconjugates indistinguishable by mass spectrometry. Structure elucidation frequently relies on assumptions that biosynthetic pathways are highly conserved. Here, we show that biosynthetic enzymes can display unexpected promiscuity, with human glycosyltransferase pp-α-GanT2 able to utilize both uridine diphosphate N-acetylglucosamine and uridine diphosphate N-acetylgalactosamine, leading to the synthesis of epimeric glycopeptides in vitro. Ion-mobility mass spectrometry (IM-MS) was used to separate these structures and, significantly, enabled characterization of the attached glycan based on the drift times of the monosaccharide product ions generated following collision-induced dissociation. Finally, ion-mobility mass spectrometry following fragmentation was used to determine the nature of both the reducing and non-reducing glycans of a series of epimeric disaccharides and the branched pentasaccharide Man3 glycan, demonstrating that this technique may prove useful for the sequencing of complex oligosaccharides.

Evaluation and application of static headspace-multicapillary column-gas chromatography-ion mobility spectrometry for complex sample analysis.

PubMed

Denawaka, Chamila J; Fowlis, Ian A; Dean, John R

2014-04-18

An evaluation of static headspace-multicapillary column-gas chromatography-ion mobility spectrometry (SHS-MCC-GC-IMS) has been undertaken to assess its applicability for the determination of 32 volatile compounds (VCs). The key experimental variables of sample incubation time and temperature have been evaluated alongside the MCC-GC variables of column polarity, syringe temperature, injection temperature, injection volume, column temperature and carrier gas flow rate coupled with the IMS variables of temperature and drift gas flow rate. This evaluation resulted in six sets of experimental variables being required to separate the 32 VCs. The optimum experimental variables for SHS-MCC-GC-IMS, the retention time and drift time operating parameters were determined; to normalise the operating parameters, the relative drift time and normalised reduced ion mobility for each VC were determined. In addition, a full theoretical explanation is provided on the formation of the monomer, dimer and trimer of a VC. The optimum operating condition for each VC calibration data was obtained alongside limit of detection (LOD) and limit of quantitation (LOQ) values. Typical detection limits ranged from 0.1ng bis(methylthio)methane, ethylbutanoate and (E)-2-nonenal to 472ng isovaleric acid with correlation coefficient (R(2)) data ranging from 0.9793 (for the dimer of octanal) through to 0.9990 (for isobutyric acid). Finally, the developed protocols were applied to the analysis of malodour in sock samples. Initial work involved spiking an inert matrix and sock samples with appropriate concentrations of eight VCs. The average recovery from the inert matrix was 101±18% (n=8), while recoveries from the sock samples were lower, that is, 54±30% (n=8) for sock type 1 and 78±24% (n=6) for sock type 2. Finally, SHS-MCC-GC-IMS was applied to sock malodour in a field trial based on 11 volunteers (mixed gender) over a 3-week period. By applying the SHS-MCC-GC-IMS database, four VCs were

Chemometric studies for the characterization and differentiation of microorganisms using in situ derivatization and thermal desorption ion mobility spectrometry.

PubMed

Ochoa, Mariela L; Harrington, Peter B

2005-02-01

Whole-cell bacteria were characterized and differentiated by thermal desorption ion mobility spectrometry and chemometric modeling. Principal component analysis was used to evaluate the differences in the ion mobility spectra of whole-cell bacteria and the fatty acid methyl esters (FAMEs) generated in situ after derivatization of the bacterial lipids. Alternating least squares served to extract bacterial peaks from the complex ion mobility spectra of intact microorganisms and, therefore, facilitated the characterization of bacterial strains, species, and Gram type. In situ thermal hydrolysis/methylation with tetramethylammonium hydroxide was necessary for the differentiation of Escherichia coli strains, which otherwise could not be distinguished by spectra acquired with the ITEMISER ion mobility spectrometer. The addition of the methylating agent had no effect on Gram-positive bacteria, and therefore, they could not be differentiated by genera. The classification of E. coli strains was possible by analysis of the IMS spectra from the FAMEs generated in situ. By using the fuzzy multivariate rule-building expert system and cross-validation, a correct classification rate of 96% (22 out of 23 spectra) was obtained. Chemometric modeling on bacterial ion mobility spectra coupled to thermal hydrolysis/methylation proved a simple, rapid (2 min/sample), inexpensive, and sensitive technique to characterize and differentiate intact microorganisms. The ITEMISER ion mobility spectrometer could detect as few as 4 x 10(6) cells/sample.

Mapping of explosive contamination using GC/chemiluminescence and ion mobility spectrometry techniques

NASA Astrophysics Data System (ADS)

Miller, Carla J.; Glenn, D. F.; Hartenstein, Steven D.; Hallowell, Susan F.

1998-12-01

Recent efforts at the Idaho National Engineering and Environmental Laboratory (INEEL) have included mapping explosive contamination resulting from manufacturing and carrying improvised explosive devices (IEDs). Two types of trace detection equipment were used to determine levels of contamination from designated sampling areas. A total of twenty IEDs were constructed: ten using TNT and ten using C-4. Two test scenarios were used. The first scenario tracked the activities of a manufacturer who straps the device onto an independent courier. The courier then performed a series of activities to simulate waiting in an airport. The second scenario tracked the activities of a manufacturer who also served as the courier. A sample set for each test consisted of thirty samples from various locations on each IED manufacturer, thirty from each IED courier, twenty-five from the manufacturing area, and twenty-five from the courier area. Pre-samples and post-samples were collected for analysis with each detection technique. Samples analyzed by gc/chemiluminescence were taken by swiping a teflon- coated sampling swipe across the surface of the sampling area to pick up any explosive particles. Samples analyzed by ion mobility spectrometry (IMS) were taken from the clothing of the manufacturer and courier by vacuuming the surface and collecting particulates on a fiberglass filter. Samples for IMS analysis from the manufacturing and courier rooms were taken by wiping a cotton sampling swipe across the surface area. Currently, building IEDs and monitoring the explosive contamination is being directed toward detection with portal monitors.

Ion mobility spectrometry evaluation of cocaine occupational exposure in forensic laboratories.

PubMed

Armenta, Sergio; de la Guardia, Miguel; Alcalà, Manel; Blanco, Marcelo; Perez-Alfonso, Clara; Galipienso, Nieves

2014-12-01

An approach, based on ion mobility spectrometry (IMS) has been developed for the control of cocaine in air of the breathing zone of operators, in laboratory surfaces and in nasal mucus of employees to evaluate cocaine exposure in a forensic laboratory. The analytical methodology has been validated in terms of accuracy, precision and limits of detection and results obtained were statistically comparable with those obtained by liquid chromatography. Cocaine concentration in laboratory air increases from 100 ± 35 ng m(-3) of a normal day to 10,000 ng m(-3) during the manipulation of cocaine seizures. The occupational exposure limit (OEL) for cocaine has not been established which difficult the evaluation of the health effects of continuous exposition to very small doses of cocaine. Cocaine was also found in almost all the analyzed sample surfaces and also was found in nasal mucus of the police officers that were present during the manipulation of cocaine seizures without using a face mask. In summary, cocaine concentrations could present a health hazard to the employees and therefore warrants remediation and some modifications of the manipulation operations have been proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

Collision Cross Sections and Ion Mobility Separation of Fragment Ions from Complex N-Glycans.

PubMed

Harvey, David J; Watanabe, Yasunori; Allen, Joel D; Rudd, Pauline; Pagel, Kevin; Crispin, Max; Struwe, Weston B

2018-06-01

Ion mobility mass spectrometry (IM-MS) holds great potential for structural glycobiology, in particular in its ability to resolve glycan isomers. Generally, IM-MS has largely been applied to intact glycoconjugate ions with reports focusing on the separation of different adduct types. Here, we explore IM separation and report the collision cross section (CCS) of complex type N-glycans and their fragments in negative ion mode following collision-induced dissociation (CID). CCSs of isomeric fragment ions were found, in some cases, to reveal structural details that were not present in CID spectra themselves. Many fragment ions were confirmed as possessing multiple structure, details of which could be obtained by comparing their drift time profiles to different glycans. By using fragmentation both before and after mobility separation, information was gathered on the fragmentation pathways producing some of the ions. These results help demonstrate the utility of IM and will contribute to the growing use of IM-MS for glycomics. Graphical Abstract ᅟ.

Collision Cross Sections and Ion Mobility Separation of Fragment Ions from Complex N-Glycans

NASA Astrophysics Data System (ADS)

Harvey, David J.; Watanabe, Yasunori; Allen, Joel D.; Rudd, Pauline; Pagel, Kevin; Crispin, Max; Struwe, Weston B.

2018-04-01

Ion mobility mass spectrometry (IM-MS) holds great potential for structural glycobiology, in particular in its ability to resolve glycan isomers. Generally, IM-MS has largely been applied to intact glycoconjugate ions with reports focusing on the separation of different adduct types. Here, we explore IM separation and report the collision cross section (CCS) of complex type N-glycans and their fragments in negative ion mode following collision-induced dissociation (CID). CCSs of isomeric fragment ions were found, in some cases, to reveal structural details that were not present in CID spectra themselves. Many fragment ions were confirmed as possessing multiple structure, details of which could be obtained by comparing their drift time profiles to different glycans. By using fragmentation both before and after mobility separation, information was gathered on the fragmentation pathways producing some of the ions. These results help demonstrate the utility of IM and will contribute to the growing use of IM-MS for glycomics. [Figure not available: see fulltext.

Protein Structural Studies by Traveling Wave Ion Mobility Spectrometry: A Critical Look at Electrospray Sources and Calibration Issues

NASA Astrophysics Data System (ADS)

Sun, Yu; Vahidi, Siavash; Sowole, Modupeola A.; Konermann, Lars

2016-01-01

The question whether electrosprayed protein ions retain solution-like conformations continues to be a matter of debate. One way to address this issue involves comparisons of collision cross sections (Ω) measured by ion mobility spectrometry (IMS) with Ω values calculated for candidate structures. Many investigations in this area employ traveling wave IMS (TWIMS). It is often implied that nanoESI is more conducive for the retention of solution structure than regular ESI. Focusing on ubiquitin, cytochrome c, myoglobin, and hemoglobin, we demonstrate that Ω values and collisional unfolding profiles are virtually indistinguishable under both conditions. These findings suggest that gas-phase structures and ion internal energies are independent of the type of electrospray source. We also note that TWIMS calibration can be challenging because differences in the extent of collisional activation relative to drift tube reference data may lead to ambiguous peak assignments. It is demonstrated that this problem can be circumvented by employing collisionally heated calibrant ions. Overall, our data are consistent with the view that exposure of native proteins to electrospray conditions can generate kinetically trapped ions that retain solution-like structures on the millisecond time scale of TWIMS experiments.

Comparison of two methods for selegiline determination: A flow-injection chemiluminescence method using cadmium sulfide quantum dots and corona discharge ion mobility spectrometry.

PubMed

Khataee, Alireza; Lotfi, Roya; Hasanzadeh, Aliyeh; Iranifam, Mortaza; Zarei, Mahmoud; Joo, Sang Woo

2016-01-15

Two analytical approaches including chemiluminescence (CL) and corona discharge ionization ion mobility spectrometry (CD-IMS) were developed for sensitive determination of selegiline (SG). We found that the CL intensity of the KMnO4-Na2S2O3 CL system was significantly enhanced in the presence of L-cysteine capped CdS quantum dots (QDs). A possible CL mechanism for this CL reaction is proposed. In the presence of SG, the enhanced CL system was inhibited. Based on this inhibition, a simple and sensitive flow-injection CL method was proposed for the determination of SG. Under optimum experimental conditions, the decreased CL intensity was proportional to SG concentration in the range of 0.01 to 30.0 mg L(-1). The detection limit (3σ) was 0.004 mg L(-1). Also, SG was determined using CD-IMS, and under optimum conditions of CD-IMS, calibration curves were linear in the range of 0.15 to 42.0 mg L(-1), with a detection limit (3σ) of 0.03 mg L(-1). The precision of the two methods was calculated by analyzing samples containing 5.0 mg L(-1) of SG (n=11). The relative standard deviations (RSDs%) of the flow-injection CL and CD-IMS methods are 2.17% and 3.83%, respectively. The proposed CL system exhibits a higher sensitivity and precision than the CD-IMS method for the determination of SG. Copyright © 2015. Published by Elsevier B.V.

High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) for Mass Spectrometry-Based Proteomics

PubMed Central

Swearingen, Kristian E.; Moritz, Robert L.

2013-01-01

SUMMARY High field asymmetric waveform ion mobility spectrometry (FAIMS) is an atmospheric pressure ion mobility technique that separates gas-phase ions by their behavior in strong and weak electric fields. FAIMS is easily interfaced with electrospray ionization and has been implemented as an additional separation mode between liquid chromatography (LC) and mass spectrometry (MS) in proteomic studies. FAIMS separation is orthogonal to both LC and MS and is used as a means of on-line fractionation to improve detection of peptides in complex samples. FAIMS improves dynamic range and concomitantly the detection limits of ions by filtering out chemical noise. FAIMS can also be used to remove interfering ion species and to select peptide charge states optimal for identification by tandem MS. Here, we review recent developments in LC-FAIMS-MS and its application to MS-based proteomics. PMID:23194268

A Simple Analytical Model for Predicting the Detectable Ion Current in Ion Mobility Spectrometry Using Corona Discharge Ionization Sources.

PubMed

Kirk, Ansgar Thomas; Kobelt, Tim; Spehlbrink, Hauke; Zimmermann, Stefan

2018-05-08

Corona discharge ionization sources are often used in ion mobility spectrometers (IMS) when a non-radioactive ion source with high ion currents is required. Typically, the corona discharge is followed by a reaction region where analyte ions are formed from the reactant ions. In this work, we present a simple yet sufficiently accurate model for predicting the ion current available at the end of this reaction region when operating at reduced pressure as in High Kinetic Energy Ion Mobility Spectrometers (HiKE-IMS) or most IMS-MS instruments. It yields excellent qualitative agreement with measurement results and is even able to calculate the ion current within an error of 15%. Additional interesting findings of this model are the ion current at the end of the reaction region being independent from the ion current generated by the corona discharge and the ion current in High Kinetic Energy Ion Mobility Spectrometers (HiKE-IMS) growing quadratically when scaling down the length of the reaction region. Graphical Abstract ᅟ.

Detection of methamphetamine in the presence of nicotine using in situ chemical derivatization and ion mobility spectrometry.

PubMed

Ochoa, Mariela L; Harrington, Peter B

2004-02-15

The detection of methamphetamine in the presence of nicotine has been successfully accomplished using in situ chemical derivatization with propyl chloroformate as the derivatization reagent and ion mobility spectrometry (IMS). The rapid detection of methamphetamine is important for forensic scientists in order to establish a chain of evidence and link criminals to the crime scene. Nicotine is pervasive in clandestine drug laboratories from cigarette smoke residue. It has been demonstrated that nicotine obscures the methamphetamine peaks in ion mobility spectrometers due to their similar charge affinities and ion mobilities, which makes their detection a challenging task. As a consequence, false positive or negative responses may arise. In situ chemical derivatization poses as a sensitive, accurate, and reproducible alternative to remove the nicotine background when detecting nanogram amounts of methamphetamine. The derivatization agent was coated onto the sample disk, and the derivatization product corresponding to propyl methamphetamine carbamate was detected. In the present study, in situ chemical derivatization was demonstrated to be a feasible method to detect methamphetamine hydrochloride as the carbamate derivative, which was baseline-resolved from the nicotine peak. Alternating least squares (ALS) was used to model the datasets. A mixture containing both compounds revealed reduced mobilities of 1.61 cm(2)/V.s and 1.54 cm(2)/V.s for methamphetamine and nicotine, respectively. The reduced mobility of propyl methamphetamine carbamate was found at 1.35 cm(2)/V.s.

Rapid and accurate detection of urinary pathogens by mobile IMS-based electronic nose: a proof-of-principle study.

PubMed

Roine, Antti; Saviauk, Taavi; Kumpulainen, Pekka; Karjalainen, Markus; Tuokko, Antti; Aittoniemi, Janne; Vuento, Risto; Lekkala, Jukka; Lehtimäki, Terho; Tammela, Teuvo L; Oksala, Niku K J

2014-01-01

Urinary tract infection (UTI) is a common disease with significant morbidity and economic burden, accounting for a significant part of the workload in clinical microbiology laboratories. Current clinical chemisty point-of-care diagnostics rely on imperfect dipstick analysis which only provides indirect and insensitive evidence of urinary bacterial pathogens. An electronic nose (eNose) is a handheld device mimicking mammalian olfaction that potentially offers affordable and rapid analysis of samples without preparation at athmospheric pressure. In this study we demonstrate the applicability of ion mobility spectrometry (IMS) -based eNose to discriminate the most common UTI pathogens from gaseous headspace of culture plates rapidly and without sample preparation. We gathered a total of 101 culture samples containing four most common UTI bacteries: E. coli, S. saprophyticus, E. faecalis, Klebsiella spp and sterile culture plates. The samples were analyzed using ChemPro 100i device, consisting of IMS cell and six semiconductor sensors. Data analysis was conducted by linear discriminant analysis (LDA) and logistic regression (LR). The results were validated by leave-one-out and 5-fold cross validation analysis. In discrimination of sterile and bacterial samples sensitivity of 95% and specificity of 97% were achieved. The bacterial species were identified with sensitivity of 95% and specificity of 96% using eNose as compared to urine bacterial cultures. These findings strongly demonstrate the ability of our eNose to discriminate bacterial cultures and provides a proof of principle to use this method in urinanalysis of UTI.

Identification of Lasso Peptide Topologies Using Native Nanoelectrospray Ionization-Trapped Ion Mobility Spectrometry-Mass Spectrometry.

PubMed

Dit Fouque, Kevin Jeanne; Moreno, Javier; Hegemann, Julian D; Zirah, Séverine; Rebuffat, Sylvie; Fernandez-Lima, Francisco

2018-04-17

Lasso peptides are a fascinating class of bioactive ribosomal natural products characterized by a mechanically interlocked topology. In contrast to their branched-cyclic forms, lasso peptides have higher stability and have become a scaffold for drug development. However, the identification and separation of lasso peptides from their unthreaded topoisomers (branched-cyclic peptides) is analytically challenging since the higher stability is based solely on differences in their tertiary structures. In the present work, a fast and effective workflow is proposed for the separation and identification of lasso from branched cyclic peptides based on differences in their mobility space under native nanoelectrospray ionization-trapped ion mobility spectrometry-mass spectrometry (nESI-TIMS-MS). The high mobility resolving power ( R) of TIMS resulted in the separation of lasso and branched-cyclic topoisomers ( R up to 250, 150 needed on average). The advantages of alkali metalation reagents (e.g., Na, K, and Cs salts) as a way to increase the analytical power of TIMS is demonstrated for topoisomers with similar mobilities as protonated species, efficiently turning the metal ion adduction into additional separation dimensions.

Using corona discharge-ion mobility spectrometry for detection of 2,4,6-Trichloroanisole.

PubMed

Lichvanová, Zuzana; Ilbeigi, Vahideh; Sabo, Martin; Tabrizchi, Mahmoud; Matejčík, Stefan

2014-09-01

In this work possible application of the corona discharge-ion mobility spectrometer (CD-IMS) for detection of 2,4,6-Trichloroanisole (TCA) has been investigated. We applied CD-IMS interfaced with orthogonal acceleration time of flight mass spectrometer (CD-IMS-oaTOF) to study the ion processes within the CD-IMS technique. The CD-IMS instrument was operated in two modes, (i) standard and (ii) reverse flow modes resulting in different chemical ionisation schemes by NO3(-)(HNO3)n (n=0,1,2) and O2(-)(H2O)n (n=0,1,2), respectively. The O2(-)(H2O)n ionisation was associated with formation of Cl(-) and (TCA-CH3)(-) ions from TCA. The NO3(-)(HNO3)n ionisation, resulted in formation of NO3(-)(HNO3)(TCA-Cl) adduct ions. Limit of detection (LOD) for TCA was determined in gas (100 ppb) and solid phases (150 ng). Copyright © 2014 Elsevier B.V. All rights reserved.

Long-term sub second-response monitoring of gaseous ammonia in ambient air by positive inhaling ion mobility spectrometry.

PubMed

Huang, Wei; Wang, Weiguo; Chen, Chuang; Li, Mei; Peng, Liying; Li, Hang; Liu, Jiwei; Hou, Keyong; Li, Haiyang

2017-12-01

A real-time dynamic measurements of ammonia (NH 3 ) is crucial for understanding the atmospheric nucleation process. A novel method was developed for on line monitoring at the sub-second time scale for the gaseous ammonia in ambient air for months, based on a positive inhaling ion mobility spectrometry (IMS) with a 63 Ni ion source. The selective detection of NH 3 was achieved using a high resolution IMS with an optimization of the drift tube temperature above 150°C. This method improved the peak-to-peak resolution significantly, thus avoided the interferences of the adjacent peaks to the quantitative analysis of NH 3 . The time resolution of the IMS was less than 0.1s at a data averaging of 10 times. The limit of detection (LOD) achieved at sub-ppb level while a linear response of peak intensity versus concentration of NH 3 in the range of 10-60ppb and 60-400ppb were obtained. The relative standard deviations (RSD), the confidence level and the errors were 1.06%, 95% and ± 0.21ppb by measuring 100ppb NH 3 for 100 times. The effect of ambient humidity could be greatly reduced by using the drift temperature of over 150°C. At last, the application of measuring the NH 3 concentration evolutions of Dalian city was performed from June 19 to December 3 in 2015. The results illustrated a potential method of using IMS for a real-time measuring atmospheric NH 3 at an unprecedented accuracy and sensitivity with long-term stability. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections.

PubMed

Campuzano, Iain; Bush, Matthew F; Robinson, Carol V; Beaumont, Claire; Richardson, Keith; Kim, Hyungjun; Kim, Hugh I

2012-01-17

We present the use of drug-like molecules as a traveling wave (T-wave) ion mobility (IM) calibration sample set, covering the m/z range of 122.1-609.3, the nitrogen collision cross-section (Ω(N(2))) range of 124.5-254.3 Å(2) and the helium collision cross-section (Ω(He)) range of 63.0-178.8 Å(2). Absolute Ω(N(2)) and Ω(He) values for the drug-like calibrants and two diastereomers were measured using a drift-tube instrument with radio frequency (RF) ion confinement. T-wave drift-times for the protonated diastereomers betamethasone and dexamethasone are reproducibly different. Calibration of these drift-times yields T-wave Ω(N(2)) values of 189.4 and 190.4 Å(2), respectively. These results demonstrate the ability of T-wave IM spectrometry to differentiate diastereomers differing in Ω(N(2)) value by only 1 Å(2), even though the resolution of these IM experiments were ∼40 (Ω/ΔΩ). Demonstrated through density functional theory optimized geometries and ionic electrostatic surface potential analysis, the small but measurable mobility difference between the two diastereomers is mainly due to short-range van der Waals interactions with the neutral buffer gas and not long-range charge-induced dipole interactions. The experimental RF-confining drift-tube and T-wave Ω(N(2)) values were also evaluated using a nitrogen based trajectory method, optimized for T-wave operating temperature and pressures, incorporating additional scaling factors to the Lennard-Jones potentials. Experimental Ω(He) values were also compared to the original and optimized helium based trajectory methods.

Accurate Drift Time Determination by Traveling Wave Ion Mobility Spectrometry: The Concept of the Diffusion Calibration.

PubMed

Kune, Christopher; Far, Johann; De Pauw, Edwin

2016-12-06

Ion mobility spectrometry (IMS) is a gas phase separation technique, which relies on differences in collision cross section (CCS) of ions. Ionic clouds of unresolved conformers overlap if the CCS difference is below the instrumental resolution expressed as CCS/ΔCCS. The experimental arrival time distribution (ATD) peak is then a superimposition of the various contributions weighted by their relative intensities. This paper introduces a strategy for accurate drift time determination using traveling wave ion mobility spectrometry (TWIMS) of poorly resolved or unresolved conformers. This method implements through a calibration procedure the link between the peak full width at half-maximum (fwhm) and the drift time of model compounds for wide range of settings for wave heights and velocities. We modified a Gaussian equation, which achieves the deconvolution of ATD peaks where the fwhm is fixed according to our calibration procedure. The new fitting Gaussian equation only depends on two parameters: The apex of the peak (A) and the mean drift time value (μ). The standard deviation parameter (correlated to fwhm) becomes a function of the drift time. This correlation function between μ and fwhm is obtained using the TWIMS calibration procedure which determines the maximum instrumental ion beam diffusion under limited and controlled space charge effect using ionic compounds which are detected as single conformers in the gas phase. This deconvolution process has been used to highlight the presence of poorly resolved conformers of crown ether complexes and peptides leading to more accurate CCS determinations in better agreement with quantum chemistry predictions.

An LC-IMS-MS Platform Providing Increased Dynamic Range for High-Throughput Proteomic Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, Erin Shammel; Livesay, Eric A.; Orton, Daniel J.

2010-02-05

A high-throughput approach and platform using 15 minute reversed-phase capillary liquid chromatography (RPLC) separations in conjunction with ion mobility spectrometry-mass spectrometry (IMS-MS) measurements was evaluated for the rapid analysis of complex proteomics samples. To test the separation quality of the short LC gradient, a sample was prepared by spiking twenty reference peptides at varying concentrations from 1 ng/mL to 10 µg/mL into a tryptic digest of mouse blood plasma and analyzed with both a LC-Linear Ion Trap Fourier Transform (FT) MS and LC-IMS-TOF MS. The LC-FT MS detected thirteen out of the twenty spiked peptides that had concentrations ≥100 ng/mL.more » In contrast, the drift time selected mass spectra from the LC-IMS-TOF MS analyses yielded identifications for nineteen of the twenty peptides with all spiking level present. The greater dynamic range of the LC-IMS-TOF MS system could be attributed to two factors. First, the LC-IMS-TOF MS system enabled drift time separation of the low concentration spiked peptides from the high concentration mouse peptide matrix components, reducing signal interference and background, and allowing species to be resolved that would otherwise be obscured by other components. Second, the automatic gain control (AGC) in the linear ion trap of the hybrid FT MS instrument limits the number of ions that are accumulated to reduce space charge effects, but in turn limits the achievable dynamic range compared to the TOF detector.« less

Development of a new ion mobility time-of-flight mass spectrometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ibrahim, Yehia M.; Baker, Erin S.; Danielson, William F.

2015-02-01

Complex samples require multidimensional measurements with high resolution for full characterization of biological and environmental systems. To address this challenge, we developed a drift tube-based ion mobility spectrometry-Orbitrap mass spectrometry (IMS-Orbitrap MS) platform. To circumvent the timing difference between the fast IMS separation and the slow Orbitrap MS acquisition, we utilized a dual gate and pseudorandom sequence to multiplex ions into the drift tube and Orbitrap. The instrument was designed to operate in signal averaging (SA), single multiplexing (SM) and double multiplexing (DM) IMS modes to fully optimize the signal-to-ratio of the measurements. For the SM measurements, a previously developedmore » algorithm was used to reconstruct the IMS data, while a new algorithm was developed for the DM analyses. The new algorithm is a two-step process that first recovers the SM data from the encoded DM data and then decoded the SM data. The algorithm also performs multiple refining procedures in order to minimize the demultiplexing artifacts traditionally observed in such scheme. The new IMS-Orbitrap MS platform was demonstrated for the analysis of proteomic and petroleum samples, where the integration of IMS and high mass resolution proved essential for accurate assignment of molecular formulae.« less

Study and optimization of key parameters of a laser ablation ion mobility spectrometer

NASA Astrophysics Data System (ADS)

Ni, Kai; Li, Jianan; Tang, Binchao; Shi, Yuan; Yu, Quan; Qian, Xiang; Wang, Xiaohao

2016-11-01

Ion Mobility Spectrometry (IMS), having an advantage in real-time and on-line detection, is an atmospheric pressure detecting technique. LA-IMS (Laser Ablation Ion Mobility Spectrometry) uses Nd-YAG laser as ionization source, whose energy is high enough to ionize metal. In this work, we tested the signal in different electric field intensity by a home-made ion mobility spectrometer, using silicon wafers the sample. The transportation of metal ions was match with the formula: Td = d/K • 1/E, when the electric field intensity is greater than 350v/cm. The relationship between signal intensity and collection angle (the angle between drift tube and the surface of the sample) was studied. With the increasing of the collection angle, signal intensity had a significant increase; while the variation of incident angle of the laser had no significant influence. The signal intensity had a 140% increase when the collection angle varied from 0 to 45 degree, while the angle between the drift tube and incident laser beam keeping the same as 90 degree. The position of ion gate in LA-IMS(Laser Ablation Ion Mobility Spectrometry) is different from the traditional ones for the kinetic energy of the ions is too big, if the distance between ion gate and sampling points less than 2.5cm the ion gate will not work, the ions could go through ion gate when it closed. The SNR had been improved by define the signal when the ion gate is closed as background signal, the signal noise including shock wave and electrical field perturbation produced during the interaction between laser beam and samples is eliminated when the signal that the ion gate opened minus the background signal.

Characterisation of serum transthyretin by electrospray ionisation-ion mobility mass spectrometry: Application to familial amyloidotic polyneuropathy type I (FAP-I).

PubMed

Pont, Laura; Benavente, Fernando; Vilaseca, Marta; Giménez, Estela; Sanz-Nebot, Victoria

2015-11-01

Transthyretin (TTR) is a homotetrameric protein which is known to misfold and aggregate causing different types of amyloidosis, such as familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR (Met30)) that can be easily detected analysing the monomeric forms of the mutant protein. Meanwhile, the mechanism of protein aggregation onset, which could be triggered by structural changes on the native tetrameric protein complex, remains uncertain. We developed and described herein a new sample pretreatment based on immunoprecipitation (IP) to purify TTR from serum under non-denaturing conditions. Later, a nano-electrospray ionization-ion mobility mass spectrometry (nano-ESI-IM-MS or IM-MS) method was optimised to analyse the protein complexes in serum samples from healthy controls and FAP-I patients. IM-MS allowed separation and characterisation of tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time, which is related to ion size and charge. The tetramer-to-dimer abundance ratio was differential between healthy controls and FAP-I patients (asymptomatic, symptomatic and an iatrogenic patient originally without the mutation who received a liver transplant from an FAP-I patient), and was also indicative of the effectiveness of liver transplantation as a treatment for FAP-I. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural Characterization of Monomers and Oligomers of D-Amino Acid-Containing Peptides Using T-Wave Ion Mobility Mass Spectrometry

NASA Astrophysics Data System (ADS)

Pang, Xueqin; Jia, Chenxi; Chen, Zhengwei; Li, Lingjun

2017-01-01

The D-residues are crucial to biological function of D-amino acid containing peptides (DAACPs). Previous ion mobility mass spectrometry (IM-MS) studies revealing oligomerization patterns of amyloid cascade demonstrated conversion from native soluble unstructured assembly to fibril ß-sheet oligomers, which has been implicated in amyloid diseases, such as Alzheimer's disease and type 2 diabetes. Although neuropeptides are typically present at very low concentrations in circulation, their local concentrations could be much higher in large dense core vesicles, forming dimers or oligomers. We studied the oligomerization of protonated and metal-adducted achatin I and dermorphin peptide isomers with IM-MS. Our results suggested that dimerization, oligomerization, and metal adduction augment the structural differences between D/L peptide isomers compared to protonated monomers. Dimers and oligomers enhanced the structural differences between D/L peptide isomers in both aqueous and organic solvent system. Furthermore, some oligomer forms were only observed for either D- or L-isomers, indicating the importance of chiral center in oligomerization process. The oligomerization patterns of D/L isomers appear to be similar. Potassium adducts were detected to enlarge the structural differences between D/L isomers.

A Simple Analytical Model for Predicting the Detectable Ion Current in Ion Mobility Spectrometry Using Corona Discharge Ionization Sources

NASA Astrophysics Data System (ADS)

Kirk, Ansgar Thomas; Kobelt, Tim; Spehlbrink, Hauke; Zimmermann, Stefan

2018-05-01

Corona discharge ionization sources are often used in ion mobility spectrometers (IMS) when a non-radioactive ion source with high ion currents is required. Typically, the corona discharge is followed by a reaction region where analyte ions are formed from the reactant ions. In this work, we present a simple yet sufficiently accurate model for predicting the ion current available at the end of this reaction region when operating at reduced pressure as in High Kinetic Energy Ion Mobility Spectrometers (HiKE-IMS) or most IMS-MS instruments. It yields excellent qualitative agreement with measurement results and is even able to calculate the ion current within an error of 15%. Additional interesting findings of this model are the ion current at the end of the reaction region being independent from the ion current generated by the corona discharge and the ion current in High Kinetic Energy Ion Mobility Spectrometers (HiKE-IMS) growing quadratically when scaling down the length of the reaction region. [Figure not available: see fulltext.

Conventional and Advanced Separations in Mass Spectrometry-Based Metabolomics: Methodologies and Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heyman, Heino M.; Zhang, Xing; Tang, Keqi

2016-02-16

Metabolomics is the quantitative analysis of all metabolites in a given sample. Due to the chemical complexity of the metabolome, optimal separations are required for comprehensive identification and quantification of sample constituents. This chapter provides an overview of both conventional and advanced separations methods in practice for reducing the complexity of metabolite extracts delivered to the mass spectrometer detector, and covers gas chromatography (GC), liquid chromatography (LC), capillary electrophoresis (CE), supercritical fluid chromatography (SFC) and ion mobility spectrometry (IMS) separation techniques coupled with mass spectrometry (MS) as both uni-dimensional and as multi-dimensional approaches.

Ultra High-Resolution Electrospray Ionization/Ion Mobility Spectrometer System for In-Situ Detection of Organic Compounds

NASA Technical Reports Server (NTRS)

Kanik, I.; Beegle, L. W.; Hill, H. H.

2001-01-01

The potential of the high-resolution Electrospray Ionization/Ion Mobility Spectrometry (ESI/IMS) technique as analytical separation tool in analyzing bio-molecular mixtures in the search for the chemical signatures of life is demonstrated. Additional information is contained in the original extended abstract.

The effects of CO2 on the negative reactant ions of IMS

NASA Technical Reports Server (NTRS)

Spangler, Glenn E.

1995-01-01

In the presence of CO2, the negative reactant ions of ion mobility spectrometry (IMS) are ion clusters of CO4(-) and CO3(-). Methyl salicylate is ionized by the CO4(-)(H2O(n))(N2(m)) reactant ions, but not by the CO3(-)(H2O(n))(N2(m)) reactant ions. While the CO4(-) ions are formed by direct association, the CO3(-) ions require additional energy to be formed. The additional energy is provided by either excited neutral gas molecules in a metastable state or UV (ultraviolet) radiation.

Native Mass Spectrometry, Ion mobility, and Collision-Induced Unfolding Categorize Malaria Antigen/Antibody Binding

NASA Astrophysics Data System (ADS)

Huang, Yining; Salinas, Nichole D.; Chen, Edwin; Tolia, Niraj H.; Gross, Michael L.

2017-09-01

Plasmodium vivax Duffy Binding Protein (PvDBP) is a promising vaccine candidate for P. vivax malaria. Recently, we reported the epitopes on PvDBP region II (PvDBP-II) for three inhibitory monoclonal antibodies (2D10, 2H2, and 2C6). In this communication, we describe the combination of native mass spectrometry and ion mobility (IM) with collision induced unfolding (CIU) to study the conformation and stabilities of three malarial antigen-antibody complexes. These complexes, when collisionally activated, undergo conformational changes that depend on the location of the epitope. CIU patterns for PvDBP-II in complex with antibody 2D10 and 2H2 are highly similar, indicating comparable binding topology and stability. A different CIU fingerprint is observed for PvDBP-II/2C6, indicating that 2C6 binds to PvDBP-II on an epitope different from 2D10 and 2H2. This work supports the use of CIU as a means of classifying antigen-antibody complexes by their epitope maps in a high throughput screening workflow. [Figure not available: see fulltext.

Online Measurement of Exhaled NO Concentration and Its Production Sites by Fast Non-equilibrium Dilution Ion Mobility Spectrometry

NASA Astrophysics Data System (ADS)

Peng, Liying; Jiang, Dandan; Wang, Zhenxin; Liu, Jiwei; Li, Haiyang

2016-03-01

Exhaled nitric oxide (NO) is one of the most promising breath markers for respiratory diseases. Its profile for exhalation and the respiratory NO production sites can provide useful information for medical disease diagnosis and therapeutic procedures. However, the high-level moisture in exhaled gas always leads to the poor selectivity and sensitivity for ion spectrometric techniques. Herein, a method based on fast non-equilibrium dilution ion mobility spectrometry (NED-IMS) was firstly proposed to directly monitor the exhaled NO profile on line. The moisture interference was eliminated by turbulently diluting the original moisture to 21% of the original with the drift gas and dilution gas. Weak enhancement was observed for humid NO response and its limit of detection at 100% relative humidity was down to 0.58 ppb. The NO concentrations at multiple exhalation flow rates were measured, while its respiratory production sites were determined by using two-compartment model (2CM) and Högman and Meriläinen algorithm (HMA). Last but not the least, the NO production sites were analyzed hourly to tentatively investigate the daily physiological process of NO. The results demonstrated the capacity of NED-IMS in the real-time analysis of exhaled NO and its production sites for clinical diagnosis and assessment.

Characterization of singly and multiply PEGylated insulin isomers by reversed-phase ultra-performance liquid chromatography interfaced with ion mobility mass spectrometry.

PubMed

Gerislioglu, Selim; Adams, Scott R; Wesdemiotis, Chrys

2018-04-03

Conjugation of poly(ethylene glycol) (PEG) to protein drugs (PEGylation) is increasingly utilized in the biotherapeutics field because it improves significantly the drugs' circulatory half-life, solubility, and shelf-life. The activity of a PEGylated drug depends on the number, size, and location of the attached PEG chain(s). This study introduces a 2D separation approach, including reversed-phase ultra-performance liquid chromatography (RP-UPLC) and ion mobility mass spectrometry (IM-MS), in order to determine the structural properties of the conjugates, as demonstrated for a PEGylated insulin sample that was prepared by random amine PEGylation. The UPLC dimension allowed separation based on polarity. Electrospray ionization (ESI) of the eluates followed by in-source dissociation (ISD) truncated the PEG chains and created insulin fragments that provided site-specific information based on whether they contained a marker at the potential conjugation sites. Separation of the latter fragments by size and charge in the orthogonal IM dimension (pseudo-4D UPLC-ISD-IM-MS approach) enabled clear detection and identification of the positional isomers formed upon PEGylation. The results showed a highly heterogeneous mixture of singly and multiply conjugated isomers plus unconjugated material. PEGylation was observed on all three possible attachment sites (ε-NH 2 of LysB29, A- and B-chain N-termini). Each PEGylation site was validated by analysis of the same product after disulfide bond cleavage, so that the PEGylated A- and B- chain could be individually characterized with the same pseudo-4D UPLC-ISD-IM-MS method. Copyright © 2018 Elsevier B.V. All rights reserved.

[Imaging Mass Spectrometry in Histopathologic Analysis].

PubMed

Yamazaki, Fumiyoshi; Seto, Mitsutoshi

2015-04-01

Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) enables visualization of the distribution of a range of biomolecules by integrating biochemical information from mass spectrometry with positional information from microscopy. IMS identifies a target molecule. In addition, IMS enables global analysis of biomolecules containing unknown molecules by detecting the ratio of the molecular weight to electric charge without any target, which makes it possible to identify novel molecules. IMS generates data on the distribution of lipids and small molecules in tissues, which is difficult to visualize with either conventional counter-staining or immunohistochemistry. In this review, we firstly introduce the principle of imaging mass spectrometry and recent advances in the sample preparation method. Secondly, we present findings regarding biological samples, especially pathological ones. Finally, we discuss the limitations and problems of the IMS technique and clinical application, such as in drug development.

Determination of furfural and hydroxymethylfurfural from baby formula using headspace solid phase microextraction based on nanostructured polypyrrole fiber coupled with ion mobility spectrometry.

