63 research outputs found
Computer-driven optimization of complex gradients in comprehensive two-dimensional liquid chromatography
Method development in comprehensive two-dimensional liquid chromatography (LC × LC) is a complicated endeavor. The dependency between the two dimensions and the possibility of incorporating complex gradient profiles, such as multi-segmented gradients or shifting gradients, renders method development by “trial-and-error” time-consuming and highly dependent on user experience. In this work, an open-source algorithm for the automated and interpretive method development of complex gradients in LC × LC-mass spectrometry (MS) was developed. A workflow was designed to operate within a closed-loop that allowed direct interaction between the LC × LC-MS system and a data-processing computer which ran in an unsupervised and automated fashion. Obtaining accurate retention models in LC × LC is difficult due to the challenges associated with the exact determination of retention times, curve fitting because of the use of gradient elution, and gradient deformation. Thus, retention models were compared in terms of repeatability of determination. Additionally, the design of shifting gradients in the second dimension and the prediction of peak widths were investigated. The algorithm was tested on separations of a tryptic digest of a monoclonal antibody using an objective function that included the sum of resolutions and analysis time as quality descriptors. The algorithm was able to improve the separation relative to a generic starting method using these complex gradient profiles after only four method-development iterations (i.e., sets of chromatographic conditions). Further iterations improved retention time and peak width predictions and thus the accuracy in the separations predicted by the algorithm.</p
Assessing the feasibility of stationary-phase-assisted modulation for two-dimensional liquid-chromatography separations
Two-dimensional liquid chromatography (2DLC) offers great separation power for complex mixtures. The frequently encountered incompatibility of two orthogonal separation systems, however, makes its application complicated. Active-modulation strategies can reduce such incompatibility issues considerably. Stationary-phase-assisted modulation (SPAM) is the most-common of these techniques, but also the least robust due to the major disadvantage that analytes may elute prematurely. The range of liquid chromatography (LC) applications continues to expand towards ever more complex mixtures. Retention modelling is increasingly indispensable to comprehend and develop LC separations. In this research, a tool was designed to assess the feasibility of applying SPAM in 2DLC. Several parameters were investigated to accurately predict isocratic retention of analytes on trap columns under dilution-flow conditions. Model parameters were derived from scanning-gradient experiments performed on analytical columns. The trap-to-trap repeatability was found to be similar to the prediction error. Dead volumes for the trap columns could not be accurately determined through direct experimentation. Instead, they were extrapolated from dead-volume measurements on analytical columns. Several known retention models were evaluated. Better predictions were found using the quadratic model than with the log-linear (“linear-solvent-strength”) model. Steep scanning gradients were found to result in inaccurate predictions. The impact of the dilution flow on the retention of analytes proved less straightforward than anticipated. Under certain conditions dilution with a weaker eluent was found to be counter productive. A tool was developed to quantify the effect of the dilution flow and to predict whether SPAM could be applied in specific situations. For nine different analytes under 36 different sets of conditions and with three different modulation times, the SPAM tool yielded a correct assessment in more than 95% of all cases (less than 5% false positives plus false negatives)
Trapped ion mobility mass spectrometry of new psychoactive substances:Isomer-specific identification of ring-substituted cathinones
