Hardware and software solutions for implementing nanospray desorption electrospray ionization (nano-DESI) sources on commercial mass spectrometers.

Nanospray desorption electrospray ionization (nano-DESI) is an ambient ionization mass spectrometry imaging (MSI) approach that enables spatial mapping of biological and environmental samples with high spatial resolution and throughput. Because nano-DESI has not yet been commercialized, researchers develop their own sources and interface them with different commercial mass spectrometers. Previously, several protocols focusing on the fabrication of nano-DESI probes have been reported. In this tutorial, we discuss different hardware requirements for coupling the nano-DESI source to commercial mass spectrometers, such as the safety interlock, inlet extension, and contact closure. In addition, we describe the structure of our custom software for controlling the nano-DESI MSI platform and provide detailed instructions for its usage. With this tutorial, interested researchers should be able to implement nano-DESI experiments in their labs.

A monolithic microfluidic probe for ambient mass spectrometry imaging of biological tissues.

Ambient mass spectrometry imaging (MSI) is a powerful technique that allows for the simultaneous mapping of hundreds of molecules in biological samples under atmospheric conditions, requiring minimal sample preparation. We have developed nanospray desorption electrospray ionization (nano-DESI), a liquid extraction-based ambient ionization technique, which has proven to be sensitive and capable of achieving high spatial resolution. We have previously described an integrated microfluidic probe, which simplifies the nano-DESI setup, but is quite difficult to fabricate. Herein, we introduce a facile and scalable strategy for fabricating microfluidic devices for nano-DESI MSI applications. Our approach involves the use of selective laser-assisted etching (SLE) of fused silica to create a monolithic microfluidic probe (SLE-MFP). Unlike the traditional photolithography-based fabrication, SLE eliminates the need for the wafer bonding process and allows for automated, scalable fabrication of the probe. The chamfered design of the sampling port and ESI emitter significantly reduces the amount of polishing required to fine-tune the probe thereby streamlining and simplifying the fabrication process. We have also examined the performance of a V-shaped probe, in which only the sampling port is fabricated using SLE technology. The V-shaped design of the probe is easy to fabricate and provides an opportunity to independently optimize the size and shape of the electrospray emitter. We have evaluated the performance of SLE-MFP by imaging mouse tissue sections. Our results demonstrate that SLE technology enables the fabrication of robust monolithic microfluidic probes for MSI experiments. This development expands the capabilities of nano-DESI MSI and makes the technique more accessible to the broader scientific community.

Nanospray Desorption Electrospray Ionization (Nano-DESI) Mass Spectrometry Imaging with High Ion Mobility Resolution.

Untargeted separation of isomeric and isobaric species in mass spectrometry imaging (MSI) is challenging. The combination of ion mobility spectrometry (IMS) with MSI has emerged as an effective strategy for differentiating isomeric and isobaric species, which substantially enhances the molecular coverage and specificity of MSI experiments. In this study, we have implemented nanospray desorption electrospray ionization (nano-DESI) MSI on a trapped ion mobility spectrometry (TIMS) mass spectrometer. A new nano-DESI source was constructed, and a specially designed inlet extension was fabricated to accommodate the new source. The nano-DESI-TIMS-MSI platform was evaluated by imaging mouse brain tissue sections. We achieved high ion mobility resolution by utilizing three narrow mobility scan windows that covered the majority of the lipid molecules. Notably, the mobility resolution reaching up to 300 in this study is much higher than the resolution obtained in our previous study using drift tube IMS. High-resolution TIMS successfully separated lipid isomers and isobars, revealing their distinct localizations in tissue samples. Our results further demonstrate the power of high-mobility-resolution IMS for unraveling the complexity of biomolecular mixtures analyzed in MSI experiments.

High-Throughput Mass Spectrometry Imaging of Biological Systems: Current Approaches and Future Directions.

In the past two decades, the power of mass spectrometry imaging (MSI) for the label free spatial mapping of molecules in biological systems has been substantially enhanced by the development of approaches for imaging with high spatial resolution. With the increase in the spatial resolution, the experimental throughput has become a limiting factor for imaging of large samples with high spatial resolution and 3D imaging of tissues. Several experimental and computational approaches have been recently developed to enhance the throughput of MSI. In this critical review, we provide a succinct summary of the current approaches used to improve the throughput of MSI experiments. These approaches are focused on speeding up sampling, reducing the mass spectrometer acquisition time, and reducing the number of sampling locations. We discuss the rate-determining steps for different MSI methods and future directions in the development of high-throughput MSI techniques.

Anatomy of Protein Electrospray Ionization Mass Spectra by Superconducting Tunnel Junction Mass and Energy Spectrometry.

