| Mass spectrometry (MS) is currently a irreplaceable tool of analysis which develops very rapidly. Modern mass spectrometry is a type of fast analytical method with high sensitivity, high specific, high throughput and universal applicability. It has the features of in-situ, real-time, online, non-destructive, high throhghput and low loss, and is the important trend for the development of mass spectrometry. It is also the research frontier and hot spot in the area of mass spectrometry both at home and abroad, and even in the whole field of analytical chemistry.The research of modern mass spectrometry mainly involves the theories, equipments, technologies and methods on developing the new ion sources, which is especially important and significant for driving the development of mass spectrometry. Sample pretreatment must be undertaken before the analysis of samples with complex matrix using the conventional ion source such as electronic bombardment ionization (EI) source, chemical ionization (CI) source, fast Atomic bombardment (FAB) source, matrix secondary laser solutions suction ionization (MALDI) source, and electric spray ionization (ESI) source, which cannot meet the actual needs of sample analysis on in-situ, real-time, online, non-damage, high throughput, and low loss. After desorption electrospray ionization (DESI) source was invented by Professor Cooks of Purdue University in 2004, direct mass spectrometric analysis without sample pretreatment was made possible. Then, the research of new ionization technique boomed all over the world, and dozens of new ion sources were invented, which makes MS analysis of samples with complex matrix develop rapidly in the direction of real-time, online, in-situ, in vivo, non-destructive analysis.Extractive electrospray ionization (EESI) is a novel ionization technology appearing in 2006 which makes in-situ, in vivo, real-time, and online analysis possible for the first time. Samples with complex matrix in various forms such as liquids, gases, aerosols, suspension liquid, solid surface, powder, colloids and other forms can be rapidly and directly analyzed without sample pretreatment using EESI-MS. Currently, EESI has been gradually applied to many research fields such as foods and supplies quality monitoring, drug detection, environmental quality monitoring, process analysis, dopes and explosives detection, biological macromolecular analysis, in vivo analysis, and metabolomics. In this thesis, we have studied the devices and mechanism of ionization involved in EESI, and the methods of EESI-MS for direct analysis of liquid, breath and viscous samples with complex matrix. The development of direct analysis of solid surface using EESI-MS has also been reviewed. These study laid a foundation for further deepening the understanding of EESI-MS, continuing to strengthen the research of EESI-MS, and expanding its application scope.The main research content of this dissertation involves as following:1) The mechanism of EESI. EESI is an ideal ionization method for the analysis of samples with complex matrix. In order to improve the controllability of the process and ensure the reliability of the results of EESI analysis, we have studied the fluorescence imaging of EESI spray, and the effect of different solvent systems of electrospray solvents and sample solvents. The results showed that, the process of EESI occurs in the liquid phase rather than the gas phase, and there is selective liquid-liquid extraction between the electrospray droplet and the neutral sample droplet.2) The application of EESI-MS for the analysis of liquid samples with complex matrix. Using the home-made EESI source and optimizing EESI working conditions, the EESI-MS method for analysis of liquid samples with complex matrix was established and applied to the detection of diethylene glycol (DEG) in toothpaste extraction and apigenin in soil solution. For the quantitative detection of DEG in toothpaste extraction, the method has a wide linear range (up to four orders of magnitude), a good linear relationship (R2 = 0.997), high sensitivity (detection limit is 0.1μg/L) and a good reproducibility (RSD<4.4%); and for the analysis of apigenin through multi-stage tandem mass spectrometry, the character and mechanism of the dissociation of apigenin in EESI-MS were discussed according to the various characteristic fragments formed. Then, on the basis of the EESI-MSn of apigenin, the rhizosphere soil solution of Beijing Euphorbia was analyzed and apigenin was found in it. Thus, EESI-MS can be successfully applied in the direct, rapid and sensitive qualitative and quantitative analysis of liquid samples with complex matrix without sample pretreatment.3) The application of EESI-MS for the analysis of breath samples with complex matrix. Using the home-made EESI source, the EESI tandem mass spectrometry platform for in vivo breath analysis has been built, and was optimized systematically using octyl amine. Under the optimized conditions, the body's metabolic changes can be observed quickly through the in vivo fingerprint spectra of the breath, and it showed that breath can be used as samples of metabolomics. According to the results of in vivo breath analysis, for nicotine in breath, the linear quantitative detection range was up to five orders of magnitude, LOD was limited to 0.05 fg/mL, RSD<5.0%, and the dynamic metabolic curve of nicotine and its metabolite cotinine in breath can also be obtained; for acetonitrile in breath, through ion / molecule reactions, a new reactive EESI-MS was established for in vivo qualitative and quantitative analysis of acetonitrile, and in order to reveal the generation mechanism of acetonitrile in breath, the concentration and degradation of acetonitrile in breath of active smokers and passive smokers were also studied. Thus, EESI-MS is a practical and convenient tool for in vivo metabolomics study based on breath analysis.4) The application of EESI-MS for the analysis of viscous samples with complex matrix. Using the home-made device of ND and EESI source, under the optimized ND and EESI working conditions, the ND-EESI-MS method for analysis of viscous samples with complex matrix was established, and then it was used in the analysis of viscous toothpaste and Sputum. It showed that non-volatile compounds (such as DEG) can be released from the gel mixture (such as toothpaste) and then be detected by EESI-MS with high speed, high sensitivity, high accuracy and good reproducibility. Through the direct analysis of the sputum of non-small cell lung cancer (NSCLC) patients and non-lung cancer patients, their mass fingerprints were obtained. Combined with principal component analysis (PCA), a method of pattern recognition, the recognition model which used to distinguish NSCLC patients and non-lung cancer patients has been established. It provides an opportunity for the rapid diagnosis and early screening of NSCLC, and clinical monitoring of tumor recurrence. Thus, these results prove that ND-EESI-MS is a useful tool for rapid analysis and characterizing of high viscosity samples with complex matrix.5) The development of solid surface analysis using EESI-MS. Neutral desorption extractive electrospray ionization mass spectrometry (ND-EESI-MS) was established by coupling ND device to the EESI-MS. ND-EESI-MS can be used not only for the direct analysis of a variety solid surface samples, but also for in vivo analysis of biological surface samples and remote analysis of solid surface samples under extreme conditions (For example, high temperature, low temperature, biological or radiological hazards, etc.). In this thesis, according to the development and improvement of the ND device, we have reviewed the applications of open-air ND-EESI, air-tight ND-EESI, geometry-independent ND-EESI and probe type ND-EESI in direct analysis of a variety of solid surface samples, and looked forward to the application prospects of ND-EESI-MS.Through the research above, we know that EESI-MS is not poisonous and polluted to samples, suitable for in-situ, in vivo, real-time, online and remote, non-destructive, direct analysis of various forms of samples with complex matrix without sample preparation, thus can be used to detect both polar and non-polar compounds in samples. So EESI-MS has broad application prospects in modern mass spectrometry.
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