Automated Chiral Analysis of Amino Acids Based on Chiral Derivatization and Trapped Ion Mobility-Mass Spectrometry.

A fast and fully automated method for chiral analysis has been developed by combining a chiral derivatization approach with high-resolution trapped ion mobility separation. Although the presented approach can be potentially applied to diverse types of chiral compounds, several benchmark amino acids were used as model compounds, focusing on the smallest amino acid alanine. An autosampler with an integrated chromatography system was used for inline chiral derivatization with (S)-naproxen chloride and subsequent preseparation. Afterwards, derivatized amino acids were directly introduced into the electrospray interface of a trapped ion mobility-mass spectrometer for rapid diastereomer separation in the gas phase. This unique combination of preseparation and trapped ion mobility spectrometry separation in the negative ion mode enabled rapid chiral analysis within 3 min per sample. Furthermore, the diastereomer separation proved to be independent of alkali salts or other metal ions, offering robustness with regard to samples containing high amounts of salts. Highly sensitive detection of amino acid diastereomers was possible down to the lower nanomolar concentration range, and enantiomeric ratios could be readily determined from the recorded mobilograms with excellent reproducibility and precision. To demonstrate the general applicability of our method, alanine and other amino acids were analyzed from soy sauces and seasonings, which revealed extraordinarily high d-Ala contents of up to 99% in all samples.

Complementing Matrix-Assisted Laser Desorption Ionization-Mass Spectrometry Imaging with Chromatography Data for Improved Assignment of Isobaric and Isomeric Phospholipids Utilizing Trapped Ion Mobility-Mass Spectrometry.

Lipids, such for example the multifaceted category of glycerophospholipids (GP), play a major role in many biological processes. High-resolution mass spectrometry is able to identify these highly diverse lipid species in combination with fragmentation experiments (MS/MS) on the basis of the accurate m/z and fragmentation pattern. However, for the differentiation of isomeric lipids or isobaric interferences, more elaborate separation methods are required. Especially for imaging techniques, such as matrix-assisted laser desorption/ionization (MALDI)-MS imaging, the identification is often exclusively based on the accurate m/z. Fragmentation via MS/MS increases the confidence in lipid annotation in imaging approaches. However, this is sometimes not feasible due to insufficient sensitivity and significantly prolonged analysis time. The use of a separation dimension such as trapped ion mobility spectrometry (TIMS) after ionization strengthens the confidence of the identification based on the collision cross section (CCS). Since CCS libraries are limited, a tissue-specific database was initially generated using hydrophilic interaction liquid chromatography-TIMS-MS. Using this database, the identification of isomeric lipid classes as well as isobaric interferences in a lipid class was performed using a mouse spleen sample in a workflow described in this study. Besides a CCS-based identification as an additional identification criterion for GP in general, the focus was on the distinction of the isomeric GP classes phosphatidylglycerol and bis(monoacylglycero)phosphate, as well as the differentiation of possible isobaric interferences based on the formation of adducts by MALDI-TIMS-MS imaging on a molecular level.

Husimi functions for coupled optical resonators.

Phase-space analysis has been widely used in the past for the study of optical resonant systems. While it is usually employed to analyze the far-field behavior of resonant systems, we focus here on its applicability to coupling problems. By looking at the phase-space description of both the resonant mode and the exciting source, it is possible to understand the coupling mechanisms as well as to gain insights and approximate the coupling behavior with reduced computational effort. In this work, we develop the framework for this idea and apply it to a system of an asymmetric dielectric resonator coupled to a waveguide.

Rotationally tunable multi-focal diffractive moiré lenses.

In this work, we show how the combination of cascaded multi-value phase diffractive optical elements can form a multi-focal moiré zone plate with tunable optical power in each diffraction order. The rotationally tunable moiré zone plate is capable of generating an array of equal intensity focal spots with a precisely adjustable axial distance along the propagation direction. Numerical simulations as well as experimental results verify that multiple focal spots are generated, and the distance between the generated uniform foci can be adjusted by a mutual rotation of one multi-value phase diffractive element with respect to the other.

Hydroperoxylated vs Dihydroxylated Lipids: Differentiation of Isomeric Cardiolipin Oxidation Products by Multidimensional Separation Techniques.

In recent years, cardiolipin (CL) oxidation products were recognized as potential markers for mitochondrial dysfunction in conjunction with age related diseases. The analysis of oxidized CL requires powerful analysis techniques due to high structural diversity. In addition, low concentrations of partly labile compounds pose a special challenge, supplemented by the occurrence of isomeric compounds, e.g., hydroperoxylated vs dihydroxylated products. Therefore, we present a hyphenated method based on liquid chromatography coupled to trapped ion mobility spectrometry (TIMS) for separation and tandem mass spectrometry (MS/MS) for structural characterization. This enables comprehensive analysis of an artificially oxidized CL extract of bovine heart. Isomeric oxidation products could be differentiated by mobility-resolved MS/MS fragmentation experiments. Our developed method could help to better understand the physiological role of oxidized CL.

Fabrication and characterization of deformed microdisk cavities in silicon dioxide with high Q-factor.

