Determination of molecular formulas of natural organic matter molecules by (ultra-) high-resolution mass spectrometry: Status and needs

Electrospray ionization (ESI) combined with ultra-high-resolution mass spectrometry on a Fourier transform ion cyclotron resonance mass spectrometer has been shown to be a very powerful tool for the analysis of fulvic and humic acids and of natural organic matter (NOM) at the molecular level. With this technique thousands of ions can be separated from each other and their m/z ratio determined with sufficient accuracy to allow molecular formula calculation. Organic biogeochemistry, water chemistry, and atmospheric chemistry greatly benefit from this technique. Methodical aspects concerning the application of Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) to NOM isolated from surface water, groundwater, marine waters, and soils as well as from secondary organic aerosol in the atmospheric are reviewed. Enrichment of NOM and its chromatographic separation as well as possible influences of the ionization process on the appearance of the mass spectra are discussed. These steps of the analytical process require more systematic investigations. A basic drawback, however, is the lack of well defined single reference compounds of NOM or fulvic acids. Approaches of molecular formula calculation from the mass spectrometric data are reviewed and available graphical presentation methods are summarized. Finally, unsolved issues that limit the quality of data generated by FTICR-MS analysis of NOM are elaborated. It is concluded that further development in NOM enrichment and chromatographic separation is required and that tools for data analysis, data comparison and data visualization ought to be improved to make full use of FTICR-MS in NOM analysis.     

人体基因组课题（HGP）计划给分析化学带来的挑战与机会

本文综述了在ＤＮＡ测序方面分析化学的最新进展，包括电泳，毛细管电泳（ＣＥ），质谱（ＭＳ），电喷雾电离－质谱（ＥＳＩ－ＭＳ），荧光光谱、共振离子谱（ＲＩＳ）和单分子测定，同时还叙述了两维技术和多段测序方法的进展。     

Technological Advancements in Mass Spectrometry and Its Impact on Proteomics

Amalgamation of mass spectrometry (MS) and proteomics has led to the most awaited technological inventions such as discovery of clinically potential biomarkers and generation of effective drugs. This review focuses on the synergistic growth in MS instrumentation, proteomics and its impact on biomedical sciences. Novel ionization methods: surface enhanced laser desorption ionization, electrospray assisted laser desorption ionization, desorption electrospray ionization, laser diode thermal desorption are discussed. Different mass analyzers: ion trap, time-of-flight, Fourier transform ion cyclotron resonance and their applications are outlined. New ion fragmentation techniques: electron capture dissociation, electron transfer dissociation, infrared multiphoton dissociation and their attributes are described.     

Measurement of laser activated electron tunneling from semiconductor zinc oxide to adsorbed organic molecules by a matrix assisted laser desorption ionization mass spectrometer

Measurement of light induced heterogeneous electron transfer is important for understanding of fundamental processes involved in chemistry, physics and biology, which is still challenging by current techniques. Laser activated electron tunneling (LAET) from semiconductor metal oxides was observed and characterized by a MALDI (matrix assisted laser desorption ionization) mass spectrometer in this work. Nanoparticles of ZnO were placed on a MALDI sample plate. Free fatty acids and derivatives were used as models of organic compounds and directly deposited on the surface of ZnO nanoparticles. Irradiation of UV laser (λ = 355 nm) with energy more than the band gap of ZnO produces ions that can be detected in negative mode. When TiO₂ nanoparticles with similar band gap but much lower electron mobility were used, these ions were not observed unless the voltage on the sample plate was increased. The experimental results indicate that laser induced electron tunneling is dependent on the electron mobility and the strength of the electric field. Capture of low energy electrons by charge-deficient atoms of adsorbed organic molecules causes unpaired electron-directed cleavages of chemical bonds in a nonergodic pathway. In positive detection mode, electron tunneling cannot be observed due to the reverse moving direction of electrons. It should be able to expect that laser desorption ionization mass spectrometry is a new technique capable of probing the dynamics of electron tunneling. LAET offers advantages as a new ionization dissociation method for mass spectrometry.     

Progress of Sonic-Spray Ionization Mass Spectrometry and Its Applications

Sonic-spray ionization (SSI) is a previously developed soft ionization technique which does not need auxiliary methods such as voltage, heating, laser, or corona discharge. Spray ionization can be achieved under normal temperature and atmospheric pressure by inputting high-speed gas coaxial within the capillary. As an atmospheric pressure ion source, this technique was widely used as the interface of liquid chromatography-mass spectrometry at the beginning of its development. Based on the principles of sonic-spray ionization, a variety of easy ambient sonic-spray ionization derived techniques have been developed, which can be used for the in-situ, rapid and real-time analysis of samples with little or without any sample pretreatment. In this paper, the principless and characteristics of sonic-spray ionization were elaborated, and the progress of its application in life sciences, food safety, forensic chemistry, reaction monitoring, and other related fields were summarized.     

