Effect of Humidity on the Mobilities of Small Ions in Ion Mobility Spectrometry.

Ions in the ion mobility spectrometry (IMS) are mostly hydrated. A single peak in the drift time spectrum is usually generated by a mixture of ions differing in the number of attached water molecules. Under real IMS detector operating conditions, ions change their composition during movement in the drift region due to the changes in the number of water molecules attached to the ion. The impact of water vapor on the drift times of small ions at different temperatures was studied experimentally using an ion mobility spectrometer. The experiments were carried out for hydronium, ammonium, oxygen, chloride, bromide, and iodide ions. A theoretical model was developed, allowing us to calculate the effective mobility of ions for a given concentration of water vapor and temperature. The basic assumption adopted in this model was the linear dependence of the effective mobility coefficient on the mobility of ions with a certain degree of hydration. The weighting factors in this relationship are the abundances of individual types of ions. These parameters were determined by calculations based on the thermodynamics of the formation and disintegration of ionic clusters. From the known values of temperature, pressure, and humidity, the values of effective mobilities can be predicted quite accurately. The dependencies of reduced mobilities on the average degree of hydration were also determined. For these dependencies, the measurement points on the graphs are gathered along specific lines. This means that the average degree of hydration unambiguously determines the value of reduced mobility for a given type of ions.

Negative-mode ion mobility spectrometry-comparison of ion-molecule reactions and electron capture processes.

The presented work concerns the impact of ionization mechanisms of analytes on detection sensitivity in negative-mode ion mobility spectrometry. The main part of the work is research conducted for selected organic analytes using DT IMS in the negative mode of operation. In the negative mode of detection, two ionization mechanisms can be used: electron capture and ion-molecule reactions. The type of ionization mechanism depends on the carrier gas. The tests were carried out using two carrier gases: air and nitrogen. This allowed for a comparison of the ionization of analytes in the ion-molecule reaction mode with ionization in electron capture mode. Experiments were carried out for tetrachloromethane, trichloromethane, benzyl chloride, 1-chlorobutane, 1-chlorohexane, 1-chloropentane, tetrachlorethylene, 1-bromobutane, 1-bromopentane, 1-bromohexane, hexafluorobenzene, 2-chloroethyl ethyl sulfide (CEES), and methyl salicylate. Most of the tested substances were ionized with the formation of ionized halogen atoms (Br- or Cl-). It was found that among the tested substances, there are those whose effective ionization is possible with the use of both nitrogen and air as carrier gases, those ionized only in electron capture mode or in ion-molecule reaction mode. The important part of the work was an investigation on the effect of oxygen and water admixtures in carrier gases on the detection efficiency of selected organic compounds.

First case series of Polish patients with cerebrotendinous xanthomatosis and systematic review of cases from the 21st century.

Cerebrotendinous xanthomatosis (CTX) is an inborn error of metabolism caused by recessive variants in the cytochrome P450 CYP27A1 gene. CTX is said to manifest with childhood-onset chronic diarrhea and the classic triad of juvenile-onset cataracts, Achilles tendons xanthomas, and progressive ataxia. It is currently one of the few inherited neurometabolic disorders amenable to a specific treatment. The diagnosis may be significantly delayed resulting in permanent neurological impairment. A retrospective review of the clinical characteristics and diagnostic findings in case series of six Polish patients with CTX. Additional retrospective review of symptoms and pathogenic variants of 568 CTX available cases and case series from the past 20 years. To the best of our knowledge, this is the widest review of CTX cases reported in years 2000-2021. We report the largest cohort of Polish patients ever published, with the identification of two hot-spot mutations. During the review of available 568 cases, we found significant differences in the clinical phenotypes and the localization of variants within the gene between Asian and non-Asian populations. These findings may facilitate molecular testing in the Polish and Asian populations. Invariably better screening for CTX and wider awareness is needed.

Immune Dysregulation in Patients With Chromosome 18q Deletions-Searching for Putative Loci for Autoimmunity and Immunodeficiency.

