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.

Rapid and in situ profiling of lipids using ambient mass spectrometry (AMS) techniques has great potential for clinical diagnosis, biological studies, and biomarker discovery. In this study, the online photochemical reaction involving carbon-carbon double bonds was coupled with a surface sampling technique to develop a direct tissue-analysis method with specificity to lipid C═C isomers. This method enabled the in situ analysis of lipids from the surface of various tissues or tissue sections, which allowed the structural characterization of lipid isomers within 2 min. Under optimized reaction conditions, we have established a method for the relative quantitation of lipid C═C location isomers by comparing the abundances of the diagnostic ions arising from each isomer, which has been proven effective through the established linear relationship ( R = 0.999) between molar ratio and diagnostic ion ratio of the FA 18:1 C═C location isomers. This method was then used for the rapid profiling of unsaturated lipid C═C isomers in the sections of rat brain, lung, liver, spleen, and kidney, as well as in normal and diseased rat tissues. Quantitative information on FA 18:1 and PC 16:0-18:1 C═C isomers was obtained, and significant differences were observed between different samples. To the best of our knowledge, this is the first study to report the direct analysis of lipid C═C isomers in tissues using AMS. Our results demonstrated that this method can serve as a rapid analytical approach for the profiling of unsaturated lipid C═C isomers in biological tissues and should contribute to functional lipidomics and clinical diagnosis.

Sensitive and spatial exploration of the metabolism of tumors at the metabolome level is highly challenging. In this study, we developed an in situ metabolomics method based on ambient mass spectrometry imaging using air flow-assisted desorption electrospray ionization (AFADESI), which can spatially explore the alteration of global metabolites in tissues with high sensitivity. Using this method, we discovered potential histopathological diagnosis biomarkers (including lipids, amino acids, choline, peptides, and carnitine) from 52 postoperative lung cancer tissue samples and then subsequently used these biomarkers to generate images for rapid and label-free histopathological diagnosis. These biomarkers were validated with a sensitivity and a specificity of 93.5% and 100%, respectively. Moreover, a single imaging analysis of a cryosection that visualized all these biomarkers, taking tens of minutes, revealed the type and subtype of the cancer. This method could potentially be used as a molecular pathological tool for rapid clinical lung cancer diagnosis and immediate image-guided surgery.

Dielectric-barrier-discharge ionization is an ambient-ionization technique. Since its first description in 2007, it has attracted much attention in such fields as biological analysis, food safety, mass-spectrometry imaging, forensic identification, and reaction monitoring for its advantages, e.g., low energy consumption, solvent-free method, and easy miniaturization. In this review a brief introduction to dielectric barrier discharge is provided, and then a detailed introduction to the dielectric-barrier-discharge-ionization technique is given, including instrumentation, applications, and mechanistic studies. Based on the summary of reported work, possible future uses of this type of ionization source are discussed at the end.

Mass spectrometry imaging (MSI) has been widely used in many research areas for the advantages of providing informative molecular distribution with high specificity. Among the recent progress, ambient MSI has attracted increasing interests owing to its characteristics of ambient, in situ, and nonpretreatment analysis. Here, we are presenting the ambient MSI for traditional Chinese medicines (TCMs) and authentication of work of art and documents using plasma assisted laser desorption ionization mass spectrometry (PALDI-MS). Compared with current ambient MSI methods, an excellent average resolution of 60 μm × 60 μm pixel size was achieved using this system. The feasibility of PALDI-based MSI was confirmed by seal imaging, and its authentication applications were demonstrated by imaging of printed Chinese characters. Imaging of the Radix Scutellariae slice showed that the two active components, baicalein and wogonin, mainly were distributed in the epidermis of the root, which proposed an approach for distinguishing TCMs' origins and the distribution of active components of TCMs and exploring the environmental effects of plant growth. PALDI-MS imaging provides a strong complement for the MSI strategy with the enhanced spatial resolution, which is promising in many research fields, such as artwork identification, TCMs' and botanic research, pharmaceutical applications, etc.

Lipid imaging plays an important role in the research of some diseases, such as cancers. Unsaturated lipids are often present as isomers that can have different functions; however, traditional tandem mass spectrometry imaging (MSI) cannot differentiate between different isomers, which presents difficulties for the pathological study of lipids. Herein, we propose a method for the MSI of the CC double-bond isomers of unsaturated lipids based on oxidative reactions coupled with air flow-assisted desorption electrospray ionization, which can conveniently achieve rapid MSI of unsaturated lipids at an isomeric level. Using this method, tissue sections can be scanned directly with MSI after only 10 min of accelerated oxidation. This method was used for the imaging of mouse lung cancer tissues, revealing a distributional difference in the unsaturated lipid isomers of normal and pathological regions. Through the MSI of unsaturated lipids at an isomeric level in tissues infected with cancer cells, the regions where the isomers were enriched were exhibited, indicating that these regions were the most concentrated regions of cancer cells. This method provides a convenient platform for studying the functional effects of the isomers of unsaturated lipids in pathological tissues.

Plasma-based ambient mass spectrometry (AMS) exhibits great potential in the direct analysis of raw samples with minimum pretreatment.

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