Paired Ion Research Articles

Chudakov effect for the most probable value of high-energy electron–positron pair ionization loss in thin targets

The ionization loss of a high-energy electron–positron pair in thin targets is considered. The targets not thinner than about 10 upmu m are discussed. The analogue of the Landau distribution function is derived for this loss under the condition when the Chudakov effect of the pair ionization loss suppression is manifested. Expression for the most probable value of the pair ionization loss E_{MP} is obtained. It is shown that the magnitude of Chudakov effect for E_{MP} can be noticeably different from the magnitude of this effect for the restricted mean value of the pair ionization loss.

Investigation on the electronic structures of thiamine and related compounds: Free base or salt?

We report the simulated photoelectron spectra of thiamine free base, thiamine and thiamine diphosphate (ThDP) in the gas phase. The structures of eighty conformers of thiamine (vitamin B1) were optimized by DFT method at the B3LYP/6-31+G(d) level. Then population ratios (PRS) with Boltzmann distribution equation were calculated using Gibbs free energy and the stable conformers were obtained. The ionization energies of these conformers were determined by two high-level computational methods. General-R-symmetry adapted cluster-configuration interaction (general-R-SAC-CI) method and electron-propagator theory (EPT) method were used to obtain vertical valence ionization energies (IP). To characterize the nature of ionization processes about different spectral bands, the natural bonding orbital (NBO) method was used to obtain orbital electron densities. The electron correlation was taken into account with SAC-CI method and MOs shapes and ionization assignments given for each spectral band. Results for ThDP show that spectra of two conformers are different: oxygen lone pair ionizations appear at higher ionization energies in the spectrum of conformer II while giving rise to the first ionization band in conformer I. The validity of Koopmans’s approximation was considered for each ionization band and the role of electron correlation was attributed to breaking down of this approximation. The implications of electronic structure results for biological activity of thiamin are discussed. Comparison with the earlier work using aerosol thermodesorption method suggests that free base was present in their photoionization spectra in addition to the deprotonated cation.

Low threshold acquisition controller for Skipper charge-coupled devices

The development of the Skipper-charge-coupled devices (Skipper-CCDs) has been a major technological breakthrough for sensing very weak ionizing particles. The sensor allows to reach the ultimate sensitivity of silicon material as a charge signal sensor by unambiguous determination of the charge signal collected by each cell or pixel, even for single electron–hole pair ionization. Extensive use of the technology was limited by the lack of specific equipment to operate the sensor at the ultimate performance. A simple, single-board Skipper-CCD controller designed by the authors is presented and aimed for the operation of the detector in high sensitivity scientific applications. Our article describes the main components and functionality of the so-called low threshold acquisition controller together with experimental results when connected to a Skipper-CCD sensor. Measurements show unprecedented deep subelectron noise of 0.039 erms−/pix by nondestructively measuring the charge 5000 times in each pixel.

Photoelectron spectroscopy of 5,12-diazatetracene

The electronic structure of 5,12-diazatetracene (DAT) has been studied in the gas phase by UV photoelectron spectroscopy and quantum chemical calculations. The comparison of DAT spectrum with the of spectrum tetracene (TC) shows the shift of outermost π-ionizations towards higher ionization energies and the appearance of nitrogen lone pair ionizations in the second and third spectral bands. The difference between nitrogen lone pair ionization energies is smaller in DAT compared to diaza analogues containing up to three fused rings. The implications for semiconductor properties are discussed.

PipeIT: A Singularity Container for Molecular Diagnostic Somatic Variant Calling on the Ion Torrent Next-Generation Sequencing Platform

The accurate identification of somatic mutations has become a pivotal component of tumor profiling and precision medicine. In molecular diagnostics laboratories, somatic mutation analyses on the Ion Torrent sequencing platform are typically performed on the Ion Reporter platform, which requires extensive manual review of the results and lacks optimized analysis workflows for custom targeted sequencing panels. Alternative solutions that involve custom bioinformatics pipelines involve the sequential execution of software tools with numerous parameters, leading to poor reproducibility and portability. We describe PipeIT, a stand-alone Singularity container of a somatic mutation calling and filtering pipeline for matched tumor-normal Ion Torrent sequencing data. PipeIT is able to identify pathogenic variants in BRAF, KRAS, PIK3CA, CTNNB1, TP53, and other cancer genes that the clinical-grade Oncomine workflow identified. In addition, PipeIT analysis of tumor-normal paired data generated on a custom targeted sequencing panel achieved 100% positive predictive value and 99% sensitivity compared with the 68% to 80% positive predictive value and 92% to 96% sensitivity using the default tumor-normal paired Ion Reporter workflow, substantially reducing the need for manual curation of the results. PipeIT can be rapidly deployed to and ensures reproducible results in any laboratory and can be executed with a single command with minimal input files from the users.

