@phdthesis{VillatoroLeal2018,
  author    = {Villatoro Leal, Jos{\´e} Andr{\´e}s},
  title     = {A combined approach for the analysis of biomolecules using IR-MALDI ion mobility spectrometry and molecular dynamics simulations of peptide ions in the gas phase},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-419723},
  school      = {Universit{\"a}t Potsdam},
  pages     = {133},
  year      = {2018},
  abstract  = {The aim of this doctoral thesis was to establish a technique for the analysis of biomolecules with infrared matrix-assisted laser dispersion (IR-MALDI) ion mobility (IM) spectrometry. The main components of the work were the characterization of the IR-MALDI process, the development and characterization of different ion mobility spectrometers, the use of IR-MALDI-IM spectrometry as a robust, standalone spectrometer and the development of a collision cross-section estimation approach for peptides based on molecular dynamics and thermodynamic reweighting. First, the IR-MALDI source was studied with atmospheric pressure ion mobility spectrometry and shadowgraphy. It consisted of a metal capillary, at the tip of which a self-renewing droplet of analyte solution was met by an IR laser beam. A relationship between peak shape, ion desolvation, diffusion and extraction pulse delay time (pulse delay) was established. First order desolvation kinetics were observed and related to peak broadening by diffusion, both influenced by the pulse delay. The transport mechanisms in IR-MALDI were then studied by relating different laser impact positions on the droplet surface to the corresponding ion mobility spectra. Two different transport mechanisms were determined: phase explosion due to the laser pulse and electrical transport due to delayed ion extraction. The velocity of the ions stemming from the phase explosion was then measured by ion mobility and shadowgraphy at different time scales and distances from the source capillary, showing an initially very high but rapidly decaying velocity. Finally, the anatomy of the dispersion plume was observed in detail with shadowgraphy and general conclusions over the process were drawn. Understanding the IR-MALDI process enabled the optimization of the different IM spectrometers at atmospheric and reduced pressure (AP and RP, respectively). At reduced pressure, both an AP and an RP IR-MALDI source were used. The influence of the pulsed ion extraction parameters (pulse delay, width and amplitude) on peak shape, resolution and area was systematically studied in both AP and RP IM spectrometers and discussed in the context of the IR-MALDI process. Under RP conditions, the influence of the closing field and of the pressure was also examined for both AP and RP sources. For the AP ionization RP IM spectrometer, the influence of the inlet field (IF) in the source region was also examined. All of these studies led to the determination of the optimal analytical parameters as well as to a better understanding of the initial ion cloud anatomy. The analytical performance of the spectrometer was then studied. Limits of detection (LOD) and linear ranges were determined under static and pulsed ion injection conditions and interpreted in the context of the IR-MALDI mechanism. Applications in the separation of simple mixtures were also illustrated, demonstrating good isomer separation capabilities and the advantages of singly charged peaks. The possibility to couple high performance liquid chromatography (HPLC) to IR-MALDI-IM spectrometry was also demonstrated. Finally, the reduced pressure spectrometer was used to study the effect of high reduced field strength on the mobility of polyatomic ions in polyatomic gases. The last focus point was on the study of peptide ions. A dataset obtained with electrospray IM spectrometry was characterized and used for the calibration of a collision cross-section (CCS) determination method based on molecular dynamics (MD) simulations at high temperature. Instead of producing candidate structures which are evaluated one by one, this semi-automated method uses the simulation as a whole to determine a single average collision cross-section value by reweighting the CCS of a few representative structures. The method was compared to the intrinsic size parameter (ISP) method and to experimental results. Additional MD data obtained from the simulations was also used to further analyze the peptides and understand the experimental results, an advantage with regard to the ISP method. Finally, the CCS of peptide ions analyzed by IR-MALDI were also evaluated with both ISP and MD methods and the results compared to experiment, resulting in a first validation of the MD method. Thus, this thesis brings together the soft ionization technique that is IR-MALDI, which produces mostly singly charged peaks, with ion mobility spectrometry, which can distinguish between isomers, and a collision cross-section determination method which also provides structural information on the analyte at hand.},