Cryogenic superconducting tunnel junction (STJ) detectors have the advantage of single-particle sensitivity, high quantum efficiency, low noise, and the ability to detect the time and relative impact energy of deposited ions. This makes them attractive for use in mass spectrometry (MS) and as a form of energy spectrometry. STJ cryodetectors have been coupled to time-of-flight (TOF) mass spectrometers equipped with a matrix-assisted laser desorption ionization (MALDI) source and to an electrospray ionization (ESI) TOF mass spectrometer. Here, a lab-made linear quadrupole ion trap (LIT) mass spectrometer system was coupled to an ESI source and a 16-channel Nb-STJ array with improved readout electronics. The goal was to investigate fundamentals of ESI-generated protein ions by further exploiting the advantage of resolving these ions in a third dimension of the relative energy deposited into the STJs. The proteins equine cytochrome c, bovine carbonic anhydrase, bovine serum albumin, and murine immunoglobulin G were studied using this ESI-LIT-STJ-MS instrument. Multiply charged monomers, multimers, and fragments from metastable ions were resolved from monomer peaks by differences in ion deposition energy even when these ions have the same mass-to-charge ratio as the corresponding monomer. The determination of a fragment mass from metastable decomposition is accomplished without knowing the charge state of the fragment. The average charge state of the multimers is reduced with each addition of a protein which is presumed to be a direct reflection of the surface area available for charging. Multiply charged in-source fragments have also been observed and distinguished in the mass spectrum of carbonic anhydrase by using the differences in the energy deposited in the STJs.

An Eight-Atom Iridium-Aluminum Oxide Cluster IrAlO6+ Catalytically Oxidizes Six CO Molecules.

Fundamental understanding regarding oxygen storage capacity involving how and why an active site can buffer a large number of oxygen atoms in redox processes is vital to the design of advanced oxygen storage materials, while it is challenging because of the complexity of heterogeneous catalysis. Herein, we identified that an eight-atom iridium-aluminum oxide cluster IrAlO6+ can transfer all the oxygen atoms to catalytically oxidize six CO molecules. This finding represents a breakthrough in cluster catalysis where at most three oxygen atoms from a heteronuclear metal oxide cluster can be catalytically involved in CO oxidation. We found that oxygen prefers to be stored on aluminum to form an O3-• radical in the energetically unfavorable IrAlO6+ isomer and generate the low-coordinated iridium that is pivotal to capturing CO and triggering the catalysis. The powerful electron cycling capability of iridium and the cooperative iridium-aluminum interplay are emphasized to drive the oxygen atom-transfer behavior.

Direct Conversion of Methane with Carbon Dioxide Mediated by RhVO3 - Cluster Anions.

Direct conversion of methane with carbon dioxide to value-added chemicals is attractive but extremely challenging because of the thermodynamic stability and kinetic inertness of both molecules. Herein, the first dinuclear cluster species, RhVO3 - , has been designed to mediate the co-conversion of CH4 and CO2 to oxygenated products, CH3 OH and CH2 O, in the temperature range of 393-600 K. The resulting cluster ions RhVO3 CO- after CH3 OH formation can further desorb the [CO] unit to regenerate the RhVO3 - cluster, leading to the successful establishment of a catalytic cycle for methanol production from CH4 and CO2 (CH4 +CO2 →CH3 OH+CO). The exceptional activity of Rh-V dinuclear oxide cluster (RhVO3 - ) identified herein provides a new mechanism for co-conversion of two very stable molecules CH4 and CO2 .

Sensitive Detection of Gas-Phase Glyoxal by Electron Attachment Reaction Ionization Mass Spectrometry.

Glyoxal (GLY) acts as a key contributor to tropospheric ozone production and secondary organic aerosol (SOA) formation on local to regional scales. The detection of GLY provides useful indicators of fast photochemistry occurring in the lower troposphere. The fast and sensitive detection of GLY is thus important, while traditional chemical ionization such as the proton-transfer reaction (PTR) is extremely limited by the poor detection limit and extensive fragmentation. To address these limitations, electron attachment reaction (EAR) ionization was applied to detect GLY. The generation of parent anions (GLY-) without fragmentation was observed, and cryogenic photoelectron imaging spectroscopy further characterized the structure of GLY-. The detection limit was estimated to be as low as (52 ± 1) pptv (parts per trillion by volume) with 1 min measurements. Other components in ambient air, such as water, carbon dioxide, and trace gases (acetone, propanal, etc.) have no effect on the detection of GLY. The EAR ionization is more promising than PTR ionization in detecting GLY. The detection of GLY in ambient air by the EAR ionization has been demonstrated.

Neutral Au1-Doped Cluster Catalysts AuTi2O3-6 for CO Oxidation by O2.