PubMed

Kamalabadi, Mahdie; Ghaemi, Elham; Mohammadi, Abdorreza; Alizadeh, Naader

2015-08-15

Furfural (Fu) and hydroxymethylfurfural (HMFu) are extracted using a dodecylbenzenesulfonate-doped polypyrrole coating as a fiber for headspace solid phase microextraction (HS-SPME) method in baby formula samples and detected using ion mobility spectrometry (IMS). Sample pH, salt effect, extraction time and temperature were investigated and optimized as effective parameters in HS-SPME. The calibration curves were linear in the range of 20-300 ng g(-1) (R(2)>0.99). Limits of detection for Fu and HMFu were 6 ng g(-1) and 5 ng g(-1), respectively. The RSD% of Fu and HMFu for five analyses was 4.4 and 4.9, respectively. The proposed method was successfully applied to determine of Fu and HMFu in the different baby formula samples with satisfactory result. The results were in agreement with those obtained using HPLC analysis. The HS-SPME-IMS is precise, selective and sensitive analytical method for determination of Fu and HMFu in baby formula samples, without any derivatization process. Copyright © 2015 Elsevier Ltd. All rights reserved.

Uncovering the stoichiometry of Pyrococcus furiosus RNase P, a multi-subunit catalytic ribonucleoprotein complex, by surface-induced dissociation and ion mobility mass spectrometry.

PubMed

Ma, Xin; Lai, Lien B; Lai, Stella M; Tanimoto, Akiko; Foster, Mark P; Wysocki, Vicki H; Gopalan, Venkat

2014-10-20

We demonstrate that surface-induced dissociation (SID) coupled with ion mobility mass spectrometry (IM-MS) is a powerful tool for determining the stoichiometry of a multi-subunit ribonucleoprotein (RNP) complex assembled in a solution containing Mg(2+). We investigated Pyrococcus furiosus (Pfu) RNase P, an archaeal RNP that catalyzes tRNA 5' maturation. Previous step-wise, Mg(2+)-dependent reconstitutions of Pfu RNase P with its catalytic RNA subunit and two interacting protein cofactor pairs (RPP21⋅RPP29 and POP5⋅RPP30) revealed functional RNP intermediates en route to the RNase P enzyme, but provided no information on subunit stoichiometry. Our native MS studies with the proteins showed RPP21⋅RPP29 and (POP5⋅RPP30)2 complexes, but indicated a 1:1 composition for all subunits when either one or both protein complexes bind the cognate RNA. These results highlight the utility of SID and IM-MS in resolving conformational heterogeneity and yielding insights on RNP assembly. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ion mobility spectrometry–mass spectrometry (IMS–MS) for on- and offline analysis of atmospheric gas and aerosol species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krechmer, Jordan E.; Groessl, Michael; Zhang, Xuan

Measurement techniques that provide molecular-level information are needed to elucidate the multiphase processes that produce secondary organic aerosol (SOA) species in the atmosphere. Here we demonstrate the application of ion mobility spectrometry-mass spectrometry (IMS–MS) to the simultaneous characterization of the elemental composition and molecular structures of organic species in the gas and particulate phases. Molecular ions of gas-phase organic species are measured online with IMS–MS after ionization with a custom-built nitrate chemical ionization (CI) source. This CI–IMS–MS technique is used to obtain time-resolved measurements (5 min) of highly oxidized organic molecules during the 2013 Southern Oxidant and Aerosol Study (SOAS)more » ambient field campaign in the forested SE US. The ambient IMS–MS signals are consistent with laboratory IMS–MS spectra obtained from single-component carboxylic acids and multicomponent mixtures of isoprene and monoterpene oxidation products. Mass-mobility correlations in the 2-D IMS–MS space provide a means of identifying ions with similar molecular structures within complex mass spectra and are used to separate and identify monoterpene oxidation products in the ambient data that are produced from different chemical pathways. Water-soluble organic carbon (WSOC) constituents of fine aerosol particles that are not resolvable with standard analytical separation methods, such as liquid chromatography (LC), are shown to be separable with IMS–MS coupled to an electrospray ionization (ESI) source. The capability to use ion mobility to differentiate between isomers is demonstrated for organosulfates derived from the reactive uptake of isomers of isoprene epoxydiols (IEPOX) onto wet acidic sulfate aerosol. As a result, controlled fragmentation of precursor ions by collisionally induced dissociation (CID) in the transfer region between the IMS and the MS is used to validate MS peak assignments, elucidate structures

Ion mobility spectrometry–mass spectrometry (IMS–MS) for on- and offline analysis of atmospheric gas and aerosol species

DOE PAGES

Krechmer, Jordan E.; Groessl, Michael; Zhang, Xuan; ...

2016-07-25

Measurement techniques that provide molecular-level information are needed to elucidate the multiphase processes that produce secondary organic aerosol (SOA) species in the atmosphere. Here we demonstrate the application of ion mobility spectrometry-mass spectrometry (IMS–MS) to the simultaneous characterization of the elemental composition and molecular structures of organic species in the gas and particulate phases. Molecular ions of gas-phase organic species are measured online with IMS–MS after ionization with a custom-built nitrate chemical ionization (CI) source. This CI–IMS–MS technique is used to obtain time-resolved measurements (5 min) of highly oxidized organic molecules during the 2013 Southern Oxidant and Aerosol Study (SOAS)more » ambient field campaign in the forested SE US. The ambient IMS–MS signals are consistent with laboratory IMS–MS spectra obtained from single-component carboxylic acids and multicomponent mixtures of isoprene and monoterpene oxidation products. Mass-mobility correlations in the 2-D IMS–MS space provide a means of identifying ions with similar molecular structures within complex mass spectra and are used to separate and identify monoterpene oxidation products in the ambient data that are produced from different chemical pathways. Water-soluble organic carbon (WSOC) constituents of fine aerosol particles that are not resolvable with standard analytical separation methods, such as liquid chromatography (LC), are shown to be separable with IMS–MS coupled to an electrospray ionization (ESI) source. The capability to use ion mobility to differentiate between isomers is demonstrated for organosulfates derived from the reactive uptake of isomers of isoprene epoxydiols (IEPOX) onto wet acidic sulfate aerosol. As a result, controlled fragmentation of precursor ions by collisionally induced dissociation (CID) in the transfer region between the IMS and the MS is used to validate MS peak assignments, elucidate structures

Characterization of Nitrated Sugar Alcohols by Atmospheric-Pressure Chemical-Ionization Mass Spectrometry

DTIC Science & Technology

2016-07-27

disclosed here will benefit the area of explosives trace detection for counterterrorism and forensics . INTRODUCTION The military-grade...plasticizer formulation.[4] As a result, methods to detect MHN, SHN, and XPN should be pursued for the same security and forensics applications as...with ion mobility mass spectrometry (IMS) provide direct detection of molecular ions,[8] and thus are preferred for most security and forensic

Modeling and prediction of peptide drift times in ion mobility spectrometry using sequence-based and structure-based approaches.

PubMed

Zhang, Yiming; Jin, Quan; Wang, Shuting; Ren, Ren

2011-05-01

The mobile behavior of 1481 peptides in ion mobility spectrometry (IMS), which are generated by protease digestion of the Drosophila melanogaster proteome, is modeled and predicted based on two different types of characterization methods, i.e. sequence-based approach and structure-based approach. In this procedure, the sequence-based approach considers both the amino acid composition of a peptide and the local environment profile of each amino acid in the peptide; the structure-based approach is performed with the CODESSA protocol, which regards a peptide as a common organic compound and generates more than 200 statistically significant variables to characterize the whole structure profile of a peptide molecule. Subsequently, the nonlinear support vector machine (SVM) and Gaussian process (GP) as well as linear partial least squares (PLS) regression is employed to correlate the structural parameters of the characterizations with the IMS drift times of these peptides. The obtained quantitative structure-spectrum relationship (QSSR) models are evaluated rigorously and investigated systematically via both one-deep and two-deep cross-validations as well as the rigorous Monte Carlo cross-validation (MCCV). We also give a comprehensive comparison on the resulting statistics arising from the different combinations of variable types with modeling methods and find that the sequence-based approach can give the QSSR models with better fitting ability and predictive power but worse interpretability than the structure-based approach. In addition, though the QSSR modeling using sequence-based approach is not needed for the preparation of the minimization structures of peptides before the modeling, it would be considerably efficient as compared to that using structure-based approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

Total hydrocarbon analysis by ion mobility spectrometry

NASA Technical Reports Server (NTRS)

Cross, John H.; Limero, Thomas F.; James, John T.

1994-01-01

Astronauts must be alerted quickly to chemical leaks that compromise their health and the success of their missions. An ideal leak detector would be equally sensitive to all compounds that might constitute a hazard and insensitive to nontoxic compounds. No ideal sensor exists; thus, selection of a methodology is a series of compromises. The commonly used methods are either insensitive at the low exposure levels set by OSHA, NASA, and other organizations or are selectively insensitive to important classes of chemicals such as Freons. After extensive study and experience, the Toxicology Group at JSC has selected ion mobility spectrometry (IMS) for development into a broad range, sensitive detector. In addition to the sensing method, signal processing is important leak detection because a background signal can be expected at all times. The leak-detecting instrument must be programmed to discriminate between authentic leaks and background fluctuations caused by routine operations. The results of an evaluation of the prototype THA is presented in terms related to spacecraft operations. The evaluation included determination of instrumental parameters such as stability and response times. We also included responses to some common components of spacecraft atmospheres in pure form and in binary and ternary mixtures. The output of the four algorithms to the mixtures was found to be noticeably different. These responses are compared on the basis of their utility for signaling a chemical leak. As a means of evaluating its resistance to a falsely positive response, the THA was challenged with carbon dioxide and methane, compounds whose concentrations normally increase in spacecraft air during human habitation. The instrument showed virtually no response to these interferences. Although the prototype THA is designed for space flight, this detector is expected to be useful for field screening at chemical waste dumps and other environmentally sensitive locations.

Method for enhancing the resolving power of ion mobility separations over a limited mobility range

DOEpatents

Shvartsburg, Alexandre A; Tang, Keqi; Smith, Richard D

2014-09-23

A method for raising the resolving power, specificity, and peak capacity of conventional ion mobility spectrometry is disclosed. Ions are separated in a dynamic electric field comprising an oscillatory field wave and opposing static field, or at least two counter propagating waves with different parameters (amplitude, profile, frequency, or speed). As the functional dependencies of mean drift velocity on the ion mobility in a wave and static field or in unequal waves differ, only single species is equilibrated while others drift in either direction and are mobility-separated. An ion mobility spectrum over a limited range is then acquired by measuring ion drift times through a fixed distance inside the gas-filled enclosure. The resolving power in the vicinity of equilibrium mobility substantially exceeds that for known traveling-wave or drift-tube IMS separations, with spectra over wider ranges obtainable by stitching multiple segments. The approach also enables low-cutoff, high-cutoff, and bandpass ion mobility filters.

The role of ion mobility spectrometry-mass spectrometry in the analysis of protein reference standards.

PubMed

Pritchard, Caroline; O'Connor, Gavin; Ashcroft, Alison E

2013-08-06

To achieve comparability of measurement results of protein amount of substance content between clinical laboratories, suitable reference materials are required. The impact on measurement comparability of potential differences in the tertiary and quaternary structure of protein reference standards is as yet not well understood. With the use of human growth hormone as a model protein, the potential of ion mobility spectrometry-mass spectrometry as a tool to assess differences in the structure of protein reference materials and their interactions with antibodies has been investigated here.

A Unique (3+2) Annulation Reaction between Meldrum's Acid and Nitrones: Mechanistic Insight by ESI-IMS-MS and DFT Studies.

PubMed

Lespes, Nicolas; Pair, Etienne; Maganga, Clisy; Bretier, Marie; Tognetti, Vincent; Joubert, Laurent; Levacher, Vincent; Hubert-Roux, Marie; Afonso, Carlos; Loutelier-Bourhis, Corinne; Brière, Jean-François

2018-03-15

The fragile intermediates of the domino process leading to an isoxazolidin-5-one, triggered by unique reactivity between Meldrum's acid and an N-benzyl nitrone in the presence of a Brønsted base, were determined thanks to the softness and accuracy of electrospray ionization mass spectrometry coupled to ion mobility spectrometry (ESI-IMS-MS). The combined DFT study shed light on the overall organocatalytic sequence that starts with a stepwise (3+2) annulation reaction that is followed by a decarboxylative protonation sequence encompassing a stereoselective pathway issue. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laser-ablation electrospray ionization mass spectrometry with ion mobility separation reveals metabolites in the symbiotic interactions of soybean roots and rhizobia.

PubMed

Stopka, Sylwia A; Agtuca, Beverly J; Koppenaal, David W; Paša-Tolić, Ljiljana; Stacey, Gary; Vertes, Akos; Anderton, Christopher R

2017-07-01

Technologies enabling in situ metabolic profiling of living plant systems are invaluable for understanding physiological processes and could be used for rapid phenotypic screening (e.g., to produce plants with superior biological nitrogen-fixing ability). The symbiotic interaction between legumes and nitrogen-fixing soil bacteria results in a specialized plant organ (i.e., root nodule) where the exchange of nutrients between host and endosymbiont occurs. Laser-ablation electrospray ionization mass spectrometry (LAESI-MS) is a method that can be performed under ambient conditions requiring minimal sample preparation. Here, we employed LAESI-MS to explore the well characterized symbiosis between soybean (Glycine max L. Merr.) and its compatible symbiont, Bradyrhizobium japonicum. The utilization of ion mobility separation (IMS) improved the molecular coverage, selectivity, and identification of the detected biomolecules. Specifically, incorporation of IMS resulted in an increase of 153 differentially abundant spectral features in the nodule samples. The data presented demonstrate the advantages of using LAESI-IMS-MS for the rapid analysis of intact root nodules, uninfected root segments, and free-living rhizobia. Untargeted pathway analysis revealed several metabolic processes within the nodule (e.g., zeatin, riboflavin, and purine synthesis). Compounds specific to the uninfected root and bacteria were also detected. Lastly, we performed depth profiling of intact nodules to reveal the location of metabolites to the cortex and inside the infected region, and lateral profiling of sectioned nodules confirmed these molecular distributions. Our results established the feasibility of LAESI-IMS-MS for the analysis and spatial mapping of plant tissues, with its specific demonstration to improve our understanding of the soybean-rhizobial symbiosis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Laser-ablation electrospray ionization mass spectrometry with ion mobility separation reveals metabolites in the symbiotic interactions of soybean roots and rhizobia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stopka, Sylwia A.; Agtuca, Beverly J.; Koppenaal, David W.

Technologies enabling in situ metabolic profiling of living plant systems are invaluable for understanding physiological processes and could be used for rapid phenotypic screening (e.g., to produce plants with superior biological nitrogen fixing ability). The symbiotic interaction between legumes and nitrogen-fixing soil bacteria results in a specialized plant organ (i.e., root nodule), where the exchange of nutrients between host and endosymbiont occurs. Laser ablation electrospray ionization mass spectrometry (LAESI-MS) is a method that can be performed under ambient conditions requiring minimal sample preparation. Here, we employed LAESI-MS to explore the well-characterized symbiosis between soybean (Glycine max L. Merr.) and itsmore » compatible symbiont, Bradyrhizobium japonicum. The utilization of ion mobility separation (IMS) improved the molecular coverage, selectivity, and identification of the detected biomolecules. Specifically, incorporation of IMS resulted in an increase of 153 detected metabolites in the nodule samples. The data presented demonstrates the advantages of using LAESI-IMS-MS for the rapid analysis of intact root nodules, uninfected root segments, and free-living rhizobia. Untargeted pathway analysis revealed several metabolic processes within the nodule (e.g., zeatin, riboflavin, and purine synthesis). Compounds specific to the uninfected root and bacteria were also detected. Lastly, we performed depth-profiling of intact nodules to reveal the location of metabolites to the cortex and inside the infected region, and lateral profiling of sectioned nodules confirmed these molecular distributions. Our results established the feasibility of LAESI-IMS-MS for the analysis and spatial mapping of plant tissues, with its specific demonstration to improve our understanding of the soybean-rhizobial symbiosis.« less

Detection of piperonal emitted from polymer controlled odor mimic permeation systems utilizing Canis familiaris and solid phase microextraction-ion mobility spectrometry.

PubMed

Macias, Michael S; Guerra-Diaz, Patricia; Almirall, José R; Furton, Kenneth G

2010-02-25

Currently, in the field of odor detection, there is generally a wider variation in limit of detections (LODs) for canines than instruments. The study presented in this paper introduces an improved protocol for the creation of controlled odor mimic permeation system (COMPS) devices for use as standards in canine training and discusses the canine detection thresholds of piperonal, a starting material for the illicit drug 3,4-methylenedioxymethamphetamine (MDMA), when exposed to these devices. Additionally, this paper describes the first-ever reported direct comparison of solid phase microextraction-ion mobility spectrometry (SPME-IMS) to canine detection for the MDMA odorant, piperonal. The research presented shows the reliability of COMPS devices as low cost field calibrants providing a wide range of odorant concentrations for biological and instrumental detectors. The canine LOD of piperonal emanating from the 100 ng s(-1) COMPS was found to be 1 ng as compared to the SPME-IMS LOD of piperonal in a static, closed system at 2 ng, with a linear dynamic range from 2 ng to 11 ng. The utilization of the COMPS devices would allow for training that will reduce the detection variability between canines and maintain improved consistency for training purposes. Since both SPME and IMS are field portable technologies, it is expected that this coupled method will be useful as a complement to canine detection for the field detection of MDMA. 2009 Elsevier Ireland Ltd. All rights reserved.

Extraction of toxic compounds from saliva by magnetic-stirring-assisted micro-solid-phase extraction step followed by headspace-gas chromatography-ion mobility spectrometry.

PubMed

Criado-García, Laura; Arce, Lourdes

2016-09-01

A new sample extraction procedure based on micro-solid-phase extraction (μSPE) using a mixture of sorbents of different polarities (polymeric reversed-phase sorbent HLB, silica-based sorbent C18, and multiwalled carbon nanotubes) was applied to extract benzene, toluene, butyraldehyde, benzaldehyde, and tolualdehyde present in saliva to avoid interference from moisture and matrix components and enhance sensitivity and selectivity of the ion mobility spectrometry (IMS) methodology proposed. The extraction of target analytes from saliva samples by using μSPE were followed by the desorption step carried out in the headspace vials placed in the autosampler of the IMS device. Then, 200 μL of headspace was injected into the GC column coupled to the IMS for its analysis. The method was fully validated in terms of sensitivity, precision, and recovery. The LODs and LOQs obtained, when analytes were dissolved in saliva samples to consider the matrix effect, were within the range of 0.38-0.49 and 1.26-1.66 μg mL(-1), respectively. The relative standard deviations were <3.5 % for retention time and drift time values, which indicate that the method proposed can be applied to determine toxic compounds in saliva samples. Graphical abstract Summary of steps followed in the experimental set up of this work.

Rapid screening of methamphetamines in human serum by headspace solid-phase microextraction using a dodecylsulfate-doped polypyrrole film coupled to ion mobility spectrometry.

PubMed

Alizadeh, Naader; Mohammadi, Abdorreza; Tabrizchi, Mahmoud

2008-03-07

A simple, rapid and highly sensitive method for simultaneous analysis of methamphetamine (MA) and 3,4-methylenedioxy methamphetamine (MDMA) in human serum was developed using the solid-phase microextraction (SPME) combined with ion mobility spectrometry (IMS). A dodecylsulfate-doped polypyrrole (PPy-DS) was applied as a new fiber for SPME. Electrochemically polymerized PPy is formed on the surface of a platinum wire and will contain charge-compensating anion (dodecylsulfate) incorporated during synthesis using cyclic voltammetry (CV) technique. The extraction properties of the fiber to MA and MDMA were examined, using a headspace-SPME (HS-SPME) device and thermal desorption in injection port of IMS. The results show that PPy-DS as a SPME fiber coating is suitable for the successful extraction of these compounds. This method is suitable for the identification and determination of MAs, is not time-consuming, requires small quantities of sample and does not require any derivatization. Parameters like pH, extraction time, ionic strength, and temperature of the sample were studied and optimized to obtain the best extraction results. The HS-SPME-IMS method provided good repeatability (RSDs<7.8 %) for spiked serum samples. The calibration graphs were linear in the range of 20-4000 ng ml(-1) (R(2)>0.99) and detection limits for MDMA and MA were 5 and 8 ng ml(-1), respectively. HS-SPME-IMS of non-spiked serum sample provided a spectrum without any peak from the matrix, supporting an effective sample clean-up. Finally, the proposed method was applied for analysis one of the ecstasy tablet.

Comparison of pulse glow discharge-ion mobility spectrometry and liquid chromatography with tandem mass spectrometry based on multiplug filtration cleanup for the analysis of tricaine mesylate residues in fish and water.

PubMed

Zou, Nan; Chen, Ronghua; Qin, Yuhong; Song, Shuangyu; Tang, Xinglin; Pan, Canping

2016-09-01

Analytical methods based on multiplug filtration cleanup coupled with pulse glow discharge-ion mobility spectrometry and liquid chromatography tandem mass spectrometry were developed for the analysis of tricaine mesylate residue in fish and fish-raising water samples. A silica fiber holder and an appropriate new interface were designed to make the direct introduction of the fiber into the pulse glow discharge-ion mobility spectrometry introduction mechanism. The multiplug filtration cleanup method with adsorption mixtures was optimized for the determination of tricaine mesylate in fish samples. Good linear relationships were obtained by the two methods. For fish samples, limits of detection were 6 and 0.6 μg/kg by ion mobility spectrometry and liquid chromatography with tandem mass spectrometry, respectively. The matrix effect of the established liquid chromatography tandem mass spectrometry method was negligible for fish samples but that of the ion mobility spectrometry method was not. The two methods were compared. The ion mobility spectrometry system could be used a rapid screening tool on site with the advantage of rapidity, simplicity, and portability, and the liquid chromatography tandem mass spectrometry system could be used for validation in laboratory conditions with the advantage of lower limit of detection, stability, and precision. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peak Detection Method Evaluation for Ion Mobility Spectrometry by Using Machine Learning Approaches

PubMed Central

Hauschild, Anne-Christin; Kopczynski, Dominik; D’Addario, Marianna; Baumbach, Jörg Ingo; Rahmann, Sven; Baumbach, Jan

2013-01-01

Ion mobility spectrometry with pre-separation by multi-capillary columns (MCC/IMS) has become an established inexpensive, non-invasive bioanalytics technology for detecting volatile organic compounds (VOCs) with various metabolomics applications in medical research. To pave the way for this technology towards daily usage in medical practice, different steps still have to be taken. With respect to modern biomarker research, one of the most important tasks is the automatic classification of patient-specific data sets into different groups, healthy or not, for instance. Although sophisticated machine learning methods exist, an inevitable preprocessing step is reliable and robust peak detection without manual intervention. In this work we evaluate four state-of-the-art approaches for automated IMS-based peak detection: local maxima search, watershed transformation with IPHEx, region-merging with VisualNow, and peak model estimation (PME). We manually generated a gold standard with the aid of a domain expert (manual) and compare the performance of the four peak calling methods with respect to two distinct criteria. We first utilize established machine learning methods and systematically study their classification performance based on the four peak detectors’ results. Second, we investigate the classification variance and robustness regarding perturbation and overfitting. Our main finding is that the power of the classification accuracy is almost equally good for all methods, the manually created gold standard as well as the four automatic peak finding methods. In addition, we note that all tools, manual and automatic, are similarly robust against perturbations. However, the classification performance is more robust against overfitting when using the PME as peak calling preprocessor. In summary, we conclude that all methods, though small differences exist, are largely reliable and enable a wide spectrum of real-world biomedical applications. PMID:24957992

Peak detection method evaluation for ion mobility spectrometry by using machine learning approaches.

PubMed

Hauschild, Anne-Christin; Kopczynski, Dominik; D'Addario, Marianna; Baumbach, Jörg Ingo; Rahmann, Sven; Baumbach, Jan

2013-04-16

Ion mobility spectrometry with pre-separation by multi-capillary columns (MCC/IMS) has become an established inexpensive, non-invasive bioanalytics technology for detecting volatile organic compounds (VOCs) with various metabolomics applications in medical research. To pave the way for this technology towards daily usage in medical practice, different steps still have to be taken. With respect to modern biomarker research, one of the most important tasks is the automatic classification of patient-specific data sets into different groups, healthy or not, for instance. Although sophisticated machine learning methods exist, an inevitable preprocessing step is reliable and robust peak detection without manual intervention. In this work we evaluate four state-of-the-art approaches for automated IMS-based peak detection: local maxima search, watershed transformation with IPHEx, region-merging with VisualNow, and peak model estimation (PME).We manually generated Metabolites 2013, 3 278 a gold standard with the aid of a domain expert (manual) and compare the performance of the four peak calling methods with respect to two distinct criteria. We first utilize established machine learning methods and systematically study their classification performance based on the four peak detectors' results. Second, we investigate the classification variance and robustness regarding perturbation and overfitting. Our main finding is that the power of the classification accuracy is almost equally good for all methods, the manually created gold standard as well as the four automatic peak finding methods. In addition, we note that all tools, manual and automatic, are similarly robust against perturbations. However, the classification performance is more robust against overfitting when using the PME as peak calling preprocessor. In summary, we conclude that all methods, though small differences exist, are largely reliable and enable a wide spectrum of real-world biomedical applications.

Rapid label-free profiling of oral cancer biomarker proteins using nano-UPLC-Q-TOF ion mobility mass spectrometry.

PubMed

Nassar, Ala F; Williams, Brad J; Yaworksy, Dustin C; Patel, Vyomesh; Rusling, James F

2016-03-01

It has become quite clear that single cancer biomarkers cannot in general provide high sensitivity and specificity for reliable clinical cancer diagnostics. This paper explores the feasibility of rapid detection of multiple biomarker proteins in model oral cancer samples using label-free protein relative quantitation. MS-based label-free quantitative proteomics offer a rapid alternative that bypasses the need for stable isotope containing compounds to chemically bind and label proteins. Total protein content in oral cancer cell culture conditioned media was precipitated, subjected to proteolytic digestion, and then analyzed using a nano-UPLC (where UPLC is ultra-performance liquid chromatography) coupled to a hybrid Q-Tof ion-mobility mass spectrometry (MS). Rapid, simultaneous identification and quantification of multiple possible cancer biomarker proteins was achieved. In a comparative study between cancer and noncancer samples, approximately 952 proteins were identified using a high-throughput 1D ion mobility assisted data independent acquisition (IM-DIA) approach. As we previously demonstrated that interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A) were readily detected in oral cancer cell conditioned media(1), we targeted these biomarker proteins to validate our approach. Target biomarker protein IL-8 was found between 3.5 and 8.8 fmol, while VEGF-A was found at 1.45 fmol in the cancer cell media. Overall, our data suggest that the nano-UPLC-IM-DIA bioassay is a feasible approach to identify and quantify proteins in complex samples without the need for stable isotope labeling. These results have significant implications for rapid tumor diagnostics and prognostics by monitoring proteins such as IL-8 and VEGF-A implicated in cancer development and progression. The analysis in tissue or plasma is not possible at this time, but the subsequent work would be needed for validation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Resolving Structural Isomers of Monosaccharide Methyl Glycosides Using Drift Tube and Traveling Wave Ion Mobility Mass Spectrometry

PubMed Central

Li, Hongli; Giles, Kevin; Bendiak, Brad; Kaplan, Kimberly; Siems, William F.; Hill, Herbert H.

2013-01-01

Monosaccharide structural isomers including sixteen methyl-D-glycopyranosides and four methyl-N-acetylhexosamines were subjected to ion mobility measurements by electrospray ion mobility mass spectrometry. Two ion mobility-MS systems were employed: atmospheric pressure drift tube ion mobility time-of-flight mass spectrometry and a Synapt G2 HDMS system which incorporates a low pressure traveling wave ion mobility separator. All the compounds were investigated as [M+Na]+ ions in the positive mode. A majority of the monosaccharide structural isomers exhibited different mobility drift times in either system, depending on differences in their anomeric and stereochemical configurations. In general, drift time patterns (relative drift times of isomers) matched between the two instruments. Higher resolving power was observed using the atmospheric pressure drift tube. Collision cross section values of monosaccharide structural isomers were directly calculated from the atmospheric pressure ion mobility experiments and a collision cross section calibration curve was made for the traveling wave ion mobility instrument. Overall, it was demonstrated that ion mobility-mass spectrometry using either drift tube or traveling wave ion mobility is a valuable technique for resolving subtle variations in stereochemistry among the sodium adducts of monosaccharide methyl glycosides. PMID:22339760

Field ion spectrometry: a new technology for cocaine and heroin detection

NASA Astrophysics Data System (ADS)

Carnahan, Byron L.; Day, Stephen; Kouznetsov, Viktor; Tarassov, Alexandre

1997-02-01

Field ion spectrometry, also known as transverse field compensation ion mobility spectrometry, is a new technique for trace gas analysis that can be applied to the detection of cocaine and heroin. Its principle is based on filtering ion species according to the functional dependence of their mobilities with electric field strength. Field ion spectrometry eliminates the gating electrodes needed in conventional IMS to pulse ions into the spectrometer; instead, ions are injected in to the spectrometer and reach the detector continuously, resulting in improved sensitivity. The technique enables analyses that are difficult with conventional constant field strength ion mobility spectrometers. We have shown that a filed ion spectrometer can selectively detect the vapors from cocaine and heroin emitted from both their base and hydrochloride forms. The estimated volumetric limits of detection are in the low pptv range, based on testing with standardized drug vapor generation systems. The spectrometer can detect cocaine base in the vapor phase, at concentrations well below its estimated 100 pptv vapor pressure equivalent at 20 degrees C. This paper describes the underlying principles of field ion spectrometry in relation to narcotic drug detection, and recent results obtained for cocaine and heroin. The work has been sponsored in part by the United States Advanced Research Projects Agency under contract DAAB10-95C-0004, for the DOD Counterdrug Technology Development Program.

A Helium GC/IMS for the Analysis of Extraterrestrial Volatiles in Exobiology Flight Experiments

NASA Technical Reports Server (NTRS)

Kojiro, Daniel R.; Carle, Glenn C.; Humphry, Donald E.; Shao, Maxine; Takeuchi, Nori

1995-01-01

For exobiology experiments on board spacecraft or space probes, a wide range of chemical species often must be detected and identified. The limited amount of power and space available for flight instruments severely limits the number of instruments that can be flown on any given mission. It is important then, that these experiments utilize instrumentation with universal response, so that all species of interest can be analyzed. Instrumentation to fulfill the analytical requirements of exobiology experiments has been developed utilizing Gas Chromatography - Ion Mobility Spectrometry. The Gas Chromatograph (GC) combines columns developed specifically for the complex mixtures anticipated with highly sensitive Metastable Ionization Detectors (a type of Helium Ionization Detector). To satisfy the limitations placed on resources, the Ion Mobility Spectrometer (IMS) uses the same ultra high purity helium as the GC. This GC-MS provides the analytical capability to fulfill a wide range of exobiology flight experiment applications and has been included on a proposed Discovery Mission and proposals for both Lander and Orbiter of the European Space Agency's Rosetta Comet Mission. A data base of helium IMS spectra is now being built for these future applications.

Quantitative analysis of volatile organic compounds using ion mobility spectra and cascade correlation neural networks

NASA Technical Reports Server (NTRS)

Harrington, Peter DEB.; Zheng, Peng

1995-01-01

Ion Mobility Spectrometry (IMS) is a powerful technique for trace organic analysis in the gas phase. Quantitative measurements are difficult, because IMS has a limited linear range. Factors that may affect the instrument response are pressure, temperature, and humidity. Nonlinear calibration methods, such as neural networks, may be ideally suited for IMS. Neural networks have the capability of modeling complex systems. Many neural networks suffer from long training times and overfitting. Cascade correlation neural networks train at very fast rates. They also build their own topology, that is a number of layers and number of units in each layer. By controlling the decay parameter in training neural networks, reproducible and general models may be obtained.

Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate.

PubMed

Marcoux, Julien; Champion, Thierry; Colas, Olivier; Wagner-Rousset, Elsa; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

2015-08-01

Antibody-drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM-MS) for the characterization of trastuzumab emtansine (T-DM1, Kadcyla(®)). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and combines the anti-HER2 antibody trastuzumab (Herceptin(®)), with the cytotoxic microtubule-inhibiting maytansine derivative, DM1. We show that native MS combined with high-resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM-MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T-DM1. © 2015 The Protein Society.

Combining Structural Probes in the Gas Phase - Ion Mobility- Resolved Action-FRET

NASA Astrophysics Data System (ADS)

Daly, Steven; MacAleese, Luke; Dugourd, Philippe; Chirot, Fabien

2018-01-01

In the context of native mass spectrometry, the development of gas-phase structural probes sensitive to the different levels of structuration of biomolecular assemblies is necessary to push forward conformational studies. In this paper, we provide the first example of the combination of ion mobility (IM) and Förster resonance energy transfer (FRET) measurements within the same experimental setup. The possibility to obtain mass- and mobility-resolved FRET measurements is demonstrated on a model peptide and applied to monitor the collision-induced unfolding of ubiquitin. [Figure not available: see fulltext.

Direct analysis of human breath ammonia using corona discharge ion mobility spectrometry.

PubMed

Jazan, Elham; Mirzaei, Hadi

2014-01-01

In this study, ammonia in human breath was directly determined using corona discharge ionization ion mobility spectrometry (CD-IMS) technique with several important advantages including high sensitivity, low cost, high speed, and ease of maintenance. The temperature effect on the ammonia signal was evaluated too. The results indicated that the best temperature for the investigation of breath ammonia was 150°C. The analytical results showed that the linear dynamic range was between 12 and 810ppb and the detection limit was 6.6ppb. The relative standard deviation (RSD) was obtained to be 5, 3, and 3 for 290, 348, and 522ppb, respectively. The amounts of ammonia in breath of eight healthy volunteers were measured. The values were between 236 and 1218ppb. Also, the inequality in breath ammonia levels was scrutinized over a 6h working day for three healthy volunteers. The results showed a drop in breath ammonia from the morning amount to the mid-day measurement and then, a progressive increase while the day continued. In addition, the amounts of ammonia were determined to be 1494-1553ppb in exhaled breath of two renal failure patients. The results obtained in this work revealed that the method was conveniently established without any considerable sample pretreatment for direct analysis of ammonia in human breath. Copyright © 2013 Elsevier B.V. All rights reserved.

Structural Characterization of Unsaturated Phosphatidylcholines Using Traveling Wave Ion Mobility Spectrometry

PubMed Central

Kim, Hugh I.; Kim, Hyungjun; Pang, Eric S.; Ryu, Ernest K.; Beegle, Luther W.; Loo, Joseph A.; Goddard, William A.; Kanik, Isik

2009-01-01

A number of phosphatidylcholine (PC) cations spanning a mass range of 400 to 1000 Da are investigated using electrospray ionization mass spectrometry coupled with traveling wave ion mobility spectrometry (TWIMS). A high correlation between mass and mobility is demonstrated with saturated phosphatidylcholine cations in N2. A significant deviation from this mass-mobility correlation line is observed for the unsaturated PC cation. We found that the double bond in the acyl chain causes a 5% reduction in drift time. The drift time is reduced at a rate of ~1% for each additional double bond. Theoretical collision cross sections of PC cations exhibit good agreement with experimentally evaluated values. Collision cross sections are determined using the recently derived relationship between mobility and drift time in TWIMS stacked ring ion guide (SRIG) and compared to estimate collision cross-sections using empiric calibration method. Computational analysis was performed using the modified trajectory (TJ) method with nonspherical N2 molecules as the drift gas. The difference between estimated collision cross-sections and theoretical collision cross-sections of PC cations is related to the sensitivity of the PC cation collision cross-sections to the details of the ion-neutral interactions. The origin of the observed correlation and deviation between mass and mobility of PC cations is discussed in terms of the structural rigidity of these molecules using molecular dynamic simulations. PMID:19764704

Identification of carbohydrate anomers using ion mobility-mass spectrometry.

PubMed

Hofmann, J; Hahm, H S; Seeberger, P H; Pagel, K

2015-10-08

Carbohydrates are ubiquitous biological polymers that are important in a broad range of biological processes. However, owing to their branched structures and the presence of stereogenic centres at each glycosidic linkage between monomers, carbohydrates are harder to characterize than are peptides and oligonucleotides. Methods such as nuclear magnetic resonance spectroscopy can be used to characterize glycosidic linkages, but this technique requires milligram amounts of material and cannot detect small amounts of coexisting isomers. Mass spectrometry, on the other hand, can provide information on carbohydrate composition and connectivity for even small amounts of sample, but it cannot be used to distinguish between stereoisomers. Here, we demonstrate that ion mobility-mass spectrometry--a method that separates molecules according to their mass, charge, size, and shape--can unambiguously identify carbohydrate linkage-isomers and stereoisomers. We analysed six synthetic carbohydrate isomers that differ in composition, connectivity, or configuration. Our data show that coexisting carbohydrate isomers can be identified, and relative concentrations of the minor isomer as low as 0.1 per cent can be detected. In addition, the analysis is rapid, and requires no derivatization and only small amounts of sample. These results indicate that ion mobility-mass spectrometry is an effective tool for the analysis of complex carbohydrates. This method could have an impact on the field of carbohydrate synthesis similar to that of the advent of high-performance liquid chromatography on the field of peptide assembly in the late 1970s.

Identification of carbohydrate anomers using ion mobility-mass spectrometry

NASA Astrophysics Data System (ADS)

Hofmann, J.; Hahm, H. S.; Seeberger, P. H.; Pagel, K.

2015-10-01

Carbohydrates are ubiquitous biological polymers that are important in a broad range of biological processes. However, owing to their branched structures and the presence of stereogenic centres at each glycosidic linkage between monomers, carbohydrates are harder to characterize than are peptides and oligonucleotides. Methods such as nuclear magnetic resonance spectroscopy can be used to characterize glycosidic linkages, but this technique requires milligram amounts of material and cannot detect small amounts of coexisting isomers. Mass spectrometry, on the other hand, can provide information on carbohydrate composition and connectivity for even small amounts of sample, but it cannot be used to distinguish between stereoisomers. Here, we demonstrate that ion mobility-mass spectrometry--a method that separates molecules according to their mass, charge, size, and shape--can unambiguously identify carbohydrate linkage-isomers and stereoisomers. We analysed six synthetic carbohydrate isomers that differ in composition, connectivity, or configuration. Our data show that coexisting carbohydrate isomers can be identified, and relative concentrations of the minor isomer as low as 0.1 per cent can be detected. In addition, the analysis is rapid, and requires no derivatization and only small amounts of sample. These results indicate that ion mobility-mass spectrometry is an effective tool for the analysis of complex carbohydrates. This method could have an impact on the field of carbohydrate synthesis similar to that of the advent of high-performance liquid chromatography on the field of peptide assembly in the late 1970s.

Direct coupling of packed column supercritical fluid chromatography to continuous corona discharge ion mobility spectrometry.

PubMed

Rahmanian, A; Ghaziaskar, H S; Khayamian, T

2013-01-11

In this study, packed column supercritical fluid chromatography (SFC) was directly coupled to a continuous corona discharge (CD) ion mobility spectrometer (IMS) with several modifications. The main advantage of the developed detector is its capability to introduce full column effluent up to 2000 mL min(-1) CO(2) gas directly into the IMS cell relative to 40 mL min(-1) CO(2) gas as a maximum tolerance, reported for the previous IMS detectors. This achievement was made possible because of using corona discharge instead of (63)Ni as an ionization source and locating the inlet and outlet of the CO(2) gas in the counter electrode of the CD in opposite direction. In addition, a heated interface was placed between back pressure regulator (BPR) and the IMS cell to heat the output of the BPR for introducing sample as the gas phase into the IMS cell. Furthermore, a make-up methanol flow was introduced between the column outlet and BPR to provide a more uniform flow through the BPR and also to prevent freezing and deposition of the analytes in the BPR. The performance of the SFC-CD-IMS was evaluated by analysis of testosterone, medroxyprogesterone, caffeine, and theophylline as test compounds and figures of merit for these compounds have been calculated. Copyright © 2012 Elsevier B.V. All rights reserved.

