A Multimodal SIMS/MALDI Mass Spectrometry Imaging Source with Secondary Electron Imaging Capabilities for Use with timsTOF Instruments.

Mass spectrometry imaging (MSI) is a surface analysis technique that produces chemical images and is commonly used for biological and biomedical research. Multimodal imaging combines multiple imaging modes in order to get a more comprehensive view of a sample. Multimodal MSI images are often acquired using multiple MSI instruments, which leads to issues regarding image registration and increases the chance of sample damage or degradation during sample transfer. These problems can be solved by using a single instrument that can image in multiple modes. In order to improve the efficiency of multimodal imaging and investigate complementary modes of MSI, we have modified a prototype Bruker timsTOF fleX by adding secondary ion mass spectrometry (SIMS) and secondary electron (SE) imaging capabilities while preserving the ability to perform matrix-assisted laser desorption/ionization (MALDI). We show multimodal images collected on this instrument that required only trivial registration and were acquired without sample transfer between imaging trials. Furthermore, we characterize the performance of SIMS, SE, and MALDI imaging and compare the performance of the modified instrument to a commercial timsTOF fleX.

Time-Resolved Imaging of High Mass Proteins and Metastable Fragments Using Matrix-Assisted Laser Desorption/Ionization, Axial Time-of-Flight Mass Spectrometry, and TPX3CAM.

The Timepix (TPX) is a position- and time-sensitive pixelated charge detector that can be coupled with time-of-flight mass spectrometry (TOF MS) in combination with microchannel plates (MCPs) for the spatially and temporally resolved detection of biomolecules. Earlier generation TPX detectors used in previous studies were limited by a moderate time resolution (at best 10 ns) and single-stop detection for each pixel that hampered the detection of ions with high mass-to-charge (m/z) values at high pixel occupancies. In this study, we have coupled an MCP-phosphor screen-TPX3CAM detection assembly that contains a silicon-coated TPX3 chip to a matrix-assisted laser desorption/ionization (MALDI)-axial TOF MS. A time resolution of 1.5625 ns, per-pixel multihit functionality, simultaneous measurement of TOF and time-over-threshold (TOT) values, and kHz readout rates of the TPX3 extended the m/z detection range of the TPX detector family. The detection of singly charged intact Immunoglobulin M ions of m/z value approaching 1 × 106 Da has been demonstrated. We also discuss the utilization of additional information on impact coordinates and TOT provided by the TPX3 compared to conventional MS detectors for the enhancement of the quality of the mass spectrum in terms of signal-to-noise (S/N) ratio. We show how the reduced dead time and event-based readout in TPX3 compared to the TPX improves the sensitivity of high m/z detection in both low and high mass measurements (m/z range: 757-970,000 Da). We further exploit the imaging capabilities of the TPX3 detector for the spatial and temporal separation of neutral fragments generated by metastable decay at different locations along the field-free flight region by simultaneous application of deflection and retarding fields.

Fast Mass Microscopy: Mass Spectrometry Imaging of a Gigapixel Image in 34 Minutes.

Mass spectrometry imaging (MSI) maps the spatial distributions of chemicals on surfaces. MSI requires improvements in throughput and spatial resolution, and often one is compromised for the other. In microprobe-mode MSI, improvements in spatial resolution increase the imaging time quadratically, thus limiting the use of high spatial resolution MSI for large areas or sample cohorts and time-sensitive measurements. Here, we bypass this quadratic relationship by combining a Timepix3 detector with a continuously sampling secondary ion mass spectrometry mass microscope. By reconstructing the data into large-field mass images, this new method, fast mass microscopy, enables orders of magnitude higher throughput than conventional MSI albeit yet at lower mass resolution. We acquired submicron, gigapixel images of fingerprints and rat tissue at acquisition speeds of 600,000 and 15,500 pixels s-1, respectively. For the first image, a comparable microprobe-mode measurement would take more than 2 months, whereas our approach took 33.3 min.

Understanding Detrimental and Beneficial Grain Boundary Effects in Halide Perovskites.