Anomalous ionization loss of high-energy e+e− pairs in thin targets

The problem of ionization loss of a high-energy electron-positron pair in a system of two plates – thick upstream, in which the pair is created, and thin downstream – is considered. It is shown that the process of transition radiation formation after the pair emission from the upstream plate significantly influences upon its ionization loss in the downstream plate. The consideration is made without the use of approximation of parallel electron and positron velocities which is widely applied for calculation of pair ionization loss. It is demonstrated that such approach reveals new peculiar features of asymptotical behavior of ionization loss in this process at large distance between the plates.

Measurement of the gamma-ray energy spectrum of the educational Kinki University Reactor (UTR-KINKI)

The gamma-ray energy spectrum of the Kinki University Reactor (UTR-KINKI) was estimated from Ge detector measurements combined with Monte Carlo N-particle transport criticality calculations. The gamma rays mainly originated from prompt fission components, although small amounts of gamma rays from (n,γ) reactions, fission product gamma rays, and activation gamma rays were detected. The averaged gamma-ray tissue kerma rate in the irradiation port during UTR-KINKI operation at 1W was calculated as 10.5cGy/h based on the estimated gamma-ray energy spectrum. This value is consistent with a previous measurement with paired ionization chambers and a tissue equivalent gas proportional counter. This result demonstrates the reliability of the estimated gamma-ray energy spectrum.

Reduced matrix effects for anionic compounds with paired ion electrospray ionization mass spectrometry

It is well-known that matrix effects in high performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS) can seriously compromise quantitative analysis and affect method reproducibility. Paired ion electrospray ionization (PIESI) mass spectrometry is an approach for analyzing ultra-low levels of anions in the positive ion mode. This approach uses a structurally optimized ion pairing reagent to post-column associate with the anionic analyte, subsequently forming positively charged complexes. These newly formed complex ions are often more surface-active as compared to either the native anion or the ion pairing reagent. No studies have examined whether or not the PIESI approach mitigates matrix effects. Consequently, a controlled study was done using five analytes in highly controlled and reproducible synthetic groundwater and urine matrices. In addition, two different mass spectrometers (linear ion trap and triple quadrupole) were used. Compared to the negative ion mode, the PIESI-MS approach was less susceptible to matrix effects when performed on two different MS platforms. Using PIESI-MS, less dilution of the sample is needed to eliminate ionization suppression which, in turn, permits lower limits of detection and quantitation.

Sensitive detection of anionic metabolites of drugs by positive ion mode HPLC-PIESI-MS

The detection window for drugs of abuse, including performance-enhancing drugs, is limited by the sensitivity of analytical methodologies. Herein, paired ion electrospray ionization mass spectrometry (PIESI-MS) was employed for sensitive analysis of performance-enhancing drugs and drugs of abuse by detecting their glucuronide and sulfate conjugates. The proposed approach provides enhanced sensitivity for these drug metabolites, and overcomes the drawbacks of the less sensitive negative ion mode ESI-MS by detecting the anionic metabolites in the positive ion mode at higher m/z where the background noise is less. Absolute LODs down to sub-pg levels were obtained with the use of the optimal symmetrical or unsymmetrical ion pairing reagents. One to three orders of magnitude improvement were obtained compared to other reported methods performed in the negative ion mode. Structurally similar steroid conjugates were chromatographically separated and detected by HPLC coupled with PIESI-MS. Finally, an off-line solid phase extraction (SPE) protocol was successfully developed to eliminate any matrix effects in the analysis of human urine samples.

