Xingchuang Xiong

Data Processing for 3D Mass Spectrometry Imaging

Data processing for three dimensional mass spectrometry (3D-MS) imaging was investigated, starting with a consideration of the challenges in its practical implementation using a series of sections of a tissue volume. The technical issues related to data reduction, 2D imaging data alignment, 3D visualization, and statistical data analysis were identified. Software solutions for these tasks were developed using functions in MATLAB. Peak detection and peak alignment were applied to reduce the data size, while retaining the mass accuracy. The main morphologic features of tissue sections were extracted using a classification method for data alignment. Data insertion was performed to construct a 3D data set with spectral information that can be used for generating 3D views and for data analysis. The imaging data previously obtained for a mouse brain using desorption electrospray ionization mass spectrometry (DESI-MS) imaging have been used to test and demonstrate the new methodology.

Space charge induced nonlinear effects in quadrupole ion traps.

AbstractA theoretical method was proposed in this work to study space charge effects in quadrupole ion traps, including ion trapping, ion motion frequency shift, and nonlinear effects on ion trajectories. The spatial distributions of ion clouds within quadrupole ion traps were first modeled for both 3D and linear ion traps. It is found that the electric field generated by space charge can be expressed as a summation of even-order fields, such as quadrupole field, octopole field, etc. Ion trajectories were then solved using the harmonic balance method. Similar to high-order field effects, space charge will result in an “ocean wave” shape nonlinear resonance curve for an ion under a dipolar excitation. However, the nonlinear resonance curve will be totally shifted to lower frequencies and bend towards ion secular frequency as ion motion amplitude increases, which is just the opposite effect of any even-order field. Based on theoretical derivations, methods to reduce space charge effects were proposed. Figureᅟ

The coupling effects of hexapole and octopole fields in quadrupole ion traps: a theoretical study

A theoretical method, the harmonic balance method, was introduced to study the coupling effects of hexapole and octopole fields on ion motion in a quadrupole ion trap. Ion motion characteristics, such as ion motion center displacement, ion secular frequency shift, nonlinear resonance curve and buffer gas damping effects, have been studied with the presence of both hexapole and octopole fields. It is found that hexapole fields have bigger impacts on ion motion center displacement, while octopole fields dominate ion secular frequency shift. Furthermore, the nonlinear features originated from hexapole and octopole fields could enhance or cancel each other, which provide us more space in a practical ion trap design process. As an example, an ion trap with improved performance was designed using a specific combination of hexapole and octopole fields. In this ion trap, a hexapole field was used to achieve efficient ion directional ejection, while an octopole field was added to correct the chemical mass shift and resolution degradation introduced by the hexapole field.

Accelerated Simulation Study of Space Charge Effects in Quadrupole Ion Traps Using GPU Techniques

Space charge effects play important roles in the performance of various types of mass analyzers. Simulation of space charge effects is often limited by the computation capability. In this study, we evaluate the method of using graphics processing unit (GPU) to accelerate ion trajectory simulation. Simulation using GPU has been compared with multi-core central processing unit (CPU), and an acceleration of about 390 times have been obtained using a single computer for simulation of up to 105 ions in quadrupole ion traps. Characteristics of trapped ions can be investigated at detailed levels within a reasonable simulation time. Space charge effects on the trapping capacities of linear and 3D ion traps, ion cloud shapes, ion motion frequency shift, mass spectrum peak coalescence effects between two ion clouds of close m/z are studied with the ion trajectory simulation using GPU.

Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy.

We had developed pulsed direct current electrospray ionization mass spectrometry (pulsed-dc-ESI-MS) for systematically profiling and determining components in small volume sample. Pulsed-dc-ESI utilized constant high voltage to induce the generation of single polarity pulsed electrospray remotely. This method had significantly boosted the sample economy, so as to obtain several minutes MS signal duration from merely picoliter volume sample. The elongated MS signal duration enable us to collect abundant MS(2) information on interested components in a small volume sample for systematical analysis. This method had been successfully applied for single cell metabolomics analysis. We had obtained 2-D profile of metabolites (including exact mass and MS(2) data) from single plant and mammalian cell, concerning 1034 components and 656 components for Allium cepa and HeLa cells, respectively. Further identification had found 162 compounds and 28 different modification groups of 141 saccharides in a single Allium cepa cell, indicating pulsed-dc-ESI a powerful tool for small volume sample systematical analysis.