Introduction: Autoimmune disorders, IgA deficiency, and allergies seem to be common among individuals with 18q deletion syndrome [OMIM 601808]. We aimed to determine the prevalence, mechanism, and genetic background of autoimmunity, immune deficiency, and allergy in a cohort of patients with 18q deletions. Material and Methods: Medical registries and social media were used to recruit the patients. Microarray oligonucleotide comparative genomic hybridization (aCGH) (Agilent, Santa Clara, CA, USA) was performed in all patients to identify size and location of chromosome 18 deletion. Clinical evaluation and medical record collection were performed in each of the study participants. The history of autoimmune disorders, severe and/or recurrent infections, and symptoms of allergy were noted. Total immunoglobulin IgG, IgA, IgM, IgE, and IgG1-4 serum levels were measured using nephelometry and ELISA methods. Lymphocyte T subset phenotyping was performed in 24 subjects from 18q del cohort. To predict the most promising candidate genes, we used the ENDEAVOUR-a free web resource for gene prioritization. Results: 18q deletion was confirmed by means of array CGH analysis in 27 individuals, 15 (55.6%) females and 12 males, referred to the project by specialists in medical genetics, diabetology, or pediatric endocrinology between May 2015 and December 2019. The mean age at examination was 11.8 years (min-max: 4.0-33.5). Autoimmune disorders were present in 14/27 (51.8%) of the cohort. In eight of patients, symptoms of immune deficiency coexisted with autoimmunity. Allergy was reported in nine of 27 (33.4%) patients. Over 89% of patients presented with at list one type of immunoglobulin (IgA, IgM, IgG, IgE, and IgG1-4) deficiency and eight of 25 (32%) had abnormalities in at least two major immunoglobulin (IgG, IgA, IgM) measurements (CVID-like phenotype). Patients with 18q del exhibited a significantly decreased CD4, Treg FOXP3+, TregFOXP3+Helios+, and TemCD4 cell numbers in comparison with the control groups of 24 T1DM patients and 28 healthy controls. Conclusions: Patients with 18q deletions frequently suffer from autoimmune disorders, recurrent infections, and allergy due to immune dysregulation presenting with variable antibody deficiencies and T-regulatory cell deficiency (CD4+CD25+CD127lowFOXP3+). The spectrum of speculations regarding which gene might be responsible for such phenotype ranges from single gene haploinsufficiency to deletion of a cluster of immunogenes located distally to 18q21.

Exome Sequencing Reveals Novel Variants and Expands the Genetic Landscape for Congenital Microcephaly.

Congenital microcephaly causes smaller than average head circumference relative to age, sex and ethnicity and is most usually associated with a variety of neurodevelopmental disorders. The underlying etiology is highly heterogeneous and can be either environmental or genetic. Disruption of any one of multiple biological processes, such as those underlying neurogenesis, cell cycle and division, DNA repair or transcription regulation, can result in microcephaly. This etiological heterogeneity manifests in a clinical variability and presents a major diagnostic and therapeutic challenge, leaving an unacceptably large proportion of over half of microcephaly patients without molecular diagnosis. To elucidate the clinical and genetic landscapes of congenital microcephaly, we sequenced the exomes of 191 clinically diagnosed patients with microcephaly as one of the features. We established a molecular basis for microcephaly in 71 patients (37%), and detected novel variants in five high confidence candidate genes previously unassociated with this condition. We report a large number of patients with mutations in tubulin-related genes in our cohort as well as higher incidence of pathogenic mutations in MCPH genes. Our study expands the phenotypic and genetic landscape of microcephaly, facilitating differential clinical diagnoses for disorders associated with most commonly disrupted genes in our cohort.

Studies on the Processes of Electron Capture and Clustering of Benzyl Chloride by Ion Mobility Spectrometry.

This paper presents the results of the study on the course of the benzyl chloride (BzCl) ionization process in a drift tube ion mobility spectrometer (DT IMS) in which nitrogen was used as the carrier gas. BzCl ionization follows the dissociative electron capture mechanism. The chloride ions produced in this process take part in the formation of cluster ions. Using DT IMS allows for estimation of the value of the electron attachment rate for BzCl and the equilibrium constant for the cluster ion formation. The basic experimental method used in this work was to analyze drift time spectra obtained for the introduction of the sample to the spectrometer with the drift gas. The theoretical interpretation of the results is based on the mathematical description of the ion transport. This description takes into account the phenomenon of diffusion, as well as the processes of formation and dissociation of ionic clusters occurring during the movement of ions in the drift section.

Broad phenotypic spectrum of germ line 7p12.1 microdeletions encompassing the IKZF1 gene includes predisposition to acute lymphoblastic leukemia.