Molar conductivities of concentrated lithium chloride–glycerol solutions at low and high temperatures: application of a quasi-lattice model

Conductivities of concentrated solutions of lithium chloride in glycerol were measured for concentrations ranging from 0.005 to 1.5 mol.dm−3. The conductivity dependencies were analysed successively using the Debye–Huckel–Onsager limiting law (DHO) at very low concentrations, the Fuoss equation of 1978 up to 0.1 mol.dm−3, the Casteel–Amis empirical equation and the quasi-lattice model (QLM) at moderate and higher concentrations. The molar conductivities at infinite dilution, obtained using DHO and QLM were quite different from each other, because the salt forms contact pairs which were underestimated in the Λ = f(C1/3) in QLM, as it may well be proved by Raman spectroscopy. Besides, the value of Madelung constant suggests that LiCl crystallises face centred cubic (FCC) at higher concentrations. On the basis of Raman spectroscopy analysis of previous lithium salts, we assume that the dissociation coefficient varies slightly with concentration and fraction of paired ion constant, the QLM equation is applied successfully in the concentration range used in this study. The temperature dependency of conductivity was also described using the Vogel–Tamman–Fulcher (VTF) empirical equation where the Arrhenius type was found. The results also suggest that as NaCl, LiCl can be considered as a structure maker electrolyte.

Paired-ion electrospray ionization – triple quadrupole tandem mass spectrometry for quantification of anionic surfactants in waters

A new paired ion electrospray ionization tandem mass spectrometry method for determination of anionic surfactants in water samples was developed. In this method, dicationic ion-pairing reagents were complexed with monoanionic analytes to facilitate analyte detection in positive mode electrospray ionization – mass spectrometry. Single ion monitoring and selected reaction monitoring on a triple quadrupole instrument were performed and compared. Four dicationic reagents were tested for the determination of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), sodium dodecyl sulfate (SDS), dodecylbenzene sulfonic acid (DBS), and stearic acid (SA), among other common anions. The obtained limits of detection were compared with those from previous literature. Solid phase extraction using a C18 cartridge was performed in order to eliminate matrix interferences. A literature review was compiled for the methods published between 2010 and 2015 for determination of anionic surfactants. The optimized method was more sensitive than previously developed methods with LOD values of 2.35, 35.4, 37.0, 1.68, and 0.675pg for SDS, SA, DBS, PFOS, and PFOA, respectively. The developed method was effectively applied for the determination of anionic surfactants in different water samples such as bottled drinking water, cooking water, tap water, and wastewater.

Improved Accuracy of Proteome Quantification by MS/MS Fragment Intensity

Quantitative proteomics facilitates the discovery of potential biomarkers. Development of novel algorithms to improve the accuracy of proteome quantification is of vital importance. MS/MS fragment intensity has arisen as a novel abundance feature with unique advantages.In isobarically labelled proteome samples, the increase of MS/MS spectra complexity has adverse effect on the identification and coverage of quantification. A paired ion based scoring algorithm (PISA) based on Morpheus, was proposed to address this issue by scoring the matches using the number plus the fraction of intensity of matched paired ions. It was applied to the identification of Lys‐C digest of protein samples isobarically labelled with two different strategies involving both in‐vivo and chemical labeling. Compared to commercially available and open source software Mascot and Morpheus, more peptide spectrum matches, distinct peptides, and proteins can be identified at a 1% false discovery rate with the increase ranging from 22 % to 60 %. Moreover, 100% quantification coverage was achieved.Summed MS/MS Total ion current (SMT) cumulates all fragment intensities of all MS/MS spectra assigned to a protein. Spectral count in Absolute Protein Expression profiling (APEX) algorithm was replaced by SMT to enhance the accuracy of absolute quantification of proteomes in label‐free manner. The combination of APEX and SMT (abbreviated as APEX‐SMT) was capable of improving the accuracy of absolute quantification by reducing the average relative deviation by ~55‐85% compared to that of APEX, through a series of tests on Universal Proteomics Standard sample with a dynamic range of 5 orders of magnitude (UPS2).

The influence of non-parallelism of electron and positron velocities upon high-energy e+e− pair ionization loss in thin plate

The problem of high-energy electron–positron pair ionization loss in thin plate is considered. It is shown that in this case the approximation of parallel electron and positron velocities which is usually used for calculation of pair ionization loss may not be strictly valid and the existence of non-zero angle of pair divergence can lead to slight suppression of the Chudakov effect of pair ionization loss reduction. The conditions under which such suppression has noticeable value are discussed.