Multidimensional Separation of Natural Products Using Liquid Chromatography Coupled to Hadamard Transform Ion Mobility Mass Spectrometry

NASA Astrophysics Data System (ADS)

Liu, Wenjie; Zhang, Xing; Knochenmuss, Richard; Siems, William F.; Hill, Herbert H.

2016-05-01

A high performance liquid chromatograph (HPLC)was interfaced to an atmospheric drift tube ion mobility time of flight mass spectrometry. The power of multidimensional separation was demonstrated using chili pepper extracts. The ambient pressure drift tube ion mobility provided high resolving powers up to 166 for the HPLC eluent. With implementation of Hadamard transform (HT), the duty cycle for the ion mobility drift tube was increased from less than 1% to 50%, and the ion transmission efficiency was improved by over 200 times compared with pulsed mode, improving signal to noise ratio 10 times. HT ion mobility and TOF mass spectrometry provide an additional dimension of separation for complex samples without increasing the analysis time compared with conventional HPLC.

Analysis of psilocybin and psilocin in Psilocybe subcubensis Guzmán by ion mobility spectrometry and gas chromatography-mass spectrometry.

PubMed

Keller, T; Schneider, A; Regenscheit, P; Dirnhofer, R; Rücker, T; Jaspers, J; Kisser, W

1999-01-11

A new method has been developed for the rapid analysis of psilocybin and/or psilocin in fungus material using ion mobility spectrometry. Quantitative analysis was performed by gas chromatography-mass spectrometry after a simple one-step extraction involving homogenization of the dried fruit bodies of fungi in chloroform and derivatization with MSTFA. The proposed methods resulted in rapid procedures useful in analyzing psychotropic fungi for psilocybin and psilocin.

Wireless Data Acquisition of Transient Signals for Mobile Spectrometry Applications.

PubMed

Trzcinski, Peter; Weagant, Scott; Karanassios, Vassili

2016-05-01

Wireless data acquisition using smartphones or handhelds offers increased mobility, it provides reduced size and weight, it has low electrical power requirements, and (in some cases) it has an ability to access the internet. Thus, it is well suited for mobile spectrometry applications using miniaturized, field-portable spectrometers, or detectors for chemical analysis in the field (i.e., on-site). There are four main wireless communications standards that can be used for wireless data acquisition, namely ZigBee, Bluetooth, Wi-Fi, and UWB (ultra-wide band). These are briefly reviewed and are evaluated for applicability to data acquisition of transient signals (i.e., time-domain) in the field (i.e., on-site) from a miniaturized, field-portable photomultiplier tube detector and from a photodiode array detector installed in a miniaturized, field-portable fiber optic spectrometer. These are two of the most widely used detectors for optical measurements in the ultraviolet-visible range of the spectrum. A miniaturized, 3D-printed, battery-operated microplasma-on-a-chip was used for generation of transient optical emission signals. Elemental analysis from liquid microsamples, a microplasma, and a handheld or a smartphone will be used as examples. Development and potential applicability of wireless data acquisition of transient optical emission signals for taking part of the lab to the sample types of mobile, field-portable spectrometry applications will be discussed. The examples presented are drawn from past and ongoing work in the authors' laboratory. A handheld or a smartphone were used as the mobile computing devices of choice. © The Author(s) 2016.

Atmospheric pressure chemical ionization studies of non-polar isomeric hydrocarbons using ion mobility spectrometry and mass spectrometry with different ionization techniques

NASA Technical Reports Server (NTRS)

Borsdorf, H.; Nazarov, E. G.; Eiceman, G. A.

2002-01-01

The ionization pathways were determined for sets of isomeric non-polar hydrocarbons (structural isomers, cis/trans isomers) using ion mobility spectrometry and mass spectrometry with different techniques of atmospheric pressure chemical ionization to assess the influence of structural features on ion formation. Depending on the structural features, different ions were observed using mass spectrometry. Unsaturated hydrocarbons formed mostly [M - 1]+ and [(M - 1)2H]+ ions while mainly [M - 3]+ and [(M - 3)H2O]+ ions were found for saturated cis/trans isomers using photoionization and 63Ni ionization. These ionization methods and corona discharge ionization were used for ion mobility measurements of these compounds. Different ions were detected for compounds with different structural features. 63Ni ionization and photoionization provide comparable ions for every set of isomers. The product ions formed can be clearly attributed to the structures identified. However, differences in relative abundance of product ions were found. Although corona discharge ionization permits the most sensitive detection of non-polar hydrocarbons, the spectra detected are complex and differ from those obtained with 63Ni ionization and photoionization. c. 2002 American Society for Mass Spectrometry.

Squeezing of Ion Populations and Peaks in Traveling Wave Ion Mobility Separations and Structures for Lossless Ion Manipulations using Compression Ratio Ion Mobility Programming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garimella, Venkata BS; Hamid, Ahmed M.; Deng, Liulin

In this work, we report an approach for spatial and temporal gas phase ion population manipulation, and demonstrate its application for the collapse of the ion distributions in ion mobility (IM) separations into tighter packets providing higher sensitivity measurements in conjunction with mass spectrometry (MS). We do this for ions moving from a conventionally traveling wave (TW)-driven region to a region where the TW is intermittently halted or ‘stuttered’. This approach causes the ion packets spanning a number of TW-created traveling traps (TT) to be redistributed into fewer TT, resulting in spatial compression. The degree of spatial compression is controllablemore » and determined by the ratio of stationary time of the TW in the second region to its moving time. This compression ratio ion mobility programming (CRIMP) approach has been implemented using Structures for Lossless Ion Manipulations (SLIM) in conjunction with MS. CRIMP with the SLIM-MS platform is shown to provide increased peak intensities, reduced peak widths, and improved S/N ratios with MS detection. CRIMP also provides a foundation for extremely long path length and multi-pass IM separations in SLIM providing greatly enhanced IM resolution by reducing the detrimental effects of diffusional peak broadening due to increasing peak widths.« less

Ion Mobility Mass Spectrometry Analysis of Isomeric Disaccharide Precursor, Product and Cluster Ions

PubMed Central

Li, Hongli; Bendiak, Brad; Siems, William F.; Gang, David R.; Hill, Herbert H.

2015-01-01

RATIONALE Carbohydrates are highly variable in structure owing to differences in their anomeric configurations, monomer stereochemistry, inter-residue linkage positions and general branching features. The separation of carbohydrate isomers poses a great challenge for current analytical techniques. METHODS The isomeric heterogeneity of disaccharide ions and monosaccharideglycolaldehyde product ions evaluated using electrospray traveling wave ion mobility mass spectrometry (Synapt G2 high definition mass spectrometer) in both positive and negative ion modes investigation. RESULTS The separation of isomeric disaccharide ions was observed but not fully achieved based on their mobility profiles. The mobilities of isomeric product ions, the monosaccharide-glycolaldehydes, derived from different disaccharide isomers were measured. Multiple mobility peaks were observed for both monosaccharide-glycolaldehyde cations and anions, indicating that there was more than one structural configuration in the gas phase as verified by NMR in solution. More importantly, the mobility patterns for isomeric monosaccharide-glycolaldehyde product ions were different, which enabled partial characterization of their respective disaccharide ions. Abundant disaccharide cluster ions were also observed. The Results showed that a majority of isomeric cluster ions had different drift times and, moreover, more than one mobility peak was detected for a number of specific cluster ions. CONCLUSIONS It is demonstrated that ion mobility mass spectrometry is an advantageous method to assess the isomeric heterogeneity of carbohydrate compounds. It is capable of differentiating different types of carbohydrate ions having identical m/z values as well as multiple structural configurations of single compounds. PMID:24591031

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

DOE PAGES

Burnum-Johnson, Kristin E.; Baker, Erin S.; Metz, Thomas O.

2017-03-29

A successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Furthermore, problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development ofmore » pregnancy related problems at the molecular level. Here, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.« less

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burnum-Johnson, Kristin E.; Baker, Erin S.; Metz, Thomas O.

Successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy relatedmore » problems at the molecular level. In this perspective, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.« less

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burnum-Johnson, Kristin E.; Baker, Erin S.; Metz, Thomas O.

A successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Furthermore, problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development ofmore » pregnancy related problems at the molecular level. Here, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.« less

Ion Mobility Derived Collision Cross Sections to Support Metabolomics Applications

PubMed Central

2015-01-01

Metabolomics is a rapidly evolving analytical approach in life and health sciences. The structural elucidation of the metabolites of interest remains a major analytical challenge in the metabolomics workflow. Here, we investigate the use of ion mobility as a tool to aid metabolite identification. Ion mobility allows for the measurement of the rotationally averaged collision cross-section (CCS), which gives information about the ionic shape of a molecule in the gas phase. We measured the CCSs of 125 common metabolites using traveling-wave ion mobility-mass spectrometry (TW-IM-MS). CCS measurements were highly reproducible on instruments located in three independent laboratories (RSD < 5% for 99%). We also determined the reproducibility of CCS measurements in various biological matrixes including urine, plasma, platelets, and red blood cells using ultra performance liquid chromatography (UPLC) coupled with TW-IM-MS. The mean RSD was < 2% for 97% of the CCS values, compared to 80% of retention times. Finally, as proof of concept, we used UPLC–TW-IM-MS to compare the cellular metabolome of epithelial and mesenchymal cells, an in vitro model used to study cancer development. Experimentally determined and computationally derived CCS values were used as orthogonal analytical parameters in combination with retention time and accurate mass information to confirm the identity of key metabolites potentially involved in cancer. Thus, our results indicate that adding CCS data to searchable databases and to routine metabolomics workflows will increase the identification confidence compared to traditional analytical approaches. PMID:24640936

Biologically-Inspired Peptide Reagents for Enhancing IMS-MS Analysis of Carbohydrates

NASA Astrophysics Data System (ADS)

Bohrer, Brian C.; Clemmer, David E.

2011-09-01

The binding properties of a peptidoglycan recognition protein are translated via combinatorial chemistry into short peptides. Non-adjacent histidine, tyrosine, and arginine residues in the protein's binding cleft that associate specifically with the glycan moiety of a peptidoglycan substrate are incorporated into linear sequences creating a library of 27 candidate tripeptide reagents (three possible residues permutated across three positions). Upon electrospraying the peptide library and carbohydrate mixtures, some noncovalent complexes are observed. The binding efficiencies of the peptides vary according to their amino acid composition as well as the disaccharide linkage and carbohydrate ring-type. In addition to providing a charge-carrier for the carbohydrate, peptide reagents can also be used to differentiate carbohydrate isomers by ion mobility spectrometry. The utility of these peptide reagents as a means of enhancing ion mobility analysis of carbohydrates is illustrated by examining four glucose-containing disaccharide isomers, including a pair that is not resolved by ion mobility alone. The specificity and stoichiometry of the peptide-carbohydrate complexes are also investigated. Trihistidine demonstrates both suitable binding efficiency and successful resolution of disaccharides isomers, suggesting it may be a useful reagent in IMS analyses of carbohydrates.

A Hybrid Constant and Oscillatory Field Ion Mobility Analyzer in Structures for Lossless Ion Manipulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prabhakaran Nair Syamala Amma, Aneesh; Hamid, Ahme

2018-02-28

Ion mobility (IM) spectrometry is becoming an important approach for analyzing molecular ions in the gas phase with applications that span a multitude of scientific areas. There are a variety of IM-based approaches that utilize either constant or oscillatory electric fields. Here, we explore the combination of constant and oscillatory fields applied in a single device to affect the separation and filtering of ions based on their mobilities. The mobility analyzer allows confining and manipulating ions utilizing a combination of radio frequency (RF), direct current (DC) fields, and traveling waves (TW) in a structures for lossless ion manipulations (SLIM) module.more » In this work, we have investigated theoretically and experimentally the concept for continuous filtering of ions based on their mobilities where ions are mobility separated and selected by a combination of TW and constant fields providing opposing forces on the ions. The SLIM module was composed of two surfaces with mirror-image arrays of electrodes and had two regions where the different TW and opposing DC fields could be applied. By appropriately choosing the DC gradient and TW parameters for the two sections, it is possible to transmit ions of a selected mobility while filtering out others. The filtering capabilities are determined by the applied DC gradient and the TW parameters, such as frequency, amplitude and the TW sequence (i.e., the duty cycle of the traveling wave). The effect of different parameters on the sensitivity and the IM resolution of the device have been investigated.« less

A Hybrid Constant and Oscillatory Field Ion Mobility Analyzer Using Structures for Lossless Ion Manipulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prabhakaran, Aneesh; Hamid, Ahmed M.; Garimella, Sandilya V. B.

Ion mobility (IM) spectrometry is becoming an important approach for analyzing molecular ions in the gas phase with applications that span a multitude of scientific areas. There are a variety of IM-based approaches that utilize either constant or oscillatory electric fields. Here, we explore the combination of constant and oscillatory fields applied in a single device to affect the separation and filtering of ions based on their mobilities. The mobility analyzer allows confining and manipulating ions utilizing a combination of radio frequency (RF), direct current (DC) fields, and traveling waves (TW) in a structures for lossless ion manipulations (SLIM) module.more » In this work, we have investigated theoretically and experimentally the concept for continuous filtering of ions based on their mobilities where ions are mobility separated and selected by a combination of TW and constant fields providing opposing forces on the ions. The SLIM module was composed of two surfaces with mirror-image arrays of electrodes and had two regions where the different TW and opposing DC fields could be applied. By appropriately choosing the DC gradient and TW parameters for the two sections, it is possible to transmit ions of a selected mobility while filtering out others. The filtering capabilities are determined by the applied DC gradient and the TW parameters, such as frequency, amplitude and the TW sequence (i.e., the duty cycle of the traveling wave). The effect of different parameters on the sensitivity and the IM resolution of the device have been investigated.« less

Atmospheric pressure chemical ionization of fluorinated phenols in atmospheric pressure chemical ionization mass spectrometry, tandem mass spectrometry, and ion mobility spectrometry

NASA Technical Reports Server (NTRS)

Eiceman, G. A.; Bergloff, J. F.; Rodriguez, J. E.; Munro, W.; Karpas, Z.

1999-01-01

Atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) for fluorinated phenols (C6H5-xFxOH Where x = 0-5) in nitrogen with Cl- as the reagent ion yielded product ions of M Cl- through ion associations or (M-H)- through proton abstractions. Proton abstraction was controllable by potentials on the orifice and first lens, suggesting that some proton abstraction occurs through collision induced dissociation (CID) in the interface region. This was proven using CID of adduct ions (M Cl-) with Q2 studies where adduct ions were dissociated to Cl- or proton abstracted to (M-H)-. The extent of proton abstraction depended upon ion energy and structure in order of calculated acidities: pentafluorophenol > tetrafluorophenol > trifluorophenol > difluorophenol. Little or no proton abstraction occurred for fluorophenol, phenol, or benzyl alcohol analogs. Ion mobility spectrometry was used to determine if proton abstraction reactions passed through an adduct intermediate with thermalized ions and mobility spectra for all chemicals were obtained from 25 to 200 degrees C. Proton abstraction from M Cl- was not observed at any temperature for phenol, monofluorophenol, or difluorophenol. Mobility spectra for trifluorophenol revealed the kinetic transformations to (M-H)- either from M Cl- or from M2 Cl- directly. Proton abstraction was the predominant reaction for tetra- and penta-fluorophenols. Consequently, the evidence suggests that proton abstraction occurs from an adduct ion where the reaction barrier is reduced with increasing acidity of the O-H bond in C6H5-xFxOH.

Profiling and Imaging Ion Mobility-Mass Spectrometry Analysis of Cholesterol and 7-Dehydrocholesterol in Cells Via Sputtered Silver MALDI

PubMed Central

Xu, Libin; Kliman, Michal; Forsythe, Jay G.; Korade, Zeljka; Hmelo, Anthony B.; Porter, Ned A.; McLean, John A.

2015-01-01

Profiling and imaging of cholesterol and its precursors by mass spectrometry (MS) are important in a number of cholesterol biosynthesis disorders, such as in Smith-Lemli-Opitz syndrome (SLOS), where 7-dehydrocholesterol (7-DHC) is accumulated in affected individuals. SLOS is caused by defects in the enzyme that reduces 7-DHC to cholesterol. However, analysis of sterols is challenging because these hydrophobic olefins are difficult to ionize for MS detection. We report here sputtered silver matrix-assisted laser desorption/ionization (MALDI)-ion mobility-MS (IM-MS) analysis of cholesterol and 7-DHC. In comparison with liquid-based AgNO3 and colloidal Ag nanoparticle (AgNP), sputtered silver NP (10–25 nm) provided the lowest limits-of-detection based on the silver coordinated [cholesterol+Ag]+ and [7-DHC+Ag]+ signals while minimizing dehydrogenation products ([M+Ag-2H]+). When analyzing human fibroblasts that were directly grown on poly-L-lysine-coated ITO glass plates with this technique, in situ, the 7-DHC/cholesterol ratios for both control and SLOS human fibroblasts are readily obtained. The m/z of 491 (specific for [7-DHC+107Ag]+) and 495 (specific for [cholesterol+109Ag]+) were subsequently imaged using MALDI-IM-MS. MS images were co-registered with optical images of the cells for metabolic ratio determination. From these comparisons, ratios of 7-DHC/cholesterol for SLOS human fibroblasts are distinctly higher than in control human fibroblasts. Thus, this strategy demonstrates the utility for diagnosing/assaying the severity of cholesterol biosynthesis disorders in vitro. PMID:25822928

Profiling and Imaging Ion Mobility-Mass Spectrometry Analysis of Cholesterol and 7-Dehydrocholesterol in Cells Via Sputtered Silver MALDI

NASA Astrophysics Data System (ADS)

Xu, Libin; Kliman, Michal; Forsythe, Jay G.; Korade, Zeljka; Hmelo, Anthony B.; Porter, Ned A.; McLean, John A.

2015-06-01

Profiling and imaging of cholesterol and its precursors by mass spectrometry (MS) are important in a number of cholesterol biosynthesis disorders, such as in Smith-Lemli-Opitz syndrome (SLOS), where 7-dehydrocholesterol (7-DHC) is accumulated in affected individuals. SLOS is caused by defects in the enzyme that reduces 7-DHC to cholesterol. However, analysis of sterols is challenging because these hydrophobic olefins are difficult to ionize for MS detection. We report here sputtered silver matrix-assisted laser desorption/ionization (MALDI)-ion mobility-MS (IM-MS) analysis of cholesterol and 7-DHC. In comparison with liquid-based AgNO3 and colloidal Ag nanoparticle (AgNP), sputtered silver NP (10-25 nm) provided the lowest limits-of-detection based on the silver coordinated [cholesterol + Ag]+ and [7-DHC + Ag]+ signals while minimizing dehydrogenation products ([M + Ag-2H]+). When analyzing human fibroblasts that were directly grown on poly-L-lysine-coated ITO glass plates with this technique, in situ, the 7-DHC/cholesterol ratios for both control and SLOS human fibroblasts are readily obtained. The m/z of 491 (specific for [7-DHC + 107Ag]+) and 495 (specific for [cholesterol + 109Ag]+) were subsequently imaged using MALDI-IM-MS. MS images were co-registered with optical images of the cells for metabolic ratio determination. From these comparisons, ratios of 7-DHC/cholesterol for SLOS human fibroblasts are distinctly higher than in control human fibroblasts. Thus, this strategy demonstrates the utility for diagnosing/assaying the severity of cholesterol biosynthesis disorders in vitro.

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging.

PubMed

Burnum-Johnson, Kristin E; Baker, Erin S; Metz, Thomas O

2017-12-01

Successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy related problems at the molecular level. In this perspective, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes. Copyright © 2017 IFPA, Elsevier Ltd. Published by Elsevier Ltd.. All rights reserved.

Biomolecular signatures of diabetic wound healing by structural mass spectrometry

PubMed Central

Hines, Kelly M.; Ashfaq, Samir; Davidson, Jeffrey M.; Opalenik, Susan R.; Wikswo, John P.; McLean, John A.

2013-01-01

Wound fluid is a complex biological sample containing byproducts associated with the wound repair process. Contemporary techniques, such as immunoblotting and enzyme immunoassays, require extensive sample manipulation and do not permit the simultaneous analysis of multiple classes of biomolecular species. Structural mass spectrometry, implemented as ion mobility-mass spectrometry (IM-MS), comprises two sequential, gas-phase dispersion techniques well suited for the study of complex biological samples due to its ability to separate and simultaneously analyze multiple classes of biomolecules. As a model of diabetic wound healing, polyvinyl alcohol (PVA) sponges were inserted subcutaneously into non-diabetic (control) and streptozotocin-induced diabetic rats to elicit a granulation tissue response and to collect acute wound fluid. Sponges were harvested at days 2 or 5 to capture different stages of the early wound healing process. Utilizing IM-MS, statistical analysis, and targeted ultra-performance liquid chromatography (UPLC) analysis, biomolecular signatures of diabetic wound healing have been identified. The protein S100-A8 was highly enriched in the wound fluids collected from day 2 diabetic rats. Lysophosphatidylcholine (20:4) and cholic acid also contributed significantly to the differences between diabetic and control groups. This report provides a generalized workflow for wound fluid analysis demonstrated with a diabetic rat model. PMID:23452326

Note: Buffer gas temperature inhomogeneities and design of drift-tube ion mobility spectrometers: Warnings for real-world applications by non-specialists

NASA Astrophysics Data System (ADS)

Fernandez-Maestre, R.

2017-09-01

Ion mobility spectrometry (IMS) separates gas phase ions moving under an electric field according to their size-to-charge ratio. IMS is the method of choice to detect illegal drugs and explosives in customs and airports making accurate determination of reduced ion mobilities (K0) important for national security. An ion mobility spectrometer with electrospray ionization coupled to a quadrupole mass spectrometer was used to study uncertainties in buffer gas temperatures during mobility experiments. Differences up to 16°C were found in the buffer gas temperatures in different regions of the drift tube and up to 42°C between the buffer gas and the drift tube temperatures. The drift tube temperature is used as an approximation to the buffer gas temperature for the calculation of K0 because the buffer gas temperature is hard to measure. This is leading to uncertainties in the determination of K0 values. Inaccurate determination of K0 values yields false positives that delay the cargo and passengers in customs and airports. Therefore, recommendations are issued for building mobility tubes to assure a homogeneous temperature of the buffer gas. Because the temperature and other instrumental parameters are difficult to measure in IMS, chemical standards should always be used when calculating K0. The difference of 42°C between the drift tube and buffer gas temperatures found in these experiments produces a 10.5% error in the calculation of K0. This large inaccuracy in K0 shows the importance of a correct temperature measurement in IMS.

Ligand induced structural isomerism in phosphine coordinated gold clusters revealed by ion mobility mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ligare, Marshall R.; Baker, Erin S.; Laskin, Julia

Structural isomerism in ligated gold clusters is revealed using electrospray ionization ion mobility spectrometry mass spectrometry. Phosphine ligated Au8 clusters are shown to adopt more “extended” type structures with increasing exchange of methyldiphenylphosphine (MePPh2) for triphenylphosphine (PPh3). These ligand-dependant structure-property relationships are critical to applications of clusters in catalysis.

Signal processing for ION mobility spectrometers

NASA Technical Reports Server (NTRS)

Taylor, S.; Hinton, M.; Turner, R.

1995-01-01

Signal processing techniques for systems based upon Ion Mobility Spectrometry will be discussed in the light of 10 years of experience in the design of real-time IMS. Among the topics to be covered are compensation techniques for variations in the number density of the gas - the use of an internal standard (a reference peak) or pressure and temperature sensors. Sources of noise and methods for noise reduction will be discussed together with resolution limitations and the ability of deconvolution techniques to improve resolving power. The use of neural networks (either by themselves or as a component part of a processing system) will be reviewed.

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids

DOE PAGES

Zhang, Xing; Romm, Michelle; Zheng, Xueyun; ...

2016-12-29

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here in this article, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with highmore » reproducibility (CV ≤ 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. Lastly, this SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure.« less

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids.

PubMed

Zhang, Xing; Romm, Michelle; Zheng, Xueyun; Zink, Erika M; Kim, Young-Mo; Burnum-Johnson, Kristin E; Orton, Daniel J; Apffel, Alex; Ibrahim, Yehia M; Monroe, Matthew E; Moore, Ronald J; Smith, Jordan N; Ma, Jian; Renslow, Ryan S; Thomas, Dennis G; Blackwell, Anne E; Swinford, Glenn; Sausen, John; Kurulugama, Ruwan T; Eno, Nathan; Darland, Ed; Stafford, George; Fjeldsted, John; Metz, Thomas O; Teeguarden, Justin G; Smith, Richard D; Baker, Erin S

2016-12-01

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV 6 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. This SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure.

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids

PubMed Central

Zhang, Xing; Romm, Michelle; Zheng, Xueyun; Zink, Erika M.; Kim, Young-Mo; Burnum-Johnson, Kristin E.; Orton, Daniel J.; Apffel, Alex; Ibrahim, Yehia M.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Jordan N.; Ma, Jian; Renslow, Ryan S.; Thomas, Dennis G.; Blackwell, Anne E.; Swinford, Glenn; Sausen, John; Kurulugama, Ruwan T.; Eno, Nathan; Darland, Ed; Stafford, George; Fjeldsted, John; Metz, Thomas O.; Teeguarden, Justin G.; Smith, Richard D.; Baker, Erin S.

2017-01-01

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV 6 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. This SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure. PMID:29276770

Use of an ion mobility spectrometer for detecting uranium compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLain, Derek R.; Steeb, Jennifer L.; Smith, Nicholas A.

The safeguards community currently lacks a method to rapidly determine the chemical form of radioactive and non-radioactive compounds in real time during inspection activities. Chemical speciation identification can provide important information on both the types of materials that are collected during environmental sampling and can inform inspectors as to where to focus efforts during inspections or complementary access visits. Ion Mobility Spectrometry (IMS) is an established field technique for the detection of explosives, narcotics, and other organic compounds. More recently, electrospray ionization (ESI) has been used to introduce inorganic compounds to IMS instruments for analysis. These techniques have shown themore » ability to supply chemical information about the compounds being analyzed. Although these laboratory based instruments use a liquid-based injection system, there is evidence in the literature of unaltered and intact pharmaceutical tablets being volatilized and ionized in open atmosphere using heat and a Ni-63 source. Lastly, this work determined that a commercial-off-the-shelf (COTS) IMS could be used for the identification of solid uranium compounds directly after sampling using a COTS sample swipe.« less

Use of an ion mobility spectrometer for detecting uranium compounds

DOE PAGES

McLain, Derek R.; Steeb, Jennifer L.; Smith, Nicholas A.

2018-03-09

The safeguards community currently lacks a method to rapidly determine the chemical form of radioactive and non-radioactive compounds in real time during inspection activities. Chemical speciation identification can provide important information on both the types of materials that are collected during environmental sampling and can inform inspectors as to where to focus efforts during inspections or complementary access visits. Ion Mobility Spectrometry (IMS) is an established field technique for the detection of explosives, narcotics, and other organic compounds. More recently, electrospray ionization (ESI) has been used to introduce inorganic compounds to IMS instruments for analysis. These techniques have shown themore » ability to supply chemical information about the compounds being analyzed. Although these laboratory based instruments use a liquid-based injection system, there is evidence in the literature of unaltered and intact pharmaceutical tablets being volatilized and ionized in open atmosphere using heat and a Ni-63 source. Lastly, this work determined that a commercial-off-the-shelf (COTS) IMS could be used for the identification of solid uranium compounds directly after sampling using a COTS sample swipe.« less

A new retrospective, multi-evidence veterinary drug screening method using drift tube ion mobility mass spectrometry.

PubMed

Xu, Zhenzhen; Li, Jianzhong; Chen, Ailiang; Ma, Xin; Yang, Shuming

2018-05-03

The retrospectivity (the ability to retrospect to a previously unknown compound in raw data) is very meaningful for food safety and risk assessment when facing new emerging drugs. Accurate mass and retention time based screening may lead false positive and false negative results so new retrospective, reliable platform is desirable. Different concentration levels of standards with and without matrix were analyzed using ion mobility (IM)-quadrupole-time-of-flight (Q-TOF) for collecting retrospective accurate mass, retention time, drift time and tandem MS evidence for identification in a single experiment. The isomer separation ability of IM and the four-dimensional (4D) feature abundance quantification abilities were evaluated for veterinary drugs for the first time. The sensitivity of the IM-Q-TOF workflow was obviously higher than that of the traditional database searching algorithm [find by formula (FbF) function] for Q-TOF. In addition, the IM-Q-TOF workflow contained most of the results from FbF and removed the false positive results. Some isomers were separated by IM and the 4D feature abundance quantitation removed interference with similar accurate mass and showed good linearity. A new retrospective, multi-evidence platform was built for veterinary drug screening in a single experiment. The sensitivity was significantly improved and the data can be used for quantification. The platform showed its potential to be used for food safety and risk assessment. This article is protected by copyright. All rights reserved.

Enhancing Bottom-up and Top-down Proteomic Measurements with Ion Mobility Separations

DOE PAGES

Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Ibrahim, Yehia M.; ...

2015-07-03

Proteomic measurements with greater throughput, sensitivity and additional structural information enhance the in-depth characterization of complex mixtures and targeted studies with additional information and higher confidence. While liquid chromatography separation coupled with mass spectrometry (LC-MS) measurements have provided information on thousands of proteins in different sample types, the additional of another rapid separation stage providing structural information has many benefits for analyses. Technical advances in ion funnels and multiplexing have enabled ion mobility separations to be easily and effectively coupled with LC-MS proteomics to enhance the information content of measurements. Finally, herein, we report on applications illustrating increased sensitivity, throughput,more » and structural information by utilizing IMS-MS and LC-IMS-MS measurements for both bottom-up and top-down proteomics measurements.« less

Rapid assessment of human amylin aggregation and its inhibition by copper(II) ions by laser ablation electrospray ionization mass spectrometry with ion mobility separation

DOE PAGES

Li, Hang; Ha, Emmeline; Donaldson, Robert P.; ...

2015-09-09

Native electrospray ionization (ESI) mass spectrometry (MS) is often used to monitor noncovalent complex formation between peptides and ligands. The relatively low throughput of this technique, however, is not compatible with extensive screening. Laser ablation electrospray ionization (LAESI) MS combined with ion mobility separation (IMS) can analyze complex formation and provide conformation information within a matter of seconds. Islet amyloid polypeptide (IAPP) or amylin, a 37-amino acid residue peptide, is produced in pancreatic beta-cells through proteolytic cleavage of its prohormone. Both amylin and its precursor can aggregate and produce toxic oligomers and fibrils leading to cell death in the pancreasmore » that can eventually contribute to the development of type 2 diabetes mellitus. The inhibitory effect of the copper(II) ion on amylin aggregation has been recently discovered, but details of the interaction remain unknown. Finding other more physiologically tolerated approaches requires large scale screening of potential inhibitors. In this paper, we demonstrate that LAESI-IMS-MS can reveal the binding stoichiometry, copper oxidation state, and the dissociation constant of human amylin–copper(II) complex. The conformations of hIAPP in the presence of copper(II) ions were also analyzed by IMS, and preferential association between the β-hairpin amylin monomer and the metal ion was found. The copper(II) ion exhibited strong association with the —HSSNN– residues of the amylin. In the absence of copper(II), amylin dimers were detected with collision cross sections consistent with monomers of β-hairpin conformation. When copper(II) was present in the solution, no dimers were detected. Thus, the copper(II) ions disrupt the association pathway to the formation of β-sheet rich amylin fibrils. Using LAESI-IMS-MS for the assessment of amylin–copper(II) interactions demonstrates the utility of this technique for the high-throughput screening of

SDS-PAGE analysis of Aβ oligomers is disserving research into Alzheimer´s disease: appealing for ESI-IM-MS

NASA Astrophysics Data System (ADS)

Pujol-Pina, Rosa; Vilaprinyó-Pascual, Sílvia; Mazzucato, Roberta; Arcella, Annalisa; Vilaseca, Marta; Orozco, Modesto; Carulla, Natàlia

2015-10-01

The characterization of amyloid-beta peptide (Aβ) oligomer forms and structures is crucial to the advancement in the field of Alzheimer´s disease (AD). Here we report a critical evaluation of two methods used for this purpose, namely sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), extensively used in the field, and ion mobility coupled to electrospray ionization mass spectrometry (ESI-IM-MS), an emerging technique with great potential for oligomer characterization. To evaluate their performance, we first obtained pure cross-linked Aβ40 and Aβ42 oligomers of well-defined order. Analysis of these samples by SDS-PAGE revealed that SDS affects the oligomerization state of Aβ42 oligomers, thus providing flawed information on their order and distribution. In contrast, ESI-IM-MS provided accurate information, while also reported on the chemical nature and on the structure of the oligomers. Our findings have important implications as they challenge scientific paradigms in the AD field built upon SDS-PAGE characterization of Aβ oligomer samples.

IMS R and D program at Canada customs

NASA Technical Reports Server (NTRS)

Pilon, Pierre; Mungham, Tony; Ng, Lay-Keow; Lawrence, Andre

1995-01-01

Over the last few years, Revenue Canada, in collaboration with Barringer Instruments Limited, has been involved in the development of a field-usable ion mobility spectrometer (IMS) for the detection of drugs of abuse. This work has culminated in the manufacturing and commercialization by Barringer of the Ionscan 350 instruments, now in use by various law enforcement agencies worldwide. Although IMS exhibits a very strong and distinctive response toward some nitrogen containing drugs, e.g., cocaine, like all separation techniques it has inherent limitations, namely moderate resolution and low chemical signal to noise ratio which may affect the reliability of IMS-based drug detectors. A program is in place at the Laboratory and Scientific Services Directorate (LSSD) to investigate the applicability of various digital signal processing (DSP) techniques to IMS output signals. The application of neural network techniques to overlapping IMS peaks is presented.

Separation and Identification of Isomeric Glycopeptides by High Field Asymmetric Waveform Ion Mobility Spectrometry

PubMed Central

2012-01-01

The analysis of intact glycopeptides by mass spectrometry is challenging due to the numerous possibilities for isomerization, both within the attached glycan and the location of the modification on the peptide backbone. Here, we demonstrate that high field asymmetric wave ion mobility spectrometry (FAIMS), also known as differential ion mobility, is able to separate isomeric O-linked glycopeptides that have identical sequences but differing sites of glycosylation. Two glycopeptides from the glycoprotein mucin 5AC, GT(GalNAc)TPSPVPTTSTTSAP and GTTPSPVPTTST(GalNAc)TSAP (where GalNAc is O-linked N-acetylgalactosamine), were shown to coelute following reversed-phase liquid chromatography. However, FAIMS analysis of the glycopeptides revealed that the compensation voltage ranges in which the peptides were transmitted differed. Thus, it is possible at certain compensation voltages to completely separate the glycopeptides. Separation of the glycopeptides was confirmed by unique reporter ions produced by supplemental activation electron transfer dissociation mass spectrometry. These fragments also enable localization of the site of glycosylation. The results suggest that glycan position plays a key role in determining gas-phase glycopeptide structure and have implications for the application of FAIMS in glycoproteomics. PMID:22280549

Preparation, Separation, and Conformational Analysis of Differentially Sulfated Heparin Octasaccharide Isomers using Ion Mobility Mass Spectrometry

PubMed Central

Seo, Youjin; Andaya, Armann; Leary, Julie A.

2012-01-01

Heparin is a linear sulfated polysaccharide widely used in medicine because of its anticoagulant properties. The various sulfation and/or acetylation patterns on heparin impart different degrees of conformational change around the glycosidic bonds and subsequently alter its function as an anticoagulant, anticancer, or antiviral drug. Characterization of these structures is important for eventual elucidation of its function but presents itself as an analytical challenge due to the inherent heterogeneity of the carbohydrates. Heparin octasaccharide structural isomers of various sulfation patterns were investigated using ion mobility mass spectrometry (IMMS). In addition to distinguishing the isomers, we report the preparation and tandem mass spectrometry analysis for multiple sulfated or acetylated oligosaccharides. Herein, our data indicate that heparin octasaccharide isomers were separated based on their structural conformations in the ion mobility cell. Subsequent to this separation, isomers were further distinguished using product ions resulting from tandem mass spectrometry. Overall, IMMS analysis was used to successfully characterize and separate individual isomers and subsequently measure their conformations. PMID:22283665

Differential Mobility Spectrometry: Preliminary Findings on Determination of Fundamental Constants

NASA Technical Reports Server (NTRS)

Limero, Thomas; Cheng, Patti; Boyd, John

2007-01-01

The electron capture detector (ECD) has been used for 40+ years (1) to derive fundamental constants such as a compound's electron affinity. Given this historical perspective, it is not surprising that differential mobility spectrometry (DMS) might be used in a like manner. This paper will present data from a gas chromatography (GC)-DMS instrument that illustrates the potential capability of this device to derive fundamental constants for electron-capturing compounds. Potential energy curves will be used to provide possible explanation of the data.

Practical application of in silico fragmentation based residue screening with ion mobility high-resolution mass spectrometry.

PubMed

Kaufmann, Anton; Butcher, Patrick; Maden, Kathry; Walker, Stephan; Widmer, Mirjam

2017-07-15

A screening concept for residues in complex matrices based on liquid chromatography coupled to ion mobility high-resolution mass spectrometry LC/IMS-HRMS is presented. The comprehensive four-dimensional data (chromatographic retention time, drift time, mass-to-charge and ion abundance) obtained in data-independent acquisition (DIA) mode was used for data mining. An in silico fragmenter utilizing a molecular structure database was used for suspect screening, instead of targeted screening with reference substances. The utilized data-independent acquisition mode relies on the MS E concept; where two constantly alternating HRMS scans (low and high fragmentation energy) are acquired. Peak deconvolution and drift time alignment of ions from the low (precursor ion) and high (product ion) energy scan result in relatively clean product ion spectra. A bond dissociation in silico fragmenter (MassFragment) supplied with mol files of compounds of interest was used to explain the observed product ions of each extracted candidate component (chromatographic peak). Two complex matrices (fish and bovine liver extract) were fortified with 98 veterinary drugs. Out of 98 screened compounds 94 could be detected with the in silico based screening approach. The high correlation among drift time and m/z value of equally charged ions was utilized for an orthogonal filtration (ranking). Such an orthogonal ion mobility based filter removes multiply charged ions (e.g. peptides and proteins from the matrix) as well as noise and artefacts. Most significantly, this filtration dramatically reduces false positive findings but hardly increases false negative findings. The proposed screening approach may offer new possibilities for applications where reference compounds are hardly or not at all commercially available. Such areas may be the analysis of metabolites of drugs, pyrrolizidine alkaloids, marine toxins, derivatives of sildenafil or novel designer drugs (new psychoactive substances

Device for two-dimensional gas-phase separation and characterization of ion mixtures

DOEpatents

Tang, Keqi [Richland, WA; Shvartsburg, Alexandre A [Richland, WA; Smith, Richard D [Richland, WA

2006-12-12

The present invention relates to a device for separation and characterization of gas-phase ions. The device incorporates an ion source, a field asymmetric waveform ion mobility spectrometry (FAIMS) analyzer, an ion mobility spectrometry (IMS) drift tube, and an ion detector. In one aspect of the invention, FAIMS operating voltages are electrically floated on top of the IMS drift voltage. In the other aspect, the FAIMS/IMS interface is implemented employing an electrodynamic ion funnel, including in particular an hourglass ion funnel. The present invention improves the efficiency (peak capacity) and sensitivity of gas-phase separations; the online FAIMS/IMS coupling creates a fundamentally novel two-dimensional gas-phase separation technology with high peak capacity, specificity, and exceptional throughput.

A four dimensional separation method based on continuous heart-cutting gas chromatography with ion mobility and high resolution mass spectrometry.