  language  = {en}
}
@article{ZuehlkeRiebeBeitzetal.2016,
  author    = {Z{\"u}hlke, Martin and Riebe, Daniel and Beitz, Toralf and L{\"o}hmannsr{\"o}ben, Hans-Gerd and Andreotti, Sandro and Reinert, Knut and Zenichowski, Karl and Diener, Marc},
  title     = {High-performance liquid chromatography with electrospray ionization ion mobility spectrometry: Characterization, data management, and applications},
  series = {Journal of separation science},
  volume    = {39},
  journal   = {Journal of separation science},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1615-9306},
  doi       = {10.1002/jssc.201600749},
  pages     = {4756 -- 4764},
  year      = {2016},
  abstract  = {The combination of high-performance liquid chromatography and electrospray ionization ion mobility spectrometry facilitates the two-dimensional separation of complex mixtures in the retention and drift time plane. The ion mobility spectrometer presented here was optimized for flow rates customarily used in high-performance liquid chromatography between 100 and 1500 mu L/min. The characterization of the system with respect to such parameters as the peak capacity of each time dimension and of the 2D spectrum was carried out based on a separation of a pesticide mixture containing 24 substances. While the total ion current chromatogram is coarsely resolved, exhibiting coelutions for a number of compounds, all substances can be separately detected in the 2D plane due to the orthogonality of the separations in retention and drift dimensions. Another major advantage of the ion mobility detector is the identification of substances based on their characteristic mobilities. Electrospray ionization allows the detection of substances lacking a chromophore. As an example, the separation of a mixture of 18 amino acids is presented. A software built upon the free mass spectrometry package OpenMS was developed for processing the extensive 2D data. The different processing steps are implemented as separate modules which can be arranged in a graphic workflow facilitating automated processing of data.},
  language  = {en}
}
@article{BrendlerRiebeRitscheletal.2013,
  author    = {Brendler, Christian and Riebe, Daniel and Ritschel, Thomas and Beitz, Toralf and L{\"o}hmannsr{\"o}ben, Hans-Gerd},
  title     = {Investigation of neuroleptics and other aromatic compounds by laser-based ion mobility mass spectrometry},
  series = {Analytical \& bioanalytical chemistry},
  volume    = {405},
  journal   = {Analytical \& bioanalytical chemistry},
  number    = {22},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1618-2642},
  doi       = {10.1007/s00216-012-6654-7},
  pages     = {7019 -- 7029},
  year      = {2013},
  abstract  = {Laser-based ion mobility (IM) spectrometry was used for the detection of neuroleptics and PAH. A gas chromatograph was connected to the IM spectrometer in order to investigate compounds with low vapour pressure. The substances were ionized by resonant two-photon ionization at the wavelengths lambda = 213 and 266 nm and pulse energies between 50 and 300 mu J. Ion mobilities, linear ranges, limits of detection and response factors are reported. Limits of detection for the substances are in the range of 1-50 fmol. Additionally, the mechanism of laser ionization at atmospheric pressure was investigated. First, the primary product ions were determined by a laser-based time-of-flight mass spectrometer with effusive sample introduction. Then, a combination of a laser-based IM spectrometer and an ion trap mass spectrometer was developed and characterized to elucidate secondary ion-molecule reactions that can occur at atmospheric pressure. Some substances, namely naphthalene, anthracene, promazine and thioridazine, could be detected as primary ions (radical cations), while other substances, in particular acridine, phenothiazine and chlorprothixene, are detected as secondary ions (protonated molecules). The results are interpreted on the basis of quantum chemical calculations, and an ionization mechanism is proposed.},
  language  = {en}
}
@article{VillatoroZuehlkeRiebeetal.2016,
  author    = {Villatoro, Jos{\´e} Andr{\´e}s and Z{\"u}hlke, Martin and Riebe, Daniel and Riedel, Jens and Beitz, Toralf and L{\"o}hmannsr{\"o}ben, Hans-Gerd},
  title     = {IR-MALDI ion mobility spectrometry},
  series = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry and Analusis},
  volume    = {408},
  journal   = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry and Analusis},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1618-2642},
  doi       = {10.1007/s00216-016-9739-x},
  pages     = {6259 -- 6268},
  year      = {2016},