New psychoactive substances (NPS) are synthetic derivatives of illicit drugs designed to mimic their psychoactive effects. NPS are typically not controlled under drug acts or their legal status depends on their molecular structure. Discriminating isomeric forms of NPS is therefore crucial for forensic laboratories. In this study, a trapped ion mobility spectrometry time-of-flight mass spectrometry (TIMS-TOFMS) approach was developed for the identification of ring-positional isomers of synthetic cathinones, a class of compounds representing two-third of all NPS seized in Europe in 2020. The optimized workflow features narrow ion-trapping regions, mobility calibration by internal reference, and a dedicated data-analysis tool, allowing for accurate relative ion-mobility assessment and high-confidence isomer identification. Ortho-, meta- and para-isomers of methylmethcathinone (MMC) and bicyclic ring isomers of methylone were assigned based on their specific ion mobilities within 5 min, including sample preparation and data analysis. The resolution of two distinct protomers per cathinone isomer added to the confidence in identification. The developed approach was successfully applied to the unambiguous assignment of MMC isomers in confiscated street samples. These findings demonstrate the potential of TIMS-TOFMS for forensic case work requiring fast and highly-confident assignment cathinone-drug isomers in confiscated samples
Living with Breakthrough: Two-Dimensional Liquid-Chromatography Separations of a Water-Soluble Synthetically Grafted Bio-Polymer
Stochastic processes with finite correlation time: modeling and application to the generalized Langevin equation
The kangaroo process (KP) is characterized by various forms of the covariance
and can serve as a useful model of random noises. We discuss properties of that
process for the exponential, stretched exponential and algebraic (power-law)
covariances. Then we apply the KP as a model of noise in the generalized
Langevin equation and simulate solutions by a Monte Carlo method. Some results
appear to be incompatible with requirements of the fluctuation-dissipation
theorem because probability distributions change when the process is inserted
into the equation. We demonstrate how one can construct a model of noise free
of that difficulty. This form of the KP is especially suitable for physical
applications.Comment: 22 pages (RevTeX) and 4 figure
Signatures of muonic activation in the Majorana Demonstrator
Experiments searching for very rare processes such as neutrinoless double-beta decay require a detailed understanding of all sources of background. Signals from radioactive impurities present in construction and detector materials can be suppressed using a number of well-understood techniques. Background from in situ cosmogenic interactions can be reduced by siting an experiment deep underground. However, the next generation of such experiments have unprecedented sensitivity goals of 1028 years half-life with background rates of 10-5cts/(keV kg yr) in the region of interest. To achieve these goals, the remaining cosmogenic background must be well understood. In the work presented here, Majorana Demonstrator data are used to search for decay signatures of metastable germanium isotopes. Contributions to the region of interest in energy and time are estimated using simulations and compared to Demonstrator data. Correlated time-delayed signals are used to identify decay signatures of isotopes produced in the germanium detectors. A good agreement between expected and measured rate is found and different simulation frameworks are used to estimate the uncertainties of the predictions. The simulation campaign is then extended to characterize the background for the LEGEND experiment, a proposed tonne-scale effort searching for neutrinoless double-beta decay in Ge76
Experimental study of C 13 (α,n) O 16 reactions in the Majorana Demonstrator calibration data
Neutron captures and delayed decays of reaction products are common sources of backgrounds in ultrarare event searches. In this work, we studied C13(α,n)O16 reactions induced by α particles emitted within the calibration sources of the Majorana Demonstrator. These sources are thorium-based calibration standards enclosed in carbon-rich materials. The reaction rate was estimated by using the 6129-keV γ rays emitted from the excited O16 states that are populated when the incoming α particles exceed the reaction Q value. Thanks to the excellent energy performance of the Demonstrator's germanium detectors, these characteristic photons can be clearly observed in the calibration data. Facilitated by Geant4 simulations, a comparison between the observed 6129-keV photon rates and predictions by a talys-based software was performed. The measurements and predictions were found to be consistent, albeit with large statistical uncertainties. This agreement provides support for background projections from (α,n) reactions in future double-beta decay search efforts
The Majorana Demonstrator readout electronics system