Determination of the Structures of Organic Molecules and Quantitative Analyses with the Field Ionization Mass Spectrometer

Field ionization and electron impact mass spectrometry complement each other well. Whereas bombardment of organic molecules with 70 eV electrons yields many characteristic fragment ions, which give valuable information about the structure of the molecules, the “soft” field ionization even of very unstable substances leads to the formation of relatively intense molecular ions which are often undetectable on ionization by electron bombardment. Field ionization also gives fragment ions that, though not very intense, are often very characteristic, and yield further information about the structure. The field desorption technique greatly reduces the degree of thermal decomposition of solid organic samples. New activation methods for field ion emitters lead to more intense ion beams and prolong the life of the emitters. Quantitative analyses using the field ionization mass spectrometer are of interest for hydrocarbon mixtures containing a very large number of components (e.g. several hundred). Simplified analyses are possible in particular for high-boiling petroleum fractions.     

Continuous‐flow extractive desorption electrospray ionization coupled to normal phase separations and for direct lipid analysis from cell extracts

Normal phase liquid chromatography is a common mode for chiral separations. Many chiral amines are used as drugs or are important intermediates for drug synthesis. Electrospray ionization mass spectrometry is well known for its high sensitivity. However, when using normal phase liquid chromatography, electrospray ionization is hampered by the poor ionization efficiency of analytes from organic eluents. Continuous‐flow extractive desorption electrospray ionization, which introduces the eluents through a hypodermic needle into the electrospray plume is demonstrated here for its success to interface normal phase liquid chromatography to mass spectrometry detection. Such an approach was shown to be as or more sensitive than ultraviolet detection for a selected set of aromatic amine‐functionalized enantiomers. Also demonstrated is the direct infusion of cell extracts to monitor phospholipids from three different bacterial cells. Despite their presence in non‐electrospray‐ionization‐friendly extraction solvents, continuous‐flow extractive desorption electrospray ionization enabled the sensitive detection of phospholipids and the ability to tune ion forms through incorporation of different spray modifiers.     

类固醇激素的低温等离子体质谱研究

将自行设计和搭建的低温等离子体装置作为离子源,成功地与常压高分辨质谱结合,并将其用于类固醇样品的定性分析.与常规电喷雾质谱相比,用低温等离子体质谱检测类固醇样品具有样品前处理简单、谱图干扰少等优点.对类固醇样品进行了一级质谱以及串联质谱的表征,发现其一级谱图能够体现出类固醇化合物的结构稳定性,而在串联质谱图中则出现了较多的丢水碎片.本工作结合能量计算详细比较分析了典型类固醇样品在碰撞诱导解离(CID)碎裂过程中的丢水过程.另外,通过比较二级质谱的不同以及对其碎裂过程的分析推测,睾酮和去氢表雄酮这对同分异构体得以区分.     

Protein profiling for cancer biomarker discovery using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and infrared imaging: a review

Cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker might be either a molecule secreted by a tumor or it can be a specific response of the body to the presence of cancer. Cancer biomarker-based diagnostics have applications for establishing disease predisposition, early detection, cancer staging, therapy selection, identifying whether or not a cancer is metastatic, therapy monitoring, assessing prognosis, and advances in the adjuvant setting. Full adoption of cancer biomarkers in the clinic has to date been slow, and only a limited number of cancer biomarker products are currently in routine use.Among proteomic technologies, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is a technique that has allowed rapid progress in cancer biology. Different further developed methods including e.g. SELDI (surface-enhanced laser desorption/ionization) and MELDI (material-enhanced laser desorption/ionization) are simple and high-throughput techniques that analyze with high sensitivity and specificity intact proteins expressed in complex biological mixtures, such as serum, urine, and tissues. The combination of mass spectrometry (MS) with infrared (IR) spectroscopic imaging is an attempt to combine different technologies in systems analytics. Both MALDI-TOF and infrared tissue imaging enable studying proteins distribution in tissue samples with a resolution down to 50 and 5 μm, respectively.In this review, we summarize recent applications and the synergistic combination of these new technologies to proteomic profiling for cancer biomarker discovery.     

ESI Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (ESI-FT-ICR-MS): A Rapid High-Resolution Analytical Method for Combinatorial Compound Libraries

The direct determination of the elemental compositions of the components of compound collections from combinatorial chemistry is achieved by ESI-FT-ICR mass spectrometry. Coupling with HPLC opens up a new dimension in high-resolution, informative analysis. The improved resolution of ESI-FT-ICR mass spectrometry in comparison to quadrupole mass spectrometry in the measurement of a compound obtained by solid-phase synthesis is illustrated.     