Selective paired ion contrast analysis: a novel algorithm for analyzing postprocessed LC-MS metabolomics data possessing high experimental noise.

One of the consequences in analyzing biological data from noisy sources, such as human subjects, is the sheer variability of experimentally irrelevant factors that cannot be controlled for. This holds true especially in metabolomics, the global study of small molecules in a particular system. While metabolomics can offer deep quantitative insight into the metabolome via easy-to-acquire biofluid samples such as urine and blood, the aforementioned confounding factors can easily overwhelm attempts to extract relevant information. This can mar potentially crucial applications such as biomarker discovery. As such, a new algorithm, called Selective Paired Ion Contrast (SPICA), has been developed with the intent of extracting potentially biologically relevant information from the noisiest of metabolomic data sets. The basic idea of SPICA is built upon redefining the fundamental unit of statistical analysis. Whereas the vast majority of algorithms analyze metabolomics data on a single-ion basis, SPICA relies on analyzing ion-pairs. A standard metabolomic data set is reinterpreted by exhaustively considering all possible ion-pair combinations. Statistical comparisons between sample groups are made only by analyzing the differences in these pairs, which may be crucial in situations where no single metabolite can be used for normalization. With SPICA, human urine data sets from patients undergoing total body irradiation (TBI) and from a colorectal cancer (CRC) relapse study were analyzed in a statistically rigorous manner not possible with conventional methods. In the TBI study, 3530 statistically significant ion-pairs were identified, from which numerous putative radiation specific metabolite-pair biomarkers that mapped to potentially perturbed metabolic pathways were elucidated. In the CRC study, SPICA identified 6461 statistically significant ion-pairs, several of which putatively mapped to folic acid biosynthesis, a key pathway in colorectal cancer. Utilizing support vector machines (SVMs), SPICA was also able to unequivocally outperform binary classifiers built from classical single-ion feature based SVMs.

Monte Carlo simulations and benchmark measurements on the response of TE(TE) and Mg(Ar) ionization chambers in photon, electron and neutron beams

The paired ionization chambers (ICs) technique is commonly employed to determine neutron and photon doses in radiology or radiotherapy neutron beams, where neutron dose shows very strong dependence on the accuracy of accompanying high energy photon dose. During the dose derivation, it is an important issue to evaluate the photon and electron response functions of two commercially available ionization chambers, denoted as TE(TE) and Mg(Ar), used in our reactor based epithermal neutron beam. Nowadays, most perturbation corrections for accurate dose determination and many treatment planning systems are based on the Monte Carlo technique. We used general purposed Monte Carlo codes, MCNP5, EGSnrc, FLUKA or GEANT4 for benchmark verifications among them and carefully measured values for a precise estimation of chamber current from absorbed dose rate of cavity gas. Also, energy dependent response functions of two chambers were calculated in a parallel beam with mono-energies from 20keV to 20MeV photons and electrons by using the optimal simple spherical and detailed IC models. The measurements were performed in the well-defined (a) four primary M-80, M-100, M120 and M150 X-ray calibration fields, (b) primary 60Co calibration beam, (c) 6MV and 10MV photon, (d) 6MeV and 18MeV electron LINACs in hospital and (e) BNCT clinical trials neutron beam. For the TE(TE) chamber, all codes were almost identical over the whole photon energy range. In the Mg(Ar) chamber, MCNP5 showed lower response than other codes for photon energy region below 0.1MeV and presented similar response above 0.2MeV (agreed within 5% in the simple spherical model). With the increase of electron energy, the response difference between MCNP5 and other codes became larger in both chambers. Compared with the measured currents, MCNP5 had the difference from the measurement data within 5% for the 60Co, 6MV, 10MV, 6MeV and 18MeV LINACs beams. But for the Mg(Ar) chamber, the derivations reached 7.8–16.5% below 120kVp X-ray beams. In this study, we were especially interested in BNCT doses where low energy photon contribution is less to ignore, MCNP model is recognized as the most suitable to simulate wide photon–electron and neutron energy distributed responses of the paired ICs. Also, MCNP provides the best prediction of BNCT source adjustment by the detector’s neutron and photon responses.