PubMed

Lipok, Christian; Hippler, Jörg; Schmitz, Oliver J

2018-02-09

A two-dimensional GC (2D-GC) method was developed and coupled to an ion mobility-high resolution mass spectrometer, which enables the separation of complex samples in four dimensions (2D-GC, ion mobilility spectrometry and mass spectrometry). This approach works as a continuous multiheart-cutting GC-system (GC+GC), using a long modulation time of 20s, which allows the complete transfer of most of the first dimension peaks to the second dimension column without fractionation, in comparison to comprehensive two-dimensional gas chromatography (GCxGC). Hence, each compound delivers only one peak in the second dimension, which simplifies the data handling even when ion mobility spectrometry as a third and mass spectrometry as a fourth dimension are introduced. The analysis of a plant extract from Calendula officinales shows the separation power of this four dimensional separation method. The introduction of ion mobility spectrometry provides an additional separation dimension and allows to determine collision cross sections (CCS) of the analytes as a further physicochemical constant supporting the identification. A CCS database with more than 800 standard substances including drug-like compounds and pesticides was used for CCS data base search in this work. Copyright © 2017 Elsevier B.V. All rights reserved.

A volatile organic analyzer for Space Station: Description and evaluation of a gas chromatography/ ion mobility

NASA Technical Reports Server (NTRS)

Limero, Thomas F.; James, John T.

1994-01-01

A Volatile Organic Analyzer (VOA) is being developed as an essential component of the Space Station's Environmental Health System (EHS) air quality monitoring strategy to provide warning to the crew and ground personnel if volatile organic compounds exceed established exposure limits. The short duration of most Shuttle flights and the relative simplicity of the contaminant removal mechanism have lessened the concern about crew exposure to air contaminants on the Shuttle. However, the longer missions associated with the Space Station, the complex air revitalization system and the proposed number of experiments have led to a desire for real-time monitoring of the contaminants in the Space Station atmosphere. Achieving the performance requirements established for the VOA within the Space Station resource (e.g., power, weight) allocations led to a novel approach that joined a gas chromatograph (GC) to an ion mobility spectrometer (IMS). The authors of this paper will discuss the rational for selecting the GC/IMS technology as opposed to the more established gas chromatography/mass spectrometry (GC/MS) for the foundation of the VOA. The data presented from preliminary evaluations will demonstrate the versatile capability of the GC/IMS to analyze the major contaminants expected in the Space Station atmosphere. The favorable GC/IMS characteristics illustrated in this paper included excellent sensitivity, dual-mode operation for selective detection, and mobility drift times to distinguish co-eluting GC peaks. Preliminary studies have shown that the GC/IMS technology can meet surpass the performance requirements of the Space Station VOA.

Gaseous phase ion detection method based on laser-induced fluorescence for ion mobility spectrometer

NASA Astrophysics Data System (ADS)

Guo, Kaitai; Ni, Kai; Ou, Guangli; Zhang, Xiaoguo; Yu, Quan; Qian, Xiang; Wang, Xiaohao

2015-08-01

Ion mobility spectrometry (IMS) is widely used in the field of chemical composition analysis. Faraday cup is the most classical method to detect ions for IMS in the atmospheric pressure. However, the performance of Faraday plate was limited by many kinds of factors, including interfering electromagnetic waves, thermal(Johnson) noise, induced current , gain bandwidth product, etc. There is a theoretical limit in detection of ions at ambient condition which is approximately 106 ions per second. In this paper, we introduced a novel way using laser-induced fluorescence (LIF) to bypass the limitation of Faraday plate. Fluorescent ions which were selected by IMS get excited when they fly through the laser excitation area. The fluorescence emitted by the excited ions was captured exponentially and amplified through proper optoelectronic system. Rhodamine 6G (R6G) was selected as the fluorochrome for the reason that excitation wavelength, emission wavelength, and fluorescence quantum yield were more appropriate than others. An orthometric light path is designed to eliminate the adverse impact which was caused by induced laser. The experiment result shows that a fluorescence signal from the sample ions of the IMS could be observed. Compared with Faraday plate, the LIF-IMS may find a potential application in more system at the atmosphere condition.

The predictive power of SIMION/SDS simulation software for modeling ion mobility spectrometry instruments

NASA Astrophysics Data System (ADS)

Lai, Hanh; McJunkin, Timothy R.; Miller, Carla J.; Scott, Jill R.; Almirall, José R.

2008-09-01

The combined use of SIMION 7.0 and the statistical diffusion simulation (SDS) user program in conjunction with SolidWorks® with COSMSOSFloWorks® fluid dynamics software to model a complete, commercial ion mobility spectrometer (IMS) was demonstrated for the first time and compared to experimental results for tests using compounds of immediate interest in the security industry (e.g., 2,4,6-trinitrotoluene, 2,7-dinitrofluorene, and cocaine). The effort of this research was to evaluate the predictive power of SIMION/SDS for application to IMS instruments. The simulation was evaluated against experimental results in three studies: (1) a drift:carrier gas flow rates study assesses the ability of SIMION/SDS to correctly predict the ion drift times; (2) a drift gas composition study evaluates the accuracy in predicting the resolution; (3) a gate width study compares the simulated peak shape and peak intensity with the experimental values. SIMION/SDS successfully predicted the correct drift time, intensity, and resolution trends for the operating parameters studied. Despite the need for estimations and assumptions in the construction of the simulated instrument, SIMION/SDS was able to predict the resolution between two ion species in air within 3% accuracy. The preliminary success of IMS simulations using SIMION/SDS software holds great promise for the design of future instruments with enhanced performance.

The Predictive Power of SIMION/SDS Simulation Software for Modeling Ion Mobility Spectrometry Instruments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanh Lai; Timothy R. McJunkin; Carla J. Miller

2008-09-01

The combined use of SIMION 7.0 and the statistical diffusion simulation (SDS) user program in conjunction with SolidWorks® with COSMSOFloWorks® fluid dynamics software to model a complete, commercial ion mobility spectrometer (IMS) was demonstrated for the first time and compared to experimental results for tests using compounds of immediate interest in the security industry (e.g., 2,4,6-trinitrotoluene and cocaine). The effort of this research was to evaluate the predictive power of SIMION/SDS for application to IMS instruments. The simulation was evaluated against experimental results in three studies: 1) a drift:carrier gas flow rates study assesses the ability of SIMION/SDS to correctlymore » predict the ion drift times; 2) a drift gas composition study evaluates the accuracy in predicting the resolution; and 3) a gate width study compares the simulated peak shape and peak intensity with the experimental values. SIMION/SDS successfully predicted the correct drift time, intensity, and resolution trends for the operating parameters studied. Despite the need for estimations and assumptions in the construction of the simulated instrument, SIMION/SDS was able to predict the resolution between two ion species in air within 3% accuracy. The preliminary success of IMS simulations using SIMION/SDS software holds great promise for the design of future instruments with enhanced performance.« less

UV-induced bond modifications in thymine and thymine dideoxynucleotide: structural elucidation of isomers by differential mobility mass spectrometry.

PubMed

St-Jacques, Antony; Anichina, Janna; Schneider, Bradley B; Covey, Thomas R; Bohme, Diethard K

2010-07-15

Differential mobility spectrometry has been applied to reveal the occurrence of isomerization of thymine nucleobase and of thymine dideoxynucleotide d(5'-TT-3') due to bond redisposition induced by UV irradiation at 254 nm of frozen aqueous solutions of these molecules. Collision-induced dissociation (CID) spectra of electrosprayed photoproducts of the thymine solution suggest the presence of two isomers (the so-called cyclobutane and 6,4-photoproducts) in addition to the proton-bound thymine dimer, and these were separated using differential mobility spectrometry/mass spectrometry (DMS/MS) techniques with water as the modifier. Similar experiments with d(5'-TT-3') revealed the formation of a new isomer of deprotonated thymine dideoxynucleotide upon UV irradiation that was easily distinguished using DMS/MS with isopropanol as the modifier. The results reinforce the usefulness of DMS/MS in isomer separation.

Ion mobility spectrometry for food quality and safety.

PubMed

Vautz, W; Zimmermann, D; Hartmann, M; Baumbach, J I; Nolte, J; Jung, J

2006-11-01

Ion mobility spectrometry is known to be a fast and sensitive technique for the detection of trace substances, and it is increasingly in demand not only for protection against explosives and chemical warfare agents, but also for new applications in medical diagnosis or process control. Generally, a gas phase sample is ionized by help of ultraviolet light, ss-radiation or partial discharges. The ions move in a weak electrical field towards a detector. During their drift they collide with a drift gas flowing in the opposite direction and, therefore, are slowed down depending on their size, shape and charge. As a result, different ions reach the detector at different drift times, which are characteristic for the ions considered. The number of ions reaching the detector are a measure of the concentration of the analyte. The method enables the identification and quantification of analytes with high sensitivity (ng l(-1) range). The selectivity can even be increased - as necessary for the analyses of complex mixtures - using pre-separation techniques such as gas chromatography or multi-capillary columns. No pre-concentration of the sample is necessary. Those characteristics of the method are preserved even in air with up to a 100% relative humidity rate. The suitability of the method for application in the field of food quality and safety - including storage, process and quality control as well as the characterization of food stuffs - was investigated in recent years for a number of representative examples, which are summarized in the following, including new studies as well: (1) the detection of metabolites from bacteria for the identification and control of their growth; (2) process control in food production - beer fermentation being an example; (3) the detection of the metabolites of mould for process control during cheese production, for quality control of raw materials or for the control of storage conditions; (4) the quality control of packaging materials during

A comparative study between different alternatives to prepare gaseous standards for calibrating UV-Ion Mobility Spectrometers.

PubMed

Criado-García, Laura; Garrido-Delgado, Rocío; Arce, Lourdes; Valcárcel, Miguel

2013-07-15

An UV-Ion Mobility Spectrometer is a simple, rapid, inexpensive instrument widely used in environmental analysis among other fields. The advantageous features of its underlying technology can be of great help towards developing reliable, economical methods for determining gaseous compounds from gaseous, liquid and solid samples. Developing an effective method using UV-Ion Mobility Spectrometry (UV-IMS) to determine volatile analytes entails using appropriate gaseous standards for calibrating the spectrometer. In this work, two home-made sample introduction systems (SISs) and a commercial gas generator were used to obtain such gaseous standards. The first home-made SIS used was a static head-space to measure compounds present in liquid samples and the other home-made system was an exponential dilution set-up to measure compounds present in gaseous samples. Gaseous compounds generated by each method were determined on-line by UV-IMS. Target analytes chosen for this comparative study were ethanol, acetone, benzene, toluene, ethylbenzene and xylene isomers. The different alternatives were acceptable in terms of sensitivity, precision and selectivity. Copyright © 2013 Elsevier B.V. All rights reserved.

Rapid detection of cocaine, benzoylecgonine and methylecgonine in fingerprints using surface mass spectrometry.

PubMed

Bailey, Melanie J; Bradshaw, Robert; Francese, Simona; Salter, Tara L; Costa, Catia; Ismail, Mahado; P Webb, Roger; Bosman, Ingrid; Wolff, Kim; de Puit, Marcel

2015-09-21

Latent fingerprints provide a potential route to the secure, high throughput and non-invasive detection of drugs of abuse. In this study we show for the first time that the excreted metabolites of drugs of abuse can be detected in fingerprints using ambient mass spectrometry. Fingerprints and oral fluid were taken from patients attending a drug and alcohol treatment service. Gas chromatography mass spectrometry (GC-MS) was used to test the oral fluid of patients for the presence of cocaine and benzoylecgonine. The corresponding fingerprints were analysed using Desorption Electrospray Ionization (DESI) which operates under ambient conditions and Ion Mobility Tandem Mass Spectrometry Matrix Assisted Laser Desorption Ionization (MALDI-IMS-MS/MS) and Secondary Ion Mass Spectrometry (SIMS). The detection of cocaine, benzoylecgonine (BZE) and methylecgonine (EME) in latent fingerprints using both DESI and MALDI showed good correlation with oral fluid testing. The sensitivity of SIMS was found to be insufficient for this application. These results provide exciting opportunities for the use of fingerprints as a new sampling medium for secure, non-invasive drug detection. The mass spectrometry techniques used here offer a high level of selectivity and consume only a small area of a single fingerprint, allowing repeat and high throughput analyses of a single sample.

Miniaturized low-cost ion mobility spectrometer for fast detection of chemical warfare agents.

PubMed

Zimmermann, Stefan; Barth, Sebastian; Baether, Wolfgang K M; Ringer, Joachim

2008-09-01

Ion mobility spectrometry (IMS) is a well-known method for detecting hazardous compounds in air. Typical applications are the detection of chemical warfare agents, highly toxic industrial compounds, explosives, and drugs of abuse. Detection limits in the low part per billion range, fast response times, and simple instrumentation make this technique more and more popular. In particular, there is an increasing demand for miniaturized low-cost IMS for hand-held devices and air monitoring of public areas by sensor networks. In this paper, we present a miniaturized aspiration condenser type ion mobility spectrometer for fast detection of chemical warfare agents. The device is easy to manufacture and allows single substance identification down to low part per billion-level concentrations within seconds. The improved separation power results from ion focusing by means of geometric constraints and fluid dynamics. A simple pattern recognition algorithm is used for the identification of trained substances in air. The device was tested at the German Armed Forces Scientific Institute for Protection Technologies-NBC-Protection. Different chemical warfare agents, such as sarin, tabun, soman, US-VX, sulfur mustard, nitrogen mustard, and lewisite were tested. The results are presented here.

Ultra-High Resolution Ion Mobility Separations Utilizing Traveling Waves in a 13 m Serpentine Path Length Structures for Lossless Ion Manipulations Module

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Liulin; Ibrahim, Yehia M.; Hamid, Ahmed M.

We report the development and initial evaluation of a 13-m path length Structures for Lossless Manipulations (SLIM) module for achieving high resolution separations using traveling waves (TW) with ion mobility (IM) spectrometry. The TW SLIM module was fabricated using two mirror-image printed circuit boards with appropriately configured RF, DC and TW electrodes and positioned with a 2.75-mm inter-surface gap. Ions were effective confined between the surfaces by RF-generated pseudopotential fields and moved losslessly through a serpentine path including 44 “U” turns using TWs. The ion mobility resolution was characterized at different pressures, gaps between the SLIM surfaces, TW and RFmore » parameters. After initial optimization the SLIM IM-MS module provided about 5-fold higher resolution separations than present commercially available drift tube or traveling wave IM-MS platforms. Peak capacity and peak generation rates achieved were 246 and 370 s-1, respectively, at a TW speed of 148 m/s. The high resolution achieved in the TW SLIM IM-MS enabled e.g., isomeric sugars (Lacto-N-fucopentaose I and Lacto-N-fucopentaose II) to be baseline resolved, and peptides from a albumin tryptic digest much better resolved than with existing commercial IM-MS platforms. The present work also provides a foundation for the development of much higher resolution SLIM devices based upon both considerably longer path lengths and multi-pass designs.« less

Mobile pastoralists in Central and West Africa: between conflict, mobile telephony and (im)mobility.

PubMed

De Bruijn, M; Amadou, A; Lewa Doksala, E; Sangaré, B

2016-11-01

The livelihoods of the Fulani mobile pastoralists in the Sahel, West and Central Africa are characterised by mobility (related to the needs of their animals), extensive social networks, and a focus on social ties as the basis of status and influence ('wealth in people'). The Sahel environment in which many Fulani nomads live has become embroiled in jihadism, conflict, and violence; at the same time, this region has experienced an increase in opportunities to connect through the wireless mobile communication system. This paper analyses the triangle of mobility, communication, and insecurity in order to understand the present-day situation of the nomadic and semi-nomadic Fulani pastoralists and their identity dynamics. The Fulani find themselves caught in between these conflicts, which end their mobility and often lead to the loss of their herds. Will they be able to keep their mobile lifestyle and identity? This article is based on qualitative case studies and the biographical narratives of nomadic and semi-nomadic pastoralists who have lived through conflict and violence in Cameroon, Chad and Mali. These case studies show that, despite the fact that mobile pastoralism has become difficult as a consequence of the conflicts and loss of cattle, the 'mobile' identity is very present and reinforced with the help of mobile telephony, through which social networks and 'wealth in people' are sustained.

An Interlaboratory Evaluation of Drift Tube Ion Mobility–Mass Spectrometry Collision Cross Section Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stow, Sarah M.; Causon, Tim J.; Zheng, Xueyun

Collision cross section (CCS) measurements resulting from ion mobility-mass spectrometry (IM-MS) experiments provide a promising orthogonal dimension of structural information in MS-based analytical separations. As with any molecular identifier, interlaboratory standardization must precede broad range integration into analytical workflows. In this study, we present a reference drift tube ion mobility mass spectrometer (DTIM-MS) where improvements on the measurement accuracy of experimental parameters influencing IM separations provide standardized drift tube, nitrogen CCS values (DTCCSN2) for over 120 unique ion species with the lowest measurement uncertainty to date. The reproducibility of these DTCCSN2 values are evaluated across three additional laboratories on amore » commercially available DTIM-MS instrument. The traditional stepped field CCS method performs with a relative standard deviation (RSD) of 0.29% for all ion species across the three additional laboratories. The calibrated single field CCS method, which is compatible with a wide range of chromatographic inlet systems, performs with an average, absolute bias of 0.54% to the standardized stepped field DTCCSN2 values on the reference system. The low RSD and biases observed in this interlaboratory study illustrate the potential of DTIM-MS for providing a molecular identifier for a broad range of discovery based analyses.« less

Tandem mass spectrometry in combination with product ion mobility for the identification of phospholipids

DOE PAGES

Berry, Karin A. Zemski; Barkley, Robert M.; Berry, Joseph J.; ...

2016-11-29

Concerted tandem and traveling wave ion mobility mass spectrometry (CTS analysis) is a unique method that results in a four-dimensional data set including nominal precursor ion mass, product ion mobility, accurate mass of product ion, and ion abundance. This nontargeted lipidomics CTS approach was applied in both positive- and negative-ion mode to phospholipids present in human serum, and the data set was used to evaluate the value of product ion mobility in identifying lipids in a complex mixture. As a result, it was determined that the combination of diagnostic product ions and unique collisional cross-section values of product ions ismore » a powerful tool in the structural identification of lipids in a complex biological sample.« less

Tandem mass spectrometry in combination with product ion mobility for the identification of phospholipids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berry, Karin A. Zemski; Barkley, Robert M.; Berry, Joseph J.

Concerted tandem and traveling wave ion mobility mass spectrometry (CTS analysis) is a unique method that results in a four-dimensional data set including nominal precursor ion mass, product ion mobility, accurate mass of product ion, and ion abundance. This nontargeted lipidomics CTS approach was applied in both positive- and negative-ion mode to phospholipids present in human serum, and the data set was used to evaluate the value of product ion mobility in identifying lipids in a complex mixture. As a result, it was determined that the combination of diagnostic product ions and unique collisional cross-section values of product ions ismore » a powerful tool in the structural identification of lipids in a complex biological sample.« less

Coupling of multi-walled carbon nanotubes/polydimethylsiloxane coated stir bar sorptive extraction with pulse glow discharge-ion mobility spectrometry for analysis of triazine herbicides in water and soil samples.

PubMed

Zou, Nan; Yuan, Chunhao; Liu, Shaowen; Han, Yongtao; Li, Yanjie; Zhang, Jialei; Xu, Xiang; Li, Xuesheng; Pan, Canping

2016-07-29

An analytical method based on stir bar sorptive extraction (SBSE) coupled with pulse glow discharge-ion mobility spectrometry (PGD-IMS) was developed for analysis of three triazine pesticide residues in water and soil samples. An injection port with sealing device and stir bars hold device were designed and constructed to directly position the SBSE fiber including the extracted samples into the heating device, making desorption and detection of analytes proceeded simultaneously. The extraction conditions such as SBSE solid phase material, extraction time, extraction temperature, pH value and salt concentration were optimized. Mixture of MWCNTs-COOH and PDMS were shown to be effective in enriching the triazines. The LODs and LOQs of three triazines were found to be 0.006-0.015μgkg(-1) and 0.02-0.05μgkg(-1), and the linear range was 0.05-10μgL(-1) with determination coefficients from 0.9987 to 0.9993. The SBSE-PGD-IMS method was environmentally friendly without organic solvent consumption in the entire experimental procedures, and it was demonstrated to be a commendable rapid analysis technique for analysis of triazine pesticide residues in environmental samples on site. The proposed method was applied for the analysis of real ground water, surface water and soil samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigating Differences in Gas-Phase Conformations of 25-Hydroxyvitamin D3 Sodiated Epimers using Ion Mobility-Mass Spectrometry and Theoretical Modeling

NASA Astrophysics Data System (ADS)

Chouinard, Christopher D.; Cruzeiro, Vinícius Wilian D.; Beekman, Christopher R.; Roitberg, Adrian E.; Yost, Richard A.

2017-08-01

Drift tube ion mobility coupled with mass spectrometry was used to investigate the gas-phase structure of 25-hydroxyvitamin D3 (25OHD3) and D2 (25OHD2) epimers, and to evaluate its potential in rapid separation of these compounds. Experimental results revealed two distinct drift species for the 25OHD3 sodiated monomer, whereas only one of these conformations was observed for its epimer (epi25OHD3). The unique species allowed 25OHD3 to be readily distinguished, and the same pattern was observed for 25OHD2 epimers. Theoretical modeling of 25OHD3 epimers identified energetically stable gas-phase structures, indicating that both compounds may adopt a compact "closed" conformation, but that 25OHD3 may also adopt a slightly less energetically favorable "open" conformation that is not accessible to its epimer. Calculated theoretical collision cross-sections for these structures agreed with experimental results to <2%. Experimentation indicated that additional energy in the ESI source (i.e., increased temperature, spray voltage) affected the ratio of 25OHD3 conformations, with the less energetically favorable "open" conformation increasing in relative intensity. Finally, LC-IM-MS results yielded linear quantitation of 25OHD3, in the presence of the epimer interference, at biologically relevant concentrations. This study demonstrates that ion mobility can be used in tandem with theoretical modeling to determine structural differences that contribute to drift separation. These separation capabilities provide potential for rapid (<60 ms) identification of 25OHD3 and 25OHD2 in mixtures with their epimers.

Isomer separation and effect of the degree of polymerization on the gas-phase structure of chondroitin sulfate oligosaccharides analyzed by ion mobility and tandem mass spectrometry.

PubMed

Poyer, Salomé; Lopin-Bon, Chrystel; Jacquinet, Jean-Claude; Salpin, Jean-Yves; Daniel, Régis

2017-12-15

Chondroitin sulfate (CS) glycosaminoglycans are bioactive sulfated polysaccharides comprising repeating units of uronic acid and N-acetyl galactose sulfated at various positions. The optimal length and sulfation pattern of the CS bioactive sequences remain elusive so that structure-activity relationships cannot be easily established. Development of efficient analytical methods allowing the differentiation of the various sulfation patterns of CS sequences is therefore of particular importance to correlate their biological functions to the sulfation pattern. Discrimination of different oligomers (dp2 to dp6) of synthetic chondroitin sulfate isomers was evaluated by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the negative-ion mode from deprotonated and alkali adduct species. In addition, ion mobility mass spectrometry (IMS-MS) was used to study the influence of both the degree of polymerization and sulfate group location on the gas-phase conformation of CS oligomers. ESI-MS/MS spectra of chondroitin sulfate isomers show characteristic product ions exclusively from alkali adduct species (Li, Na, K and Cs). Whatever the alkali adducts studied, MS/MS of chondroitin oligosaccharides sulfated at position 6 yields a specific product ion at m/z 139 while CS oligosaccharides sulfated at position 4 show a specific product ion at m/z 154. Being observed for the different CS oligomers di-, tetra- and hexasaccharides, these fragment ions are considered as diagnostic ions for chondroitin 6-O-sulfate and chondroitin 4-O-sulfate, respectively. IMS-MS experiments reveal that collision cross-sections (CCS) of CS oligomers with low charge states evolved linearly with degrees of polymerization indicating a similar gas-phase conformation. This study allows the fast and unambiguous differentiation of CS isomers sulfated at position 6 or 4 for both saturated and unsaturated analogues from MS/MS experiments. In addition, the CCS linear evolution of CS oligomers in

Detection of Radiation-Exposure Biomarkers by Differential Mobility Prefiltered Mass Spectrometry (DMS-MS)

PubMed Central

Coy, Stephen L.; Krylov, Evgeny V.; Schneider, Bradley B.; Covey, Thomas R.; Brenner, David J.; Tyburski, John B.; Patterson, Andrew D.; Krausz, Kris W.; Fornace, Albert J.; Nazarov, Erkinjon G.

2010-01-01

Technology to enable rapid screening for radiation exposure has been identified as an important need, and, as a part of a NIH / NIAD effort in this direction, metabolomic biomarkers for radiation exposure have been identified in a recent series of papers. To reduce the time necessary to detect and measure these biomarkers, differential mobility spectrometry – mass spectrometry (DMS-MS) systems have been developed and tested. Differential mobility ion filters preselect specific ions and also suppress chemical noise created in typical atmospheric-pressure ionization sources (ESI, MALDI, and others). Differential-mobility-based ion selection is based on the field dependence of ion mobility, which, in turn, depends on ion characteristics that include conformation, charge distribution, molecular polarizability, and other properties, and on the transport gas composition which can be modified to enhance resolution. DMS-MS is able to resolve small-molecule biomarkers from nearly-isobaric interferences, and suppresses chemical noise generated in the ion source and in the mass spectrometer, improving selectivity and quantitative accuracy. Our planar DMS design is rapid, operating in a few milliseconds, and analyzes ions before fragmentation. Depending on MS inlet conditions, DMS-selected ions can be dissociated in the MS inlet expansion, before mass analysis, providing a capability similar to MS/MS with simpler instrumentation. This report presents selected DMS-MS experimental results, including resolution of complex test mixtures of isobaric compounds, separation of charge states, separation of isobaric biomarkers (citrate and isocitrate), and separation of nearly-isobaric biomarker anions in direct analysis of a bio-fluid sample from the radiation-treated group of a mouse-model study. These uses of DMS combined with moderate resolution MS instrumentation indicate the feasibility of field-deployable instrumentation for biomarker evaluation. PMID:20305793

Using different drift gases to change separation factors (alpha) in ion mobility spectrometry

PubMed

Asbury; Hill

2000-02-01

The use of different drift gases to alter separation factors (alpha) in ion mobility spectrometry has been demonstrated. The mobility of a series of low molecular weight compounds and three small peptides was determined in four different drift gases. The drift gases chosen were helium, argon, nitrogen, and carbon dioxide. These drift gases provide a range of polarizabilities and molecular weights. In all instances, the compounds showed the greatest mobility in helium and the lowest mobility in carbon dioxide; however the percentage change of mobility for each compound was different, effectively changing the alpha value. The alpha value changes were primarily due to differences in drift gas polarizability but were also influenced by the mass of the drift gas. In addition, gas-phase ion radii were calculated in each of the different drift gases. These radii were then plotted against drift gas polarizability producing linear plots with r2 values greater than 0.99. The intercept of these plots provides the gas-phase radius of an ion in a nonpolarizing environment, whereas the slope is indicative of the magnitude of the ion's mobility change related to polarizability. It therefore, should be possible to separate any two compounds that have different slopes with the appropriate drift gas.

Achieving High Resolution Ion Mobility Separations Using Traveling Waves in Compact Multiturn Structures for Lossless Ion Manipulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamid, Ahmed M.; Garimella, Sandilya V. B.; Ibrahim, Yehia M.

We report on ion mobility separations (IMS) achievable using traveling waves in a Structures for Lossless Ion Manipulations (TW-SLIM) module having a 44-cm path length and sixteen 90º turns. The performance of the TW-SLIM module was evaluated for ion transmission, and ion mobility separations with different RF, TW parameters and SLIM surface gaps in conjunction with mass spectrometry. In this work TWs were created by the transient and dynamic application of DC potentials. The TW-SLIM module demonstrated highly robust performance and the ion mobility resolution achieved even with sixteen close spaced turns was comparable to a similar straight path TW-SLIMmore » module. We found an ion mobility peak capacity of ~ 31 and peak generation rate of 780 s-1 for TW speeds of <210 m/s using the current multi-turn TW-SLIM module. The separations achieved for isomers of peptides and tetrasaccharides were found to be comparable to those from a ~ 0.9-m drift tube-based IMS-MS platform operated at the same pressure (4 torr). The combined attributes of flexible design, low voltage requirements and lossless ion transmission through multiple turns for the present TW-SLIM module provides a basis for SLIM devices capable of achieving much greater ion mobility resolutions via greatly extended ion path lengths and compact serpentine designs that do not significantly impact the instrumentation profile, a direction described in a companion manuscript.« less

A differential mobility spectrometry/mass spectrometry platform for the rapid detection and quantitation of DNA adduct dG-ABP.

PubMed

Kafle, Amol; Klaene, Joshua; Hall, Adam B; Glick, James; Coy, Stephen L; Vouros, Paul

2013-07-15

There is continued interest in exploring new analytical technologies for the detection and quantitation of DNA adducts, biomarkers which provide direct evidence of exposure and genetic damage in cells. With the goal of reducing clean-up steps and improving sample throughput, a Differential Mobility Spectrometry/Mass Spectrometry (DMS/MS) platform has been introduced for adduct analysis. A DMS/MS platform has been utilized for the analysis of dG-ABP, the deoxyguanosine adduct of the bladder carcinogen 4-aminobiphenyl (4-ABP). After optimization of the DMS parameters, each sample was analyzed in just 30 s following a simple protein precipitation step of the digested DNA. A detection limit of one modification in 10^6 nucleosides has been achieved using only 2 µg of DNA. A brief comparison (quantitative and qualitative) with liquid chromatography/mass spectrometry is also presented highlighting the advantages of using the DMS/MS method as a high-throughput platform. The data presented demonstrate the successful application of a DMS/MS/MS platform for the rapid quantitation of DNA adducts using, as a model analyte, the deoxyguanosine adduct of the bladder carcinogen 4-aminobiphenyl. Copyright © 2013 John Wiley & Sons, Ltd.

Large-scale collision cross-section profiling on a travelling wave ion mobility mass spectrometer

PubMed Central

Lietz, Christopher B.; Yu, Qing; Li, Lingjun

2014-01-01

Ion mobility (IM) is a gas-phase electrophoretic method that separates ions according to charge and ion-neutral collision cross-section (CCS). Herein, we attempt to apply a travelling wave (TW) IM polyalanine calibration method to shotgun proteomics and create a large peptide CCS database. Mass spectrometry methods that utilize IM, such as HDMSE, often use high transmission voltages for sensitive analysis. However, polyalanine calibration has only been demonstrated with low voltage transmission used to prevent gas-phase activation. If polyalanine ions change conformation under higher transmission voltages used for HDMSE, the calibration may no longer be valid. Thus, we aimed to characterize the accuracy of calibration and CCS measurement under high transmission voltages on a TW IM instrument using the polyalanine calibration method and found that the additional error was not significant. We also evaluated the potential error introduced by liquid chromatography (LC)-HDMSE analysis, and found it to be insignificant as well, validating the calibration method. Finally, we demonstrated the utility of building a large-population peptide CCS database by investigating the effects of terminal lysine position, via LysC or LysN digestion, on the formation of two structural sub-families formed by triply charged ions. PMID:24845359

Sizing and Discovery of Nanosized Polyoxometalate Clusters by Mass Spectrometry

PubMed Central

2016-01-01

Ion mobility-mass spectrometry (IM-MS) is a powerful technique for structural characterization, e.g., sizing and conformation, particularly when combined with quantitative modeling and comparison to theoretical values. Traveling wave IM-MS (TW-IM-MS) has recently become commercially available to nonspecialist groups and has been exploited in the structural study of large biomolecules, however reliable calibrants for large anions have not been available. Polyoxometalate (POM) species—nanoscale inorganic anions—share many of the facets of large biomolecules, however, the full potential of IM-MS in their study has yet to be realized due to a lack of suitable calibration data or validated theoretical models. Herein we address these limitations by reporting DT-IM (drift tube) data for a set of POM clusters {M12} Keggin 1, {M18} Dawson 2, and two {M7} Anderson derivatives 3 and 4 which demonstrate their use as a TW-IM-MS calibrant set to facilitate characterization of very large (ca. 1–4 nm) anionic species. The data was also used to assess the validity of standard techniques to model the collision cross sections of large inorganic anions using the nanoscale family of compounds based upon the {Se2W29} unit including the trimer, {Se8W86O299} A, tetramer, {Se8W116O408} B, and hexamer {Se12W174O612} C, including their relative sizing in solution. Furthermore, using this data set, we demonstrated how IM-MS can be used to conveniently characterize and identify the synthesis of two new, i.e., previously unreported POM species, {P8W116}, unknown D, and {Te8W116}, unknown E, which are not amenable to analysis by other means with the approximate formulation of [H34W118X8M2O416]44–, where X = P and M = Co for D and X = Te and M = Mn for E. This work establishes a new type of inorganic calibrant for IM-MS allowing sizing, structural analysis, and discovery of molecular nanostructures directly from solution. PMID:26906879

MALDI Mass Spectrometry Imaging: A Novel Tool for the Identification and Classification of Amyloidosis.

PubMed

Winter, Martin; Tholey, Andreas; Kristen, Arnt; Röcken, Christoph

2017-11-01

Amyloidosis is a group of diseases caused by extracellular accumulation of fibrillar polypeptide aggregates. So far, diagnosis is performed by Congo red staining of tissue sections in combination with polarization microscopy. Subsequent identification of the causative protein by immunohistochemistry harbors some difficulties regarding sensitivity and specificity. Mass spectrometry based approaches have been demonstrated to constitute a reliable method to supplement typing of amyloidosis, but still depend on Congo red staining. In the present study, we used matrix-assisted laser desorption/ionization mass spectrometry imaging coupled with ion mobility separation (MALDI-IMS MSI) to investigate amyloid deposits in formalin-fixed and paraffin-embedded tissue samples. Utilizing a novel peptide filter method, we found a universal peptide signature for amyloidoses. Furthermore, differences in the peptide composition of ALλ and ATTR amyloid were revealed and used to build a reliable classification model. Integrating the peptide filter in MALDI-IMS MSI analysis, we developed a bioinformatics workflow facilitating the identification and classification of amyloidosis in a less time and sample-consuming experimental setup. Our findings demonstrate also the feasibility to investigate the amyloid's protein composition, thus paving the way to establish classification models for the diverse types of amyloidoses and to shed further light on the complex process of amyloidogenesis. © 2017 The Authors, Proteomics Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Performance evaluation of oxygen adsorbents using negative corona discharge-ion mobility spectrometry.

PubMed

Azadkish, Kamal; Jafari, Mohammad T; Ghaziaskar, Hassan S

2017-02-08

Trace amounts of oxygen was determined using negative corona discharge as an ionization source for ion mobility spectrometry. A point-in-cylinder geometry with novel design was used to establish the corona discharge without interferences of negative ions such as NO X - . The desirable background spectrum shows only electrons peak, providing the instrument capable of trace analysis of oxygen in gaseous samples. The limit of detection and linear dynamic range with high coefficient of determination (r 2  = 0.9997), were obtained for oxygen as 8.5 and 28-14204 ppm, respectively. The relative standard deviations of the method for intraday and interday were obtained 4 and 11%, respectively. The satisfactory results revealed the ability of the negative corona discharge ion mobility spectrometry for investigating the performance of synthesized oxygen adsorbents in nitrogen streams. Two oxygen scavengers of MnO and Cu powder were prepared and the optimum temperature of the reactor containing MnO and Cu powder were obtained as 180 and 230 °C, respectively. Due to higher lifetime of copper powder, it was selected as the oxygen scavenger and some parameters such as: the type of adsorbent support, the size of adsorbent particles, and the amount of copper were studied for preparation of more efficient oxygen adsorbent. Copyright © 2016 Elsevier B.V. All rights reserved.

Determination of ammonia in ethylene using ion mobility spectrometry

NASA Technical Reports Server (NTRS)

Cross, J. H.; Limero, T. F.; Lane, J. L.; Wang, F.

1997-01-01

A simple procedure to analyze ammonia in ethylene by ion mobility spectrometry is described. The spectrometer is operated with a silane polymer membrane., 63Ni ion source, H+ (H2O)n reactant ion, and nitrogen drift and source gas. Ethylene containing parts per billion (ppb) (v/v) concentrations of ammonia is pulled across the membrane and diffuses into the spectrometer. Preconcentration or preseparation is unnecessary, because the ethylene in the spectrometer has no noticeable effect on the analytical results. Ethylene does not polymerize in the radioactive source. Ethylene's flammability is negated by the nitrogen inside the spectrometer. Response to ammonia concentrations between 200 ppb and 1.5 ppm is near linear, and a detection limit of 25 ppb is calculated.

Ion mobility spectrometry as a simple and rapid method to measure the plasma propofol concentrations for intravenous anaesthesia monitoring

NASA Astrophysics Data System (ADS)

Wang, Xin; Zhou, Qinghua; Jiang, Dandan; Gong, Yulei; Li, Enyou; Li, Haiyang

2016-11-01

The plasma propofol concentration is important information for anaesthetists to monitor and adjust the anaesthesia depth for patients during a surgery operation. In this paper, a stand-alone ion mobility spectrometer (IMS) was constructed for the rapid measurement of the plasma propofol concentrations. Without any sample pre-treatment, the plasma samples were dropped on a piece of glass microfiber paper and then introduced into the IMS cell by the thermal desorption directly. Each individual measurement could be accomplished within 1 min. For the plasma propofol concentrations from 1 to 12 μg mL-1, the IMS response was linear with a correlation coefficient R2 of 0.998, while the limit of detection was evaluated to be 0.1 μg mL-1. These measurement results did meet the clinical application requirements. Furthermore, other clinically-often-used drugs, including remifentanil, flurbiprofen and atracurium, were found no significant interference with the qualitative and quantitative analysis of the plasma propofol. The plasma propofol concentrations measured by IMS were correlated well with those measured by the high performance liquid chromatography (HPLC). The results confirmed an excellent agreement between these two methods. Finally, this method was applied to monitor the plasma propofol concentrations for a patient undergoing surgery, demonstrating its capability of anaesthesia monitoring in real clinical environments.

Multi-capillary column-ion mobility spectrometry: a potential screening system to differentiate virgin olive oils.

PubMed

Garrido-Delgado, Rocío; Arce, Lourdes; Valcárcel, Miguel

2012-01-01

The potential of a headspace device coupled to multi-capillary column-ion mobility spectrometry has been studied as a screening system to differentiate virgin olive oils ("lampante," "virgin," and "extra virgin" olive oil). The last two types are virgin olive oil samples of very similar characteristics, which were very difficult to distinguish with the existing analytical method. The procedure involves the direct introduction of the virgin olive oil sample into a vial, headspace generation, and automatic injection of the volatiles into a gas chromatograph-ion mobility spectrometer. The data obtained after the analysis by duplicate of 98 samples of three different categories of virgin olive oils, were preprocessed and submitted to a detailed chemometric treatment to classify the virgin olive oil samples according to their sensory quality. The same virgin olive oil samples were also analyzed by an expert's panel to establish their category and use these data as reference values to check the potential of this new screening system. This comparison confirms the potential of the results presented here. The model was able to classify 97% of virgin olive oil samples in their corresponding group. Finally, the chemometric method was validated obtaining a percentage of prediction of 87%. These results provide promising perspectives for the use of ion mobility spectrometry to differentiate virgin olive oil samples according to their quality instead of using the classical analytical procedure.

Desorption atmospheric pressure photoionization and direct analysis in real time coupled with travelling wave ion mobility mass spectrometry.