  abstract  = {The novel combination of infrared matrix-assisted laser dispersion and ionization (IR-MALDI) with ion mobility (IM) spectrometry makes it possible to investigate biomolecules in their natural environment, liquid water. As an alternative to an ESI source, the IR-MALDI source was implemented in an in-house-developed ion mobility (IM) spectrometer. The release of ions directly from an aqueous solution is based on a phase explosion, induced by the absorption of an IR laser pulse (lambda = 2.94 mu m, 6 ns pulse width), which disperses the liquid as nano- and micro-droplets. The prerequisites for the application of IR-MALDI-IM spectrometry as an analytical method are narrow analyte ion signal peaks for a high spectrometer resolution. This can only be achieved by improving the desolvation of ions. One way to full desolvation is to give the cluster ions sufficient time to desolvate. Two methods for achieving this are studied: the implementation of an additional drift tube, as in ESI-IM-spectrometry, and the delayed extraction of the ions. As a result of this optimization procedure, limits of detection between 5 nM and 2.5 mu M as well as linear dynamic ranges of 2-3 orders of magnitude were obtained for a number of substances. The ability of this method to analyze simple mixtures is illustrated by the separation of two different surfactant mixtures.},
  language  = {en}
}
@article{VillatoroZuehlkeRiebeetal.2016,
  author    = {Villatoro, Jos{\´e} Andr{\´e}s and Z{\"u}hlke, Martin and Riebe, Daniel and Beitz, Toralf and Weber, Marcus and Riedel, Jens and L{\"o}hmannsr{\"o}ben, Hans-Gerd},
  title     = {IR-MALDI ion mobility spectrometry: physical source characterization and application as HPLC detector},
  series = {International journal for ion mobility spectrometry : official publication of the International Society for Ion Mobility Spectrometry},
  volume    = {19},
  journal   = {International journal for ion mobility spectrometry : official publication of the International Society for Ion Mobility Spectrometry},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1435-6163},
  doi       = {10.1007/s12127-016-0208-1},
  pages     = {197 -- 207},
  year      = {2016},
  abstract  = {Infrared matrix-assisted laser dispersion and ionization (IR-MALDI) in combination with ion mobility (IM) spectrometry enables the direct analysis of biomolecules in aqueous solution. The release of ions directly from an aqueous solution is based on a phase explosion, induced by the absorption of an IR laser pulse, which disperses the liquid as vapor, nano-and micro-droplets. The ionization process is characterized initially by a broad spatial distribution of the ions, which is a result of complex fluid dynamics and desolvation kinetics. These processes have a profound effect on the shape and width of the peaks in the IM spectra. In this work, the transport of ions by the phase explosion-induced shockwave could be studied independently from the transport by the electric field. The shockwave-induced mean velocities of the ions at different time scales were determined through IM spectrometry and shadowgraphy. The results show a deceleration of the ions from 118 m.s(-1) at a distance of 400 mu m from the liquid surface to 7.1 m.s(-1) at a distance of 10 mm, which is caused by a pile-up effect. Furthermore, the desolvation kinetics were investigated and a first-order desolvation constant of 325 +/- 50 s(-1) was obtained. In the second part, the IR-MALDI-IM spectrometer is used as an HPLC detector for the two-dimensional separation of a pesticide mixture.},
  language  = {en}
}
@article{RiebeLaudienBrendleretal.2013,
  author    = {Riebe, Daniel and Laudien, Robert and Brendler, Christian and Beitz, Toralf and L{\"o}hmannsr{\"o}ben, Hans-Gerd},
  title     = {Laser ionization of H2S and ion-molecule reactions of H3S+ in laser-based ion mobility spectrometry and drift cell time-of-flight mass spectrometry},
  series = {Analytical \& bioanalytical chemistry},
  volume    = {405},
  journal   = {Analytical \& bioanalytical chemistry},
  number    = {22},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1618-2642},
  doi       = {10.1007/s00216-013-7186-5},
  pages     = {7031 -- 7039},
  year      = {2013},
