Rapid Imaging of Unsaturated Lipids at an Isomeric Level Achieved by Controllable Oxidation.

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.

Rapid In Situ Profiling of Lipid C═C Location Isomers in Tissue Using Ambient Mass Spectrometry with Photochemical Reactions.

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 ( R2 = 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.

Interlayer spray ionization mass spectrometry for the simple direct analysis of low amounts of sample.

Interlayer spray is proposed as a convenient ionization source for direct analysis by mass spectrometry. Two slices of non-absorbent substrate hold the liquid sample to form a sandwich structure. By applying a high voltage to the sample, spray is generated at the tip of the substrate. The sampling procedure can be operated easily in an open condition and the spray is processed in a semi-enclosed condition, which leads to a relatively stable process. An ultralow amount (<2 µL) of the liquid sample can be analyzed without dilution, which ensures that the natural concentration and properties of the target are maintained. Less influence from the substrate is achieved compared with the spray methods based on porous absorbent materials, which results in a sensitivity enhancement of large molecule samples. It is demonstrated that the interlayer spray is applicable for the analysis of various compounds, including therapeutic drugs, peptides, and proteins. Good linearity can be obtained at a concentration as low as 50 ng/mL in the quantitative analysis for imatinib. We also show the ability to identify the chemical residuals on surfaces with high sensitivity by the "wipe-spray" method, which is useful for the fast screening of illicit substances. Interlayer spray working with mass spectrometry provides a promising method for direct analysis in an ambient environment. Graphical Abstract The schematic of the interlayer spray ionization source.

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.

Development of dielectric-barrier-discharge ionization.

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.

Cataluminescence-based sensors: principle, instrument and application.

The cataluminescence (CTL)-based sensor is a new promising type of chemical transducer, and has attracted much attention of researchers for its potential versatile applications in public safety, emission control and environmental protection. In this review, we briefly introduce the development history of CTL-based sensors and summarize existing explanations of the CTL reaction mechanism as well as three research strategies for mechanism the CTL mechanism. In the following, all the function units of a typical CTL-based sensor system are described and the investigation of the sensor materials. CTL-based sensor arrays, are discussed in detail. We classify the recent novel hyphenated techniques based on CTL coupled to other analysis techniques into the preconcentration-CTL hyphenated technique, nebulization-CTL hyphenated technique, plasma-assisted CTL technique and tandem CTL technique according to the type of analysis combined with CTL and provide a detailed account of novel hyphenated techniques. Owing to the appearance of these novel techniques, the application range of CTL has been expanded as well as the sensitivity and selectivity of CTL system has been greatly improved. Finally, the applications of CTL-based sensor and sensor arrays in the last several years are classified and summarized.

Ambient mass spectrometry imaging: plasma assisted laser desorption ionization mass spectrometry imaging and its applications.

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.

Quantification and evaluation of ion transmission efficiency in two-stage vacuum chamber miniature mass spectrometer.

Miniature mass spectrometer is more compact and portable than traditional commercial mass spectrometry, with more potential for application outside the laboratory. However, a miniature mass spectrometer is less sensitive than a commercial instrument, limiting its application scenarios. The ion transmission efficiency of the instrument is an essential factor affecting the sensitivity. Still, there are few works of literature on the quantitative study of the ion transmission efficiency of each component from a systematic perspective. In this paper, the Faraday cup coupled with a microcurrent signal testing instrument was used to measure the ions generated by nanoelectrospray ionization (nano-ESI), which have successfully gone through several components. Then the ion transmission efficiency of each component was quantified. Results showed that the front lens had the highest ion transmission efficiency of 39.7%, whereas the inlet and skimmer had the lowest ion transfer efficiency of 0.8% and 17.1%. Next, the influence of control parameters on ion transmission efficiency of critical components was investigated. If optimized, the ion funnel and the skimmer had the potential to improve their transmission efficiency by 120% and 79%, respectively. This paper shows the decreasing intensity distribution of ions in the whole transmission process and the transmission efficiency of each component, which can guide for improving the sensitivity of the miniature mass spectrometer.

Automatic Diagnosis of Alzheimer's Disease and Mild Cognitive Impairment Based on CNN + SVM Networks with End-to-End Training.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease, and, at present, once it has been diagnosed, there is no effective curative treatment. Accurate and early diagnosis of Alzheimer's disease is crucial for improving the condition of patients since effective preventive measures can be taken in advance to delay the onset time of the disease. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET : PET) is an effective biomarker of the symptom of AD and has been used as medical imaging data for diagnosing AD. Mild cognitive impairment (MCI) is regarded as an early symptom of AD, and it has been shown that MCI also has a certain biomedical correlation with PET. In this paper, we explore how to use 3D PET images to realize the effective recognition of MCI and thus achieve the early prediction of AD. This problem is then taken as the classification of three categories of PET images, including MCI, AD, and NC (normal controls). In order to get better classification performance, a novel network model is proposed in the paper based on 3D convolution neural networks (CNN) and support vector machines (SVM) by utilizing both the excellent abilities of CNN in feature extraction and SVM in classification. In order to make full use of the optimal property of SVM in solving binary classification problems, the three-category classification problem is divided into three binary classifications, and each binary classification is being realized with a CNN + SVM network. Then, the outputs of the three CNN + SVM networks are fused into a final three-category classification result. An end-to-end learning algorithm is developed to train the CNN + SVM networks, and a decision fusion algorithm is exploited to realize the fusion of the outputs of three CNN + SVM networks. Experimental results obtained in the work with comparative analyses confirm the effectiveness of the proposed method.