PubMed

Räsänen, Riikka-Marjaana; Dwivedi, Prabha; Fernández, Facundo M; Kauppila, Tiina J

2014-11-15

Ambient mass spectrometry (MS) is a tool for screening analytes directly from sample surfaces. However, background impurities may complicate the spectra and therefore fast separation techniques are needed. Here, we demonstrate the use of travelling wave ion mobility spectrometry in a comparative study of two ambient MS techniques. Desorption atmospheric pressure photoionization (DAPPI) and direct analysis in real time (DART) were coupled with travelling wave ion mobility mass spectrometry (TWIM-MS) for highly selective surface analysis. The ionization efficiencies of DAPPI and DART were compared. Test compounds were: bisphenol A, benzo[a]pyrene, ranitidine, cortisol and α-tocopherol. DAPPI-MS and DART-TWIM-MS were also applied to the analysis of chloroquine from dried blood spots, and α-tocopherol from almond surface, and DAPPI-TWIM-MS was applied to analysis of pharmaceuticals and multivitamin tablets. DAPPI was approximately 100 times more sensitive than DART for bisphenol A and 10-20 times more sensitive for the other compounds. The limits of detection were between 30-290 and 330-8200 fmol for DAPPI and DART, respectively. Also, from the authentic samples, DAPPI ionized chloroquine and α-tocopherol more efficiently than DART. The mobility separation enabled the detection of species with low signal intensities, e.g. thiamine and cholecalciferol, in the DAPPI-TWIM-MS analysis of multivitamin tablets. DAPPI ionized the studied compounds of interest more efficiently than DART. For both DAPPI and DART, the mobility separation prior to MS analysis reduced the amount of chemical noise in the mass spectrum and significantly increased the signal-to-noise ratio for the analytes. Copyright © 2014 John Wiley & Sons, Ltd.

Detection of explosives using negative ion mobility spectrometry in air based on dopant-assisted thermal ionization.

PubMed

Shahraki, Hassan; Tabrizchi, Mahmoud; Farrokhpor, Hossein

2018-05-26

The ionization source is an essential component of most explosive detectors based on negative ion mobility spectrometry. Conventional ion sources suffer from such inherent limitations as special safety regulations on radioactive sources or generating interfering ions (for non-radioactive sources) such as corona discharge operating in the air. In this study, a new negative ion source is introduced for ion mobility spectrometry that is based on thermal ionization and operates in the air, applicable to explosives detection. Our system consists of a heating filament powered by an isolated power supply connected to negative high voltage. The ionization is assisted by doping chlorinated compounds in the gas phase using chlorinated hydrocarbons in contact with the heating element to yield Cl - reactant ions. Several chlorinated hydrocarbons are evaluated as the reagent chemicals for providing Cl- reactant ions, of which CCl 4 is identified as the best ionizing reagent. The ion source is evaluated by recording the ion mobility spectra of common explosives, including TNT, RDX, and PETN in the air. A detection limit of 150 pg is obtained for TNT. Compared to other ionization sources, the new source is found to be low-cost, simple, and long-lived, making it suited to portable explosives detection devices. Copyright © 2018 Elsevier B.V. All rights reserved.

Volatile-Compound Fingerprinting by Headspace-Gas-Chromatography Ion-Mobility Spectrometry (HS-GC-IMS) as a Benchtop Alternative to 1H NMR Profiling for Assessment of the Authenticity of Honey.

PubMed

Gerhardt, Natalie; Birkenmeier, Markus; Schwolow, Sebastian; Rohn, Sascha; Weller, Philipp

2018-02-06

This work describes a simple approach for the untargeted profiling of volatile compounds for the authentication of the botanical origins of honey based on resolution-optimized HS-GC-IMS combined with optimized chemometric techniques, namely PCA, LDA, and kNN. A direct comparison of the PCA-LDA models between the HS-GC-IMS and 1 H NMR data demonstrated that HS-GC-IMS profiling could be used as a complementary tool to NMR-based profiling of honey samples. Whereas NMR profiling still requires comparatively precise sample preparation, pH adjustment in particular, HS-GC-IMS fingerprinting may be considered an alternative approach for a truly fully automatable, cost-efficient, and in particular highly sensitive method. It was demonstrated that all tested honey samples could be distinguished on the basis of their botanical origins. Loading plots revealed the volatile compounds responsible for the differences among the monofloral honeys. The HS-GC-IMS-based PCA-LDA model was composed of two linear functions of discrimination and 10 selected PCs that discriminated canola, acacia, and honeydew honeys with a predictive accuracy of 98.6%. Application of the LDA model to an external test set of 10 authentic honeys clearly proved the high predictive ability of the model by correctly classifying them into three variety groups with 100% correct classifications. The constructed model presents a simple and efficient method of analysis and may serve as a basis for the authentication of other food types.

Compression Ratio Ion Mobility Programming (CRIMP) Accumulation and Compression of Billions of Ions for Ion Mobility-Mass Spectrometry Using Traveling Waves in Structures for Lossless Ion Manipulations (SLIM)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Liulin; Garimella, Sandilya V. B.; Hamid, Ahmed M.

We report on the implementation of a traveling wave (TW) based compression ratio ion mobility programming (CRIMP) approach within Structures for Lossless Ion Manipulations (SLIM) that enables both greatly enlarged trapped ion charge capacities and also their subsequent efficient compression for use in ion mobility (IM) separations. Ion accumulation is conducted in a long serpentine path TW SLIM region after which CRIMP allows the large ion populations to be ‘squeezed’. The compression process occurs at an interface between two SLIM regions, one operating conventionally and the second having an intermittently pausing or ‘stuttering’ TW, allowing the contents of multiple binsmore » of ions from the first region to be merged into a single bin in the second region. In this initial work stationary voltages in the second region were used to block ions from exiting the first (trapping) region, and the resumption of TWs in the second region allows ions to exit, and the population to also be compressed if CRIMP is applied. In our initial evaluation we show that the number of charges trapped for a 40 s accumulation period was ~5×109, more than two orders of magnitude greater than the previously reported charge capacity using an ion funnel trap. We also show that over 1×109 ions can be accumulated with high efficiency in the present device, and that the extent of subsequent compression is only limited by the space charge capacity of the trapping region. Lower compression ratios allow increased IM peak heights without significant loss of signal, while excessively large compression ratios can lead to ion losses and other artifacts. Importantly, we show that extended ion accumulation in conjunction with CRIMP and multiple passes provides the basis for a highly desirable combination of ultra-high sensitivity and ultra-high resolution IM separations using SLIM.« less

Selective Sampling with Direct Ion Mobility Spectrometric Detection for Explosives Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harvey, Scott D; Ewing, Robert G; Waltman, Melanie J

2009-06-29

This study investigates the potential and limitations of a streamlined, field-deployable analytical approach that involves selective capture of explosive materials with direct analysis by ion mobility spectrometry (IMS). Selective capture of explosives was performed on deactivated quartz fiber filters impregnated with metal β-diketonate polymers. These Lewis acidic polymers selectively interact with Lewis base analytes such as explosives. The filter coupons could be directly inserted into an IMS instrument for analysis. The uptake kinetics of 2,4,6-trinitrotoluene (TNT) from a saturated atmosphere were characterized, and based on these studies, passive equilibrium sampling was applied to estimate the TNT concentration within an ammunitionmore » magazine that contained bulk TNT. Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) uptake from a saturated environment also was examined over a one-month period. Each incremental sampling period showed increasing quantities of RDX culminating with collection of approximately 5 ng of RDX on the coupon at the end of one month. This is the first time that gas-phase uptake of RDX has been demonstrated.« less

Combination of corona discharge ion mobility spectrometry with a novel reagent gas and two immiscible organic solvent liquid-liquid-liquid microextraction for analysis of clomipramine in biological samples.

PubMed

Saraji, Mohammad; Bidgoli, Ali Akbar Hajialiakbari; Khayamian, Taghi; Moradmand, Ali

2011-12-02

A novel and sensitive method based on combination of two immiscible organic solvents hollow fiber-based liquid-liquid-liquid microextraction and corona discharge ion mobility spectrometry (HF-LLLME-CD-IMS) was employed for the analysis of clomipramine in human urine and plasma. The effect of formic, acetic and propionic acid as the reagent gas (dopant) on the corona discharge ion mobility signal was investigated. The influence of dopant amount was also studied. Optimum mass flow rates of the dopants were 3.7, 1.1 and 1.0 μmol min(-1) for formic, acetic and propionic acid, respectively. Experimental parameters influencing the extraction efficiency of HF-LLLME, such as NaOH concentration as donor solution, ionic strength of the sample, stirring rate, and extraction time were investigated and optimized. Under the optimum conditions, analytical parameters such as linearity, precision and limit of detection were also evaluated. The linear dynamic range was from 1 to 100 μg L(-1) (r(2)=0.9980) and the limit of detection was 0.35 μg L(-1). Intra- and inter-day precisions were satisfactory with a relative standard deviation (RSD) of 5.9 and 6.7%, respectively. The proposed method was satisfactorily applied for the determination of clomipramine in human plasma and urine. Copyright © 2011 Elsevier B.V. All rights reserved.

Security for IP Multimedia Services in the 3GPP Third Generation Mobile System.

ERIC Educational Resources Information Center

Horn, G.; Kroselberg, D.; Muller, K.

2003-01-01

Presents an overview of the security architecture of the IP multimedia core network subsystem (IMS) of the third generation mobile system, known in Europe as UMTS. Discusses IMS security requirements; IMS security architecture; authentication between IMS user and home network; integrity and confidentiality for IMS signalling; and future aspects of…

Analysis of Bacterial Lipooligosaccharides by MALDI-TOF MS with Traveling Wave Ion Mobility

NASA Astrophysics Data System (ADS)

Phillips, Nancy J.; John, Constance M.; Jarvis, Gary A.

2016-07-01

Lipooligosaccharides (LOS) are major microbial virulence factors displayed on the outer membrane of rough-type Gram-negative bacteria. These amphipathic glycolipids are comprised of two domains, a core oligosaccharide linked to a lipid A moiety. Isolated LOS samples are generally heterogeneous mixtures of glycoforms, with structural variability in both domains. Traditionally, the oligosaccharide and lipid A components of LOS have been analyzed separately following mild acid hydrolysis, although important acid-labile moieties can be cleaved. Recently, an improved method was introduced for analysis of intact LOS by MALDI-TOF MS using a thin layer matrix composed of 2,4,6-trihydroxyacetophenone (THAP) and nitrocellulose. In addition to molecular ions, the spectra show in-source "prompt" fragments arising from regiospecific cleavage between the lipid A and oligosaccharide domains. Here, we demonstrate the use of traveling wave ion mobility spectrometry (TWIMS) for IMS-MS and IMS-MS/MS analyses of intact LOS from Neisseria spp. ionized by MALDI. Using IMS, the singly charged prompt fragments for the oligosaccharide and lipid A domains of LOS were readily separated into resolved ion plumes, permitting the extraction of specific subspectra, which led to increased confidence in assigning compositions and improved detection of less abundant ions. Moreover, IMS separation of precursor ions prior to collision-induced dissociation (CID) generated time-aligned, clean MS/MS spectra devoid of fragments from interfering species. Incorporating IMS into the profiling of intact LOS by MALDI-TOF MS exploits the unique domain structure of the molecule and offers a new means of extracting more detailed information from the analysis.

Polypyrrole nanowire as an excellent solid phase microextraction fiber for bisphenol A analysis in food samples followed by ion mobility spectrometry.

PubMed

Kamalabadi, Mahdie; Mohammadi, Abdorreza; Alizadeh, Naader

2016-08-15

A polypyrrole nanowire coated fiber was prepared and used in head-space solid phase microextraction coupled with ion mobility spectrometry (HS-SPME-IMS) to the analysis of bisphenol A (BPA) in canned food samples, for the first time. This fiber was synthesized by electrochemical oxidation of the monomer in aqueous solution. The fiber characterization by scanning electron microscopy (SEM) revealed that the new fiber exhibited two-dimensional structures with a nanowire morphology. The effects of important extraction parameters on the efficiency of HS-SPME were investigated and optimized. Under the optimum conditions, the linearity of 10-150ngg(-1) and limit of detection (based on S/N=3) of 1ngg(-1) were obtained in BPA analysis. The repeatability (n=5) expressed as the relative standard deviation (RSD%) was 5.8%. At the end, the proposed method was successfully applied to determine BPA in various canned food samples (peas, corns, beans). Relative recoveries were obtained 93-96%. Method validation was conducted by comparing our results with those obtained through HPLC with fluorescence detection (FLD). Compatible results indicate that the proposed method can be successfully used in BPA analysis. This method is simple and cheaper than chromatographic methods, with no need of extra organic solvent consumption and derivatization prior to sample introduction. Copyright © 2016 Elsevier B.V. All rights reserved.

Peptide profiling of Internet-obtained Cerebrolysin using high performance liquid chromatography - electrospray ionization ion trap and ultra high performance liquid chromatography - ion mobility - quadrupole time of flight mass spectrometry.

PubMed

Gevaert, Bert; D'Hondt, Matthias; Bracke, Nathalie; Yao, Han; Wynendaele, Evelien; Vissers, Johannes Petrus Cornelis; De Cecco, Martin; Claereboudt, Jan; De Spiegeleer, Bart

2015-09-01

Cerebrolysin, a parenteral peptide preparation produced by controlled digestion of porcine brain proteins, is an approved nootropic medicine in some countries. However, it is also easily and globally available on the Internet. Nevertheless, until now, its exact chemical composition was unknown. Using high performance liquid chromatography (HPLC) coupled to ion trap and ultra high performance liquid chromatography (UHPLC) coupled to quadrupole-ion mobility-time-of-flight mass spectrometry (Q-IM-TOF MS), combined with UniProt pig protein database search and PEAKS de novo sequencing, we identified 638 unique peptides in an Internet-obtained Cerebrolysin sample. The main components in this sample originate from tubulin alpha- and beta-chain, actin, and myelin basic protein. No fragments of known neurotrophic factors like glial cell-derived neurotrophic factor (GDNF), neurotrophin nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) were found, suggesting that the activities reported in the literature are likely the result of new, hitherto unknown cryptic peptides with nootropic properties. Copyright © 2015 John Wiley & Sons, Ltd.

Determination of N-linked glycosylation in viral glycoproteins by negative ion mass spectrometry and ion mobility

PubMed Central

Bitto, David; Harvey, David J.; Halldorsson, Steinar; Doores, Katie J.; Pritchard, Laura K.; Huiskonen, Juha T.; Bowden, Thomas A.; Crispin, Max

2016-01-01

Summary Glycan analysis of virion-derived glycoproteins is challenging due to the difficulties in glycoprotein isolation and low sample abundance. Here, we describe how ion mobility mass spectrometry can be used to obtain spectra from virion samples. We also describe how negative ion fragmentation of glycans can be used to probe structural features of virion glycans. PMID:26169737

Atmospheric pressure ionization of chlorinated ethanes in ion mobility spectrometry and mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ewing, Robert G.; Atkinson, David A.; Benson, Michael T.

2015-05-16

This study investigates the APCI mechanisms associated with chlorinated ethanes in an attempt to define conditions under which unique pseudo-molecular adducts, in addition to chloride ion, can be produced for analytical measurements using IMS and MS. The ionization chemistry of chlorinated compounds typically leads to the detection of only the halide ions. Using molecular modeling, which provides insights into the ion formation and relative binding energies, predictions for the formation of pseudo-molecular adducts are postulated. Predicted structures of the chloride ion with multiple hydrogens on the ethane backbone was supported by the observation of specific pseudo-molecular adducts in IMS andmore » MS spectra. With the proper instrumental conditions, such as short reaction times and low temp.« less

Optimization of a Differential Ion Mobility Spectrometry-Tandem Mass Spectrometry Method for High-Throughput Analysis of Nicotine and Related Compounds: Application to Electronic Cigarette Refill Liquids.

PubMed

Regueiro, Jorge; Giri, Anupam; Wenzl, Thomas

2016-06-21

Fast market penetration of electronic cigarettes is leading to an exponentially growing number of electronic refill liquids with different nicotine contents and an endless list of flavors. Therefore, rapid and simple methods allowing a fast screening of these products are necessary to detect harmful substances which can negatively impact the health of consumers. In this regard, the present work explores the capabilities of differential ion mobility spectrometry coupled to tandem mass spectrometry for high-throughput analysis of nicotine and 11 related compounds in commercial refill liquids for electronic cigarettes. The influence of main factors affecting the ion mobility separation, such as modifier types and concentration, separation voltage, and temperature, was systematically investigated. Despite small molecular weight differences among the studied compounds, a good separation was achieved in the ion mobility cell under the optimized conditions, which involved the use of ethanol as a polar gas-phase chemical modifier. Indeed, differential ion mobility was able to resolve (resolution >4) nicotine from its structural isomer anabasine without the use of any chromatographic separation. The quantitative performance of the proposed method was then evaluated, showing satisfactory precision (RSD ≤ 16%) and recoveries ranging from 85 to 100% for nicotine, and from 84 to 126% for the rest of the target analytes. Several commercial electronic cigarette refill liquids were analyzed to demonstrate the applicability of the method. In some cases, significant differences were found between labeled and measured levels of nicotine. Anatabine, cotinine, myosmine, and nornicotine were also found in some of the analyzed samples.

Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry.

PubMed

Blincoe, William D; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A; Joyce, Leo A; Mangion, Ian; Sheng, Huaming

2018-04-01

Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS 1 ). Significant water/alcohol loss (>30% abundance in MS 1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. Graphical Abstract ᅟ.

Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry

NASA Astrophysics Data System (ADS)

Blincoe, William D.; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A.; Joyce, Leo A.; Mangion, Ian; Sheng, Huaming

2018-02-01

Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS1). Significant water/alcohol loss (>30% abundance in MS1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. [Figure not available: see fulltext.

Fast quantitation of opioid isomers in human plasma by differential mobility spectrometry/mass spectrometry via SPME/open-port probe sampling interface.

PubMed

Liu, Chang; Gómez-Ríos, Germán Augusto; Schneider, Bradley B; Le Blanc, J C Yves; Reyes-Garcés, Nathaly; Arnold, Don W; Covey, Thomas R; Pawliszyn, Janusz

2017-10-23

Mass spectrometry (MS) based quantitative approaches typically require a thorough sample clean-up and a decent chromatographic step in order to achieve needed figures of merit. However, in most cases, such processes are not optimal for urgent assessments and high-throughput determinations. The direct coupling of solid phase microextraction (SPME) to MS has shown great potential to shorten the total sample analysis time of complex matrices, as well as to diminish potential matrix effects and instrument contamination. In this study, we demonstrate the use of the open-port probe (OPP) as a direct and robust sampling interface to couple biocompatible-SPME (Bio-SPME) fibres to MS for the rapid quantitation of opioid isomers (i.e. codeine and hydrocodone) in human plasma. In place of chromatography, a differential mobility spectrometry (DMS) device was implemented to provide the essential selectivity required to quantify these constitutional isomers. Taking advantage of the simplified sample preparation process based on Bio-SPME and the fast separation with DMS-MS coupling via OPP, a high-throughput assay (10-15 s per sample) with limits of detection in the sub-ng/mL range was developed. Succinctly, we demonstrated that by tuning adequate ion mobility separation conditions, SPME-OPP-MS can be employed to quantify non-resolved compounds or those otherwise hindered by co-extracted isobaric interferences without further need of coupling to other separation platforms. Copyright © 2017 Elsevier B.V. All rights reserved.

Polypyrrole/montmorillonite nanocomposite as a new solid phase microextraction fiber combined with gas chromatography-corona discharge ion mobility spectrometry for the simultaneous determination of diazinon and fenthion organophosphorus pesticides.

PubMed

Jafari, Mohammad T; Saraji, Mohammad; Sherafatmand, Hossein

2014-03-03

A novel solid phase microextraction (SPME) fiber was prepared and coupled with gas chromatography corona discharge ion mobility spectrometry (GC-CD-IMS) based on polypyrrole/montmorillonite nanocomposites for the simultaneous determination of diazinon and fenthion. The nanocomposite polymer was coated using a three-electrode electrochemical system and directly deposited on a Ni-Cr wire by applying a constant potential. The scanning electron microscopy images revealed that the new fiber exhibited a rather porous and homogenous surface. The thermal stability of the fabricated fiber was investigated by thermogravimetric analysis. The effects of different parameters influencing the extraction efficiency such as extraction temperature and time, salt addition, stirring rate, the amount of nanoclay, and desorption temperature were investigated and optimized. The method was exhaustively evaluated in terms of sensitivity, recovery, and reproducibility. The linearity ranges of 0.05-10 and 0.08-10 μg L(-1), and the detection limits of 0.020 and 0.035 μg L(-1) were obtained for diazinon and fenthion, respectively. The relative standard deviation values were calculated to be lower than 5% and 8% for intra-day and inter-day, respectively. Finally, the developed method was applied to determine the diazinon and fenthion (as model compounds) in cucumber, lettuce, apple, tap and river water samples. The satisfactory recoveries revealed the capability of the two-dimensional separation technique (retention time in GC and drift time in IMS) for the analysis of complex matrices extracted by SPME. Copyright © 2014 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xing; Ibrahim, Yehia M.; Chen, Tsung-Chi

We report the first evaluation of a platform coupling a high speed field asymmetric ion mobility spectrometry microchip (µFAIMS) with drift tube ion mobility and mass spectrometry (IMS-MS). The µFAIMS/IMS-MS platform was used to analyze biological samples and simultaneously acquire multidimensional information of detected features from the measured FAIMS compensation fields and IMS drift times, while also obtaining accurate ion masses. These separations thereby increase the overall separation power, resulting increased information content, and provide more complete characterization of more complex samples. The separation conditions were optimized for sensitivity and resolving power by the selection of gas compositions and pressuresmore » in the FAIMS and IMS separation stages. The resulting performance provided three dimensional separations, benefitting both broad complex mixture studies and targeted analyses by e.g. improving isomeric separations and allowing detection of species obscured by “chemical noise” and other interfering peaks.« less

Effective Ion Mobility Peak Width as a New Isomeric Descriptor for the Untargeted Analysis of Complex Mixtures Using Ion Mobility-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Farenc, Mathilde; Paupy, Benoit; Marceau, Sabrina; Riches, Eleanor; Afonso, Carlos; Giusti, Pierre

2017-07-01

Ion mobility coupled with mass spectrometry was proven to be an efficient way to characterize complex mixtures such as petroleum samples. However, the identification of isomeric species is difficult owing to the molecular complexity of petroleum and no availability of standard molecules. This paper proposes a new simple indicator to estimate the isomeric content of highly complex mixtures. This indicator is based on the full width at half maximum (FWHM) of the extracted ion mobility peak measured in millisecond or square angstrom that is corrected for instrumental factors such as ion diffusion. This value can be easily obtained without precisely identifying the number of isomeric species under the ion mobility peaks. Considering the Boduszynski model, the ion mobility profile for a particular elemental composition is expected to be a continuum of various isomeric species. The drift time-dependent fragmentation profile was studied and confirmed this hypothesis, a continuous evolution of the fragmentation profile showing that the larger alkyl chain species were detected at higher drift time values. This new indicator was proven to be a fast and efficient method to compare vacuum gas oils for which no difference was found using other analytical techniques.

Deep learning for tumor classification in imaging mass spectrometry.

PubMed

Behrmann, Jens; Etmann, Christian; Boskamp, Tobias; Casadonte, Rita; Kriegsmann, Jörg; Maaß, Peter

2018-04-01

Tumor classification using imaging mass spectrometry (IMS) data has a high potential for future applications in pathology. Due to the complexity and size of the data, automated feature extraction and classification steps are required to fully process the data. Since mass spectra exhibit certain structural similarities to image data, deep learning may offer a promising strategy for classification of IMS data as it has been successfully applied to image classification. Methodologically, we propose an adapted architecture based on deep convolutional networks to handle the characteristics of mass spectrometry data, as well as a strategy to interpret the learned model in the spectral domain based on a sensitivity analysis. The proposed methods are evaluated on two algorithmically challenging tumor classification tasks and compared to a baseline approach. Competitiveness of the proposed methods is shown on both tasks by studying the performance via cross-validation. Moreover, the learned models are analyzed by the proposed sensitivity analysis revealing biologically plausible effects as well as confounding factors of the considered tasks. Thus, this study may serve as a starting point for further development of deep learning approaches in IMS classification tasks. https://gitlab.informatik.uni-bremen.de/digipath/Deep_Learning_for_Tumor_Classification_in_IMS. jbehrmann@uni-bremen.de or christianetmann@uni-bremen.de. Supplementary data are available at Bioinformatics online.

VoIM-Mediated Cooperative Tasks for English Language Learners

ERIC Educational Resources Information Center

Chinnery, George M.

2008-01-01

The use of telephones--even mobile phones--in language learning is not unique (see Chinnery 2006). The literature is also The literature is also replete with imaginative ideas on how to apply Internet chat software like instant messengers (IM) to language learning. A more recent technological development of use to educators is Internet telephony,…

Mass spectrometry and tandem mass spectrometry of citrus limonoids.

PubMed

Tian, Qingguo; Schwartz, Steven J

2003-10-15

Methods for atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) of citrus limonoid aglycones and electrospray ionization tandem mass spectrometry (ESI-MS/MS) of limonoid glucosides are reported. The fragmentation patterns of four citrus limonoid aglycones (limonin, nomilin, obacunone, and deacetylnomilin) and six limonoid glucosides, that is, limonin 17-beta-D-glucopyranoside (LG), nomilin 17-beta-D-glucopyranoside (NG), nomilinic acid 17-beta-D-glucopyranoside (NAG), deacetyl nomilinic acid 17-beta-D-glucopyranoside (DNAG), obacunone 17-beta-D-glucopyranoside (OG), and obacunoic acid 17-beta-D-glucopyranoside (OAG) were investigated using a quadruple mass spectrometer in low-energy collisionally activated dissociation (CAD). The four limonoid aglycones and four limonoid glucosides (LG, OG, NAG, and DNAG) were purified from citrus seeds; the other two limonoid glucosides (NG and OAG) were tentatively identified in the crude extract of grapefruit seeds by ESI mass spectrometry in both positive and negative ion analysis. Ammonium hydroxide or acetic acid was added to the mobile phase to facilitate ionization. During positive ion APCI analysis of limonoid aglycones, protonated molecular ion, [M + H]+, or adduct ion, [M + NH3 + H]-, was formed as base peaks when ammonium hydroxide was added to the mobile phase. Molecular anions or adduct ions with acetic acid ([M + HOAc - H] and [M + HOAc]-) or a deprotonated molecular ion were produced during negative ion APCI analysis of limonoid aglycones, depending on the mobile-phase modifier used. Positive ion ESI-MS of limonoid glucosides produced adduct ions of [M + H + NH3]+, [M + Na]+, and [M + K]+ when ammonium hydroxide was added to the mobile phase. After collisionally activated dissociation (CAD) of the limonoid aglycone molecular ions in negative ion APCI analysis, fragment ions indicated structural information of the precursor ions, showing the presence of methyl, carboxyl, and oxygenated ring

Real-Time Cellular Exometabolome Analysis with a Microfluidic-Mass Spectrometry Platform

PubMed Central

Marasco, Christina C.; Enders, Jeffrey R.; Seale, Kevin T.; McLean, John A.; Wikswo, John P.

2015-01-01

To address the challenges of tracking the multitude of signaling molecules and metabolites that is the basis of biological complexity, we describe a strategy to expand the analytical techniques for dynamic systems biology. Using microfluidics, online desalting, and mass spectrometry technologies, we constructed and validated a platform well suited for sampling the cellular microenvironment with high temporal resolution. Our platform achieves success in: automated cellular stimulation and microenvironment control; reduced non-specific adsorption to polydimethylsiloxane due to surface passivation; real-time online sample collection; near real-time sample preparation for salt removal; and real-time online mass spectrometry. When compared against the benchmark of “in-culture” experiments combined with ultraperformance liquid chromatography-electrospray ionization-ion mobility-mass spectrometry (UPLC-ESI-IM-MS), our platform alleviates the volume challenge issues caused by dilution of autocrine and paracrine signaling and dramatically reduces sample preparation and data collection time, while reducing undesirable external influence from various manual methods of manipulating cells and media (e.g., cell centrifugation). To validate this system biologically, we focused on cellular responses of Jurkat T cells to microenvironmental stimuli. Application of these stimuli, in conjunction with the cell’s metabolic processes, results in changes in consumption of nutrients and secretion of biomolecules (collectively, the exometabolome), which enable communication with other cells or tissues and elimination of waste. Naïve and experienced T-cell metabolism of cocaine is used as an exemplary system to confirm the platform’s capability, highlight its potential for metabolite discovery applications, and explore immunological memory of T-cell drug exposure. Our platform proved capable of detecting metabolomic variations between naïve and experienced Jurkat T cells and

Fast vaporization solid phase microextraction and ion mobility spectrometry: A new approach for determination of creatinine in biological fluids.

PubMed

Jafari, Mostafa; Ebrahimzadeh, Homeira; Banitaba, Mohamma Hossein

2015-11-01

In this work a rapid and simple method for creatinine determination in urine and plasma samples based on aqueous derivatization of creatinine and complete vaporization of sample (as low as 10 µL), followed by ion mobility spectrometry analysis has been proposed. The effect of four important parameters (extraction temperature, total volume of solution, desorption temperature and extraction time) on ion mobility signal has been studied. Under the optimized conditions, the quantitative response of ion mobility spectrometry for creatinine was linear in the range of 0-500 mg L(-1) with a detection limit of 0.6 mg L(-1) in urine and 0-250 mg L(-1) with a detection limit of 2.6 mg L(-1) in plasma sample. The limit of quantitation of creatinine was 2.1 mg L(-1) and 8.7 mg L(-1) in urine and plasma samples, respectively. The relative standard deviation of the method was found to be 13%. The method was successfully applied to the analysis of creatinine in biological samples, showing recoveries from 92% to 104% in urine and 101-110% in plasma samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Laser-stimulated desorption of organic molecules from surfaces, as a method of increasing the efficiency of ion mobility spectrometry analysis.

PubMed

Akmalov, Artem E; Chistyakov, Alexander A; Kotkovskii, Gennadii E

2017-08-01

Application of laser-induced desorption was investigated as a method of increasing the efficiency of gas phase analyzers on principles of field asymmetric ion mobility spectrometry. Mass spectrometric data of investigations of laser desorption of pentaerythritoltetranitrate molecules and cyclotetramethylenetetranitramine molecules from quartz substrate under vacuum were obtained. Laser sources a Nd 3+ :YAG with nanosecond pulse duration (λ = 532 nm) and a continuous wave diode laser (λ = 440 nm) were used. It was shown that both laser sources have different desorption abilities. This is expressed in various time of appearance of desorbed products that is caused by different heating mechanisms of surface layer. The desorbed quantity under action of both laser sources exceeds the detection threshold for all modern gas phase analyzers. It should be noted that despite the presence of surface dissociation of explosives under laser radiation, the quantity of nondissociated molecules is large enough for detection by ion mobility and field asymmetric ion mobility spectrometers. The optimal parameters of laser radiation for effective removal (evaporation) molecules of low-volatile compounds from surfaces are defined. The conclusion about preferable use of a Nd 3+ :YAG laser for increasing the detection ability of detectors based on ion mobility spectrometry was made.

Serpentine Ultralong Path with Extended Routing (SUPER) High Resolution Traveling Wave Ion Mobility-MS using Structures for Lossless Ion Manipulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Liulin; Webb, Ian K.; Garimella, Sandilya V. B.

Ion mobility (IM) separations have a broad range of analytical applications, but insufficient resolution limits many applications. Here we report on traveling wave (TW) ion mobility (IM) separations in a Serpentine Ultra-long Path with Extended Routing (SUPER) Structures for Lossless Ion Manipulations (SLIM) module in conjunction with mass spectrometry (MS). The extended routing utilized multiple passes was facilitated by the introduction of a lossless ion switch at the end of the ion path that either directed ions to the MS detector or to another pass through the serpentine separation region, providing theoretically unlimited TWIM path lengths. Ions were confined inmore » the SLIM by rf fields in conjunction with a DC guard bias, enabling essentially lossless TW transmission over greatly extended paths (e.g., ~1094 meters over 81 passes through the 13.5 m serpentine path). In this multi-pass SUPER TWIM provided resolution approximately proportional to the square root of the number of passes (or path length). More than 30-fold higher IM resolution for Agilent tuning mix m/z 622 and 922 ions (~340 vs. ~10) was achieved for 40 passes compared to commercially available drift tube IM and other TWIM-based platforms. An initial evaluation of the isomeric sugars Lacto-N-hexaose and Lacto-N-neohexaose showed the isomeric structures to be baseline resolved, and a new conformational feature for Lacto-N-neohexaose was revealed after 9 passes. The new SLIM SUPER high resolution TWIM platform has broad utility in conjunction with MS and is expected to enable a broad range of previously challenging or intractable separations.« less

Time resolved native ion-mobility mass spectrometry to monitor dynamics of IgG4 Fab arm exchange and "bispecific" monoclonal antibody formation.

PubMed

Debaene, François; Wagner-Rousset, Elsa; Colas, Olivier; Ayoub, Daniel; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

2013-10-15

Monoclonal antibodies (mAbs) and derivatives such as antibody-drug conjugates (ADC) and bispecific antibodies (bsAb), are the fastest growing class of human therapeutics. Most of the therapeutic antibodies currently on the market and in clinical trials are chimeric, humanized, and human immunoglobulin G1 (IgG1). An increasing number of IgG2s and IgG4s that have distinct structural and functional properties are also investigated to develop products that lack or have diminished antibody effector functions compared to IgG1. Importantly, wild type IgG4 has been shown to form half molecules (one heavy chain and one light chain) that lack interheavy chain disulfide bonds and form intrachain disulfide bonds. Moreover, IgG4 undergoes a process of Fab-arm exchange (FAE) in which the heavy chains of antibodies of different specificities can dissociate and recombine in bispecific antibodies both in vitro and in vivo. Here, native mass spectrometry (MS) and time-resolved traveling wave ion mobility MS (TWIM-MS) were used for the first time for online monitoring of FAE and bsAb formation using Hz6F4-2v3 and natalizumab, two humanized IgG4s which bind to human Junctional Adhesion Molecule-A (JAM-A) and alpha4 integrin, respectively. In addition, native MS analysis of bsAb/JAM-A immune complexes revealed that bsAb can bind up to two antigen molecules, confirming that the Hz6F4 family preferentially binds dimeric JAM-A. Our results illustrate how IM-MS can rapidly assess bsAb structural heterogeneity and be easily implemented into MS workflows for bsAb production follow up and bsAb/antigen complex characterization. Altogether, these results provide new MS-based methodologies for in-depth FAE and bsAb formation monitoring. Native MS and IM-MS will play an increasing role in next generation biopharmaceutical product characterization like bsAbs, antibody mixtures, and antibody-drug conjugates (ADC) as well as for biosimilar and biobetter antibodies.

Interrogating viral capsid assembly with ion mobility-mass spectrometry

NASA Astrophysics Data System (ADS)

Uetrecht, Charlotte; Barbu, Ioana M.; Shoemaker, Glen K.; van Duijn, Esther; Heck, Albert J. R.

2011-02-01

Most proteins fulfil their function as part of large protein complexes. Surprisingly, little is known about the pathways and regulation of protein assembly. Several viral coat proteins can spontaneously assemble into capsids in vitro with morphologies identical to the native virion and thus resemble ideal model systems for studying protein complex formation. Even for these systems, the mechanism for self-assembly is still poorly understood, although it is generally thought that smaller oligomeric structures form key intermediates. This assembly nucleus and larger viral assembly intermediates are typically low abundant and difficult to monitor. Here, we characterised small oligomers of Hepatitis B virus (HBV) and norovirus under equilibrium conditions using native ion mobility mass spectrometry. This data in conjunction with computational modelling enabled us to elucidate structural features of these oligomers. Instead of more globular shapes, the intermediates exhibit sheet-like structures suggesting that they are assembly competent. We propose pathways for the formation of both capsids.

Miniaturized Ion Mobility Spectrometer

NASA Technical Reports Server (NTRS)

Stimac, Robert M. (Inventor); Kaye, William J (Inventor)

2017-01-01

By utilizing the combination of a unique electronic ion injection control circuit in conjunction with a particularly designed drift cell construction, the instantly disclosed ion mobility spectrometer (IMS) achieves increased levels of sensitivity, while achieving significant reductions in size and weight. The instant IMS is of a much simpler and easy to manufacture design, rugged and hermetically sealed, capable of operation at high temperatures to at least 250 degrees Centigrade, and is uniquely sensitive, particularly to explosive chemicals.

Investigation of sliding DNA clamp dynamics by single-molecule fluorescence, mass spectrometry and structure-based modeling

PubMed Central

Gadkari, Varun V; Harvey, Sophie R; Raper, Austin T; Chu, Wen-Ting; Wang, Jin; Wysocki, Vicki H; Suo, Zucai

2018-01-01

Abstract Proliferating cell nuclear antigen (PCNA) is a trimeric ring-shaped clamp protein that encircles DNA and interacts with many proteins involved in DNA replication and repair. Despite extensive structural work to characterize the monomeric, dimeric, and trimeric forms of PCNA alone and in complex with interacting proteins, no structure of PCNA in a ring-open conformation has been published. Here, we use a multidisciplinary approach, including single-molecule Förster resonance energy transfer (smFRET), native ion mobility-mass spectrometry (IM-MS), and structure-based computational modeling, to explore the conformational dynamics of a model PCNA from Sulfolobus solfataricus (Sso), an archaeon. We found that Sso PCNA samples ring-open and ring-closed conformations even in the absence of its clamp loader complex, replication factor C, and transition to the ring-open conformation is modulated by the ionic strength of the solution. The IM-MS results corroborate the smFRET findings suggesting that PCNA dynamics are maintained in the gas phase and further establishing IM-MS as a reliable strategy to investigate macromolecular motions. Our molecular dynamic simulations agree with the experimental data and reveal that ring-open PCNA often adopts an out-of-plane left-hand geometry. Collectively, these results implore future studies to define the roles of PCNA dynamics in DNA loading and other PCNA-mediated interactions. PMID:29529283

Untrapping Kinetically Trapped Ions: The Role of Water Vapor and Ion-Source Activation Conditions on the Gas-Phase Protomer Ratio of Benzocaine Revealed by Ion-Mobility Mass Spectrometry.

PubMed

Xia, Hanxue; Attygalle, Athula B

2017-12-01

The role of water vapor in transforming the thermodynamically preferred species of protonated benzocaine to the less favored protomer was investigated using helium-plasma ionization (HePI) in conjunction with ion-mobility mass spectrometry (IM-MS). The IM arrival-time distribution (ATD) recorded from a neat benzocaine sample desorbed to the gas phase by a stream of dry nitrogen and ionized by HePI showed essentially one peak for the O-protonated species. However, when water vapor was introduced to the enclosed ion source, within a span of about 150 ms the ATD profile changed completely to one dominated by the N-protonated species. Under spray-based ionization conditions, the nature and composition of the solvents have been postulated to play a decisive role in defining the manifested protomer ratios. In reality, the solvent vapors present in the ion source (particularly the ambient humidity) indirectly dictate the gas-phase ratio of the protomers. Evidently, the gas-phase protomer ratio established at the confinement of the ions is readjusted by the ion-activation that takes place during the transmission of ions to the vacuum. Although it has been repeatedly stated that ions can retain a "memory" of their solution structures because they can be kinetically trapped, and thereby represent their solution-based stabilities, we show that the initial airborne ions can undergo significant transformations in the transit through the intermediate vacuum zones between the ion source and the mass detector. In this context, we demonstrate that the kinetically trapped N-protomer of benzocaine can be untrapped by reducing the humidity of the enclosed ion source. Graphical Abstract ᅟ.

Untrapping Kinetically Trapped Ions: The Role of Water Vapor and Ion-Source Activation Conditions on the Gas-Phase Protomer Ratio of Benzocaine Revealed by Ion-Mobility Mass Spectrometry

NASA Astrophysics Data System (ADS)

Xia, Hanxue; Attygalle, Athula B.