Oxide supported gold catalysts (e.g., Au/TiO2) are of great significance in heterogeneous catalysis owing to their extraordinary catalytic activity. Study of heteronuclear metal oxide clusters (HMOCs, e.g., Au xTi yO z q) is an important way to uncover the molecular-level mechanisms of gold catalysis in the related heterogeneous catalytic systems. However, the current studies of HMOCs are focused on charged clusters with little attention paid to neutral species. The reactivity study of neutral HMOCs is vital to have a comprehensive understanding of heterogeneous catalysis, but it is experimentally challenging because of the difficulty of cluster ionization and detection without fragmentation. Herein, benefiting from a homemade time-of-flight mass spectrometer coupled with a vacuum ultraviolet laser system, the reactivity of neutral Au1-doped titanium oxide clusters AuTi2O3-6 in catalytic CO oxidation by O2 has been successfully identified. The mechanistic details of the catalysis have been elucidated by quantum chemistry calculations. The crucial roles of the mobile AuCO species that can facilitate not only the process of CO oxidation but also the process of O2 activation have been discovered in the cluster catalysis. The fascinating results are of substantial importance to understand the mechanisms of CO oxidation over Au/TiO2, one type of the best studied gold catalysts.

Electron Attachment Reaction Ionization of Gas-Phase Methylglyoxal.

Methylglyoxal (MGLY) plays a significant role in atmospheric chemistry by serving as a key contributor to the formation of active free radicals, ozone, and secondary organic aerosol. Detection of MGLY by traditional chemical ionization such as proton-transfer reaction has several shortcomings such as parent molecule fragmentation. In this study, an electron attachment reaction (EAR) ionization method has been developed for the effective detection of MGLY. Almost no fragmentation was observed during the EAR. The generation of MGLY- anion in the EAR was further confirmed by cryogenic photoelectron imaging spectroscopy. The concentration of MGLY can be calibrated by using dibromomethane (CH2Br2) as reference gas. The detection sensitivity of MGLY was estimated to be (100 ± 2) mV/ppbv (parts per billion by volume). The O2, H2O, CO2, and trace gases in ambient air have no obvious effects on the detection of MGLY- anion by the EAR ionization method.

Coupling of Methane and Carbon Dioxide Mediated by Diatomic Copper Boride Cations.

The use of CH4 and CO2 to produce value-added chemicals via direct C-C coupling is a challenging chemistry problem because of the inertness of these two molecules. Herein, mass spectrometric experiments and high-level quantum-chemical calculations have identified the first diatomic species (CuB+ ) that can couple CH4 with CO2 under thermal collision conditions to produce ketene (H2 C=C=O), an important intermediate in synthetic chemistry. The order to feed the reactants (CH4 and CO2 ) is important and CH4 should be firstly fed to produce the C2 product. Molecular-level mechanisms including control of product selectivity have been revealed for coupling of CH4 with CO2 under mild conditions.

Mechanistic Variants in Methane Activation Mediated by Gold(I) Supported on Silicon Oxide Clusters.

Cationic gold has been frequently identified as a suitable reactive species for activating methane in condensed-phase studies. However, it is far from clear how the coordination site manipulates the activity of such species. Herein, by anchoring AuI on silicon oxide cluster supports of variable sizes, the site-specific methane activation by AuI -Ox has been clarified by mass spectrometry in conjunction with quantum chemistry calculations. An unexpected mechanistic switch in C-H activation was identified for the cluster anions Au(SiO2 )n O- (n=1-3) that selectively activate one of the four C-H bonds of methane with different reaction efficiencies: a low efficiency was observed for the two-fold-coordinated gold ion (AuI, 2f ), which was anchored on an AuSiO3 - or AuSi2 O5 - cluster, through an oxidative addition mechanism (a homolytic process), and high efficiency was observed for the one-fold-coordinated gold ion (AuI, 1f ), which was supported on an AuSi3 O7 - cluster, through Lewis acid/base pairs mechanism (AuI, 1f ⋅⋅⋅O2- , a heterolytic process). Fine regulation of the 5d orbital level of the Au atom by the oxygen ligands accounted for the mechanistic difference between AuI, 2f and AuI, 1f species. The mechanistic understanding of the reactivity of AuI -Ox at a strictly molecular level can be used to clarify the dissimilar activity of gold anchored on different oxide supports.

Formation of Acetylene in the Reaction of Methane with Iron Carbide Cluster Anions FeC3- under High-Temperature Conditions.

The underlying mechanism for non-oxidative methane aromatization remains controversial owing to the lack of experimental evidence for the formation of the first C-C bond. For the first time, the elementary reaction of methane with atomic clusters (FeC3- ) under high-temperature conditions to produce C-C coupling products has been characterized by mass spectrometry. With the elevation of temperature from 300 K to 610 K, the production of acetylene, the important intermediate proposed in a monofunctional mechanism of methane aromatization, was significantly enhanced, which can be well-rationalized by quantum chemistry calculations. This study narrows the gap between gas-phase and condensed-phase studies on methane conversion and suggests that the monofunctional mechanism probably operates in non-oxidative methane aromatization.