Microdeletions of 7p12.1 encompassing the IKZF1 gene locus are rare, with few cases reported. The common phenotype includes intellectual disability, overgrowth, and facial dysmorphism accompanied, albeit rarely, by congenital anomalies. Haploinsufficiency of IKZF1 predisposes individuals to childhood acute lymphoblastic leukemia (ALL). In this study, we comprehensively analyzed the frequency of 7p12.1 deletions among 4581 Polish individuals who underwent chromosomal microarray testing for unexplained developmental delay, intellectual disability, and/or congenital anomalies. Two unrelated individuals (0.04%) with a de novo interstitial 7p12.1 microdeletion encompassing IKZF1 were identified. One developed ALL. Analysis of the incidence and the phenotype of constitutional 7p12.1 microdeletion, which based on the previously annotated patients data in public databases and literature reports, revealed 21 cases including five patients diagnosed with ALL.

Application of Ion Mobility Spectrometry for Permeability Studies of Organic Substances through Polymeric Materials.

Drift tube ion mobility spectrometers (DT IMS) allow the concentration of different organic compounds to be measured. This gives the opportunity to use these detectors in measuring the penetration of various substances through polymer membranes. Permeation measurements of two substances (2-heptanone and dimethyl methylphosphonate (DMMP)) through a cylindrical silicone rubber membrane were carried out. The membrane separated the aqueous solution from the air. The analyte was introduced into water, and then its concentration in air on the opposite side of the membrane was recorded. Based on the dynamics of detector signal changes, the diffusion coefficients for both tested substances were determined. Determination of permeability coefficients was based on precise quantitative measurements, which took into account the non-linearity of the detector characteristics and the effect of water on detection sensitivity. The analysis of measurement results was based on a mathematical description of diffusion process.

Analysis of e-liquids for electronic cigarettes using GC-IMS/MS with headspace sampling.

Electronic cigarettes (e-cigarettes) are continuously increasing in popularity due to being considered healthier compared with traditional cigarettes. Based on the European directive 2014/40/EU [1] the German legislation restricts the usage of potential harmful substances in these tobacco related products [2,3]. The aim of this work was to establish a method for the detection and quantification of selected substances covered by the above regulation. For this purpose, one-of-a-kind gas chromatograph with ion mobility spectrometer (GC-IMS) was used. Instrument was parallelly coupled with conventional chromatograph equipped with quadrupole mass spectrometer (GC-MS). Headspace (HS) was used as a sample preparation technique. During initial tests both systems were correlated by using a mixture of simple carbonyl compounds. The identification of the selected analytes was performed by mass spectrometry and calibration curves for the quantification were recorded. For all tested substances the limit of detection (LOD) and limit of quantification (LOQ) were determined. The LOD ranges are from 8 to 70 µg/L, the LOQ are from 25 to 200 µg/L. For testing the usability of the developed method 20 samples of commercially available refills for e-cigarettes (e-liquids), produced in Germany and Poland, were analyzed. Substances listed in the directive were found in all samples. In two of them an according to the regulations forbidden substance (estragole) was detected.

Ion mobility spectrometers and electron capture detector - A comparison of detection capabilities.

Electron capture detectors (ECDs) and detectors used in ion mobility spectrometry (IMS) have been successfully used for the detection of numerous compounds including hazardous substances. The general principles of their operations are similar and based on sample component ionization and measurement of the signal using the differences in the mobility of electric charge carriers. Differences in sensitivity result from various parameters of these instruments. Value of electric field intensity in ionic reactors have an influence on ionization process. The main goal of the performed tests was to compare the analytical properties of ECD and two types of IMS detectors: a drift tube spectrometer (DT IMS) and a differential mobility spectrometer (DMS). In the work performed, the efficiency of ionization and the response of detectors to selected analytes were compared. ECD, DT IMS and DMS were equipped with 63-Ni radioactive sources. Analytes have been ionized via electron capture process or dissociative electron transfer. Results obtained for oxygen and chloro-substituted organic compounds (carbon tetrachloride, benzyl chloride, chloroform, 2-chloroethyl ethyl sulfide) were used to calculate the relative signal and to compare the ionization efficiency for three detectors. The phenomena observed experimentally were related to energy dependencies and electron capture cross-sections of analytes. The efficiency of ionization in DT IMS was also compared for electron capture when nitrogen was used as the carrier gas, and when the ionization process was based on the collisions of the analyte molecules with the O2- with the use of air.