2017-12-01

The role of water vapor in transforming the thermodynamically preferred species of protonated benzocaine to the less favored protomer was investigated using helium-plasma ionization (HePI) in conjunction with ion-mobility mass spectrometry (IM-MS). The IM arrival-time distribution (ATD) recorded from a neat benzocaine sample desorbed to the gas phase by a stream of dry nitrogen and ionized by HePI showed essentially one peak for the O-protonated species. However, when water vapor was introduced to the enclosed ion source, within a span of about 150 ms the ATD profile changed completely to one dominated by the N-protonated species. Under spray-based ionization conditions, the nature and composition of the solvents have been postulated to play a decisive role in defining the manifested protomer ratios. In reality, the solvent vapors present in the ion source (particularly the ambient humidity) indirectly dictate the gas-phase ratio of the protomers. Evidently, the gas-phase protomer ratio established at the confinement of the ions is readjusted by the ion-activation that takes place during the transmission of ions to the vacuum. Although it has been repeatedly stated that ions can retain a "memory" of their solution structures because they can be kinetically trapped, and thereby represent their solution-based stabilities, we show that the initial airborne ions can undergo significant transformations in the transit through the intermediate vacuum zones between the ion source and the mass detector. In this context, we demonstrate that the kinetically trapped N-protomer of benzocaine can be untrapped by reducing the humidity of the enclosed ion source. [Figure not available: see fulltext.

Towards unsupervised polyaromatic hydrocarbons structural assignment from SA-TIMS-FTMS data.

PubMed

Benigni, Paolo; Marin, Rebecca; Fernandez-Lima, Francisco

2015-10-01

With the advent of high resolution ion mobility analyzers and their coupling to ultrahigh resolution mass spectrometers, there is a need to further develop a theoretical workflow capable of correlating experimental accurate mass and mobility measurements with tridimensional candidate structures. In the present work, a general workflow is described for unsupervised tridimensional structural assignment based on accurate mass measurements, mobility measurements, in silico 2D-3D structure generation, and theoretical mobility calculations. In particular, the potential of this workflow will be shown for the analysis of polyaromatic hydrocarbons from Coal Tar SRM 1597a using selected accumulation - trapped ion mobility spectrometry (SA-TIMS) coupled to Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). The proposed workflow can be adapted to different IMS scenarios, can utilize different collisional cross-section calculators and has the potential to include MS n and IMS n measurements for faster and more accurate tridimensional structural assignment.

Determining Double Bond Position in Lipids Using Online Ozonolysis Coupled to Liquid Chromatography and Ion Mobility-Mass Spectrometry.

PubMed

Harris, Rachel A; May, Jody C; Stinson, Craig A; Xia, Yu; McLean, John A

2018-02-06

The increasing focus on lipid metabolism has revealed a need for analytical techniques capable of structurally characterizing lipids with a high degree of specificity. Lipids can exist as any one of a large number of double bond positional isomers, which are indistinguishable by single-stage mass spectrometry alone. Ozonolysis reactions coupled to mass spectrometry have previously been demonstrated as a means for localizing double bonds in unsaturated lipids. Here we describe an online, solution-phase reactor using ozone produced via a low-pressure mercury lamp, which generates aldehyde products diagnostic of cleavage at a particular double bond position. This flow-cell device is utilized in conjunction with structurally selective ion mobility-mass spectrometry. The lamp-mediated reaction was found to be effective for multiple lipid species in both positive and negative ionization modes, and the conversion efficiency from precursor to product ions was tunable across a wide range (20-95%) by varying the flow rate through the ozonolysis device. Ion mobility separation of the ozonolysis products generated additional structural information and revealed the presence of saturated species in a complex mixture. The method presented here is simple, robust, and readily coupled to existing instrument platforms with minimal modifications necessary. For these reasons, application to standard lipidomic workflows is possible and aids in more comprehensive structural characterization of a myriad of lipid species.

Ion mobility analyzer - quadrupole mass spectrometer system design

NASA Astrophysics Data System (ADS)

Cuna, C.; Leuca, M.; Lupsa, N.; Mirel, V.; Bocos-Bintintan, V.; Cuna, Stela; Cosma, V.; Tusa, Florina

2009-08-01

Because of their extremely high sensitivity for chemicals with elevated electronegativity or high proton affinity the ion mobility analysers are ideal for the ultra-trace detection of toxic or explosive chemicals, most of these situated often at concentration levels of sub-ppb (parts-per-billion). Ion mobility spectrometers (IMS) can be used to identify illicit drugs or environmental pollutants. Since resolution of an IMS is relatively low, to achieve an accurate identification of target analyte it is recommended to couple the IMS with a quadrupole mass spectrometer (QMS) or a time of flight mass spectrometer, acquiring in this way confirmatory information. This coupling is made through a specific interface. In this paper, an experimental model of such a tandem instrument, IMS-QMS is described. Accomplishment of this general purpose will be done, overcoming a series of specific issues. This implies the solving, using innovative solutions, of a series of complex issues: ensuring the stability of the ions beam generated by ion source; transfer with a good efficiency of the ionic current from IMS analyser to QMS; and realization of a special electronic circuitry which will be able to detect both positive and negative ions.

Separation of Opiate Isomers Using Electrospray Ionization and Paper Spray Coupled to High-Field Asymmetric Waveform Ion Mobility Spectrometry

NASA Astrophysics Data System (ADS)

Manicke, Nicholas E.; Belford, Michael

2015-05-01

One limitation in the growing field of ambient or direct analysis methods is reduced selectivity caused by the elimination of chromatographic separations prior to mass spectrometric analysis. We explored the use of high-field asymmetric waveform ion mobility spectrometry (FAIMS), an ambient pressure ion mobility technique, to separate the closely related opiate isomers of morphine, hydromorphone, and norcodeine. These isomers cannot be distinguished by tandem mass spectrometry. Separation prior to MS analysis is, therefore, required to distinguish these compounds, which are important in clinical chemistry and toxicology. FAIMS was coupled to a triple quadrupole mass spectrometer, and ionization was performed using either a pneumatically assisted heated electrospray ionization source (H-ESI) or paper spray, a direct analysis method that has been applied to the direct analysis of dried blood spots and other complex samples. We found that FAIMS was capable of separating the three opiate structural isomers using both H-ESI and paper spray as the ionization source.

Identification of oligosaccharides from histopathological sections by MALDI imaging mass spectrometry.

PubMed

Yamada, Masanori; Yao, Ikuko; Hayasaka, Takahiro; Ushijima, Masaru; Matsuura, Masaaki; Takada, Hideho; Shikata, Nobuaki; Setou, Mitsutoshi; Kwon, A-Hon; Ito, Seiji

2012-02-01

Direct tissue analysis using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) provides the means for in situ molecular analysis of a wide variety of biomolecules. This technology--known as imaging mass spectrometry (IMS)--allows the measurement of biomolecules in their native biological environments without the need for target-specific reagents such as antibodies. In this study, we applied the IMS technique to formalin-fixed paraffin-embedded samples to identify a substance(s) responsible for the intestinal obstruction caused by an unidentified foreign body. In advance of IMS analysis, some pretreatments were applied. After the deparaffinization of sections, samples were subjected to enzyme digestion. The sections co-crystallized with matrix were desorbed and ionized by a laser pulse with scanning. A combination of α-amylase digestion and the 2,5-dihydroxybenzoic acid matrix gave the best mass spectrum. With the IMS Convolution software which we developed, we could automatically extract meaningful signals from the IMS datasets. The representative peak values were m/z 1,013, 1,175, 1,337, 1,499, 1,661, 1,823, and 1,985. Thus, it was revealed that the material was polymer with a 162-Da unit size, calculated from the even intervals. In comparison with the mass spectra of the histopathological specimen and authentic materials, the main component coincided with amylopectin rather than amylose. Tandem MS analysis proved that the main components were oligosaccharides. Finally, we confirmed the identification of amylopectin by staining with periodic acid-Schiff and iodine. These results for the first time show the advantages of MALDI-IMS in combination with enzyme digestion for the direct analysis of oligosaccharides as a major component of histopathological samples.

Polymers for Traveling Wave Ion Mobility Spectrometry Calibration

NASA Astrophysics Data System (ADS)

Duez, Quentin; Chirot, Fabien; Liénard, Romain; Josse, Thomas; Choi, ChangMin; Coulembier, Olivier; Dugourd, Philippe; Cornil, Jérôme; Gerbaux, Pascal; De Winter, Julien

2017-07-01

One of the main issues when using traveling wave ion mobility spectrometry (TWIMS) for the determination of collisional cross-section (CCS) concerns the need for a robust calibration procedure built from referent ions of known CCS. Here, we implement synthetic polymer ions as CCS calibrants in positive ion mode. Based on their intrinsic polydispersities, polymers offer in a single sample the opportunity to generate, upon electrospray ionization, numerous ions covering a broad mass range and a large CCS window for different charge states at a time. In addition, the key advantage of polymer ions as CCS calibrants lies in the robustness of their gas-phase structure with respect to the instrumental conditions, making them less prone to collisional-induced unfolding (CIU) than protein ions. In this paper, we present a CCS calibration procedure using sodium cationized polylactide and polyethylene glycol, PLA and PEG, as calibrants with reference CCS determined on a home-made drift tube. Our calibration procedure is further validated by testing the polymer calibration to determine CCS of numerous different ions for which CCS are reported in the literature. [Figure not available: see fulltext.

Molecular Basis for Structural Heterogeneity of an Intrinsically Disordered Protein Bound to a Partner by Combined ESI-IM-MS and Modeling

NASA Astrophysics Data System (ADS)

D'Urzo, Annalisa; Konijnenberg, Albert; Rossetti, Giulia; Habchi, Johnny; Li, Jinyu; Carloni, Paolo; Sobott, Frank; Longhi, Sonia; Grandori, Rita

2015-03-01

Intrinsically disordered proteins (IDPs) form biologically active complexes that can retain a high degree of conformational disorder, escaping structural characterization by conventional approaches. An example is offered by the complex between the intrinsically disordered NTAIL domain and the phosphoprotein X domain (PXD) from measles virus (MeV). Here, distinct conformers of the complex are detected by electrospray ionization-mass spectrometry (ESI-MS) and ion mobility (IM) techniques yielding estimates for the solvent-accessible surface area (SASA) in solution and the average collision cross-section (CCS) in the gas phase. Computational modeling of the complex in solution, based on experimental constraints, provides atomic-resolution structural models featuring different levels of compactness. The resulting models indicate high structural heterogeneity. The intermolecular interactions are predominantly hydrophobic, not only in the ordered core of the complex, but also in the dynamic, disordered regions. Electrostatic interactions become involved in the more compact states. This system represents an illustrative example of a hydrophobic complex that could be directly detected in the gas phase by native mass spectrometry. This work represents the first attempt to modeling the entire NTAIL domain bound to PXD at atomic resolution.

Confirmation of diosmetin 3-O-glucuronide as major metabolite of diosmin in humans, using micro-liquid-chromatography-mass spectrometry and ion mobility mass spectrometry.

PubMed

Silvestro, Luigi; Tarcomnicu, Isabela; Dulea, Constanta; Attili, Nageswara Rao B N; Ciuca, Valentin; Peru, Dan; Rizea Savu, Simona

2013-10-01

Diosmin is a flavonoid often administered in the treatment of chronic venous insufficiency, hemorrhoids, and related affections. Diosmin is rapidly hydrolized in the intestine to its aglicone, diosmetin, which is further metabolized to conjugates. In this study, the development and validations of three new methods for the determination of diosmetin, free and after enzymatic deconjugation, and of its potential glucuronide metabolites, diosmetin-3-O-glucuronide, diosmetin-7-O-glucuronide, and diosmetin-3,7-O-glucuronide from human plasma and urine are presented. First, the quantification of diosmetin, free and after deconjugation, was carried out by high-performance liquid chromatography coupled with tandem mass spectrometry, on an Ascentis RP-Amide column (150 × 2.1 mm, 5 μm), in reversed-phase conditions, after enzymatic digestion. Then glucuronide metabolites from plasma were separated by micro-liquid chromatography coupled with tandem mass spectrometry on a HALO C18 (50 × 0.3 mm, 2.7 μm, 90 Å) column, after solid-phase extraction. Finally, glucuronides from urine were measured using a Discovery HSF5 (100 × 2.1 mm, 5 μm) column, after simple dilution with mobile phase. The methods were validated by assessing linearity, accuracy, precision, low limit of quantification, selectivity, extraction recovery, stability, and matrix effects; results in agreement with regulatory (Food and Drug Administration and European Medicines Agency) guidelines acceptance criteria were obtained in all cases. The methods were applied to a pharmacokinetic study with diosmin (450 mg orally administered tablets). The mean C max of diosmetin in plasma was 6,049.3 ± 5,548.6 pg/mL. A very good correlation between measured diosmetin and glucuronide metabolites concentrations was obtained. Diosmetin-3-O-glucuronide was identified as a major circulating metabolite of diosmetin in plasma and in urine, and this finding was confirmed by supplementary experiments with differential ion-mobility

High-Definition Differential Ion Mobility Spectrometry with Resolving Power up to 500

PubMed Central

Shvartsburg, Alexandre A.; Seim, Tom A.; Danielson, William F.; Norheim, Randy; Moore, Ronald J.; Anderson, Gordon A.; Smith, Richard D.

2013-01-01

As the resolution of analytical methods improves, further progress tends to be increasingly limited by instrumental parameter instabilities that could be ignored before. This is now the case with differential ion mobility spectrometry (FAIMS), where fluctuations of the voltages and gas pressure have become critical. A new high-definition generator for FAIMS compensation voltage reported here provides a stable and accurate output than can be scanned with negligible steps. This reduces the spectral drift and peak width, thus improving the resolving power (R) and resolution. The gain for multiply-charged peptides that have narrowest peaks is up to ~40%, and R ~ 400 – 500 is achievable using He/N2 or H2/N2 gas mixtures. PMID:23345059

Gas-Phase Analysis of the Complex of Fibroblast GrowthFactor 1 with Heparan Sulfate: A Traveling Wave Ion Mobility Spectrometry (TWIMS) and Molecular Modeling Study

NASA Astrophysics Data System (ADS)

Zhao, Yuejie; Singh, Arunima; Xu, Yongmei; Zong, Chengli; Zhang, Fuming; Boons, Geert-Jan; Liu, Jian; Linhardt, Robert J.; Woods, Robert J.; Amster, I. Jonathan

2017-01-01

Fibroblast growth factors (FGFs) regulate several cellular developmental processes by interacting with cell surface heparan proteoglycans and transmembrane cell surface receptors (FGFR). The interaction of FGF with heparan sulfate (HS) is known to induce protein oligomerization, increase the affinity of FGF towards its receptor FGFR, promoting the formation of the HS-FGF-FGFR signaling complex. Although the role of HS in the signaling pathways is well recognized, the details of FGF oligomerization and formation of the ternary signaling complex are still not clear, with several conflicting models proposed in literature. Here, we examine the effect of size and sulfation pattern of HS upon FGF1 oligomerization, binding stoichiometry and conformational stability, through a combination of ion mobility (IM) and theoretical modeling approaches. Ion mobility-mass spectrometry (IMMS) of FGF1 in the presence of several HS fragments ranging from tetrasaccharide (dp4) to dodecasaccharide (dp12) in length was performed. A comparison of the binding stoichiometry of variably sulfated dp4 HS to FGF1 confirmed the significance of the previously known high-affinity binding motif in FGF1 dimerization, and demonstrated that certain tetrasaccharide-length fragments are also capable of inducing dimerization of FGF1. The degree of oligomerization was found to increase in the presence of dp12 HS, and a general lack of specificity for longer HS was observed. Additionally, collision cross-sections (CCSs) of several FGF1-HS complexes were calculated, and were found to be in close agreement with experimental results. Based on the (CCSs) a number of plausible binding modes of 2:1 and 3:1 FGF1-HS are proposed.

Combining Ion Mobility and Cryogenic Spectroscopy for Structural and Analytical Studies of Biomolecular Ions.

PubMed

Kamrath, Michael Z; Rizzo, Thomas R

2018-05-10

Ion mobility spectrometry (IMS) has become a valuable tool in biophysical and bioanalytical chemistry because of its ability to separate and characterize the structure of gas-phase biomolecular ions on the basis of their collisional cross section (CCS). Its importance has grown with the realization that in many cases, biomolecular ions retain important structural characteristics when produced in the gas phase by electrospray ionization (ESI). While a CCS can help distinguish between structures of radically different types, one cannot expect a single number to differentiate similar conformations of a complex molecule. Molecular spectroscopy has also played an increasingly important role for structural characterization of biomolecular ions. Spectroscopic measurements, particularly when performed at cryogenic temperatures, can be extremely sensitive to small changes in a molecule's conformation and provide tight constraints for calculations of biomolecular structures. However, spectra of complex molecules can be heavily congested due to the presence of multiple stable conformations, each of which can have a distinct spectrum. This congestion can inhibit spectral analysis and complicate the extraction of structural information. Even when a single conformation is present, the conformational search process needed to match a measured spectrum with a computed structure can be overwhelming for peptides of more than a few amino acids, for example. We have recently combined ion mobility spectrometry and cryogenic ion spectroscopy (CIS) to characterize the structures of gas-phase biomolecular ions. In this Account, we illustrate how the coupling of IMS and CIS is by nature synergistic. On the one hand, IMS can be used as a conformational filter to reduce spectral congestion that arises from heterogeneous samples, facilitating structural analysis. On the other hand, highly resolved, cryogenic spectra can serve as a selective detector for IMS that can increase the effective

Feasibility and inter-rater reliability of the ICU Mobility Scale.

PubMed

Hodgson, Carol; Needham, Dale; Haines, Kimberley; Bailey, Michael; Ward, Alison; Harrold, Megan; Young, Paul; Zanni, Jennifer; Buhr, Heidi; Higgins, Alisa; Presneill, Jeff; Berney, Sue

2014-01-01

The objectives of this study were to develop a scale for measuring the highest level of mobility in adult ICU patients and to assess its feasibility and inter-rater reliability. Growing evidence supports the feasibility, safety and efficacy of early mobilization in the intensive care unit (ICU). However, there are no adequately validated tools to quickly, easily, and reliably describe the mobility milestones of adult patients in ICU. Identifying or developing such a tool is a priority for evaluating mobility and rehabilitation activities for research and clinical care purposes. This study was performed at two ICUs in Australia. Thirty ICU nursing, and physiotherapy staff assessed the feasibility of the 'ICU Mobility Scale' (IMS) using a 10-item questionnaire. The inter-rater reliability of the IMS was assessed by 2 junior physical therapists, 2 senior physical therapists, and 16 nursing staff in 100 consecutive medical, surgical or trauma ICU patients. An 11 point IMS scale was developed based on multidisciplinary input. Participating clinicians reported that the scale was clear, with 95% of respondents reporting that it took <1 min to complete. The junior and senior physical therapists showed the highest inter-rater reliability with a weighted Kappa (95% confidence interval) of 0.83 (0.76-0.90), while the senior physical therapists and nurses and the junior physical therapists and nurses had a weighted Kappa of 0.72 (0.61-0.83) and 0.69 (0.56-0.81) respectively. The IMS is a feasible tool with strong inter-rater reliability for measuring the maximum level of mobility of adult patients in the ICU. Copyright © 2014 Elsevier Inc. All rights reserved.

Travelling-wave ion mobility and negative ion fragmentation of high mannose N-glycans

PubMed Central

Harvey, David J.; Scarff, Charlotte A.; Edgeworth, Matthew; Struwe, Weston B.; Pagel, Kevin; Thalassinos, Konstantinos; Crispin, Max; Scrivens, Jim

2016-01-01

The isomeric structure of high-mannose N-glycans can significantly impact biological recognition events. Here, the utility of travelling-wave ion mobility-mass spectrometry (TW IM-MS)for isomer separation of high-mannose N-glycans is investigated. Negative ion fragmentation using collision-induced dissociation (CID) gave more informative spectra than positive ion spectra with mass-different fragment ions characterizing many of the isomers. Isomer separation by ion mobility in both ionization modes was generally limited, with the arrival time distributions (ATD) often showing little sign of isomers. However, isomers could be partially resolved by plotting extracted fragment ATDs of the diagnostic fragment ions from the negative ion spectra and the fragmentation spectra of the isomers could be extracted by using ions from limited areas of the ATD peak. In some cases, asymmetric ATDs were observed but no isomers could be detected by fragmentation. In these cases, it was assumed that conformers were being separated. Collision cross sections (CCSs) of the isomers in positive and negative fragmentation mode were estimated from TW IM-MS data using dextran glycans as calibrant. More complete CCS data were achieved in negative ion mode by utilizing the diagnostic fragment ions. Examples of isomer separations are shown for N-glycans released from the well-characterized glycoproteins chicken ovalbumin, porcine thyroglobulin and gp120 from the human immunodeficiency virus. In addition to the cross sectional data, details of the negative ion collision-induced dissociation (CID) spectra of all resolved isomers are discussed. PMID:26956389

Mass spectrometry in the U.S. space program: past, present, and future.

PubMed

Palmer, P T; Limero, T F

2001-06-01

Recent years have witnessed significant progress on the miniaturization of mass spectrometers for a variety of field applications. This article describes the development and application of mass spectrometry (MS) instrumentation to support of goals of the U.S. space program. Its main focus is on the two most common space-related applications of MS: studying the composition of planetary atmospheres and monitoring air quality on manned space missions. Both sets of applications present special requirements in terms of analytical performance (sensitivity, selectivity, speed, etc.), logistical considerations (space, weight, and power requirements), and deployment in perhaps the harshest of all possible environments (space). The MS instruments deployed on the Pioneer Venus and Mars Viking Lander missions are reviewed for the purposes of illustrating the unique features of the sample introduction systems, mass analyzers, and vacuum systems, and for presenting their specifications which are impressive even by today's standards. The various approaches for monitoring volatile organic compounds (VOCs) in cabin atmospheres are also reviewed. In the past, ground-based GC/MS instruments have been used to identify and quantify VOCs in archival samples collected during the Mercury, Apollo, Skylab, Space Shuttle, and Mir missions. Some of the data from the more recent missions are provided to illustrate the composition data obtained and to underscore the need for instrumentation to perform such monitoring in situ. Lastly, the development of two emerging technologies, Direct Sampling Ion Trap Mass Spectrometry (DSITMS) and GC/Ion Mobility Spectrometry (GC/IMS), will be discussed to illustrate their potential utility for future missions. c 2001 American Society for Mass Spectrometry.

Mass spectrometry in the U.S. space program: past, present, and future

NASA Technical Reports Server (NTRS)

Palmer, P. T.; Limero, T. F.

2001-01-01

Recent years have witnessed significant progress on the miniaturization of mass spectrometers for a variety of field applications. This article describes the development and application of mass spectrometry (MS) instrumentation to support of goals of the U.S. space program. Its main focus is on the two most common space-related applications of MS: studying the composition of planetary atmospheres and monitoring air quality on manned space missions. Both sets of applications present special requirements in terms of analytical performance (sensitivity, selectivity, speed, etc.), logistical considerations (space, weight, and power requirements), and deployment in perhaps the harshest of all possible environments (space). The MS instruments deployed on the Pioneer Venus and Mars Viking Lander missions are reviewed for the purposes of illustrating the unique features of the sample introduction systems, mass analyzers, and vacuum systems, and for presenting their specifications which are impressive even by today's standards. The various approaches for monitoring volatile organic compounds (VOCs) in cabin atmospheres are also reviewed. In the past, ground-based GC/MS instruments have been used to identify and quantify VOCs in archival samples collected during the Mercury, Apollo, Skylab, Space Shuttle, and Mir missions. Some of the data from the more recent missions are provided to illustrate the composition data obtained and to underscore the need for instrumentation to perform such monitoring in situ. Lastly, the development of two emerging technologies, Direct Sampling Ion Trap Mass Spectrometry (DSITMS) and GC/Ion Mobility Spectrometry (GC/IMS), will be discussed to illustrate their potential utility for future missions. c 2001 American Society for Mass Spectrometry.

Imaging mass spectrometry tackles interfacial challenges in electrochemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Xiao-Ying

Electrochemistry has played a significant role in many research fields. Owing to its sensitivity and selectivity, in situ electroanalysis has been widely used as a fast and economical means for achieving outstanding results. Although many spectroscopic techniques have been used in electrochemistry, the challenges to capture short-lived intermediate species as a result of electron transfer in the buried solid electrode and electrolyte solution interface remains a grand challenge. In situ imaging mass spectrometry (IMS) recently has been extended to capture transient species in electrochemistry. This review intends to summarize newest development of IMS and its applications in advancing fundamental electrochemistry.

A novel four-dimensional analytical approach for analysis of complex samples.

PubMed

Stephan, Susanne; Jakob, Cornelia; Hippler, Jörg; Schmitz, Oliver J

2016-05-01

A two-dimensional LC (2D-LC) method, based on the work of Erni and Frei in 1978, was developed and coupled to an ion mobility-high-resolution mass spectrometer (IM-MS), which enabled the separation of complex samples in four dimensions (2D-LC, ion mobility spectrometry (IMS), and mass spectrometry (MS)). This approach works as a continuous multiheart-cutting LC system, using a long modulation time of 4 min, which allows the complete transfer of most of the first - dimension peaks to the second - dimension column without fractionation, in comparison to comprehensive two-dimensional liquid chromatography. Hence, each compound delivers only one peak in the second dimension, which simplifies the data handling even when ion mobility spectrometry as a third and mass spectrometry as a fourth dimension are introduced. The analysis of a plant extract from Ginkgo biloba shows the separation power of this four-dimensional separation method with a calculated total peak capacity of more than 8700. Furthermore, the advantage of ion mobility for characterizing unknown compounds by their collision cross section (CCS) and accurate mass in a non-target approach is shown for different matrices like plant extracts and coffee. Graphical abstract Principle of the four-dimensional separation.

Tandem Mass Spectrometry and Ion Mobility Reveals Structural Insight into Eicosanoid Product Ion Formation

NASA Astrophysics Data System (ADS)

Di Giovanni, James P.; Barkley, Robert M.; Jones, David N. M.; Hankin, Joseph A.; Murphy, Robert C.

2018-04-01

Ion mobility measurements of product ions were used to characterize the collisional cross section (CCS) of various complex lipid [M-H]- ions using traveling wave ion mobility mass spectrometry (TWIMS). TWIMS analysis of various product ions derived after collisional activation of mono- and dihydroxy arachidonate metabolites was found to be more complex than the analysis of intact molecular ions and provided some insight into molecular mechanisms involved in product ion formation. The CCS observed for the molecular ion [M-H]- and certain product ions were consistent with a folded ion structure, the latter predicted by the proposed mechanisms of product ion formation. Unexpectedly, product ions from [M-H-H2O-CO2]- and [M-H-H2O]- displayed complex ion mobility profiles suggesting multiple mechanisms of ion formation. The [M-H-H2O]- ion from LTB4 was studied in more detail using both nitrogen and helium as the drift gas in the ion mobility cell. One population of [M-H-H2O]- product ions from LTB4 was consistent with formation of covalent ring structures, while the ions displaying a higher CCS were consistent with a more open-chain structure. Using molecular dynamics and theoretical CCS calculations, energy minimized structures of those product ions with the open-chain structures were found to have a higher CCS than a folded molecular ion structure. The measurement of product ion mobility can be an additional and unique signature of eicosanoids measured by LC-MS/MS techniques. [Figure not available: see fulltext.

Tandem Mass Spectrometry and Ion Mobility Reveals Structural Insight into Eicosanoid Product Ion Formation.

PubMed

Di Giovanni, James P; Barkley, Robert M; Jones, David N M; Hankin, Joseph A; Murphy, Robert C

2018-04-23

Ion mobility measurements of product ions were used to characterize the collisional cross section (CCS) of various complex lipid [M-H] - ions using traveling wave ion mobility mass spectrometry (TWIMS). TWIMS analysis of various product ions derived after collisional activation of mono- and dihydroxy arachidonate metabolites was found to be more complex than the analysis of intact molecular ions and provided some insight into molecular mechanisms involved in product ion formation. The CCS observed for the molecular ion [M-H] - and certain product ions were consistent with a folded ion structure, the latter predicted by the proposed mechanisms of product ion formation. Unexpectedly, product ions from [M-H-H 2 O-CO 2 ] - and [M-H-H 2 O] - displayed complex ion mobility profiles suggesting multiple mechanisms of ion formation. The [M-H-H 2 O] - ion from LTB 4 was studied in more detail using both nitrogen and helium as the drift gas in the ion mobility cell. One population of [M-H-H 2 O] - product ions from LTB 4 was consistent with formation of covalent ring structures, while the ions displaying a higher CCS were consistent with a more open-chain structure. Using molecular dynamics and theoretical CCS calculations, energy minimized structures of those product ions with the open-chain structures were found to have a higher CCS than a folded molecular ion structure. The measurement of product ion mobility can be an additional and unique signature of eicosanoids measured by LC-MS/MS techniques. Graphical Abstract ᅟ.

I'm a Map, I'm a Green Tree

ERIC Educational Resources Information Center

Anderson, Daniel

2010-01-01

I'm talking about the ways we represent ourselves and our world. I've put some thoughts on the topic together here--a gathering that enacts new media creating and takes up conceptual layers like metaphors, models, and composing. The primary sources are videos from the Get a Mac campaign, aka I'm a Mac; I'm a PC ads. Posthuman concepts blending…

High-Definition Differential Ion Mobility Spectrometry with Resolving Power up to 500

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shvartsburg, Alexandre A.; Seim, Thomas A.; Danielson, William F.

2013-01-20

As the resolution of analytical methods improve, further progress tends to be increasingly limited by instrumental parameter instabilities that could be ignored before. This is now the case with differential ion mobility spectrometry (FAIMS), where fluctuations of the voltages and gas pressure have become critical. A new high-definition generator for FAIMS compensation voltage reported here provides a stable and accurate output than can be scanned with negligible steps. This reduces the spectral drift and peak width, thus improving the resolving power (R) and resolution. The gain for multiply-charged peptides that have narrowest peaks is up to ~40%, and R ~more » 400 - 500 is achievable using He/N2 or H2/N2 gas mixtures.« less

An intelligent detection method for high-field asymmetric waveform ion mobility spectrometry.

PubMed

Li, Yue; Yu, Jianwen; Ruan, Zhiming; Chen, Chilai; Chen, Ran; Wang, Han; Liu, Youjiang; Wang, Xiaozhi; Li, Shan

2018-04-01

In conventional high-field asymmetric waveform ion mobility spectrometry signal acquisition, multi-cycle detection is time consuming and limits somewhat the technique's scope for rapid field detection. In this study, a novel intelligent detection approach has been developed in which a threshold was set on the relative error of α parameters, which can eliminate unnecessary time spent on detection. In this method, two full-spectrum scans were made in advance to obtain the estimated compensation voltage at different dispersion voltages, resulting in a narrowing down of the whole scan area to just the peak area(s) of interest. This intelligent detection method can reduce the detection time to 5-10% of that of the original full-spectrum scan in a single cycle.

Laser-Induced Breakdown Spectroscopy: A Review of Applied Explosive Detection

DTIC Science & Technology

2013-09-01

Based Techniques ..........................................................................................7 2.5 Ion Mobility and Mass Spectrometry...proximal trace detection. We show that the algorithms for material identification could be improved by including the critical signatures (e.g., C2...IMS), desorption electrospray ionization (DESI), laser electrospray mass spectrometry (LEMS), emerging efforts like antibody/antigen-based efforts

Ion Mobility Studies on the Negative Ion-Molecule Chemistry of Isoflurane and Enflurane.

PubMed

González-Méndez, Ramón; Watts, Peter; Howse, David C; Procino, Immacolata; McIntyre, Henry; Mayhew, Chris A

2017-05-01

In the present work we present an investigation of the negative ion-molecule chemistry of the anaesthetics isoflurane, ISOF, and enflurane, ENF, in an ion mobility spectrometry/mass spectrometry (IMS/MS), in both air and nitrogen. Hexachloroethane (HCE) was introduced in both air and nitrogen to produce Cl - as a reactant ion. This study was undertaken owing to uncertainties in the chemical processes, which lead to the cluster ions reported in other work (Eiceman et al. Anal. Chem. 61, 1093-1099, 1). In particular for ISOF the product ion observed was ISOF.Cl - , and it was suggested that the Cl - was formed by dissociative electron attachment (DEA) although there was mention of a chlorine containing contaminant. We show in this study that ISOF and ENF do not produce Cl - in an IMS system either by capture of free electrons or reaction with O 2 - . This demonstrates that the Cl - containing ions, reported in the earlier study, must have been the result of a chlorine containing contaminant as suggested. The failure of ISOF and ENF to undergo DEA was initially surprising given the high calculated electron affinities, but further calculations showed that this was a result of the large positive vertical attachment energies (VAEs). This experimental work has been supported by electronic structure calculations at the B3LYP level, and is consistent with those obtained in a crossed electron-molecular beam two sector field mass spectrometer. An unusual observation is that the monomer complexes of ISOF and ENF with O 2 - are relatively unstable compared with the dimer complexes. Graphical Abstract ᅟ.

Ion Mobility Studies on the Negative Ion-Molecule Chemistry of Isoflurane and Enflurane

NASA Astrophysics Data System (ADS)

González-Méndez, Ramón; Watts, Peter; Howse, David C.; Procino, Immacolata; McIntyre, Henry; Mayhew, Chris A.

2017-05-01

In the present work we present an investigation of the negative ion-molecule chemistry of the anaesthetics isoflurane, ISOF, and enflurane, ENF, in an ion mobility spectrometry/mass spectrometry (IMS/MS), in both air and nitrogen. Hexachloroethane (HCE) was introduced in both air and nitrogen to produce Cl- as a reactant ion. This study was undertaken owing to uncertainties in the chemical processes, which lead to the cluster ions reported in other work (Eiceman et al. Anal. Chem. 61, 1093-1099, 1). In particular for ISOF the product ion observed was ISOF.Cl-, and it was suggested that the Cl- was formed by dissociative electron attachment (DEA) although there was mention of a chlorine containing contaminant. We show in this study that ISOF and ENF do not produce Cl- in an IMS system either by capture of free electrons or reaction with O2 -. This demonstrates that the Cl- containing ions, reported in the earlier study, must have been the result of a chlorine containing contaminant as suggested. The failure of ISOF and ENF to undergo DEA was initially surprising given the high calculated electron affinities, but further calculations showed that this was a result of the large positive vertical attachment energies (VAEs). This experimental work has been supported by electronic structure calculations at the B3LYP level, and is consistent with those obtained in a crossed electron-molecular beam two sector field mass spectrometer. An unusual observation is that the monomer complexes of ISOF and ENF with O2 - are relatively unstable compared with the dimer complexes.

Multiple, Relational and Emotional Mobilities: Understanding Student Mobilities in Higher Education as More than "Staying Local" and "Going Away"

ERIC Educational Resources Information Center

Finn, Kirsty

2017-01-01

This paper advances theorising around student geographies in higher education (HE). It extends recent work, which has problematised the primacy of social class and binary thinking about student mobilities, and presents local/non-local experiences and im/mobility as a defining dualism. Drawing on a qualitative longitudinal study of women's…

MALDI TOF imaging mass spectrometry in clinical pathology: a valuable tool for cancer diagnostics (review).

PubMed

Kriegsmann, Jörg; Kriegsmann, Mark; Casadonte, Rita

2015-03-01

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) is an evolving technique in cancer diagnostics and combines the advantages of mass spectrometry (proteomics), detection of numerous molecules, and spatial resolution in histological tissue sections and cytological preparations. This method allows the detection of proteins, peptides, lipids, carbohydrates or glycoconjugates and small molecules.Formalin-fixed paraffin-embedded tissue can also be investigated by IMS, thus, this method seems to be an ideal tool for cancer diagnostics and biomarker discovery. It may add information to the identification of tumor margins and tumor heterogeneity. The technique allows tumor typing, especially identification of the tumor of origin in metastatic tissue, as well as grading and may provide prognostic information. IMS is a valuable method for the identification of biomarkers and can complement histology, immunohistology and molecular pathology in various fields of histopathological diagnostics, especially with regard to identification and grading of tumors.

High-Performance Ion Mobility Spectrometry Using Hourglass Electrodynamic Funnel And Internal Ion Funnel

DOEpatents

Smith, Richard D.; Tang, Keqi; Shvartsburg, Alexandre A.

2004-11-16

A method and apparatus enabling increased sensitivity in ion mobility spectrometry/mass spectrometry instruments which substantially reduces or eliminates the loss of ions in ion mobility spectrometer drift tubes utilizing an hourglass electrodynamic ion funnel at the entrance to the drift tube and/or an internal ion funnel at the exit of the drift tube. An hourglass electrodynamic funnel is formed of at least an entry element, a center element, and an exit element, wherein the aperture of the center element is smaller than the aperture of the entry element and the aperture of the exit elements. Ions generated in a relatively high pressure region by an ion source at the exterior of the hourglass electrodynamic funnel are transmitted to a relatively low pressure region at the entrance of the hourglass funnel through a conductance limiting orifice. Alternating and direct electrical potentials are applied to the elements of the hourglass electrodynamic funnel thereby drawing ions into and through the hourglass electrodynamic funnel thereby introducing relatively large quantities of ions into the drift tube while maintaining the gas pressure and composition at the interior of the drift tube as distinct from those at the entrance of the electrodynamic funnel and allowing a positive gas pressure to be maintained within the drift tube, if desired. An internal ion funnel is provided within the drift tube and is positioned at the exit of said drift tube. The advantage of the internal ion funnel is that ions that are dispersed away from the exit aperture within the drift tube, such as those that are typically lost in conventional drift tubes to any subsequent analysis or measurement, are instead directed through the exit of the drift tube, vastly increasing the amount of ions exiting the drift tube.

High Performance Ion Mobility Spectrometry Using Hourglass Electrodynamic Funnel And Internal Ion Funnel

DOEpatents

Smith, Richard D.; Tang, Keqi; Shvartsburg, Alexandre A.

2005-11-22

A method and apparatus enabling increased sensitivity in ion mobility spectrometry/mass spectrometry instruments which substantially reduces or eliminates the loss of ions in ion mobility spectrometer drift tubes utilizing a device for transmitting ions from an ion source which allows the transmission of ions without significant delay to an hourglass electrodynamic ion funnel at the entrance to the drift tube and/or an internal ion funnel at the exit of the drift tube. An hourglass electrodynamic funnel is formed of at least an entry element, a center element, and an exit element, wherein the aperture of the center element is smaller than the aperture of the entry element and the aperture of the exit elements. Ions generated in a relatively high pressure region by an ion source at the exterior of the hourglass electrodynamic funnel are transmitted to a relatively low pressure region at the entrance of the hourglass funnel through a conductance limiting orifice. Alternating and direct electrical potentials are applied to the elements of the hourglass electrodynamic funnel thereby drawing ions into and through the hourglass electrodynamic funnel thereby introducing relatively large quantities of ions into the drift tube while maintaining the gas pressure and composition at the interior of the drift tube as distinct from those at the entrance of the electrodynamic funnel and allowing a positive gas pressure to be maintained within the drift tube, if desired. An internal ion funnel is provided within the drift tube and is positioned at the exit of said drift tube. The advantage of the internal ion funnel is that ions that are dispersed away from the exit aperture within the drift tube, such as those that are typically lost in conventional drift tubes to any subsequent analysis or measurement, are instead directed through the exit of the drift tube, vastly increasing the amount of ions exiting the drift tube.

A mass spectrometer based explosives trace detector

NASA Astrophysics Data System (ADS)

Vilkov, Andrey; Jorabchi, Kaveh; Hanold, Karl; Syage, Jack A.