Thermal activation of methane by vanadium boride cluster cations VBn+ (n = 3-6).

Investigation on the reactivity of atomic clusters represents an important approach to discover new species to activate and transform methane, the most stable alkane molecule. While a few types of transition metal species have been found to be capable of cleaving the C-H bond of methane, methane activation by the transition metal boride species has not been explored yet. This study reports that vanadium boride cluster cations VBn+ (n = 3-6) can dehydrogenate methane under thermal collision conditions. The mechanistic details of the efficient reactions have been elucidated by quantum chemistry calculations on the VB3+ reaction system. Compared to the non-polar bare B3 cluster, the B3 moiety in VB3+ can be polarized by the V+ cation and thus its reactivity toward methane can be much enhanced. This study provides new insights into the rational design of boron-based catalysts for methane activation.

Catalytic CO Oxidation by O2 Mediated by Noble-Metal-Free Cluster Anions Cu2 VO3-5.

Catalytic CO oxidation by molecular O2 is an important model reaction in both the condensed phase and gas-phase studies. Available gas-phase studies indicate that noble metal is indispensable in catalytic CO oxidation by O2 under thermal collision conditions. Herein, we identified the first example of noble-metal-free heteronuclear oxide cluster catalysts, the copper-vanadium bimetallic oxide clusters Cu2 VO3-5- for CO oxidation by O2 . The reactions were characterized by mass spectrometry, photoelectron spectroscopy, and density functional calculations. The dynamic nature of the Cu-Cu unit in terms of the electron storage and release is the driving force to promote CO oxidation and O2 activation during the catalysis.

Design and Application of a High-Temperature Linear Ion Trap Reactor.

A high-temperature linear ion trap reactor with hexapole design was homemade to study ion-molecule reactions at variable temperatures. The highest temperature for the trapped ions is up to 773 K, which is much higher than those in available reports. The reaction between V2O6- cluster anions and CO at different temperatures was investigated to evaluate the performance of this reactor. The apparent activation energy was determined to be 0.10 ± 0.02 eV, which is consistent with the barrier of 0.12 eV calculated by density functional theory. This indicates that the current experimental apparatus is prospective to study ion-molecule reactions at variable temperatures, and more kinetic details can be obtained to have a better understanding of chemical reactions that have overall barriers. Graphical Abstract.

Formation of Gas-Phase Formate in Thermal Reactions of Carbon Dioxide with Diatomic Iron Hydride Anions.

The hydrogenation of carbon dioxide involves the activation of the thermodynamically very stable molecule CO2 and formation of a C-H bond. Herein, we report that HCO2- and CO can be formed in the thermal reaction of CO2 with a diatomic metal hydride species, FeH- . The FeH- anions were produced by laser ablation, and the reaction with CO2 was analyzed by mass spectrometry and quantum-chemical calculations. Gas-phase HCO2- was observed directly as a product, and its formation was predicted to proceed by facile hydride transfer. The mechanism of CO2 hydrogenation in this gas-phase study parallels similar behavior of a condensed-phase iron catalyst.

Generation of Hydroxyl Radicals in the Reaction of Dihydrogen with AuNbO4+ Cluster Cations.

A molecular-level insight into the nature of reactive oxygen species involved in dihydrogen (H2 ) dissociation is of great importance to understand gold catalysis. In this study, laser ablation generated and mass-selected AuNbO4+ oxide cluster cations could dissociate H2 in an ion-trap reactor. The reaction has been characterized by time-of-flight mass spectrometric experiments and density functional calculations. The lowest energy isomer of AuNbO4+ contains two lattice oxygen (O2- ) and one superoxide (O2.- ) species. The gold atom anchors the H2 molecule in the first step and then delivers one hydrogen atom to the O2- ion in H2 dissociation. At the same time, O2.- is reduced into a peroxide unit that can accept the second hydrogen atom of H2 with the generation of a hydroxyl radical as the main product. In this study, the important roles of the O2.- unit in the dissociation of H2 have been identified.

Ultrathin nanosheets constructed CoMoO4 porous flowers with high activity for electrocatalytic oxygen evolution.

Hierarchical CoMoO4 porous micro-flowers assembled from numerous ultrathin nanosheets were synthesized by a facile hydrothermal method. Benefiting from the high specific surface area and constituent nanosheets with an ultrathin thickness, the CoMoO4 micro-flowers exhibit substantially higher electrocatalytic activity and stability than the IrO2 benchmark for the oxygen evolution reaction.