Mechanism and Sensitivity of Anion Detection Using Rationally Designed Unsymmetrical Dications in Paired Ion Electrospray Ionization Mass Spectrometry

Paired ion electrospray ionization (PIESI) mass spectrometry was developed as a useful technique that provides sensitive detection for anions in the positive ion mode. The ion-pairing reagent (IPR) utilized plays an essential role affecting the detection limits. This work describes the design and synthesis of two novel dications with unsymmetrical structures and their utilization for anion detection and mechanistic insights. The performance of dications was evaluated for seven selected anions in both single ion monitoring (SIM) mode and selected reaction monitoring (SRM) mode. The unsymmetrical dications allowed sensitive detection for these anions with down to subpicogram limits of detection (LOD) and an improved sensitivity from 1.5 to 12 times compared to the corresponding symmetrical dications. The enhanced sensitivity could be attributed to the surface activity of the unsymmetrical dications, which results in a concurrent strong partitioning of the anion to the aerosol droplet surface. Surface activity measurements of the anion/IPR complex were conducted, and a correlation between the observed ESI responses and the surface activity of the complex was found. The mechanism was further explored and explained based on the concepts of the equilibrium partitioning model (EPM).

Separation and sensitive determination of sphingolipids at low femtomole level by using HPLC-PIESI-MS/MS

A highly sensitive paired ion electrospray ionization mass spectrometry (PIESI-MS) approach was developed for the trace determination of sphingolipids. Apart from their structure role, specific sphingolipids can play a role in cell signaling and as disease markers. With the optimal pairing reagents, detection limits ranged from low femtomole to picomole levels for 14 selected sphingolipids. This improved the detection sensitivity of ESI-MS for many of these analytes up to ~4000 times.

Anti-Chudakov effect in high-energy electron–positron pair ionization loss in thin target

Abstract The problem of electron–positron pair ionization loss on different distances from its creation point in substance is considered. It is shown that together with the Chudakov effect of pair loss reduction the opposite effect of exceeding by the pair loss of the doubled value of single electron (positron) loss may take place. It is demonstrated that for pair ionization loss in the same substance where the pair is created such effect is rather small but can enhance by the order of magnitude if consider the pair loss in thin plate situated in the direction of pair motion on some distance from this substance. It is pointed out that such effect should be most significant at relatively low pair energies of several hundreds MeV.

On ionization energy losses of high-energy electron–positron pair in thin targets

The present Letter deals with consideration of high-energy electron–positron pair ionization losses in thin dielectric plate which it traverses after being emitted from substance where it is created. It is shown that in this case the Chudakov effect of reduction of pair energy losses takes place on much larger distance from its creation point than in the case of the pair motion in homogeneous infinite medium. It is demonstrated that due to transition radiation which appears during the pair emission from the substance the ratio of the pair energy losses in two plates situated on different distances from it is noticeably different from the case when the radiation is neglected.

High-performance liquid chromatography with paired ion electrospray ionization (PIESI) tandem mass spectrometry for the highly sensitive determination of acidic pesticides in water

A novel method based on the paired ion electrospray ionization (PIESI) mass spectrometry has been developed for determination of acidic pesticides at ultratrace levels in surface and ground waters. The proposed approach provides greatly enhanced sensitivity for acidic pesticides and overcomes the drawbacks of the less sensitive negative ion mode ESI-MS. The limits of detection (LODs) of 19 acidic pesticides were evaluated with four types of dicationic ion-pairing reagent (IPR) in both single ion monitoring (SIM) and selected reaction monitoring (SRM) mode. The LOD of 19 pesticides obtained with the use the optimal dicationic ion-pairing reagent ranged from 0.6pg to 19pg, indicating the superior sensitivity provided by this method. The transition pathways for different pesticide-IPR complexes during the collision induced dissociation (CID) were identified. To evaluate and eliminate any matrix effects and further decrease the detection limits, off-line solid-phase extraction (SPE) was performed for DI water and a river water matrix spiked with 2000ngL−1 and 20ngL−1 pesticides standards respectively, which showed an average percent recovery of 93%. The chromatographic separation of the acidic pesticides was conducted by high-performance liquid chromatography (HPLC) using a C18 column (250mm×2.1mm) in the reversed phase mode using linear gradient elution. The optimized HPLC–PIESI-MS/MS method was utilized for determination of acidic pesticide at ngL−1 level in stream/pond water samples. This experimental approach is 1–3 orders of magnitude more sensitive for these analytes than other reported methods performed in the negative ion mode.