2011-05-01

In this paper we describe the application of mass spectrometry (MS) to the detection of trace explosives. We begin by reviewing the issue of explosives trace detection (ETD) and describe the method of mass spectrometry (MS) as an alternative to existing technologies. Effective security screening devices must be accurate (high detection and low false positive rate), fast and cost effective (upfront and operating costs). Ion mobility spectrometry (IMS) is the most commonly deployed method for ETD devices. Its advantages are compact size and relatively low price. For applications requiring a handheld detector, IMS is an excellent choice. For applications that are more stationary (e.g., checkpoint and alternatives to IMS are available. MS is recognized for its superior performance with regard to sensitivity and specificity, which translate to lower false negative and false positive rates. In almost all applications outside of security where accurate chemical analysis is needed, MS is usually the method of choice and is often referred to as the gold standard for chemical analysis. There are many review articles and proceedings that describe detection technologies for explosives. 1,2,3,4 Here we compare MS and IMS and identify the strengths and weaknesses of each method. - Mass spectrometry (MS): MS offers high levels of sensitivity and specificity compared to other technologies for chemical detection. Its traditional disadvantages have been high cost and complexity. Over the last few years, however, the economics have greatly improved and MS is now capable of routine and automated operation. Here we compare MS and IMS and identify the strengths and weaknesses of each method. - Ion mobility spectrometry (IMS): 5 MS-ETD Screening System IMS is similar in concept to MS except that the ions are dispersed by gas-phase viscosity and not by molecular weight. The main advantage of IMS is that it does not use a vacuum system, which greatly reduces the size, cost, and complexity

The use of ion mobility spectrometry and gas chromatography/mass spectrometry for the detection of illicit drugs on clandestine records

NASA Technical Reports Server (NTRS)

Donnelly, Brian; Jourdan, Thomas; Fetterolf, Dean D.; Beasley, James O., II

1995-01-01

the records. The detection of trace drug residue on surfaces by ion mobility spectrometry (IMS) is well documented in literature. The following procedure will deal primarily with the newer techniques of trace drug analysis and drug record analysis developed by the Chemistry/Toxicology Unit of the FBI Laboratory since the more traditional techniques of latent finger print analysis and document analysis are well known.

Stability of proton-bound clusters of alkyl alcohols, aldehydes and ketones in Ion Mobility Spectrometry.

PubMed

Jurado-Campos, Natividad; Garrido-Delgado, Rocío; Martínez-Haya, Bruno; Eiceman, Gary A; Arce, Lourdes

2018-08-01

Significant substances in emerging applications of ion mobility spectrometry such as breath analysis for clinical diagnostics and headspace analysis for food purity include low molar mass alcohols, ketones, aldehydes and esters which produce mobility spectra containing protonated monomers and proton-bound dimers. Spectra for all n- alcohols, aldehydes and ketones from carbon number three to eight exhibited protonated monomers and proton-bound dimers with ion drift times of 6.5-13.3 ms at ambient pressure and from 35° to 80 °C in nitrogen. Only n-alcohols from 1-pentanol to 1-octanol produced proton-bound trimers which were sufficiently stable to be observed at these temperatures and drift times of 12.8-16.3 ms. Polar functional groups were protected in compact structures in ab initio models for proton-bound dimers of alcohols, ketones and aldehydes. Only alcohols formed a V-shaped arrangement for proton-bound trimers strengthening ion stability and lifetime. In contrast, models for proton-bound trimers of aldehydes and ketones showed association of the third neutral through weak, non-specific, long-range interactions consistent with ion dissociation in the ion mobility drift tube before arriving at the detector. Collision cross sections derived from reduced mobility coefficients in nitrogen gas atmosphere support the predicted ion structures and approximate degrees of hydration. Copyright © 2018 Elsevier B.V. All rights reserved.

An ion mobility-mass spectrometry investigation of monocyte chemoattractant protein-1

NASA Astrophysics Data System (ADS)

Schenauer, Matthew R.; Leary, Julie A.

2009-10-01

In the present article we describe the gas-phase dissociation behavior of the dimeric form of monocyte chemoattractant protein-1 (MCP-1) using quadrupole-traveling wave ion mobility spectrometry-time of flight mass spectrometry (q-TWIMS-TOF MS) (Waters Synapt(TM)). Through investigation of the 9+ charge state of the dimer, we were able to monitor dissociation product ion (monomer) formation as a function of activation energy. Using ion mobility, we were able to observe precursor ion structural changes occurring throughout the activation process. Arrival time distributions (ATDs) for the 5+ monomeric MCP-1 product ions, derived from the gas-phase dissociation of the 9+ dimer, were then compared with ATDs obtained for the 5+ MCP-1 monomer isolated directly from solution. The results show that the dissociated monomer is as compact as the monomer arising from solution, regardless of the trap collision energy (CE) used in the dissociation. The solution-derived monomer, when collisionally activated, also resists significant unfolding within measure. Finally, we compared the collisional activation data for the MCP-1 dimer with an MCP-1 dimer non-covalently bound to a single molecule of the semi-synthetic glycosaminoglycan (GAG) analog Arixtra(TM); the latter a therapeutic anti-thrombin III-activating pentasaccharide. We observed that while dimeric MCP-1 dissociated at relatively low trap CEs, the Arixtra-bound dimer required much higher energies, which also induced covalent bond cleavage in the bound Arixtra molecule. Both the free and Arixtra-bound dimers became less compact and exhibited longer arrival times with increasing trap CEs, albeit the Arixtra-bound complex at slightly higher energies. That both dimers shifted to longer arrival times with increasing activation energy, while the dissociated MCP-1 monomers remained compact, suggests that the longer arrival times of the Arixtra-free and Arixtra-bound dimers may represent a partial breach of non

Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Chen, Zhidan; Coy, Stephen L.; Pannkuk, Evan L.; Laiakis, Evagelia C.; Hall, Adam B.; Fornace, Albert J.; Vouros, Paul

2016-10-01

Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX-SPE). The dramatic suppression of background and chemical noise provided by DMS-MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure.

Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space.

PubMed

Schenk, Emily R; Nau, Frederic; Fernandez-Lima, Francisco

2015-06-01

The ability to correlate experimental ion mobility data with candidate structures from theoretical modeling provides a powerful analytical and structural tool for the characterization of biomolecules. In the present paper, a theoretical workflow is described to generate and assign candidate structures for experimental trapped ion mobility and H/D exchange (HDX-TIMS-MS) data following molecular dynamics simulations and statistical filtering. The applicability of the theoretical predictor is illustrated for a peptide and protein example with multiple conformations and kinetic intermediates. The described methodology yields a low computational cost and a simple workflow by incorporating statistical filtering and molecular dynamics simulations. The workflow can be adapted to different IMS scenarios and CCS calculators for a more accurate description of the IMS experimental conditions. For the case of the HDX-TIMS-MS experiments, molecular dynamics in the "TIMS box" accounts for a better sampling of the molecular intermediates and local energy minima.

Matrix-Assisted Laser Desorption Ionization Imaging Mass Spectrometry: In Situ Molecular Mapping

PubMed Central

Angel, Peggi M.; Caprioli, Richard M.

2013-01-01

Matrix-assisted laser desorption ionization imaging mass spectrometry (IMS) is a relatively new imaging modality that allows mapping of a wide range of biomolecules within a thin tissue section. The technology uses a laser beam to directly desorb and ionize molecules from discrete locations on the tissue that are subsequently recorded in a mass spectrometer. IMS is distinguished by the ability to directly measure molecules in situ ranging from small metabolites to proteins, reporting hundreds to thousands of expression patterns from a single imaging experiment. This article reviews recent advances in IMS technology, applications, and experimental strategies that allow it to significantly aid in the discovery and understanding of molecular processes in biological and clinical samples. PMID:23259809

How Hot are Your Ions in TWAVE Ion Mobility Spectrometry?

PubMed Central

Merenbloom, Samuel I.; Flick, Tawnya G.; Williams, Evan R.

2012-01-01

Effective temperatures of ions during traveling wave ion mobility spectrometry (TWIMS) analysis were measured using singly protonated leucine enkephalin dimer as a chemical thermometer by monitoring dissociation of the dimer into monomer, as well as the subsequent dissociation of monomer into a-, b-, and y-ions, as a function of instrumental parameters. At fixed helium cell and TWIMS cell gas flow rates, the extent of dissociation does not vary significantly with either the wave velocity or wave height, except at low (<500 m/s) wave velocities that are not commonly used. Increasing the flow rate of nitrogen gas into the TWIMS cell and decreasing the flow rate of helium gas into the helium cell resulted in greater dissociation. However, the mobility distributions of the fragment ions formed by dissociation of the dimer upon injection into the TWIMS cell are nearly indistinguishable from those of fragment ions formed in the collision cell prior to TWIMS analysis for all TWIMS experiments. These results indicate that heating and dissociation occur when ions are injected into the TWIMS cell, and that the effective temperature subsequently decreases to a point at which no further dissociation is observed during the TWIMS analysis. An upper limit to the effective ion temperature of 449 K during TWIMS analysis is obtained at a helium flow rate of 180 mL/min, TWIMS flow rate of 80 mL/min and traveling wave height of 40 V, which is well below previously reported values. Effects of ion heating in TWIMS on gas-phase protein conformation are presented. PMID:22203576

Fast detection of narcotics by single photon ionization mass spectrometry and laser ion mobility spectrometry

NASA Astrophysics Data System (ADS)

Laudien, Robert; Schultze, Rainer; Wieser, Jochen

2010-10-01

In this contribution two analytical devices for the fast detection of security-relevant substances like narcotics and explosives are presented. One system is based on an ion trap mass spectrometer (ITMS) with single photon ionization (SPI). This soft ionization technique, unlike electron impact ionization (EI), reduces unwanted fragment ions in the mass spectra allowing the clear determination of characteristic (usually molecular) ions. Their enrichment in the ion trap and identification by tandem MS investigations (MS/MS) enables the detection of the target substances in complex matrices at low concentrations without time-consuming sample preparation. For SPI an electron beam pumped excimer light source of own fabrication (E-Lux) is used. The SPI-ITMS system was characterized by the analytical study of different drugs like cannabis, heroin, cocaine, amphetamines, and some precursors. Additionally, it was successfully tested on-site in a closed illegal drug laboratory, where low quantities of MDMA could be directly detected in samples from floors, walls and lab equipments. The second analytical system is based on an ion mobility (IM) spectrometer with resonant multiphoton ionization (REMPI). With the frequency quadrupled Nd:YAG laser (266 nm), used for ionization, a selective and sensitive detection of aromatic compounds is possible. By application of suited aromatic dopants, in addition, also non-aromatic polar compounds are accessible by ion molecule reactions like proton transfer or complex formation. Selected drug precursors could be successfully detected with this device as well, qualifying it to a lower-priced alternative or useful supplement of the SPI-ITMS system for security analysis.

Secure Mobile Distributed File System (MDFS)

DTIC Science & Technology

2011-03-01

dissemination of data. In a mobile ad - hoc network, there are two classes of devices: content generators and content consumers. One im- plementation of...use of infrastructure mode is necessary because current Android implemen- tations do not support Mobile Ad - Hoc network without modification of the...NUMBER (include area code ) Standard Form 298 (Rev. 8–98) Prescribed by ANSI Std. Z39.18 24–3–2011 Master’s Thesis 2009-03-01—2011-03-31 Secure Mobile

Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Xueyun; Smith, Richard D.; Baker, Erin S.

Lipids are a vital class of molecules that play important and varied roles in biological processes. Fully understanding lipid roles, however, is extremely difficult since the number and diversity of lipid species is immense, with cells expressing hundreds of enzymes that synthesize tens of thousands of different lipids. While recent advances in chromatography and high resolution mass spectrometry have greatly progressed the understanding of lipid species and functions, effectively separating many lipids still remains problematic. Isomeric lipids have made lipid characterization especially difficult and occur due to subclasses having the same chemical composition, or species having multiple acyl chains connectivitiesmore » (sn-1, sn-2, or sn-3), double bond positions and orientations (cis or trans), and functional group stereochemistry (R versus S). Fully understanding the roles of lipids in biological processes therefore requires separating and evaluating how isomers change in biological and environmental samples. To address this challenge, ion mobility spectrometry separations, ion-molecule reactions and fragmentation techniques have increasingly been added to lipid analysis workflows to improve identifications. In this manuscript, we review the current state of these approaches and their capabilities for improving the identification of specific lipid species.« less

A structural examination and collision cross section database for over 500 metabolites and xenobiotics using drift tube ion mobility spectrometry† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc03464d

PubMed Central

Zheng, Xueyun; Aly, Noor A.; Zhou, Yuxuan; Dupuis, Kevin T.; Bilbao, Aivett; Paurus, Vanessa L.; Orton, Daniel J.; Wilson, Ryan; Payne, Samuel H.; Smith, Richard D.

2017-01-01

The confident identification of metabolites and xenobiotics in biological and environmental studies is an analytical challenge due to their immense dynamic range, vast chemical space and structural diversity. Ion mobility spectrometry (IMS) is widely used for small molecule analyses since it can separate isomeric species and be easily coupled with front end separations and mass spectrometry for multidimensional characterizations. However, to date IMS metabolomic and exposomic studies have been limited by an inadequate number of accurate collision cross section (CCS) values for small molecules, causing features to be detected but not confidently identified. In this work, we utilized drift tube IMS (DTIMS) to directly measure CCS values for over 500 small molecules including primary metabolites, secondary metabolites and xenobiotics. Since DTIMS measurements do not need calibrant ions or calibration like some other IMS techniques, they avoid calibration errors which can cause problems in distinguishing structurally similar molecules. All measurements were performed in triplicate in both positive and negative polarities with nitrogen gas and seven different electric fields, so that relative standard deviations (RSD) could be assessed for each molecule and structural differences studied. The primary metabolites analyzed to date have come from key metabolism pathways such as glycolysis, the pentose phosphate pathway and the tricarboxylic acid cycle, while the secondary metabolites consisted of classes such as terpenes and flavonoids, and the xenobiotics represented a range of molecules from antibiotics to polycyclic aromatic hydrocarbons. Different CCS trends were observed for several of the diverse small molecule classes and when urine features were matched to the database, the addition of the IMS dimension greatly reduced the possible number of candidate molecules. This CCS database and structural information are freely available for download at http

Two-dimensional wavelet analysis based classification of gas chromatogram differential mobility spectrometry signals.

PubMed

Zhao, Weixiang; Sankaran, Shankar; Ibáñez, Ana M; Dandekar, Abhaya M; Davis, Cristina E

2009-08-04

This study introduces two-dimensional (2-D) wavelet analysis to the classification of gas chromatogram differential mobility spectrometry (GC/DMS) data which are composed of retention time, compensation voltage, and corresponding intensities. One reported method to process such large data sets is to convert 2-D signals to 1-D signals by summing intensities either across retention time or compensation voltage, but it can lose important signal information in one data dimension. A 2-D wavelet analysis approach keeps the 2-D structure of original signals, while significantly reducing data size. We applied this feature extraction method to 2-D GC/DMS signals measured from control and disordered fruit and then employed two typical classification algorithms to testify the effects of the resultant features on chemical pattern recognition. Yielding a 93.3% accuracy of separating data from control and disordered fruit samples, 2-D wavelet analysis not only proves its feasibility to extract feature from original 2-D signals but also shows its superiority over the conventional feature extraction methods including converting 2-D to 1-D and selecting distinguishable pixels from training set. Furthermore, this process does not require coupling with specific pattern recognition methods, which may help ensure wide applications of this method to 2-D spectrometry data.

Rapid analysis of pesticide residues in drinking water samples by dispersive solid-phase extraction based on multiwalled carbon nanotubes and pulse glow discharge ion source ion mobility spectrometry.

PubMed

Zou, Nan; Gu, Kejia; Liu, Shaowen; Hou, Yanbing; Zhang, Jialei; Xu, Xiang; Li, Xuesheng; Pan, Canping

2016-03-01

An analytical method based on dispersive solid-phase extraction with a multiwalled carbon nanotubes sorbent coupled with positive pulse glow discharge ion mobility spectrometry was developed for analysis of 30 pesticide residues in drinking water samples. Reduced ion mobilities and the mass-mobility correlation of 30 pesticides were measured. The pesticides were divided into five groups to verify the separation capability of pulse glow discharge in mobility spectrometry. The extraction conditions such as desorption solvent, ionic strength, conditions of adsorption and desorption, the amounts of multiwalled carbon nanotubes, and solution pH were optimized. The enrichment factors of pesticides were 5.4- to 48.7-fold (theoretical enrichment factor was 50-fold). The detection limits of pesticides were 0.01∼0.77 μg/kg. The linear range was 0.005-0.2 mg/L for pesticide standard solutions, with determination coefficients from 0.9616 to 0.9999. The method was applied for the analysis of practical and spiked drinking water samples. All results were confirmed by high-performance liquid chromatography with tandem mass spectrometry. The proposed method was proven to be a commendably rapid screening qualitative and semiquantitative technique for the analysis of pesticide residues in drinking water samples on site. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Detection of Pseudomonas aeruginosa biomarkers from thermally injured mice in situ using imaging mass spectrometry.

PubMed

Hamerly, Timothy; Everett, Jake A; Paris, Nina; Fisher, Steve T; Karunamurthy, Arivarasan; James, Garth A; Rumbaugh, Kendra P; Rhoads, Daniel D; Bothner, Brian

2017-12-15

Monitoring patients with burn wounds for infection is standard practice because failure to rapidly and specifically identify a pathogen can result in poor clinical outcomes, including death. Therefore, a method that facilitates detection and identification of pathogens in situ within minutes of biopsy would be a significant benefit to clinicians. Mass spectrometry is rapidly becoming a standard tool in clinical settings, capable of identifying specific pathogens from complex samples. Imaging mass spectrometry (IMS) expands the information content by enabling spatial resolution of biomarkers in tissue samples as in histology, without the need for specific stains/antibodies. Herein, a murine model of thermal injury was used to study infection of burn tissue by Pseudomonas aeruginosa. This is the first use of IMS to detect P. aeruginosa infection in situ from thermally injured tissue. Multiple molecular features could be spatially resolved to infected or uninfected tissue. This demonstrates the potential use of IMS in a clinical setting to aid doctors in identifying both presence and species of pathogens in tissue. Copyright © 2017. Published by Elsevier Inc.

Collision cross sections of high-mannose N-glycans in commonly observed adduct states--identification of gas-phase conformers unique to [M-H](-) ions.

PubMed

Struwe, W B; Benesch, J L; Harvey, D J; Pagel, K

2015-10-21

We report collision cross sections (CCS) of high-mannose N-glycans as [M + Na](+), [M + K](+), [M + H](+), [M + Cl](-), [M + H2PO4](-) and [M - H](-) ions, measured by drift tube (DT) ion mobility-mass spectrometry (IM-MS) in helium and nitrogen gases. Further analysis using traveling wave (TW) IM-MS reveal the existence of distinct conformers exclusive to [M - H](-) ions.

High-Field Asymmetric-Waveform Ion Mobility Spectrometry and Electron Detachment Dissociation of Isobaric Mixtures of Glycosaminoglycans

NASA Astrophysics Data System (ADS)

Kailemia, Muchena J.; Park, Melvin; Kaplan, Desmond A.; Venot, Andre; Boons, Geert-Jan; Li, Lingyun; Linhardt, Robert J.; Amster, I. Jonathan

2014-02-01

High-field asymmetric waveform ion mobility spectrometry (FAIMS) is shown to be capable of resolving isomeric and isobaric glycosaminoglycan negative ions and to have great utility for the analysis of this class of molecules when combined with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and tandem mass spectrometry. Electron detachment dissociation (EDD) and other ion activation methods for tandem mass spectrometry can be used to determine the sites of labile sulfate modifications and for assigning the stereochemistry of hexuronic acid residues of glycosaminoglycans (GAGs). However, mixtures with overlapping mass-to-charge values present a challenge, as their precursor species cannot be resolved by a mass analyzer prior to ion activation. FAIMS is shown to resolve two types of mass-to-charge overlaps. A mixture of chondroitin sulfate A (CSA) oligomers with 4-10 saccharides units produces ions of a single mass-to-charge by electrospray ionization, as the charge state increases in direct proportion to the degree of polymerization for these sulfated carbohydrates. FAIMS is shown to resolve the overlapping charge. A more challenging type of mass-to-charge overlap occurs for mixtures of diastereomers. FAIMS is shown to separate two sets of epimeric GAG tetramers. For the epimer pairs, the complexity of the separation is reduced when the reducing end is alkylated, suggesting that anomers are also resolved by FAIMS. The resolved components were activated by EDD and the fragment ions were analyzed by FTICR-MS. The resulting tandem mass spectra were able to distinguish the two epimers from each other.

MALDI-Imaging Mass Spectrometry: a step forward in the anatomopathological characterization of stenotic aortic valve tissue.

PubMed

Mourino-Alvarez, Laura; Iloro, Ibon; de la Cuesta, Fernando; Azkargorta, Mikel; Sastre-Oliva, Tamara; Escobes, Iraide; Lopez-Almodovar, Luis F; Sanchez, Pedro L; Urreta, Harkaitz; Fernandez-Aviles, Francisco; Pinto, Angel; Padial, Luis R; Akerström, Finn; Elortza, Felix; Barderas, Maria G

2016-06-03

Aortic stenosis (AS) is the most common form of valve disease. Once symptoms develop, there is an inexorable deterioration with a poor prognosis; currently there are no therapies capable of modifying disease progression, and aortic valve replacement is the only available treatment. Our goal is to study the progression of calcification by matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) and get new insights at molecular level that could help in the understanding of this disease. In this work, we analyzed consecutive slices from aortic valve tissue by MALDI-IMS, to establish the spatial distribution of proteins and peptides directly from the surface of the histological sections. The analysis showed different structures corresponding to regions observed in conventional histology, including large calcification areas and zones rich in collagen and elastic fibers. Peptide extraction from the tissue, followed by liquid chromatography mass spectrometry analysis, provided the identification of collagen VI α-3 and NDRG2 proteins which correlated with the masses obtained by MALDI-IMS and were confirmed by immunohistochemistry. These results highlighted the molecular mechanism implied in AS using MALDI-IMS, a novel technique never used before in this pathology. In addition, we can define specific regions proving a complementary resolution of the molecular histology.

Behaviour of tetraalkylammonium ions in high-field asymmetric waveform ion mobility spectrometry.

PubMed

Aksenov, Alexander A; Kapron, James T

2010-05-30

High-field asymmetric waveform ion mobility spectrometry (FAIMS) is an ion-filtering technique recently adapted for use with liquid chromatography/mass spectrometry (LC/MS) to remove interferences during analysis of complex matrices. This is the first systematic study of a series of singly charged tetraalkylammonium ions by FAIMS-MS. The compensation voltage (CV) is the DC offset of the waveform which permits the ion to emerge from FAIMS and it was determined for each member of the series under various conditions. The electrospray ionization conditions explored included spray voltage, vaporizer temperature, and sheath and auxiliary gas pressure. The FAIMS conditions explored included carrier gas flow rate, electrode temperature and composition of the carrier gas. Optimum desolvation was achieved using sufficient carrier gas (flow rate > or = 2 L/min) to ensure stable response. Low-mass ions (m/z 100-200) are more susceptible to changes in electrode temperature and gas composition than high mass ions (m/z 200-700). As a result of this study, ions are reliably analyzed using standard FAIMS conditions (dispersion voltage -5000 V, carrier gas flow rate 3 L/min, 50% helium/50%nitrogen, inner electrode temperature 70 degrees C and outer electrode temperature 90 degrees C). Variation of FAIMS conditions may be of great use for the separation of very low mass tetraalkylammonium (TAA) ions from other TAA ions. The FAIMS conditions do not appear to have a major effect on higher mass ions. Copyright 2010 John Wiley & Sons, Ltd.

Design for Social Presence and Exploring Its Mediating Effect in Mobile Data Communication Services

ERIC Educational Resources Information Center

Ogara, Solomon Omondi

2011-01-01

The mobility, flexibility, convenience, and ubiquity of mobile data services (MDS) have contributed to their enormous growth and popularity with users. MDS allow users to communicate through mobile texting (mTexting), mobile Instant Messaging (mIM), multimedia messaging services (MMS), and email. A unique feature of MDS that enhances its…

Exchange, interpretation, and database-search of ion mobility spectra supported by data format JCAMP-DX

NASA Technical Reports Server (NTRS)

Baumback, J. I.; Davies, A. N.; Vonirmer, A.; Lampen, P. H.

1995-01-01

To assist peak assignment in ion mobility spectrometry it is important to have quality reference data. The reference collection should be stored in a database system which is capable of being searched using spectral or substance information. We propose to build such a database customized for ion mobility spectra. To start off with it is important to quickly reach a critical mass of data in the collection. We wish to obtain as many spectra combined with their IMS parameters as possible. Spectra suppliers will be rewarded for their participation with access to the database. To make the data exchange between users and system administration possible, it is important to define a file format specially made for the requirements of ion mobility spectra. The format should be computer readable and flexible enough for extensive comments to be included. In this document we propose a data exchange format, and we would like you to give comments on it. For the international data exchange it is important, to have a standard data exchange format. We propose to base the definition of this format on the JCAMP-DX protocol, which was developed for the exchange of infrared spectra. This standard made by the Joint Committee on Atomic and Molecular Physical Data is of a flexible design. The aim of this paper is to adopt JCAMP-DX to the special requirements of ion mobility spectra.

The hypertrehalosemic neuropeptides of cicadas are structural isomers-evidence by ion mobility mass spectrometry.

PubMed

König, Simone; Marco, Heather; Gäde, Gerd

2017-11-01

It has been known for more than 20 years that the neurosecretory glands of the cicadas, the corpora cardiaca, synthesize two isobaric peptides with hypertrehalosemic activity. Both decapeptides have exactly the same amino acid sequence (pGlu-Val-Asn-Phe-Ser-Pro-Ser-Trp-Gly-Asn-NH 2 ) and mass but differ in their retention time in reversed-phase liquid chromatography. A synthetic peptide with the same sequence elutes together with the second more hydrophobic peptide peak of the natural cicada extract. It is not clear what modification is causing the described observations. Therefore, in the current study, ion mobility separation in conjunction with high-resolution mass spectrometry was used to investigate this phenomenon as it was sensitive to changes in conformation. It detected different drift times in buffer gas for both the intact peptides and some of their fragment ions. Based on the ion mobility and fragment ion intensity of the corresponding ions, it is concluded that the region Pro 6 -Ser 7 -Trp 8 contains a structural feature differing from the L-amino acids present in the known peptide. Whether the conformer is the result of racemization or other biochemical processes needs to be further investigated.

23 CFR 500.111 - IMS.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false IMS. 500.111 Section 500.111 Highways FEDERAL HIGHWAY... SYSTEMS Management Systems § 500.111 IMS. An effective IMS for intermodal facilities and systems provides... the various land-based transportation facilities and systems. An IMS should include, at a minimum: (a...

Ultrahigh-Resolution Differential Ion Mobility Separations of Conformers for Proteins above 10 kDa: Onset of Dipole Alignment?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shvartsburg, Alexandre A.

2014-11-04

Biomacromolecules tend to assume numerous structures in solution or the gas phase. It has been possible to resolve disparate conformational families but not unique geometries within each, and drastic peak broadening has been the bane of protein analyses by chromatography, electrophoresis, and ion mobility spectrometry (IMS). The new differential IMS (FAIMS) approach using hydrogen-rich gases was recently found to separate conformers of a small protein ubiquitin with same peak width and resolving power up to ~400 as for peptides. Present work explores the reach of this approach for larger proteins, exemplified by cytochrome c and myoglobin. Resolution similar to thatmore » for ubiquitin was largely achieved with longer separations, while the onset of peak broadening and coalescence with shorter separations suggests the limitation of present technique to proteins under ~20 kDa. This capability may enable distinguishing whole proteins with differing residue sequences or localizations of posttranslational modifications. Small features at negative compensation voltages that markedly grow from cytochrome c to myoglobin indicate the dipole alignment of rare conformers in accord with theory, further supporting the concept of pendular macroions in FAIMS.« less

Quantum Chemical Mass Spectrometry: Verification and Extension of the Mobile Proton Model for Histidine

NASA Astrophysics Data System (ADS)

Cautereels, Julie; Blockhuys, Frank

2017-06-01

The quantum chemical mass spectrometry for materials science (QCMS2) method is used to verify the proposed mechanism for proton transfer - the Mobile Proton Model (MPM) - by histidine for ten XHS tripeptides, based on quantum chemical calculations at the DFT/B3LYP/6-311+G* level of theory. The fragmentations of the different intermediate structures in the MPM mechanism are studied within the QCMS2 framework, and the energetics of the proposed mechanism itself and those of the fragmentations of the intermediate structures are compared, leading to the computational confirmation of the MPM. In addition, the calculations suggest that the mechanism should be extended from considering only the formation of five-membered ring intermediates to include larger-ring intermediates. [Figure not available: see fulltext.

Secondary electrospray ionization-ion mobility spectrometry for explosive vapor detection.

PubMed

Tam, Maggie; Hill, Herbert H

2004-05-15

The unique capability of secondary electrospray ionization (SESI) as a nonradioactive ionization source to detect analytes in both liquid and gaseous samples was evaluated using aqueous solutions of three common military explosives: cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), nitroglycerin (NG) and pentaerythritol tetranitrate (PETN). The adducts formed between the compounds and their respective dissociation product, RDX.NO(2)(-), NG.NO(3)(-), and PETN.NO(3)(-), gave the most intense signal for the individual compound but were more sensitive to temperature than other species. These autoadducts were identified as RDX.NO(2)(-), NG.NO(3)(-), and PETN.NO(3)(-) and had maximum signal intensity at 137, 100, and 125 degrees C, respectively. The reduced mobility values of the three compounds were constant over the temperature range from 75 to 225 degrees C. The signal-to-noise ratios for RDX, NG, and PETN at 50 mg L(-1) in methanol-water were 340, 270, and 170, respectively, with a nominal noise of 8 +/- 2 pA. In addition to the investigation of autoadduct formation, the concept of doping the ionization source with nonvolatile adduct-forming agents was investigated and described for the first time. The SESI-IMS detection limit for RDX was 116 microg L(-1) in the presence of a traditional volatile chloride dopant and 5.30 microg L(-1) in the presence of a nonvolatile nitrate dopant. In addition to a lower detection limit, the nitrate dopant also produced a greater response sensitivity and a higher limit of linearity than did the traditional volatile chloride dopant.

Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions

NASA Astrophysics Data System (ADS)

Harvey, David J.; Struwe, Weston B.

2018-05-01

There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods. Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes. These epitopes are involved in processes such as cell-cell recognition and are important as cancer biomarkers. Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans. Information on the location of the fucose residues was also readily obtainable from ions specific to each antenna. Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.

Insights from native mass spectrometry approaches for top- and middle- level characterization of site-specific antibody-drug conjugates

PubMed Central

Botzanowski, Thomas; Erb, Stéphane; Hernandez-Alba, Oscar; Ehkirch, Anthony; Colas, Olivier; Wagner-Rousset, Elsa; Rabuka, David; Beck, Alain; Drake, Penelope M.; Cianférani, Sarah

2017-01-01

ABSTRACT Antibody-drug conjugates (ADCs) have emerged as a family of compounds with promise as efficient immunotherapies. First-generation ADCs were generated mostly via reactions on either lysine side-chain amines or cysteine thiol groups after reduction of the interchain disulfide bonds, resulting in heterogeneous populations with a variable number of drug loads per antibody. To control the position and the number of drug loads, new conjugation strategies aiming at the generation of more homogeneous site-specific conjugates have been developed. We report here the first multi-level characterization of a site-specific ADC by state-of-the-art mass spectrometry (MS) methods, including native MS and its hyphenation to ion mobility (IM-MS). We demonstrate the versatility of native MS methodologies for site-specific ADC analysis, with the unique ability to provide several critical quality attributes within one single run, along with a direct snapshot of ADC homogeneity/heterogeneity without extensive data interpretation. The capabilities of native IM-MS to directly access site-specific ADC conformational information are also highlighted. Finally, the potential of these techniques for assessing an ADC's heterogeneity/homogeneity is illustrated by comparing the analytical characterization of a site-specific DAR4 ADC to that of first-generation ADCs. Altogether, our results highlight the compatibility, versatility, and benefits of native MS approaches for the analytical characterization of all types of ADCs, including site-specific conjugates. Thus, we envision integrating native MS and IM-MS approaches, even in their latest state-of-the-art forms, into workflows that benchmark bioconjugation strategies. PMID:28406343

Dynamic planar solid phase microextraction-ion mobility spectrometry for rapid field air sampling and analysis of illicit drugs and explosives.

PubMed

Guerra-Diaz, Patricia; Gura, Sigalit; Almirall, José R

2010-04-01

A preconcentration device that targets the volatile chemical signatures associated with illicit drugs and explosives (high and low) has been designed to fit in the inlet of an ion mobility spectrometer (IMS). This is the first reporting of a fast and sensitive method for dynamic sampling of large volumes of air using planar solid phase microextraction (PSPME) incorporating a high surface area for absorption of analytes onto a sol-gel polydimethylsiloxane (PDMS) coating for direct thermal desorption into an IMS. This device affords high extraction efficiencies due to strong retention properties at ambient temperature, resulting in the detection of analyte concentrations in the parts per trillion range when as low as 3.5 L of air are sampled over the course of 10 s (absolute mass detection of less than a nanogram). Dynamic PSPME was used to sample the headspace over the following: 3,4-methylenedioxymethamphetamine (MDMA) tablets resulting in the detection of 12-40 ng of piperonal, high explosives (Pentolite) resulting in the detection of 0.6 ng of 2,4,6-trinitrotoluene (TNT), and low explosives (several smokeless powders) resulting in the detection of 26-35 ng of 2,4-dinitrotoluene (2,4-DNT) and 11-74 ng of diphenylamine (DPA).

PIXiE: an algorithm for automated ion mobility arrival time extraction and collision cross section calculation using global data association

PubMed Central

Ma, Jian; Casey, Cameron P.; Zheng, Xueyun; Ibrahim, Yehia M.; Wilkins, Christopher S.; Renslow, Ryan S.; Thomas, Dennis G.; Payne, Samuel H.; Monroe, Matthew E.; Smith, Richard D.; Teeguarden, Justin G.; Baker, Erin S.; Metz, Thomas O.

2017-01-01

Abstract Motivation: Drift tube ion mobility spectrometry coupled with mass spectrometry (DTIMS-MS) is increasingly implemented in high throughput omics workflows, and new informatics approaches are necessary for processing the associated data. To automatically extract arrival times for molecules measured by DTIMS at multiple electric fields and compute their associated collisional cross sections (CCS), we created the PNNL Ion Mobility Cross Section Extractor (PIXiE). The primary application presented for this algorithm is the extraction of data that can then be used to create a reference library of experimental CCS values for use in high throughput omics analyses. Results: We demonstrate the utility of this approach by automatically extracting arrival times and calculating the associated CCSs for a set of endogenous metabolites and xenobiotics. The PIXiE-generated CCS values were within error of those calculated using commercially available instrument vendor software. Availability and implementation: PIXiE is an open-source tool, freely available on Github. The documentation, source code of the software, and a GUI can be found at https://github.com/PNNL-Comp-Mass-Spec/PIXiE and the source code of the backend workflow library used by PIXiE can be found at https://github.com/PNNL-Comp-Mass-Spec/IMS-Informed-Library. Contact: erin.baker@pnnl.gov or thomas.metz@pnnl.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28505286

PIXiE: an algorithm for automated ion mobility arrival time extraction and collision cross section calculation using global data association.

PubMed

Ma, Jian; Casey, Cameron P; Zheng, Xueyun; Ibrahim, Yehia M; Wilkins, Christopher S; Renslow, Ryan S; Thomas, Dennis G; Payne, Samuel H; Monroe, Matthew E; Smith, Richard D; Teeguarden, Justin G; Baker, Erin S; Metz, Thomas O

2017-09-01

Drift tube ion mobility spectrometry coupled with mass spectrometry (DTIMS-MS) is increasingly implemented in high throughput omics workflows, and new informatics approaches are necessary for processing the associated data. To automatically extract arrival times for molecules measured by DTIMS at multiple electric fields and compute their associated collisional cross sections (CCS), we created the PNNL Ion Mobility Cross Section Extractor (PIXiE). The primary application presented for this algorithm is the extraction of data that can then be used to create a reference library of experimental CCS values for use in high throughput omics analyses. We demonstrate the utility of this approach by automatically extracting arrival times and calculating the associated CCSs for a set of endogenous metabolites and xenobiotics. The PIXiE-generated CCS values were within error of those calculated using commercially available instrument vendor software. PIXiE is an open-source tool, freely available on Github. The documentation, source code of the software, and a GUI can be found at https://github.com/PNNL-Comp-Mass-Spec/PIXiE and the source code of the backend workflow library used by PIXiE can be found at https://github.com/PNNL-Comp-Mass-Spec/IMS-Informed-Library . erin.baker@pnnl.gov or thomas.metz@pnnl.gov. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Comprehensive characterization of ethoxyquin transformation products in fish feed by traveling-wave ion mobility spectrometry coupled to quadrupole time-of-flight mass spectrometry.

PubMed

Negreira, Noelia; Regueiro, Jorge; Valdersnes, Stig; Berntssen, Marc H G; Ørnsrud, Robin

2017-05-01

Feed additives are typically used in intensive farming production over long periods, and hence, they can accumulate in farmed animal tissues. Concerns regarding the use of ethoxyquin as an antioxidant feed additive, have recently arisen due to its potential conversion into a series of transformation products (TPs). The aim of this work was to characterize the TPs of ethoxyquin in fish feed by a novel approach based on the use of traveling-wave ion mobility spectrometry (TWIMS) coupled to high-resolution quadrupole time-of-flight mass spectrometry (QTOFMS). First, ethoxyquin was oxidized under controlled conditions and the generated TPs were added to a comprehensive database. Atlantic salmon feeds were then screened for ethoxyquin TPs using both targeted and untargeted approaches. Twenty-seven TPs were tentatively identified during the oxidation experiments, fifteen of them also being present in the feed samples. In addition, ten other potential TPs were detected in fish feed following the untargeted approach. Thirty-one of these TPs have been reported for the first time in this work through the oxidation experiments and the feed samples. Therefore, this study provides valuable information on the oxidative fate of ethoxyquin in feed, which can be used for future evaluations of potential risk related to this additive. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteomic analysis of formalin-fixed paraffin embedded tissue by MALDI imaging mass spectrometry

PubMed Central

Casadonte, Rita; Caprioli, Richard M

2012-01-01

Archived formalin-fixed paraffin-embedded (FFPE) tissue collections represent a valuable informational resource for proteomic studies. Multiple FFPE core biopsies can be assembled in a single block to form tissue microarrays (TMAs). We describe a protocol for analyzing protein in FFPE -TMAs using matrix-assisted laser desorption/ionization (MAL DI) imaging mass spectrometry (IMS). The workflow incorporates an antigen retrieval step following deparaffinization, in situ trypsin digestion, matrix application and then mass spectrometry signal acquisition. The direct analysis of FFPE -TMA tissue using IMS allows direct analysis of multiple tissue samples in a single experiment without extraction and purification of proteins. The advantages of high speed and throughput, easy sample handling and excellent reproducibility make this technology a favorable approach for the proteomic analysis of clinical research cohorts with large sample numbers. For example, TMA analysis of 300 FFPE cores would typically require 6 h of total time through data acquisition, not including data analysis. PMID:22011652

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garimella, Sandilya V. B.; Ibrahim, Yehia M.; Tang, Keqi

A novel concept for ion spatial peak compression is described, and discussed primarily in the context of ion mobility spectrometry (IMS). Using theoretical and numerical methods, the effects of using non-constant (e.g., linearly varying) electric fields on ion distributions (e.g., an ion mobility peak) is evaluated both in the physical and temporal domains. The application of linearly decreasing electric field in conjunction with conventional drift field arrangements is shown to lead to a reduction in IMS physical peak width. When multiple ion packets in a selected mobility window are simultaneously subjected to such fields, there is ion packet compression, i.e.,more » a reduction in peak widths of all species. This peak compression occurs with a modest reduction of resolution, but which can be quickly recovered as ions drift in a constant field after the compression event. Compression also yields a significant increase in peak intensities. In addition, approaches for peak compression in traveling wave IMS are also discussed. Ion mobility peak compression can be particularly useful for mitigating diffusion driven peak spreading over very long path length separations (e.g., in cyclic multi-pass arrangements), and for achieving higher S/N and IMS resolution over a selected mobility range.« less

W8...b4 IM, how did u rite??! Digital Writing in the Composition Classroom

ERIC Educational Resources Information Center

Partridge, Bryan

2011-01-01

From word processing computers, to mobile telephones, to the advent of the Internet, and finally to online communication venues like Instant Messenger (IM), the past four decades have brought an increasing prevalence of technology into our culture that is altering the English language. While decried by parents and lamented by teachers, these…

Progress in mass spectrometry for the analysis of set-off phenomena in plastic food packaging materials.