Mass spectrometry of natural organic phosphorus

This article provides a review of the use of modern mass spectrometry (MS) for quantitative and qualitative measurements of organic phosphorus compounds in nature. Included is a brief discussion of recent developments in large molecule mass spectrometry, focusing on time-of-flight (TOF) and ion cyclotron resonance (ICR) mass analysis techniques, as well as electrospray (ESI) and inductively coupled plasma (ICP) ionization. The use of ICP with high-resolution mass spectrometry for quantitative measurements of total phosphorus and as a detector coupled to HPLC and CE for defining organic phosphorus speciation is demonstrated using results from a study of phosphorus cycling in a treatment wetland. Qualitative identifications of individual phosphorus compounds by ultrahigh resolution Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is demonstrated using dissolved organic phosphorus isolated from this same wetland.     

Assessment of metastable atom bombardment (MAB) ionization mass spectrometry for the fast determination of heterocyclic aromatic amines in cooked meat

An investigation of metastable atom bombardment (MAB) ionization mass spectrometry for the fast characterization of mutagenic/carcinogenic heterocyclic aromatic amines (HAAs) formed during heating processes of meats is presented. The aim of our study was to use the selective ionization of MAB to develop a detection method for HAAs in non-purified meat extracts, thus avoiding purification and concentration steps and reducing analysis time. Sample introduction into the MAB ion source was achieved by pyrolysis, allowing the direct and fast insertion of complex food extracts into the mass spectrometer. Analysis conditions were optimized on standard HAAs by using different ionization gases for the MAB process. Metastable nitrogen was selected as the best MAB gas for the analysis of HAAs. Ionization selectivity is shown by the detection of heterocyclic amines in non-purified chicken meat extracts spiked with HAAs. A quantitative approach is also presented by using pyrograms as chromatograms for quantification purposes. HAAs determination using Py-MAB-ToF was finally performed on cooked chicken breast extracts and compared to an LC-APCI-MS/MS method. Although Py-MAB-ToF sensitivity remains to be improved in the present state of development of our prototype device, only 2 h from the cooking were required to obtain quantitative results in good agreement with HAAs concentrations measured by LC-MS/MS in 36 h. Figure Experimental set-up for pyrolysis-MAB-ToF mass spectrometry experiments.     

Exploration of cardanol-based phenolated and epoxidized resins by size exclusion chromatography and MALDI mass spectrometry

Cardanol and cardanol derivatives are among the most important biobased materials currently investigated in green chemistry, as renewable and promising building blocks in lieu of traditional raw materials from non renewable resources, in particular owing to the olefinic linkages on the C15 alkyl side-chain. Despite the increasing interest they arouse, analytical chemistry dedicated to cardanol and associated resins has been rarely reported in the literature, found even poorer when dealing with chromatography and mass spectrometry. In this work, a thorough molecular characterization was conducted using matrix assisted laser desorption ionization (MALDI) mass spectrometry, size exclusion chromatography (SEC), and SEC–MALDI coupling to gain insights into the composition of phenolated, epoxidized, and epoxidized phenolated cardanol. A nomenclature was proposed to properly describe the numerous species found in these materials, while simulations of the unsaturation patterns and their comparison with the detected patterns in MALDI-MS gave useful details about the phenolation treatment expected to occur on the polyunsaturated C15 side chain. Finally, the SEC–MALDI off-line coupling allowed SEC peaks to be deconvoluted by mass spectrometry and MALDI artefacts related to matrix adduction to be pointed out.     

Characterization of smokeless powders using nanoelectrospray ionization mass spectrometry (nESI-MS)

Smokeless powder is one of the most common types of explosives used in civilian ammunition and, hence, its detection and identification is of great forensic value. Based on comparison of physical properties, extraction yield in methanol, and the spectra obtained using nanoelectrospray ionization and multistage tandem mass spectrometry (MS/MS) in a quadrupole ion trap mass spectrometer, a method was developed to identify and differentiate unburned smokeless powders from different brands of ammunition. The mass spectrometry method was optimized for the simultaneous detection of the organic stabilizers commonly present in smokeless powders: methyl centralite, ethyl centralite, and diphenylamine. All but two of the powders were differentiated; however, the two that were not differentiated were produced by the same manufacturer. Gunshot residue from the cartridges was deposited on cotton cloth and collision-induced dissociation MS/MS was used to identify low levels of ethyl centralite in the residue, despite the presence of contaminants.     