Grain boundaries play a key role in the performance of thin-film optoelectronic devices and yet their effect in halide perovskite materials is still not understood. The biggest factor limiting progress is the inability to identify grain boundaries. Noncrystallographic techniques can misidentify grain boundaries, leading to conflicting literature reports about their influence; however, the gold standard - electron backscatter diffraction (EBSD) - destroys halide perovskite thin films. Here, this problem is solved by using a solid-state EBSD detector with 6000 times higher sensitivity than the traditional phosphor screen and camera. Correlating true grain size with photoluminescence lifetime, carrier diffusion length, and mobility shows that grain boundaries are not benign but have a recombination velocity of 1670 cm s-1 , comparable to that of crystalline silicon. Amorphous grain boundaries are also observed that give rise to locally brighter photoluminescence intensity and longer lifetimes. This anomalous grain boundary character offers a possible explanation for the mysteriously long lifetime and record efficiency achieved in small grain halide perovskite thin films. It also suggests a new approach for passivating grain boundaries, independent of surface passivation, to lead to even better performance in optoelectronic devices.

Atmospheric Pressure Drift Tube Ion Mobility-Orbitrap Mass Spectrometry: Initial Performance Characterization.

Atmospheric pressure drift tube ion mobility spectrometry (AP-DTIMS) was coupled with Fourier transform Orbitrap mass spectrometry. The performance capabilities of this versatile new arrangement were demonstrated for different DTIMS ion gating operation modes and Orbitrap mass spectrometer parameters with regard to sensitivity and resolving power. Showcasing the optimized AP-DTIMS-Orbitrap MS system, isobaric peptide and sugar isomers were successfully resolved and the identities of separated species validated by high-energy collision dissociation experiments.

Microplasma Ionization of Volatile Organics for Improving Air/Water Monitoring Systems On-Board the International Space Station.

Low molecular weight polar organics are commonly observed in spacecraft environments. Increasing concentrations of one or more of these contaminants can negatively impact Environmental Control and Life Support (ECLS) systems and/or the health of crew members, posing potential risks to the success of manned space missions. Ambient plasma ionization mass spectrometry (MS) is finding effective use as part of the analytical methodologies being tested for next-generation space module environmental analysis. However, ambient ionization methods employing atmospheric plasmas typically require relatively high operation voltages and power, thus limiting their applicability in combination with fieldable mass spectrometers. In this work, we investigate the use of a low power microplasma device in the microhollow cathode discharge (MHCD) configuration for the analysis of polar organics encountered in space missions. A metal-insulator-metal (MIM) structure with molybdenum foil disc electrodes and a mica insulator was used to form a 300 µm diameter plasma discharge cavity. We demonstrate the application of these MIM microplasmas as part of a versatile miniature ion source for the analysis of typical volatile contaminants found in the International Space Station (ISS) environment, highlighting their advantages as low cost and simple analytical devices. Graphical Abstract ᅟ.

Multimodal Vacuum-Assisted Plasma Ion (VaPI) Source with Transmission Mode and Laser Ablation Sampling Capabilities.

We have developed a multimodal ion source design that can be configured on the fly for various analysis modes, designed for more efficient and reproducible sampling at the mass spectrometer atmospheric pressure (AP) interface in a number of different applications. This vacuum-assisted plasma ionization (VaPI) source features interchangeable transmission mode and laser ablation sampling geometries. Operating in both AC and DC power regimes with similar results, the ion source was optimized for parameters including helium flow rate and gas temperature using transmission mode to analyze volatile standards and drug tablets. Using laser ablation, matrix effects were studied, and the source was used to monitor the products of model prebiotic synthetic reactions.

Schlieren visualization of fluid dynamics effects in direct analysis in real time mass spectrometry.

RATIONALE: The success of ambient analysis using plasma-based ion sources depends heavily on fluid dynamics and mass transport efficiency in the sample region. To help characterize the influence of these determining factors, visualization of the gas flow profile for a Direct Analysis in Real Time (DART) ion source at the mass spectrometer atmospheric pressure (AP) interface was performed using the Schlieren technique. METHODS: The DART helium flow pattern was imaged in model systems incorporating different interface designs, i.e. skimmer or capillary inlet, and for sampling strategies using several types of traditional DART sample probes including a glass capillary, swab, and drug tablet. Notably, Schlieren experiments were conducted on instruments equipped with the gas-ion separator tube (GIST) adapter and Vapur® pump, and on setups featuring the transmission mode (TM) DART module used in standard practice. RESULTS: DART sources were seen to expel a collimated, highly laminar helium stream across interface distances up to ~8 cm. The helium stream was robust to the influence of gas temperature (50-500 °C) and flow rate (≤3.5 L min(-1) ), but considerable DART gas deflection or full disruption was observed in each sampling scenario. The severity of the flow disturbance depended on probe size and placement, the GIST/Vapur® settings, or counter-current gas movements present at the interface. CONCLUSIONS: The real-time Schlieren visualizations introduced in this work provide new insight on the fluid dynamics within the DART-MS sample gap while also helping to identify those experimental parameters requiring optimization for improved transmission.