PubMed

Aznar, Margarita; Alfaro, Pilar; Nerín, Cristina; Jones, Emrys; Riches, Eleanor

2016-07-01

In most cases, food packaging materials contain inks whose components can migrate to food by diffusion through the material as well as by set-off phenomena. In this work, different mass spectrometry approaches had been used in order to identify and confirm the presence of ink components in ethanol (95%) and Tenax(®) as food simulants. Three different sets of materials, manufactured with different printing technologies and with different structures, were analyzed. Sample analysis by ultra performance liquid chromatography mass spectrometry (UPLC-MS), using a quadrupole-time of flight (Q-TOF) as a mass analyser proved to be an excellent tool for identification purposes while ion mobility mass spectrometry (IM-MS) shown to be very useful for the confirmation of the candidates proposed. The results showed the presence of different non-volatile ink components in migration such as colorants (Solvent Red 49), plasticizers (dimethyl sebacate, tributyl o-acetyl citrate) or surfactants (SchercodineM, triethylene glycol caprilate). An oxidation product of an ink additive (triphenyl phosphine oxide) was also detected. In addition, a surface analysis technique, desorption electrospray mass spectrometry (DESI-MS), was used for analyzing the distribution of some ink components (tributyl o-acetyl citrate Schercodine L, phthalates) in the material. The detection of some of these compounds in the back-printed side confirmed the transference of this compound from the non-food to the food contact side. The results also showed that concentration of ink migrants decreased when an aluminum or polypropylene layer covered the ink. When aluminum was used, concentration of most of ink migrants decreased, and for 5 out of the 9 even disappeared. Copyright © 2016 Elsevier B.V. All rights reserved.

Imaging mass spectrometry in drug development and toxicology.

PubMed

Karlsson, Oskar; Hanrieder, Jörg

2017-06-01

During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

Analysis of chemical warfare agents in food products by atmospheric pressure ionization-high field asymmetric waveform ion mobility spectrometry-mass spectrometry.

PubMed

Kolakowski, Beata M; D'Agostino, Paul A; Chenier, Claude; Mester, Zoltán

2007-11-01

Flow injection high field asymmetric waveform ion mobility spectrometry (FAIMS)-mass spectrometry (MS) methodology was developed for the detection and identification of chemical warfare (CW) agents in spiked food products. The CW agents, soman (GD), sarin (GB), tabun (GA), cyclohexyl sarin (GF), and four hydrolysis products, ethylphosphonic acid (EPA), methylphosphonic acid (MPA), pinacolyl methylphosphonic acid (Pin MPA), and isopropyl methylphosphonic acid (IMPA) were separated and detected by positive ion and negative ion atmospheric pressure ionization-FAIMS-MS. Under optimized conditions, the compensation voltages were 7.2 V for GD, 8.0 V for GA, 7.2 V for GF, 7.6 V for GB, 18.2 V for EPA, 25.9 V for MPA, -1.9 V for PinMPA, and +6.8 V for IMPA. Sample preparation was kept to a minimum, resulting in analysis times of 3 min or less per sample. The developed methodology was evaluated by spiking bottled water, canola oil, cornmeal, and honey samples at low microgram per gram (or microg/mL) levels with the CW agents or CW agent hydrolysis products. The detection limits observed for the CW agents in the spiked food samples ranged from 3 to 15 ng/mL in bottled water, 1-33 ng/mL in canola oil, 1-34 ng/g in cornmeal, and 13-18 ng/g in honey. Detection limits were much higher for the CW agent hydrolysis products, with only MPA being detected in spiked honey samples.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Tsung-Chi; Ibrahim, Yehia M.; Webb, Ian K.

The integration of ion mobility spectrometry (IMS) with mass spectrometry (MS) and the ability to trap ions in IMS-MS measurements is of great importance for performing reactions, accumulating ions, and increasing analytical measurement sensitivity. The development of Structures for Lossless Ion Manipulations (SLIM) offers the potential for ion manipulations in a more reliable and cost-effective manner, while opening opportunities for much more complex sequences of manipulations. Here, we demonstrate an ion separation and trapping module and a method based upon SLIM that consists of a linear mobility ion drift region, a switch/tee and a trapping region that allows the isolationmore » and accumulation of mobility-separated species. The operation and optimization of the SLIM switch/tee and trap are described and demonstrated for the enrichment of the low abundance ions. Lastly, we observed a linear increase in ion intensity with the number of trapping/accumulation events using the SLIM trap, illustrating its potential for enhancing the sensitivity of low abundance or targeted species.« less

Utilizing Ion-Mobility Data to Estimate Molecular Masses

NASA Technical Reports Server (NTRS)

Duong, Tuan; Kanik, Isik

2008-01-01

A method is being developed for utilizing readings of an ion-mobility spectrometer (IMS) to estimate molecular masses of ions that have passed through the spectrometer. The method involves the use of (1) some feature-based descriptors of structures of molecules of interest and (2) reduced ion mobilities calculated from IMS readings as inputs to (3) a neural network. This development is part of a larger effort to enable the use of IMSs as relatively inexpensive, robust, lightweight instruments to identify, via molecular masses, individual compounds or groups of compounds (especially organic compounds) that may be present in specific environments or samples. Potential applications include detection of organic molecules as signs of life on remote planets, modeling and detection of biochemicals of interest in the pharmaceutical and agricultural industries, and detection of chemical and biological hazards in industrial, homeland-security, and industrial settings.

Deprotonation effect of tetrahydrofuran-2-carbonitrile buffer gas dopant in ion mobility spectrometry.

PubMed

Fernandez-Maestre, Roberto; Meza-Morelos, Dairo; Wu, Ching

2016-06-15

When dopants are introduced into the buffer gas of an ion mobility spectrometer, spectra are simplified due to charge competition. We used electrospray ionization to inject tetrahydrofuran-2-carbonitrile (F, 2-furonitrile or 2-furancarbonitrile) as a buffer gas dopant into an ion mobility spectrometer coupled to a quadrupole mass spectrometer. Density functional theory was used for theoretical calculations of dopant-ion interaction energies and proton affinities, using the hybrid functional X3LYP/6-311++(d,p) with the Gaussian 09 program that accounts for the basis set superposition error; analytes structures and theoretical calculations with Gaussian were used to explain the behavior of the analytes upon interaction with F. When F was used as a dopant at concentrations below 1.5 mmol m(-3) in the buffer gas, ions were not observed for α-amino acids due to charge competition with the dopant; this deprotonation capability arises from the production of a dimer with a high formation energy that stabilized the positive charge and created steric hindrance that deterred the equilibrium with analyte ions. F could not completely strip other compounds of their charge because they either showed steric hindrance at the charge site that deterred the approach of the dopant (2,4-lutidine, and DTBP), formed intramolecular bonds that stabilized the positive charge (atenolol), had high proton affinity (2,4-lutidine, DTBP, valinol and atenolol), or were inherently ionic (tetraalkylammonium ions). This selective deprotonation suggests the use of F to simplify spectra of complex mixtures in ion mobility and mass spectrometry in metabolomics, proteomics and other studies that generate complex spectra with thousands of peaks. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A detailed comparison of analysis processes for MCC-IMS data in disease classification—Automated methods can replace manual peak annotations

PubMed Central

Horsch, Salome; Kopczynski, Dominik; Kuthe, Elias; Baumbach, Jörg Ingo; Rahmann, Sven

2017-01-01

Motivation Disease classification from molecular measurements typically requires an analysis pipeline from raw noisy measurements to final classification results. Multi capillary column—ion mobility spectrometry (MCC-IMS) is a promising technology for the detection of volatile organic compounds in the air of exhaled breath. From raw measurements, the peak regions representing the compounds have to be identified, quantified, and clustered across different experiments. Currently, several steps of this analysis process require manual intervention of human experts. Our goal is to identify a fully automatic pipeline that yields competitive disease classification results compared to an established but subjective and tedious semi-manual process. Method We combine a large number of modern methods for peak detection, peak clustering, and multivariate classification into analysis pipelines for raw MCC-IMS data. We evaluate all combinations on three different real datasets in an unbiased cross-validation setting. We determine which specific algorithmic combinations lead to high AUC values in disease classifications across the different medical application scenarios. Results The best fully automated analysis process achieves even better classification results than the established manual process. The best algorithms for the three analysis steps are (i) SGLTR (Savitzky-Golay Laplace-operator filter thresholding regions) and LM (Local Maxima) for automated peak identification, (ii) EM clustering (Expectation Maximization) and DBSCAN (Density-Based Spatial Clustering of Applications with Noise) for the clustering step and (iii) RF (Random Forest) for multivariate classification. Thus, automated methods can replace the manual steps in the analysis process to enable an unbiased high throughput use of the technology. PMID:28910313

[Interview]: Alexandre Shvartsburg, Pacific Northwest National Laboratory, Richland, WA, USA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shvartsburg, Alexandre A.

2012-12-01

Q1. What are your main research activities in ion mobility mass spectrometry (past or present)? My early efforts focused on the structural characterization of atomic (carbon and semiconductor) clusters. After the production of bulk fullerenes, many hoped that other nanoclusters discovered in the gas phase could also coalesce into new materials. As these studies required accurate and robust mobility calculations for any ion geometry, I strived to build the needed theory and implement it in the Mobcal software widely employed today. Since 2004, I have been developing methods and novel applications of differential IMS (FAIMS) at PNNL. The principal achievementmore » has been raising the resolving power by over tenfold (up to ~400 for multiply-charged peptides) using elevated fields, helium and hydrogen-rich buffers, and extended filtering times. This performance broadly allows previously unthinkable separations of very similar species, for example sequence inversions and post-translational modification localization isomers of peptides (including “middle-down” peptides such as histone tails), lipid regioisomers, and even isotopomers. Another major direction is investigating the dipole alignment of larger proteins, which creates an exceptionally strong FAIMS effect that is a potential tool for structural biology. Q2: What have been the most significant instrumentation or applications developments in the history of ion mobility - mass spectrometry? In 1995 when I started graduate research at Northwestern, only two groups worldwide worked with IMS/MS and “the literature” meant papers by Bowers (UCSB). Well-wishers counseled me to “learn something useful like HPLC, as IMS would never have real utility”. This booklet showcases the scale of change since. First, the practical IMS/ToF platforms for complex biological analyses demonstrated by Clemmer have turned IMS/MS from an esoteric physical chemistry technique into a powerful analytical tool. By

Trypsin and MALDI matrix pre-coated targets simplify sample preparation for mapping proteomic distributions within biological tissues by imaging mass spectrometry

PubMed Central

Zubair, Faizan; Laibinis, Paul E.; Swisher, William G.; Yang, Junhai; Spraggins, Jeffrey M.; Norris, Jeremy L.; Caprioli, Richard M.

2017-01-01

Prefabricated surfaces containing α-cyano-4-hydroxycinnamic acid and trypsin have been developed to facilitate enzymatic digestion of endogenous tissue proteins prior to matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). Tissue sections are placed onto slides that were previously coated with α-cyano-4-hydroxycinnamic acid and trypsin. After incubation to promote enzymatic digestion, the tissue is analyzed by MALDI IMS to determine the spatial distribution of the tryptic fragments. The peptides detected in the MALDI IMS dataset were identified by Liquid chromatography-tandem mass spectrometry/mass spectrometry. Protein identification was further confirmed by correlating the localization of unique tryptic fragments originating from common parent proteins. Using this procedure, proteins with molecular weights as large as 300 kDa were identified and their distributions were imaged in sections of rat brain. In particular, large proteins such as myristoylated alanine-rich C-kinase substrate (29.8 kDa) and spectrin alpha chain, non-erythrocytic 1 (284 kDa) were detected that are not observed without trypsin. The pre-coated targets simplify workflow and increase sample throughput by decreasing the sample preparation time. Further, the approach allows imaging at higher spatial resolution compared with robotic spotters that apply one drop at a time. PMID:27676701

Ambient ionisation mass spectrometry for in situ analysis of intact proteins

PubMed Central

Kocurek, Klaudia I.; Griffiths, Rian L.

2018-01-01

Abstract Ambient surface mass spectrometry is an emerging field which shows great promise for the analysis of biomolecules directly from their biological substrate. In this article, we describe ambient ionisation mass spectrometry techniques for the in situ analysis of intact proteins. As a broad approach, the analysis of intact proteins offers unique advantages for the determination of primary sequence variations and posttranslational modifications, as well as interrogation of tertiary and quaternary structure and protein‐protein/ligand interactions. In situ analysis of intact proteins offers the potential to couple these advantages with information relating to their biological environment, for example, their spatial distributions within healthy and diseased tissues. Here, we describe the techniques most commonly applied to in situ protein analysis (liquid extraction surface analysis, continuous flow liquid microjunction surface sampling, nano desorption electrospray ionisation, and desorption electrospray ionisation), their advantages, and limitations and describe their applications to date. We also discuss the incorporation of ion mobility spectrometry techniques (high field asymmetric waveform ion mobility spectrometry and travelling wave ion mobility spectrometry) into ambient workflows. Finally, future directions for the field are discussed. PMID:29607564

The Effect of Collimating Lens Focusing on Laser Beam Shape in Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS)

NASA Astrophysics Data System (ADS)

O'Rourke, Matthew B.; Raymond, Benjamin B. A.; Djordjevic, Steven P.; Padula, Matthew P.

2018-03-01

Tissue imaging using matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a well-established technique that, in recent years, has seen wider adoption and novel application. Applications such imaging mass spectrometry (IMS) and biotyping are beginning to gain greater exposure and use; however, with limitations in optimization methods, producing the best result often relies on the ability to customize the physical characteristics of the instrumentation, a task that is challenging for most mass spectrometry laboratories. With this in mind, we have described the effect of making simple adjustments to the laser optics at the final collimating lens area, to adjust the laser beam size and shape in order to allow greater customization of the instrument for improving techniques such as IMS. We have therefore been able to demonstrate that improvements can be made without requiring the help of an electrical engineer or external funding in a way that only costs a small amount of time. [Figure not available: see fulltext.

The Effect of Collimating Lens Focusing on Laser Beam Shape in Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS).

PubMed

O'Rourke, Matthew B; Raymond, Benjamin B A; Djordjevic, Steven P; Padula, Matthew P

2018-03-01

Tissue imaging using matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a well-established technique that, in recent years, has seen wider adoption and novel application. Applications such imaging mass spectrometry (IMS) and biotyping are beginning to gain greater exposure and use; however, with limitations in optimization methods, producing the best result often relies on the ability to customize the physical characteristics of the instrumentation, a task that is challenging for most mass spectrometry laboratories. With this in mind, we have described the effect of making simple adjustments to the laser optics at the final collimating lens area, to adjust the laser beam size and shape in order to allow greater customization of the instrument for improving techniques such as IMS. We have therefore been able to demonstrate that improvements can be made without requiring the help of an electrical engineer or external funding in a way that only costs a small amount of time. Graphical Abstract ᅟ.

Development of a sensitive monitor for hydrazine

NASA Technical Reports Server (NTRS)

Eiceman, Gary A.; Limero, Thomas; James, John T.

1991-01-01

The development of hand-held, ambient-temperature instruments that utilize ion mobility spectrometry (IMS) in the detection of hydrazine and monomethylhydrazine is reviewed. A development effort to eliminate ammonia interference through altering the ionization chemistry, based on adding 5-nonanone as dopant in the ionization region of the IMS, is presented. Calibration of this instrument conducted before and after STS-37 revealed no more than a 5 percent difference between calibration curves, without any appreciable loss of equipment function.

High pressure effects in high-field asymmetric waveform ion mobility spectrometry.

PubMed

Wang, Yonghuan; Wang, Xiaozhi; Li, Lingfen; Chen, Chilai; Xu, Tianbai; Wang, Tao; Luo, Jikui

2016-08-30

High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) is an analytical technique based on the principle of non-linear electric field dependence of coefficient of mobility of ions for separation that was originally conceived in the Soviet Union in the early 1980s. Being well developed over the past decades, FAIMS has become an efficient method for the separation and characterization of gas-phase ions at ambient pressure, often in air, to detect trace amounts of chemical species including explosives, toxic chemicals, chemical warfare agents and other compounds. However the resolution of FAIMS and ion separation capability need to be improved for more applications of the technique. The effects of above-ambient pressure varying from 1 to 3 atm on peak position, resolving power, peak width, and peak intensity are investigated theoretically and experimentally using micro-fabricated planar FAIMS in purified air. Peak positions, varying with pressure in a way as a function of dispersion voltage, could be simplified by expressing both compensation and dispersion fields in Townsend units for E/N, the ratio of electric field intensity (E) to the gas number density (N). It is demonstrated that ion Townsend-scale peak positions remain unchanged for a range of pressures investigated, implying that the higher the pressure is, stronger compensation and separation fields are needed within limits of air breakdown field. Increase in pressure is found to separate ions that could not be distinguished in ambient pressure, which could be interpreted as the differentials of ions' peak compensation voltage expanded wider than the dilation of peak widths leading to resolving power enhancement with pressure. Increase in pressure can also result in an increase in peak intensity. Copyright © 2016 John Wiley & Sons, Ltd.

Enhanced direct ambient analysis by differential mobility-filtered desorption electrospray ionization-mass spectrometry.

PubMed

Galhena, Asiri S; Harris, Glenn A; Kwasnik, Mark; Fernández, Facundo M

2010-11-15

Desorption electrospray ionization (DESI) is rapidly becoming established as one of the most powerful ionization techniques allowing direct surface analysis by mass spectrometry (MS) in the ambient environment. DESI provides a significant number of unique analytical capabilities for a broad range of applications, both quantitative and qualitative in nature including biological tissue imaging, pharmaceutical quality control, in vivo analysis, proteomics, metabolomics, forensics, and explosives detection. Despite its growing adoption as a powerful high throughput analysis tool, DESI-MS analysis at trace levels often suffers from background chemical interferences generated during the electrospray ionization processes. In order to improve sensitivity and selectivity, a differential mobility (DM) ion separation cell was successfully interfaced to a custom-built DESI ion source. This new hybrid platform can be operated in two modes: the "DM-off" mode for standard DESI analysis and "DM-on mode" where DESI-generated ions are detected after discrimination by the differential mobility cell. The performance of the DESI-DM-MS platform was tested with several samples typically amenable to DESI analysis, including counterfeit pharmaceuticals and binary mixtures of isobaric chemicals of importance in the pharmaceutical and food industries. In the DM-on mode, DESI-MS signal-to-noise ratios were improved by 70-190% when compared to the DM-off mode. Also, the addition of the DM cell enabled selective in-source ion activation of specific DESI-generated precursor ions, providing tandem MS-like spectra in a single stage mass spectrometer.

Detection of chlorinated and brominated byproducts of drinking water disinfection using electrospray ionization-high-field asymmetric waveform ion mobility spectrometry-mass spectrometry.

PubMed

Ells, B; Barnett, D A; Froese, K; Purves, R W; Hrudey, S; Guevremont, R

1999-10-15

The lower limit of detection for low molecular weight polar and ionic analytes using electrospray ionization-mass spectrometry (ESI-MS) is often severely compromised by an intense background that obscures ions of trace components in solution. Recently, a new technique, referred to as high-field asymmetric waveform ion mobility spectrometry (FAIMS), has been shown to separate gas-phase ions at atmospheric pressure and room temperature. A FAIMS instrument is an ion filter that may be tuned, by control of electrical voltages, to continuously transmit selected ions from a complex mixture. This capability offers significant advantages when FAIMS is coupled with ESI, a source that generates a wide variety of ions, including solvent clusters and salt adducts. In this report, the tandem arrangement of ESI-FAIMS-MS is used for the analysis of haloacetic acids, a class of disinfection byproducts regulated by the US EPA. FAIMS is shown to effectively discriminate against background ions resulting from the electrospray of tap water solutions containing the haloacetic acids. Consequently, mass spectra are simplified, the selectivity of the method is improved, and the limits of detection are lowered compared with conventional ESI-MS. The detection limits of ESI-FAIMS-MS for six haloacetic acids ranged between 0.5 and 4 ng/mL in 9:1 methanol/tap water (5 and 40 ng/mL in the original tap water samples) with no preconcentration, derivatization, or chromatographic separation prior to analysis.

Integrating cell phones and mobile technologies into public health practice: a social marketing perspective.

PubMed

Lefebvre, Craig

2009-10-01

Mobile communications are being used for many purposes, from instant messaging (IM), mobile or microblogging (Twitter), social networking sites (Facebook, MySpace), e-mail to basic voicemail. A brief background on cell phone and mobile technology use in public health is reviewed. The focus of the article is framing the use of mobile technologies in public health from a social marketer's perspective--using the 4 Ps marketing mix as a guide.

Dynamic multiplexed analysis method using ion mobility spectrometer

DOEpatents

Belov, Mikhail E [Richland, WA

2010-05-18

A method for multiplexed analysis using ion mobility spectrometer in which the effectiveness and efficiency of the multiplexed method is optimized by automatically adjusting rates of passage of analyte materials through an IMS drift tube during operation of the system. This automatic adjustment is performed by the IMS instrument itself after determining the appropriate levels of adjustment according to the method of the present invention. In one example, the adjustment of the rates of passage for these materials is determined by quantifying the total number of analyte molecules delivered to the ion trap in a preselected period of time, comparing this number to the charge capacity of the ion trap, selecting a gate opening sequence; and implementing the selected gate opening sequence to obtain a preselected rate of analytes within said IMS drift tube.

Metabolism of the synthetic cannabinoids AMB-CHMICA and 5C-AKB48 in pooled human hepatocytes and rat hepatocytes analyzed by UHPLC-(IMS)-HR-MSE.

PubMed

Mardal, Marie; Dalsgaard, Petur Weihe; Qi, Bing; Mollerup, Christian Brinch; Annaert, Pieter; Linnet, Kristian

2018-04-15

The main analytical targets of synthetic cannabinoids are often metabolites. With the high number of new psychoactive substances entering the market, suitable workflows are needed for analytical target identification in biological samples. The aims of this study were to identify the main metabolites of the synthetic cannabinoids, AMB-CHMICA and 5C-AKB48, using an in silico-assisted workflow with analytical data acquired using ultra-high-performance liquid chromatography-(ion mobility spectroscopy)-high resolution-mass spectrometry in data-independent acquisition mode (UHPLC-(IMS)-HR-MS E ). The metabolites were identified after incubation with rat and pooled human hepatocytes using UHPLC-HR-MS E , followed by UHPLC-IMS-HR-MS E . Metabolites of AMB-CHMICA and 5C-AKB48 were predicted with Meteor (Lhasa Ltd) and imported to the UNIFI software (Waters). The predicted metabolites were assigned to analytical components supported by the UNIFI in silico fragmentation tool. The main metabolic pathway of AMB-CHMICA was O-demethylation and hydroxylation of the methylhexyl moiety. For 5C-AKB48, the main metabolic pathways were hydroxylation(s) of the adamantyl moiety and oxidative dechlorination with subsequent oxidation to the ω-COOH. The matrix components in the metabolite spectra were reduced with IMS, which improved the accuracy of the spectral interpretation; however, this left fewer fragment ions for assigning sites of metabolism. Meteor was able to predict the majority of the metabolites, with the most notable exception being the oxidative dechlorination and, consequently, all metabolites that underwent that transformation pathway. Oxidative dechlorination of ω-chloroalkanes in humans has not been previously reported in the literature. The postulated metabolites can be used for screening of biological samples, with four-dimensional identification based on retention time, collision cross section, precursor ion, and fragment ions. Copyright © 2018 Elsevier B.V. All

Luminescent Copper(I) Halide Butterfly Dimers Coordinated to [Au(CH3imCH2py)2]BF4 and [Au(CH3imCH2quin)2]BF4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catalano, V.; Moore, A; Shearer, J

2009-01-01

The coordination chemistry of copper(I) halides to the homoleptic, N-heterocyclic carbene Au(I) complexes [Au(CH{sub 3}imCH{sub 2}quin){sub 2}]BF{sub 4} and [Au(CH{sub 3}imCH{sub 2}py){sub 2}]BF{sub 4} was explored. The reaction of CuX (X = Cl, Br, I) with either [Au(CH{sub 3}imCH{sub 2}quin){sub 2}]BF{sub 4} or [Au(CH{sub 3}imCH{sub 2}py){sub 2}]BF{sub 4} produces trimetallic complexes containing Cu{sub 2}X{sub 2}-butterfly copper clusters coordinated to the two imine moieties. The triangular arrangement of the metals places the gold(I) center in close proximity ({approx}2.5-2.6 {angstrom}) to the centroid of the Cu-Cu vector. The Cu-Cu separations vary as a function of bridging halide with the shortest Cu-Cu separationsmore » of {approx}2.5 {angstrom} found in the iodo-complexes and the longest separations of 2.9 {angstrom} found in the bridging chloride complexes. In all six complexes the Au-Cu separations range from {approx}2.8 to 3.0 {angstrom}. In the absence of halides, the dimetallic complex [AuCu(CH{sub 3}imCH{sub 2}py){sub 2}(NCCH{sub 3}){sub 2}](BF{sub 4}){sub 2}, containing a long Au-Cu distance of {approx}4.72 {angstrom} is formed. Additionally, as the byproduct of the reaction of CuBr with [Au(CH{sub 3}imCH{sub 2}quin){sub 2}]BF{sub 4} the deep-red, dimetallic compound, AuCuBr{sub 2}(CH{sub 3}imCH{sub 2}quin){sub 2}, was isolated in very low yield. All of these complexes were studied by NMR spectroscopy, mass spectrometry, and the copper containing species were additionally characterized by X-ray crystallography. In solution the copper centers dissociate from the gold complexes, but as shown by XANES and EXAFS spectroscopy, at low temperature the Cu-Cu linkage is broken, and the individual copper(I) halides reposition themselves to opposite sides of the gold complex while remaining coordinated to one imine moiety. In the solid state all of the complexes are photoluminescent, though the nature of the excited state was not determined.« less

Microbial competition between Bacillus subtilis and Staphylococcus aureus monitored by imaging mass spectrometry

PubMed Central

Gonzalez, David J.; Haste, Nina M.; Hollands, Andrew; Fleming, Tinya C.; Hamby, Matthew; Pogliano, Kit; Nizet, Victor

2011-01-01

Microbial competition exists in the general environment, such as soil or aquatic habitats, upon or within unicellular or multicellular eukaryotic life forms. The molecular actions that govern microbial competition, leading to niche establishment and microbial monopolization, remain undetermined. The emerging technology of imaging mass spectrometry (IMS) enabled the observation that there is directionality in the metabolic output of the organism Bacillus subtilis when co-cultured with Staphylococcus aureus. The directionally released antibiotic alters S. aureus virulence factor production and colonization. Therefore, IMS provides insight into the largely hidden nature of competitive microbial encounters and niche establishment, and provides a paradigm for future antibiotic discovery. PMID:21719540

Characterization of chiral amino acids from different milk origins using ultra-performance liquid chromatography coupled to ion-mobility mass spectrometry

NASA Astrophysics Data System (ADS)

Tian, He; Zheng, Nan; Li, Songli; Zhang, Yangdong; Zhao, Shengguo; Wen, Fang; Wang, Jiaqi

2017-04-01

Milk contains free amino acids (AAs) that play essential roles in maintaining the growth and health of infants, and D-AA isomers are increasingly being recognized as important signalling molecules. However, there are no studies of the different characteristics of chiral AA (C-AA) from different milk origins. Here, UPLC coupled to ion-mobility high-resolution MS (IM-HRMS) was employed to characterize 18 pairs of C-AAs in human, cow, yak, buffalo, goat, and camel milk. The results proved that milk origins can be differentiated based on the D- to L- AA ratio-based projection scores by principal component analysis. The present study gives a deeper understanding of the D- to L- AA ratio underlying the biological functions of different animal milks, and provide a new strategy for the study of AA metabolic pathways.

A parallelization scheme of the periodic signals tracking algorithm for isochronous mass spectrometry on GPUs

NASA Astrophysics Data System (ADS)

Chen, R. J.; Wang, M.; Yan, X. L.; Yang, Q.; Lam, Y. H.; Yang, L.; Zhang, Y. H.

2017-12-01

The periodic signals tracking algorithm has been used to determine the revolution times of ions stored in storage rings in isochronous mass spectrometry (IMS) experiments. It has been a challenge to perform real-time data analysis by using the periodic signals tracking algorithm in the IMS experiments. In this paper, a parallelization scheme of the periodic signals tracking algorithm is introduced and a new program is developed. The computing time of data analysis can be reduced by a factor of ∼71 and of ∼346 by using our new program on Tesla C1060 GPU and Tesla K20c GPU, compared to using old program on Xeon E5540 CPU. We succeed in performing real-time data analysis for the IMS experiments by using the new program on Tesla K20c GPU.

Correlation of Mass Spectrometry Identified Bacterial Biomarkers From a Fielded Pyrolysis-Gas Chromatography-Ion Mobility Spectrometry Biodetector With the Microbiological Gram Stain Classification Scheme

DTIC Science & Technology

2005-09-01

Escherichia coliphage virus, and ovalbumnin (OV) protein species. The work suggests certain improvements that can be made to the IMS detection System...Escherichia coliphage virus, and ovalbumin (OV) protein species. However, the origin and structural identities of the pyrolyzate peaks observed in the GC-IMS...niger), Gram-negative Pantoea agglomerans ((EH) formerly Erwinia herbicola ), ovalbumin protein (OV), and the MS-2 Escherichia coliphage virus were

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simon, Anne-Laure; Choi, Chang Min; Clavier, Christian

This manuscript describes a new experimental setup that allows to perform tandem ion mobility spectrometry (IMS) measurements and which is coupled to a high resolution time-of-flight mass spectrometer. It consists of two 79 cm long drift tubes connected by a dual ion funnel assembly. The setup was built to permit laser irradiation of the ions in the transfer region between the two drift tubes. This geometry allows selecting ions according to their ion mobility in the first drift tube, to irradiate selected ions, and examine the ion mobility of the product ions in the second drift tube. Activation by collisionmore » is possible in the same region (between the two tubes) and between the second tube and the time-of-flight. IMS-IMS experiments on Ubiquitin are reported. We selected a given isomer of charge state +7 and explored its structural rearrangement following collisional activation between the two drift tubes. An example of IMS-laser-IMS experiment is reported on eosin Y, where laser irradiation was used to produce radical ions by electron photodetachment starting from doubly deprotonated species. This allowed measuring the collision cross section of the radical photo-product, which cannot be directly produced with an electrospray source.« less

Systematic profiling and comparison of the lipidomes from Panax ginseng, P. quinquefolius, and P. notoginseng by ultrahigh performance supercritical fluid chromatography/high-resolution mass spectrometry and ion mobility-derived collision cross section measurement.

PubMed

Shi, Xiaojian; Yang, Wenzhi; Qiu, Shi; Hou, Jinjun; Wu, Wanying; Guo, Dean

2018-05-04

Lipidomics currently is still confronted with challenges from chromatographic separation and lipids identification. Here we report a lipidomics platform by integrating ultrahigh performance supercritical fluid chromatography/quadrupole time-of-flight mass spectrometry (UHPSFC/QTOF-MS) and collision cross section (CCS) measurement using ion mobility spectroscopy/time-of-flight mass spectrometry (IMS/QTOF-MS), aiming to enhance the profiling performance and identification reliability of lipids. The lipidomes extracted from three congeneric Panax species (P. ginseng, P. quinquefolius, and P. notoginseng) by methyl tert-butyl ether are comprehensively profiled and compared by use of this platform. A potent UHPSFC/QTOF-MS approach was developed on a 1.7-μm particles packed Torus 2-PIC column using CH 3 OH (in CO 2 ) as a modifier and CH 3 OH/0.2 mM ammonium acetate as the makeup liquid, enabling well resolution of six lipid subclasses by both positive and negative MS E modes. In contrast to the reversed-phase chromatography, "normal-phase" like elution order and better resolution of polar lipids and some lipid isomers were achieved by UHPSFC separation. Pattern recognition chemometric analysis of 60 batches of Ginseng samples ultimately unveiled 24 lipid markers, of which triacylglycerols were the most important. Aside from the automated MS database searching against HMDB and LIPID MAPS, the application of CCS retrieval or CCS prediction improved lipid identification by reducing the possible hits. In conclusion, this integral platform can significantly improve the chromatographic separation and the reliability of lipids identification in lipidomics studies. It is the first report that systematically compares the lipidomic difference of three reputable Panax species, providing useful information for their quality control in addition to ginsenoside analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Risk analysis of information security in a mobile instant messaging and presence system for healthcare.

PubMed

Bønes, Erlend; Hasvold, Per; Henriksen, Eva; Strandenaes, Thomas

2007-09-01

Instant messaging (IM) is suited for immediate communication because messages are delivered almost in real time. Results from studies of IM use in enterprise work settings make us believe that IM based services may prove useful also within the healthcare sector. However, today's public instant messaging services do not have the level of information security required for adoption of IM in healthcare. We proposed MedIMob, our own architecture for a secure enterprise IM service for use in healthcare. MedIMob supports IM clients on mobile devices in addition to desktop based clients. Security threats were identified in a risk analysis of the MedIMob architecture. The risk analysis process consists of context identification, threat identification, analysis of consequences and likelihood, risk evaluation, and proposals for risk treatment. The risk analysis revealed a number of potential threats to the information security of a service like this. Many of the identified threats are general when dealing with mobile devices and sensitive data; others are threats which are more specific to our service and architecture. Individual threats identified in the risks analysis are discussed and possible counter measures presented. The risk analysis showed that most of the proposed risk treatment measures must be implemented to obtain an acceptable risk level; among others blocking much of the additional functionality of the smartphone. To conclude on the usefulness of this IM service, it will be evaluated in a trial study of the human-computer interaction. Further work also includes an improved design of the proposed MedIMob architecture. 2006 Elsevier Ireland Ltd

Learning on the Move: A Reassessment of Mobility through the Lens of Bateson's Learning Theory

ERIC Educational Resources Information Center

Janand, Anne; Notais, Amélie

2018-01-01

Purpose: This paper aims to explore the types of learning engendered by internal mobility (IM) by referring to the principles elaborated by Bateson (1972). Design/methodology/approach: A qualitative methodology is followed with interviews among 50 professionals working at four large French firms. Findings: A system of classification for IM is…

Visualisation of abscisic acid and 12-oxo-phytodienoic acid in immature Phaseolus vulgaris L. seeds using desorption electrospray ionisation-imaging mass spectrometry

NASA Astrophysics Data System (ADS)

Enomoto, Hirofumi; Sensu, Takuya; Sato, Kei; Sato, Futoshi; Paxton, Thanai; Yumoto, Emi; Miyamoto, Koji; Asahina, Masashi; Yokota, Takao; Yamane, Hisakazu

2017-02-01

The plant hormone abscisic acid (ABA) and the jasmonic acid related-compound 12-oxo-phytodienoic acid (OPDA) play crucial roles in seed development, dormancy, and germination. However, a lack of suitable techniques for visualising plant hormones has restricted the investigation of their biological mechanisms. In the present study, desorption electrospray ionisation-imaging mass spectrometry (DESI-IMS), a powerful tool for visualising metabolites in biological tissues, was used to visualise ABA and OPDA in immature Phaseolus vulgaris L. seed sections. The mass spectra, peak values and chemical formulae obtained from the analysis of seed sections were consistent with those determined for ABA and OPDA standards, as were the precursor and major fragment ions observed in tandem mass spectrometry (MS/MS) imaging. Furthermore, the precursor and fragment ion images showed similar distribution patterns. In addition, the localisation of ABA and OPDA using DESI-IMS was confirmed using liquid chromatography-MS/MS (LC-MS/MS). The results indicated that ABA was mainly distributed in the radical and cotyledon of the embryo, whereas OPDA was distributed exclusively in external structures, such as the hilum and seed coat. The present study is the first to report the visualisation of plant hormones using IMS, and demonstrates that DESI-IMS is a promising technique for future plant hormone research.

Visualisation of abscisic acid and 12-oxo-phytodienoic acid in immature Phaseolus vulgaris L. seeds using desorption electrospray ionisation-imaging mass spectrometry

PubMed Central

Enomoto, Hirofumi; Sensu, Takuya; Sato, Kei; Sato, Futoshi; Paxton, Thanai; Yumoto, Emi; Miyamoto, Koji; Asahina, Masashi; Yokota, Takao; Yamane, Hisakazu

2017-01-01

The plant hormone abscisic acid (ABA) and the jasmonic acid related-compound 12-oxo-phytodienoic acid (OPDA) play crucial roles in seed development, dormancy, and germination. However, a lack of suitable techniques for visualising plant hormones has restricted the investigation of their biological mechanisms. In the present study, desorption electrospray ionisation-imaging mass spectrometry (DESI-IMS), a powerful tool for visualising metabolites in biological tissues, was used to visualise ABA and OPDA in immature Phaseolus vulgaris L. seed sections. The mass spectra, peak values and chemical formulae obtained from the analysis of seed sections were consistent with those determined for ABA and OPDA standards, as were the precursor and major fragment ions observed in tandem mass spectrometry (MS/MS) imaging. Furthermore, the precursor and fragment ion images showed similar distribution patterns. In addition, the localisation of ABA and OPDA using DESI-IMS was confirmed using liquid chromatography-MS/MS (LC-MS/MS). The results indicated that ABA was mainly distributed in the radical and cotyledon of the embryo, whereas OPDA was distributed exclusively in external structures, such as the hilum and seed coat. The present study is the first to report the visualisation of plant hormones using IMS, and demonstrates that DESI-IMS is a promising technique for future plant hormone research. PMID:28211480

Post-column mobile phase adjustment: a strategy to eliminate the contradiction between liquid chromatography and mass spectrometry in the determination of flavonoids in rat plasma.

PubMed

Zheng, Shirui; Ma, Zhiyuan; Han, Haixia; Ye, Jianfeng; Wang, Ruwei; Cai, Sheng; Zhou, Hui; Yu, Lushan; Zeng, Su; Jiang, Huidi

2014-07-01

Flavonoids are a group of important naturally occurring polyphenolic compounds with a wide range of biological effects. In this study, a sensitive liquid chromatography tandem mass spectrometry method was developed to simultaneously determine multiple active flavonoids, including quercetin (Que), kaempferol (Kae), apigenin (Api), isorhamnetin (Iso), luteolin (Lut), and naringenin (Nar), in rat plasma. To achieve a satisfied peak shape and LC separation, formic acid with the concentration between 0.05 and 0.2%, or in some case 5%, was generally used to acidify the LC mobile phase in reported studies. Here we found that even 0.05% formic acid could lead to strong mass signal suppression, and the absence of formic acid could reverse the signal suppression but cause serious peak tailing. There is an irreconcilable contradiction between liquid chromatography (LC) and mass spectrometry (MS). In order to simultaneously satisfy LC and MS, LC mobile phase with 0.00075% formic acid and post column mobile phase adjustment with 0.0677% ammonium solution in isopropanol were applied. Compared with the conventional method with mobile phase containing 0.05% formic acid, the mass signal response of Que, Kae, Api, Iso, Lut, Nar, and Oka increased 26.2, 18.6, 13.6, 23.5, 17.5, 15.6 and 15.4 fold, respectively. In addition, the post column mobile phase addition exhibited the better peak shape for the reduction of analytes longitudinal diffusion. The method has been fully validated according to FDA guidelines within the linear range between 0.328 ng mL⁻¹ and 168 ng mL⁻¹, and successfully applied to a pilot pharmacokinetic study of rats after administering 5.43 g kg⁻¹ Pollen of Brassica campestris. Copyright © 2014 Elsevier B.V. All rights reserved.

Ammonium Sulfate Improves Detection of Hydrophilic Quaternary Ammonium Compounds through Decreased Ion Suppression in Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry.

PubMed