质谱技术在免疫分子的结构研究中的应用

质谱技术用于生物大分子的研究具有直接、简单、快速、经济等优点。近十年来 ,基质辅助激光解吸质谱 (MALDI MS)和电喷雾质谱 (ESI MS)在免疫学领域的研究中作出了重要贡献。本文着重对抗原、抗体、抗原 抗体复合物、抗原决定簇等免疫分子结构的质谱研究作一评述。大体分为四方面内容 :免疫分子的分子量、翻译后修饰、异质性、构象变化的分析 ;质谱指纹图的取得和串联质谱测序 ;抗原 抗体复合物的证明 ;B 细胞表位和T 细胞表位序列的测定。这些研究结果对于理解免疫分子的免疫功能、对于疾病的早期诊断、对于发展新药和疫苗具有重要意义     

嗜酸性氧化亚铁硫杆菌代谢产物的常压化学电离质谱分析

本研究以721矿和745矿嗜酸性氧化亚铁硫杆菌为研究对象,采用常压化学电离质谱直接分析其代谢产物,分别考察了顶空采样( Headspace sampling)、界面采样( Interface sampling)和中性解吸采样( Neutral desorption sampling)3种进样方式对电离效果的影响。在优化条件下,常压化学电离质谱对微生物纯菌种和混合菌种的代谢产物均具有良好的分析能力,可根据获得的代谢产物指纹谱图结合主成分分析( PCA)方法和聚类分析( CA)方法区分2个放射性强弱不同区域共4类嗜酸性微生物样品,并对主要胺类、酯类等代谢成分进行串联质谱鉴定,为耐辐射微生物的相关研究提供了一种可借鉴的分析方法。     

Progress of laser ionization mass spectrometry for elemental analysis — A review of the past decade

Mass spectrometry using a laser ionization source has played a significant role in elemental analysis. Three types of techniques are widely used: high irradiance laser ionization mass spectrometry is capable of rapid determination of elements in solids; single particle mass spectrometry is a powerful tool for single particle characterization; and resonance ionization mass spectrometry is applied for isotope ratio measurements with high sensitivity and selectivity. In this review, the main features of the laser ablation process and plasma characterization by mass spectrometry are summarized. Applications of these three techniques for elemental analysis are discussed.     

On‐Line Electrochemistry/Electrospray Ionization Mass Spectrometry (EC/ESI‐MS) for the Generation and Identification of Nucleotide Oxidation Products

The oxidation behavior of DNA and RNA nucleotides is studied by an on‐line set‐up consisting of an electrochemical thin‐layer cell (EC) directly coupled to electrospray ionization mass spectrometry (ESI‐MS). This set‐up allows the generation of nucleotide oxidation products in the electrochemical cell at increasing potentials. Moreover, the products are determined directly, without isolation or derivatization steps, by electrospray ionization time of flight mass spectrometry (ESI‐ToF/MS). The dependence of the mass spectra on the applied potential is displayed as ‘mass voltammograms’. An advanced set‐up, consisting of the electrochemical cell coupled to electrospray ionization tandem mass spectrometry (EC/ESI‐MS/MS) allows further structure elucidation based on fragmentation experiments. The electrochemical conversion is performed using a boron doped diamond (BDD) working electrode, which is known to generate hydroxyl radicals at high potentials. The capability of the EC‐MS system to generate highly relevant oxidation products which also occur upon oxidative damage in vivo is demonstrated in this study by the formation of well known biomarkers for DNA damage, including 2′‐deoxy‐8‐oxo‐guanosine 5′‐monophosphate.     

Nanomaterials in mass spectrometry ionization and prospects for biological application

The rapid development of nanotechnology has revolutionized scientific developments in recent decades. Mass spectrometry (MS) measurements are no exception and have benefited greatly from integration of nanomaterials in every step of analysis. This brief review summarizes recent developments in the field with the focus on the use of nanomaterials as alternative media to facilitate analyte ionization in laser-desorption ionization–mass spectrometry (LDI–MS) and secondary ion mass spectrometry (SIMS). The biological applications of both techniques are also detailed. The use of nanomaterials in other aspects of MS analysis, for example in sample clean-up and indirect analyte quantification, is briefly discussed.     

Research Progress and Application of Ion Funnel Technique

Ion funnel is a new-style ion guider which can reduce spatial divergence and energy dispersity of the transmission ions by using radio frequency (RF) electric field to confine the ions radially and the direct current (DC) axial electric field to move the ions toward the exit, and thus it can greatly increase the ion transmission efficiency and improve the sensitivity of the mass spectrometry. Since ion funnel was invented in 1997, it has attracted a close attention of mass spectrometry scientists all over the world. Ion funnel has been used in various kinds of mass spectrometry, and built a bridge with high efficiency ion transmission between low vacuum ionization source and high vacuum mass analyzer. In this paper, the principle, technology development, and application progress of ion funnel are reviewed, and the future prospects are prospected.