The concept of the diffusion calibration for accurate drift time measurement by traveling wave ion mobilty

Ion mobility spectrometry (IMS) is a gas phase separation technique which relies on differences in the collisional cross section (CCS) of ions. Ionic clouds of unresolved conformers overlapped if the CCS difference is below the instrumental resolution expressed as Ω/ΔΩ. The experimental arrival time distribution (ATD) peak is then a superimposition of the various contributions weighted by their relative intensities. We have developed a strategy for accurate drift time determination using traveling wave ion mobility spectrometry (TWIMS) of poorly and 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 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 for couples of crown ethers and peptides leading to CCS determination in better agreement with quantum chemistry predictions

Geometric Analysis of Shapes in Ion Mobility-Mass Spectrometry.

peer reviewedExperimental ion mobility-mass spectrometry (IM-MS) results are often correlated to three-dimensional structures based on theoretical chemistry calculations. The bottleneck of this approach is the need for accurate values, both experimentally and theoretically predicted. Here, we continue the development of the trend-based analyses to extract structural information from experimental IM-MS data sets. The experimental collision cross-sections (CCSs) of synthetic systems such as homopolymers and small ionic clusters are investigated in terms of CCS trends as a function of the number of repetitive units (e.g., degree of polymerization (DP) for homopolymers) and for each detected charge state. Then, we computed the projected areas of expanding but perfectly defined geometric objects using an in-house software called MoShade. The shapes were modeled using computer-aided design software where we considered only geometric factors: no atoms, mass, chemical potentials, or interactions were taken into consideration to make the method orthogonal to classical methods for 3D shape assessments using time-consuming computational chemistry. Our modeled shape evolutions favorably compared to experimentally obtained CCS trends, meaning that the apparent volume or envelope of homogeneously distributed mass effectively modeled the ion-drift gas interactions as sampled by IM-MS. The CCSs of convex shapes could be directly related to their surface area. More importantly, this relationship seems to hold even for moderately concave shapes, such as those obtained by geometry-optimized structures of ions from conventional computational chemistry methods. Theoretical sets of expanding beads-on-a-string shapes allowed extracting accurate bead and string dimensions for two homopolymers, without modeling any chemical interactions

Label-free higher order structure and dynamic investigation method of proteins in solution using an enzymatic reactor coupled to electrospray high-resolution mass spectrometry

peer reviewe

Investigation of structure-stabilizing elements in proteins by ion mobility mass spectrometry and collision-induced unfolding

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Design considerations in a sib-pair study of linkage for susceptibility loci in cancer

<p>Abstract</p> <p>Background</p> <p>Modern approaches to identifying new genes associated with disease allow very fine analysis of associaton and can be performed in population based case-control studies. However, the sibpair design is still valuable because it requires few assumptions other than acceptably high penetrance to identify genetic loci.</p> <p>Methods</p> <p>We conducted simulation studies to assess the impact of design factors on relative efficiency for a linkage study of colorectal cancer. We considered two test statistics, one comparing the mean IBD probability in affected pairs to its null value of 0.5, and one comparing the mean IBD probabilities between affected and discordant pairs. We varied numbers of parents available, numbers of affected and unaffected siblings, reconstructing the genotype of an unavailable affected sibling by a spouse and offspring, and elimination of sibships where the proband carries a mutation at another locus.</p> <p>Results</p> <p>Power and efficiency were most affected by the number of affected sibs, the number of sib pairs genotyped, and the risk attributable to linked and unlinked loci. Genotyping unaffected siblings added little power for low penetrance models, but improved validity of tests when there was genetic heterogeneity and for multipoint testing. The efficiency of the concordant-only test was nearly always better than the concordant-discordant test. Replacement of an unavailable affected sibling by a spouse and offspring recovered some linkage information, particularly if several offspring were available. In multipoint analysis, the concordant-only test was showed a small anticonservative bias at 5 cM, while the multipoint concordant-discordant test was generally the most powerful test, and was not biased away from the null at 5 cM.</p> <p>Conclusion</p> <p>Genotyping parents and unaffected siblings is useful for detecting genotyping errors and if allele frequencies are uncertain. If adequate allele frequency data are available, we suggest a single-point affecteds-only analysis for an initial scan, followed by a multipoint analysis of affected and unaffected members of all available sibships with additional markers around initial hits.</p

Pushing the limits of mass spectrometry for the separation and identification of analytes using ion mobility and mass accuracy

The structural characterization and elucidation of compounds is one of the main fields of the physical chemistry that is based on the determination of the spatial organization of the compound particles. From the available techniques allowing the investigation of the three-dimensional structure of compounds, ion mobility mass spectrometry has undeniable advantages for the structural studies in the gas phase. The reconciliation of ion mobility mass spectrometry experiment and theoretical simulations is often considered for de-novo structure elucidation based on the determination of the experimental and theoretical collision cross section values. However, this approach requires accurate experimental determination and confident prediction of collision cross section to ensure relevant structure characterization based on collision cross section values matching. Here, we report in this work the development of analytical strategies for a better understanding of structural characterization of molecular systems by pushing the current limits of mass spectrometry and ion mobility mass spectrometry. These new strategies have allowed increasing the confidence level of the structure characterisation involving the increase of ion mobility separation and the refinement of the experimental collision cross section determination by refining the raw data reprocessing. New structure descriptors are also be investigated for helping the reconciliation of experimental and predicted collision cross section values. Finally, the reliability of ion mobility mass spectrometry for the investigation of native physicochemical properties is discussed in regard with data obtained from capillary zone electrophoresis. This work highlights that the use of ion mobility mass spectrometry for structural characterization and de-novo structure elucidation has a bright future

Exploitation de la plateforme e-Campus pour l’apprentissage de la Chimie de Première année pour les étudiants non acquis à la matière

De nos jours, les étudiants sont de plus en plus ouverts à l’e-Learning. La plateforme e-Campus, de par sa facilité à rendre disponible des contenus et des activés en ligne, permet à tout corps enseignant de répondre à cette demande grandissante. Pour les étudiants en première année de kinésithérapie et sciences de la motricité, l’e-Learning est devenu un complément incontournable du cours de Chimie. Lors de cette présentation, nous aborderons le développement de ce projet E-Learning pour le cours de chimie, de l’idée à la réalisation, en découvrant les outils offerts par la plateforme E-Campus, tels les questionnaires en ligne, les forums, les médiathèques

Contribution of ion mobility for structural analysis and analytical chemistry: Use of selective IMS shift reagents (SSR)

Ion mobility is a gas phase separation technique based on the Collisional Cross Section (CCS) of ions. It discriminates isobaric and isomeric ions provided their CCS difference is larger than the instrumental resolution. This work proposes a new method to overcome this limitation while providing additional structural information. A Selective Shift Reagent (SSR) is a ligand specifically modifying the CCS of ions. Indeed specific non-covalent complexes can be form with a suitable SSR to reach the required selectivity and the CCS induced shift. A CID dissociation of the complex may be used after IMS separation to produce specific MS/MS spectra of the targeted analyte. This concept paves the way for new analytical strategies by ion mobility based on non-covalent complex formation