Unsaturated lipid isomeric imaging based on the Paternò-Büchi reaction in the solid phase in ambient conditions.

In recent years, the development of unsaturated lipid isomeric imaging based on the Paternò-Büchi (PB) reaction has improved significantly. However, research on this imaging method in ambient conditions needs to expand. In this paper, a method of PB reaction in the solid phase in ambient conditions is developed, which is combined with air-flow-assisted desorption electrospray ionisation mass spectrometry (AFADESI-MS) to achieve in situ imaging of lipids at an isomeric level. Experiments showed that the efficiency of the PB reaction was much higher when spraying the reagent solution than when sprinkling the reactant powder directly, and it was not lower than that in the liquid phase. This method can simplify the reaction conditions in the imaging process and can be applied to tissue section samples with only 10 min of pre-processing. The study successfully demonstrated the spatial distribution of unsaturated lipid isomers, and the isomeric ratio corresponded to the lesion areas in mouse brain cancer tissues. Due to its simple operation and performance in ambient conditions, this method may be useful for future studies on lipid isomers in tissues.

Asymmetric rectilinear ion trap with unidirectional ion ejection capability.

In this paper, the shapes of the electrodes are modified based on a rectilinear ion trap to achieve unidirectional ejection of ions. The designed asymmetric rectilinear ion trap (ARIT) analyzer adds convex and concave circular structures with a height of 0.5 mm on the two X-electrodes, so that the electric field center of the ion trap is inclined to the concave side. The electric field lines of the convex side are compressed to the concave side. Both simulations and experimental results show that ions are more likely to emit from the slit on the concave side plate when performing ion resonance ejection. The mass spectrum signal intensity can reach more than twice that of the original rectilinear trap when using only one detector. Calculations of the electric field components in the trap show that the even-order higher field proportion in the ion trap has not been significantly affected. Combined with the experimental test results, the study further confirmed that the developed ARIT has no significant loss in mass resolution, tandem mass spectrometry capability, and quantitative analysis capability. The proposed asymmetric structure modification scheme can achieve single-side ejection without significantly affecting other performances of the analyzer, which provides a new idea for the structural optimization of the subsequent ion trap analyzers.

Novel control modes to improve the performance of rectilinear ion trap mass spectrometer with dual pressure chambers.

The rectilinear ion trap (RIT) has gradually become one of the preferred mass analyzers for portable mass spectrometers because of its simple configuration. In order to enhance the performance, including sensitivity, quantitation capability, throughput, and resolution, a novel RIT mass spectrometer with dual pressure chambers was designed and characterized. The studied system constituted a quadrupole linear ion trap (QLIT) in the first chamber and a RIT in the second chamber. Two control modes are hereby proposed: Storage Quadrupole Linear Ion Trap-Rectilinear Ion Trap (SQLIT-RIT) mode, in which the QLIT was used at high pressure for ion storage and isolation, and the RIT was used for analysis; and Analysis Quadrupole Linear Ion Trap-Rectilinear Ion Trap (AQLIT-RIT) mode, in which the QLIT was used for ion storage and cooling. Subsequently, synchronous scanning and analysis were carried out by QLIT and RIT. In SQLIT-RIT mode, signal intensity was improved by a factor of 30; the limit of quantitation was reduced more than tenfold to 50 ng mL-1, and an optimal duty cycle of 96.4% was achieved. In AQLIT-RIT mode, the number of ions coexisting in the RIT was reduced, which weakened the space-charge effect and reduced the mass shift. Furthermore, the mass resolution was enhanced by a factor of 3. The results indicate that the novel control modes achieve satisfactory performance without adding any system complexity, which provides a viable pathway to guarantee good analytical performance in miniaturization of the mass spectrometer.

A Neurodynamic Optimization Method for Recovery of Compressive Sensed Signals With Globally Converged Solution Approximating to l0 Minimization.

Finding the optimal solution to the constrained l0 -norm minimization problems in the recovery of compressive sensed signals is an NP-hard problem and it usually requires intractable combinatorial searching operations for getting the global optimal solution, unless using other objective functions (e.g., the l1 norm or lp norm) for approximate solutions or using greedy search methods for locally optimal solutions (e.g., the orthogonal matching pursuit type algorithms). In this paper, a neurodynamic optimization method is proposed to solve the l0 -norm minimization problems for obtaining the global optimum using a recurrent neural network (RNN) model. For the RNN model, a group of modified Gaussian functions are constructed and their sum is taken as the objective function for approximating the l0 norm and for optimization. The constructed objective function sets up a convexity condition under which the neurodynamic system is guaranteed to obtain the globally convergent optimal solution. An adaptive adjustment scheme is developed for improving the performance of the optimization algorithm further. Extensive experiments are conducted to test the proposed approach in this paper and the output results validate the effectiveness of the new method.

In situ biomarker discovery and label-free molecular histopathological diagnosis of lung cancer by ambient mass spectrometry imaging.

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.