The Majorana Demonstrator comprises two arrays of high-purity germanium detectors constructed to search for neutrinoless double-beta decay in 76Ge and other physics beyond the Standard Model. Its readout electronics were designed to have low electronic noise, and radioactive backgrounds were minimized by using low-mass components and low-radioactivity materials near the detectors. This paper provides a description of all components of the Majorana Demonstrator readout electronics, spanning the front-end electronics and internal cabling, back-end electronics, digitizer, and power supplies, along with the grounding scheme. The spectroscopic performance achieved with these readout electronics is also demonstrated
Initial results of coring at Prees, Cheshire Basin, UK (ICDP JET project): Towards an integrated stratigraphy, timescale, and Earth system understanding for the Early Jurassic
Drilling for the International Continental Scientific Drilling Program (ICDP) Early Jurassic Earth System and Timescale project (JET) was undertaken between October 2020 and January 2021. The drill site is situated in a small-scale synformal basin of the latest Triassic to Early Jurassic age that formed above the major Permian-Triassic half-graben system of the Cheshire Basin. The borehole is located to recover an expanded and complete succession to complement the legacy core from the Llanbedr (Mochras Farm) borehole drilled through 1967-1969 on the edge of the Cardigan Bay Basin, North Wales. The overall aim of the project is to construct an astronomically calibrated integrated timescale for the Early Jurassic and to provide insights into the operation of the Early Jurassic Earth system. Core of Quaternary age cover and Early Jurassic mudstone was obtained from two shallow partially cored geotechnical holes (Prees 2A to 32.2g¯m below surface (mg¯b.s.) and Prees 2B to 37.0g¯mg¯b.s.) together with Early Jurassic and Late Triassic mudstone from the principal hole, Prees 2C, which was cored from 32.92 to 651.32g¯m (corrected core depth scale). Core recovery was 99.7g¯% for Prees 2C. The ages of the recovered stratigraphy range from the Late Triassic (probably Rhaetian) to the Early Jurassic, Early Pliensbachian (Ibex Ammonoid Chronozone). All ammonoid chronozones have been identified for the drilled Early Jurassic strata. The full lithological succession comprises the Branscombe Mudstone and Blue Anchor formations of the Mercia Mudstone Group, the Westbury and Lilstock formations of the Penarth Group, and the Redcar Mudstone Formation of the Lias Group. A distinct interval of siltstone is recognized within the Late Sinemurian of the Redcar Mudstone Formation, and the name "Prees Siltstone Member"is proposed. Depositional environments range from playa lake in the Late Triassic to distal offshore marine in the Early Jurassic. Initial datasets compiled from the core include radiography, natural gamma ray, density, magnetic susceptibility, and X-ray fluorescence (XRF). A full suite of downhole logs was also run. Intervals of organic carbon enrichment occur in the Rhaetian (Late Triassic) Westbury Formation and in the earliest Hettangian and earliest Pliensbachian strata of the Redcar Mudstone Formation, where up to 4g¯% total organic carbon (TOC) is recorded. Other parts of the succession are generally organic-lean, containing less than 1g¯% TOC. Carbon-isotope values from bulk organic matter have also been determined, initially at a resolution of g1/4g¯1g¯m, and these provide the basis for detailed correlation between the Prees 2 succession and adjacent boreholes and Global Stratotype Section and Point (GSSP) outcrops. Multiple complementary studies are currently underway and preliminary results promise an astronomically calibrated biostratigraphy, magnetostratigraphy, and chemostratigraphy for the combined Prees and Mochras successions as well as insights into the dynamics of background processes and major palaeo-environmental changes
Search for Neutrinoless Double- β Decay in Ge 76 with the Majorana Demonstrator
The Majorana Collaboration is operating an array of high purity Ge detectors to search for neutrinoless double-β decay in Ge76. The Majorana Demonstrator comprises 44.1 kg of Ge detectors (29.7 kg enriched in Ge76) split between two modules contained in a low background shield at the Sanford Underground Research Facility in Lead, South Dakota. Here we present results from data taken during construction, commissioning, and the start of full operations. We achieve unprecedented energy resolution of 2.5 keV FWHM at Qββ and a very low background with no observed candidate events in 9.95 kg yr of enriched Ge exposure, resulting in a lower limit on the half-life of 1.9×1025 yr (90% C.L.). This result constrains the effective Majorana neutrino mass to below 240-520 meV, depending on the matrix elements used. In our experimental configuration with the lowest background, the background is 4.0-2.5+3.1 counts/(FWHM t yr)
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