Desalting by Crystallization: Detection of Attomole Biomolecules in Picoliter Buffers by Mass Spectrometry

Sensitive detection of biomolecules in small-volume samples by mass spectrometry is, in many cases, challenging because of the use of buffers to maintain the biological activities of proteins and cells. Here, we report a highly effective desalting method for picoliter samples. It was based on the spontaneous separation of biomolecules from salts during crystallization of the salts. After desalting, the biomolecules were deposited in the tip of the quartz pipet because of the evaporation of the solvent. Subsequent detection of the separated biomolecules was achieved using solvent assisted electric field induced desorption/ionization (SAEFIDI) coupled with mass spectrometry. It allowed for direct desorption/ionization of the biomolecules in situ from the tip of the pipet. The organic component in the assistant solvent inhibited the desorption/ionization of salts, thus assured successful detection of biomolecules. Proteins and peptides down to 50 amol were successfully detected using our method even if there were 3 × 10(5) folds more amount of salts in the sample. The concentration and ion species of the salts had little influence on the detection results.

Observation of Replacement of Carbon in Benzene with Nitrogen in a Low-Temperature Plasma

Selective activation of benzene has been mainly limited to the C-H activation. Simple replacement of one carbon in benzene with another atom remains unresolved due to the high dissociation energy. Herein, we demonstrate a direct breakage of the particularly strong C = C bond in benzene through ion-molecule reaction in a low-temperature plasma, in which one carbon atom was replaced by one atomic nitrogen with the formation of pyridine. The mechanism for the formation of pyridine from benzene has been proposed based on the extensive investigation with tandem mass spectrometry. The reaction pathway also works to other aromatics such as toluene and o-xylene. This finding provides a new avenue for selective conversion of aromatics into nitrogen-containing compounds.

Metal–organic framework coated paper substrates for paper spray mass spectrometry

Metal–organic frameworks (MOFs) have emerged as novel materials owing to their inherent structural characteristics, i.e., a large surface area and a well-ordered porous structure, but there are no reports on their application to paper spray mass spectrometry. Herein we explore the capability of paper substrates coated with three types of MOFs [e.g., MIL-53(Al), ZIF-8 and UiO-66(Zr)] for paper spray, in which the as-prepared UiO-66(Zr) coated paper demonstrated the highest sensitivity in the analysis of therapeutic drugs in dried blood spots relative to MIL-53(Al) and ZIF-8 coated paper substrates. To get a better understanding on the interactions between drugs and MOF coated papers, much effort has been focused on the elution behaviors of target drug verapamil from the MOF coated papers and the adsorption ability of the studied analyte to MOF particles in solution systems. Due to the more favorable elution behaviors and weaker adsorption ability of the tested drugs at the surface of UiO-66(Zr) coated paper relative to the other two papers, the estimated lower limit of quantitation (LLOQ) values of the examined drugs with UiO-66(Zr) coated paper have improvements of 8.5–46.6-fold relative to those from uncoated filter paper, and the values were in the range of 0.04–0.65 ng mL−1. Based on the high sensitivity of UiO-66(Zr) coated paper in drug quantitative analysis, the developed paper has also been successfully applied for the analysis of five anti-psychotic drugs (e.g., clozapine, amisulpride, quetiapine, risperidone and aripiprazole) in 40 human blood samples.

Realistic modeling of ion-neutral collisions in quadrupole ion traps.

In this study, three ion-neutral collision models have been discussed and compared, including the Langevin, the hard-sphere and the mixed collision models. With the pseudo-potential approximation, analytical expressions of ion secular motions with the hard-sphere and mixed collision models have been obtained for the first time. Through numerical simulations and theoretical calculations, it is found that the mixed collision model could be used as a general description of ion-neutral collisions under different conditions. Langevin collision model is a good description of low energy collisions between small ions and neutrals, while hard-sphere collision model could be used to describe high energy collisions and/or ions with higher masses (larger physical sizes). These analytical expressions of ion motion decay profiles enable the creation of direct relationships between time-domain image currents with ion collision cross sections.

Feature Extraction Approach for Mass Spectrometry Imaging Data Using Non-negative Matrix Factorization

Abstract Mass spectrometry imaging (MSI) provides molecules composition information and corresponding spatial information on complex biological surfaces in a single experiment without label. It is a hotspot for getting significant amount of attention in the mass spectrometric community currently. However, the MSI data are large and complexity, which makes the reduction and feature extraction difficult. Some multivariate statistical analysis methods, for example, the famous principal component analysis (PCA), were developed to address this issue. But the results with negative value are hard to be interpreted as features about molecules. In this study, a feature extraction approach for MSI data by applying non-negative matrix factorization was developed. It could extract single molecules composition feature and corresponding distribution (basic images) feature, and further integrated the basic images to create a profile showing the whole sample by RGB (red, green and blue) color overlaid model clearly. The MSI data of a mouse brain section was used to test the efficiency of this approach. The white matter regions, the grey matter regions and the background regions were clearly observed and the corresponding molecules mass spectrums were extracted, which indicated that the approach was easier than PCA approach in results interpreting. Moreover, the MSI data of a human cancerous and adjacent normal bladder tissue sections on the same sample target were analyzed by the approach, and the cancerous regions and the normal regions were clearly differentiated. The software developed in this paper could be downloaded from the website http://www.msimaging.net .