We demonstrate the excitation and characterization of whispering gallery modes in a deformed optical microcavity. To fabricate deformed microdisk microresonators we established a fabrication process relying on dry plasma etching tools for many degrees of freedom and a shape-accurate morphology. This approach allowed us to fabricate resonators of different sizes with a controlled sidewall angle and underetching in large quantities with reproducible properties such as a surface roughness RQ≤2nm. The excitation and characterization of these modes were achieved by using a state-of-the-art tapered fiber coupling setup with a narrow linewidth tunable laser source. The conducted measurements in shortegg resonators showed at least two modes within a spectral range of about 237 pm. The highest Q-factors measured were in the range of 105. Wave optical eigenmode and frequency domain simulations were conducted that could partially reproduce the observed behavior and therefore allow us to compare the experimental results.

Mass-Spectrometric Imaging of Electrode Surfaces-a View on Electrochemical Side Reactions.

Electrochemical side reactions, often referred to as "electrode fouling", are known to be a major challenge in electro-organic synthesis and the functionality of modern batteries. Often, polymerization of one or more components is observed. When reaching their limit of solubility, those polymers tend to adsorb on the surface of the electrode, resulting in a passivation of the respective electrode area, which may impact electrochemical performance. Here, matrix-assisted laser-desorption/ionization mass spectrometry (MALDI-MS) is presented as valuable imaging technique to visualize polymer deposition on electrode surfaces. Oligomer size distribution and its dependency on the contact time were imaged on a boron-doped diamond (BDD) anode of an electrochemical flow-through cell. The approach allows to detect weak spots, where electrode fouling may take place and provides insight into the identity of side-product pathways.

Laser desorption/ionization-mass spectrometry for the analysis of interphases in lithium ion batteries.

Laser desorption/ionization-mass spectrometry (LDI-MS) is introduced as a complementary technique for the analysis of interphases formed at electrode|electrolyte interfaces in lithium ion batteries (LIBs). An understanding of these interphases is crucial for designing interphase-forming electrolyte formulations and increasing battery lifetime. Especially organic species are analyzed more effectively using LDI-MS than with established methodologies. The combination with trapped ion mobility spectrometry and tandem mass spectrometry yields additional structural information of interphase components. Furthermore, LDI-MS imaging reveals the lateral distribution of compounds on the electrode surface. Using the introduced methods, a deeper understanding of the mechanism of action of the established solid electrolyte interphase-forming electrolyte additive 3,4-dimethyloxazolidine-2,5-dione (Ala-N-CA) for silicon/graphite anodes is obtained, and active electrochemical transformation products are unambiguously identified. In the future, LDI-MS will help to provide a deeper understanding of interfacial processes in LIBs by using it in a multimodal approach with other surface analysis methods to obtain complementary information.

Mobility-resolved broadband dissociation and parallel reaction monitoring for laser desorption/ionization-mass spectrometry - Tattoo pigment identification supported by trapped ion mobility spectrometry.

In this work, trapped ion mobility spectrometry (TIMS) was introduced to facilitate tandem mass spectrometry (MS2) experiments for laser desorption/ionization-mass spectrometry (LDI-MS) as mobility-resolved fragmentation. The mobility separation of desorbed ions was followed by subsequent fragmentation using data-independent broadband collision-induced dissociation (bbCID) or targeted fragmentation through a prototypic version of parallel reaction monitoring-parallel accumulation serial fragmentation (prm-PASEF) for LDI. Both mobility-resolved fragmentation options, TIMS-bbCID and prm-PASEF, were applied to LDI point measurements to identify organic pigments in tattoo inks. Furthermore, the prototypic prm-PASEF algorithm was used in imaging applications to increase confidence in annotating organic tattoo pigments in skin samples with adverse reactions. Due to less complex spectra in matrix-free LDI, both fragmentation methods yielded fast and reliable MS2 identification workflows. TIMS-bbCID was especially beneficial for the rapid acquisition of multiple fragment spectra. For the targeted prm-PASEF approach, analytes' mobilities needed to be collected prior to simplified fragmentation. Therefore, a reference list for 14 pigments was created. The possible number of experiments per thin section and the associated savings in analysis time compared to conventional MS2 were particularly suitable for the imaging application. Furthermore, the mobility dimension enabled a new orthogonal identification parameter, increasing the annotation confidence of tattoo pigments through compound specific mobilities.

On-tissue dataset-dependent MALDI-TIMS-MS2 bioimaging.

Trapped ion mobility spectrometry (TIMS) adds an additional separation dimension to mass spectrometry (MS) imaging, however, the lack of fragmentation spectra (MS2) impedes confident compound annotation in spatial metabolomics. Here, we describe spatial ion mobility-scheduled exhaustive fragmentation (SIMSEF), a dataset-dependent acquisition strategy that augments TIMS-MS imaging datasets with MS2 spectra. The fragmentation experiments are systematically distributed across the sample and scheduled for multiple collision energies per precursor ion. Extendable data processing and evaluation workflows are implemented into the open source software MZmine. The workflow and annotation capabilities are demonstrated on rat brain tissue thin sections, measured by matrix-assisted laser desorption/ionisation (MALDI)-TIMS-MS, where SIMSEF enables on-tissue compound annotation through spectral library matching and rule-based lipid annotation within MZmine and maps the (un)known chemical space by molecular networking. The SIMSEF algorithm and data analysis pipelines are open source and modular to provide a community resource.