  abstract  = {The detection of hydrogen sulfide (H2S) by 2 + 1 resonance-enhanced multi-photon ionization (REMPI) and the application of H2S as a laser dopant for the detection of polar compounds in laser ion mobility (IM) spectrometry at atmospheric pressure were investigated. Underlying ionization mechanisms were elucidated by additional studies employing a drift cell interfaced to a time-of-flight mass spectrometer. Depending on the pressure, the primary ions H2S+, HS+, S+, and secondary ions, such as H3S+, were observed. The 2 + 1 REMPI spectrum of H2S near lambda = 302.5 nm was recorded at atmospheric pressure. Furthermore, the limit of detection and the linear range were established. In the second part of the work, H2S was investigated as an H2O analogous laser dopant for the ionization of polar substances by proton transfer. H2S exhibits a proton affinity (PA) similar to that of H2O, but a significantly lower ionization energy facilitating laser ionization. Ion-molecule reactions (IMR) of H3S+ with a variety of polar substances with PA between 754.6 and 841.6 kJ/mol were investigated. Representatives of different compound classes, including alcohols, ketones, esters, and nitroaromatics were analyzed. The IM spectra resulting from IMR of H3S+ and H3O+ with these substances are similar in structure, i.e., protonated monomer and dimer ion peaks are found depending on the analyte concentration.},
  language  = {en}
}
@misc{LoehmannsroebenBeitzLuadienetal.2004,
  author    = {L{\"o}hmannsr{\"o}ben, Hans-Gerd and Beitz, Toralf and Luadien, Robert and Schultze, Rainer},
  title     = {Laser-based ion mobility spectrometry for sensing of aromatic compounds},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-11892},
  year      = {2004},
  abstract  = {The drift time spectra of polycyclic aromatic hydrocarbons (PAH), alkylbenzenes and alkylphenylethers were recorded with a laser-based ion mobility (IM) spectrometer. The ion mobilities of all compounds were determined in helium as drift gas. This allows the calculation of the diffusion cross sections (Omegacalc) on the basis of the exact hard sphere scattering model (EHSSM) and their comparison with the experimentally determined diffusion cross sections (Omegaexp). These Omegaexp/Omegacalc-correlations are presented for molecules with a rigid structure like PAH and prove the reliability of the theoretical model and experimental method. The increase of the selectivity of IM spectrometry is demonstrated using resonance enhanced multiphoton ionisation (REMPI) at atmospheric pressure, realized by tuneable lasers. The REMPI spectra of nine alkylbenzenes and alkylphenylethers are investigated. On the basis of these spectra, the complete qualitative distinction of eight compounds in a mixture is shown. These experiments are extended to alkylbenzene isomer mixtures.},
  language  = {en}
}
@article{MichalikOnichimowskaBeitzPanneetal.2017,
  author    = {Michalik-Onichimowska, Aleksandra and Beitz, Toralf and Panne, Ulrich and L{\"o}hmannsr{\"o}ben, Hans-Gerd and Riedel, Jens},
  title     = {Microsecond mid-infrared laser pulses for atmospheric pressure laser ablation/ionization of liquid samples},
  series = {Sensors and actuators : B, Chemical},
  volume    = {238},
  journal   = {Sensors and actuators : B, Chemical},
  publisher = {Elsevier},
  address   = {Lausanne},
  issn      = {0925-4005},
  doi       = {10.1016/j.snb.2016.06.155},
  pages     = {298 -- 305},
  year      = {2017},
  abstract  = {In many laser based ionization techniques with a subsequent drift time separation, the laser pulse generating the ions is considered as the start time to. Therefore, an accurate temporal definition of this event is crucial for the resolution of the experiments. In this contribution, the laser induced plume dynamics of liquids evaporating into atmospheric pressure are visualized for two distinctively different laser pulse widths, Delta t = 6 nanoseconds and Delta tau = 280 microseconds. For ns-pulses the expansion of the generated vapour against atmospheric pressure is found to lead to turbulences inside the gas phase. This results in spatial and temporal broadening of the nascent clouds. A more equilibrated expansion, without artificial smearing of the temporal resolution can, in contrast, be observed to follow mu s-pulse excitation. This leads to the counterintuitive finding that longer laser pulses results in an increased temporal vapour formation definition. To examine if this fume expansion also eventually results in a better definition of ion formation, the nascent vapour plumes were expanded into a linear drift tube ion mobility spectrometer (IMS). This time resolved detection of ion formation corroborates the temporal broadening caused by collisional impeding of the supersonic expansion at atmospheric pressure and the overall better defined ion formation by evaporation with long laser pulses. A direct comparison of the observed results strongly suggests the coexistence of two individual ion formation mechanisms that can be specifically addressed by the use of appropriate laser sources.},
  language  = {en}
}
@article{VillatoroWeberZuehlkeetal.2019,
  author    = {Villatoro, Jos{\´e} Andr{\´e}s and Weber, M. and Z{\"u}hlke, Martin and Lehmann, A. and Zenichowski, Karl and Riebe, Daniel and Beitz, Toralf and L{\"o}hmannsr{\"o}ben, Hans-Gerd and Kreuzer, O.},