An effective approach for coupling direct analysis in real time with atmospheric pressure drift tube ion mobility spectrometry.

Drift tube ion mobility spectrometry (DTIMS) has evolved as a robust analytical platform routinely used for screening small molecules across a broad suite of chemistries ranging from food and pharmaceuticals to explosives and environmental toxins. Most modern atmospheric pressure IM detectors employ corona discharge, photoionization, radioactive, or electrospray ion sources for efficient ion production. Coupling standalone DTIMS with ambient plasma-based techniques, however, has proven to be an exceptional challenge. Device sensitivity with near-ground ambient plasma sources is hindered by poor ion transmission at the source-instrument interface, where ion repulsion is caused by the strong electric field barrier of the high potential ion mobility spectrometry (IMS) inlet. To overcome this shortfall, we introduce a new ion source design incorporating a repeller point electrode used to shape the electric field profile and enable ion transmission from a direct analysis in real time (DART) plasma ion source. Parameter space characterization studies of the DART DTIMS setup were performed to ascertain the optimal configuration for the source assembly favoring ion transport. Preliminary system capabilities for the direct screening of solid pharmaceuticals are briefly demonstrated.

Electro-thermal vaporization direct analysis in real time-mass spectrometry for water contaminant analysis during space missions.

The development of a direct analysis in real time-mass spectrometry (DART-MS) method and first prototype vaporizer for the detection of low molecular weight (∼30-100 Da) contaminants representative of those detected in water samples from the International Space Station is reported. A temperature-programmable, electro-thermal vaporizer (ETV) was designed, constructed, and evaluated as a sampling interface for DART-MS. The ETV facilitates analysis of water samples with minimum user intervention while maximizing analytical sensitivity and sample throughput. The integrated DART-ETV-MS methodology was evaluated in both positive and negative ion modes to (1) determine experimental conditions suitable for coupling DART with ETV as a sample inlet and ionization platform for time-of-flight MS, (2) to identify analyte response ions, (3) to determine the detection limit and dynamic range for target analyte measurement, and (4) to determine the reproducibility of measurements made with the method when using manual sample introduction into the vaporizer. Nitrogen was used as the DART working gas, and the target analytes chosen for the study were ethyl acetate, acetone, acetaldehyde, ethanol, ethylene glycol, dimethylsilanediol, formaldehyde, isopropanol, methanol, methylethyl ketone, methylsulfone, propylene glycol, and trimethylsilanol.

Selective detection of gas-phase TNT by integrated optical waveguide spectrometry using molecularly imprinted sol-gel sensing films.

A chemical sensor was developed to detect the explosive 2,4,6-trinitrotoluene (TNT) utilizing planar integrated optical waveguide (IOW) attenuated total reflection spectrometry. Submicron thick films of organically modified sol-gel polymers were deposited on the waveguide surface as the sensing layer. Sol-gels were molecularly imprinted for TNT using covalently bound template molecules linked to the matrix through 1 or 2 carbamate linkages. Upon chemical cleavage of the template and displacement of the TNT-like pendant groups from the matrix, shape-selective binding sites were created that possess a primary amine group. The amine was used to deprotonate bound TNT yielding an anionic form that absorbs visible light. Binding of TNT and subsequent conversion to the anion results in the attenuation of light propagating through the waveguide, thus creating a spectrophotometric device. Sensitivity can be achieved by taking advantage of the substantial pathlength provided by the use of single mode IOWs. The limit-of-detection to gas-phase TNT was found to be five parts-per-billion (ppbV) in ambient air at a flow rate of 40 mL min(-1) given a 60 s sampling time. The sensor is highly selective for TNT due to the selectivity of binding site recognition of TNT and the subsequent generation of the TNT anion. Response to TNT is not reversible which results in an integrating sensor device which, in theory, can improve the ability to detect small amounts of the explosive if the exposure time is sufficient in length.