  title     = {Structural characterization of synthetic peptides using electrospray ion mobility spectrometry and molecular dynamics simulations},
  series = {International Journal of Mass Spectrometry},
  volume    = {436},
  journal   = {International Journal of Mass Spectrometry},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1387-3806},
  doi       = {10.1016/j.ijms.2018.10.036},
  pages     = {108 -- 117},
  year      = {2019},
  abstract  = {Electrospray ionization-ion mobility spectrometry was employed for the determination of collision cross sections (CCS) of 25 synthetically produced peptides in the mass range between 540-3310 Da. The experimental measurement of the CCS is complemented by their calculation applying two different methods. One prediction method is the intrinsic size parameter (ISP) method developed by the Clemmer group. The second new method is based on the evaluation of molecular dynamics (MD) simulation trajectories as a whole, resulting in a single, averaged collision cross-section value for a given peptide in the gas phase. A high temperature MD simulation is run in order to scan through the whole conformational space. The lower temperature conformational distribution is obtained through thermodynamic reweighting. In the first part, various correlations, e.g. CCS vs. mass and inverse mobility vs. m/z correlations, are presented. Differences in CCS between peptides are also discussed in terms of their respective mass and m/z differences, as well as their respective structures. In the second part, measured and calculated CCS are compared. The agreement between the prediction results and the experimental values is in the same range for both calculation methods. While the calculation effort of the ISP method is much lower, the MD method comprises several tools providing deeper insights into the conformations of peptides. Advantages and limitations of both methods are discussed. Based on the separation of two pairs of linear and cyclic peptides of virtually the same mass, the influence of the structure on the cross sections is discussed. The shift in cross section differences and peak shape after transition from the linear to the cyclic peptide can be well understood by applying different MD tools, e.g. the root-mean-square deviation (RMSD) and the root mean square fluctuation (RMSF). (C) 2018 Elsevier B.V. All rights reserved.},
  language  = {en}
}
@article{ZuehlkeZenichowskiRiebeetal.2017,
  author    = {Z{\"u}hlke, Martin and Zenichowski, Karl and Riebe, Daniel and Beitz, Toralf and L{\"o}hmannsr{\"o}ben, Hans-Gerd},
  title     = {Subambient pressure electrospray ionization ion mobility spectrometry},
  series = {International journal for ion mobility spectrometry : official publication of the International Society for Ion Mobility Spectrometry},
  volume    = {20},
  journal   = {International journal for ion mobility spectrometry : official publication of the International Society for Ion Mobility Spectrometry},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1435-6163},
  doi       = {10.1007/s12127-017-0215-x},
  pages     = {47 -- 56},
  year      = {2017},
  abstract  = {The pressure dependence of sheath gas assisted electrospray ionization (ESI) was investigated based on two complementary experimental setups, namely an ESI-ion mobility (IM) spectrometer and an ESI capillary - Faraday plate setup housed in an optically accessible vacuum chamber. The ESI-IM spectrometer is capable of working in the pressure range between 300 and 1000 mbar. Another aim was the assessment of the analytical capabilities of a subambient pressure ESI-IM spectrometer. The pressure dependence of ESI was characterized by imaging the electrospray and recording current-voltage (I-U) curves. Qualitatively different behavior was observed in both setups. While the current rises continuously with the voltage in the capillary-plate setup, a sharp increase of the current was measured in the IM spectrometer above a pressure-dependent threshold voltage. The different character can be attributed to the detection of different species in both experiments. In the capillary-plate experiment, a multitude of charged species are detected while only desolvated ions attribute to the IM spectrometer signal. This finding demonstrates the utility of IM spectrometry for the characterization of ESI, since in contrast to the capillary-plate setup, the release of ions from the electrospray droplets can be observed. The I-U curves change significantly with pressure. An important result is the reduction of the maximum current with decreasing pressure. The connected loss of ionization efficiency can be compensated by a more efficient transfer of ions in the IM spectrometer at increased E/N. Thus, similar limits of detection could be obtained at 500 mbar and 1 bar.},
  language  = {en}
}