辉光放电清洗在同步辐射光束线上的应用

同步辐射光束线上存在的碳污染是影响光束线特别是软X光束线传输效率的重要原因,污染的生成与镜箱腔壁上存在有少量的油有关。为了获得更加洁净的真空室,通过辉光放电对镜箱真空室壁进行清洗,力争从源头上减少光学元件碳污染的产生。设计并搭建了一套应用在同步辐射光束线镜箱上的辉光放电清洗系统,并研究了装置在不同真空度下辉光的伏安特性。利用四极质谱对辉光放电前后及过程中镜箱内的残气进行分析。研究得出,真空室表面残留油分子的初步裂解产物主要是分子量为69的粒子。通过辉光放电清洗,真空室内残存的微量油大分子的(分子量为39,41,43,55,57,69,71)减少幅度达到50%。辉光放电清洗对真空腔体内表面油分子有明显的去除效果。本文研究的内容对于减少光束线站特别是软X射线光束线上碳污染具有重要意义。     

Preparation of cells cultured on silicon wafers for mass spectrometry analysis

The distribution of specific atoms and molecules within living cells is of high interest in bio-medical research. Laser secondary neutral mass spectrometry (laser-SNMS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) detect atoms with high sensitivity and spatial resolution. The application of these methods to cultured cells requires special preparation techniques preserving morphological and chemical integrity of the living cells. The cells should, therefore, be grown on a conducting material preventing charging of the sample during ion bombardment. Silicon is currently used as the preferred support material for non-biological samples in mass spectrometry. This study investigates (1) the influence of silicon surfaces on cell growth and (2) the suitability of a sandwiched, rapid freezing method to analyse transmembrane ion gradients. Human melanoma cells were grown on silicon with polished or etched surfaces. Growth kinetics were studied using the Sulforhodamine-B assay. Number, shape, and morphology of the cells were assessed by epifluorescence microscopy of calcein AM- and DAPI-stained cells. Cells were subjected to rapid freezing, freeze-fracturing, and freeze-drying prior to analysis by TOF-SIMS and laser-SNMS. While cell numbers and morphology on the rough silicon wafers were impaired, morphology and growth kinetics of cells on polished silicon were identical to control cells on cell culture tested polystyrene. TOF-SIMS and laser-SNMS resulted in high-resolution elemental images and mass spectra. Measurement of the intracellular Na+ and K+ concentrations revealed a ratio as observed in living cells. In conclusion, culturing cells on polished silicon wafers followed by sandwiched, rapid freezing is an adequate preparation method to study intracellular ion distribution with mass spectrometry.     

The role of mass spectrometry in atomic weight determinations

The 1914 Nobel Prize for Chemistry was awarded to Theodore Richards, whose work provided an insight into the history of the birth and evolution of matter as embedded in the atomic weights. However, the secret to unlocking the hieroglyphics contained in the atomic weights is revealed by a study of the relative abundances of the isotopes. A consistent set of internationally accepted atomic weights has been a goal of the scientific community for over a century. Atomic weights were originally determined by chemical stoichiometry--the so-called "Harvard Method," but this methodology has now been superseded by the "physical method," in which the isotopic composition and atomic masses of the isotopes comprising an element are used to calculate the atomic weight with far greater accuracy than before. The role of mass spectrometry in atomic weight determinations was initiated by the discovery of isotopes by Thomson, and established by the pioneering work of Aston, Dempster, and Nier using sophisticated mass spectrographs. The advent of the sector field mass spectrometer in 1947, revolutionized the application of mass spectrometry for both solids and gases to other fields of science including atomic weights. Subsequently, technological advances in mass spectrometry have enabled atomic masses to be determined with an accuracy better than one part in 10(7), whilst the absolute isotopic composition of many elements has been determined to produce accurate values of their atomic weights. Conversely, those same technological developments have revealed significant variations in the isotope abundances of many elements caused by a variety of physiochemical mechanisms in natural materials. Although these variations were initially seen as an impediment to the accuracy with which atomic weights could be determined, it was quickly realized that nature had provided a new tool to investigate physiochemical and biogeochemical mechanisms in nature, which could be exploited by precise and accurate isotopic measurements. Atomic weights can no longer be regarded as constants of nature, except for the monoisotopic elements whose atomic weights are determined solely by the relative atomic mass of that nuclide. Stable isotope geochemists developed mass spectrometric protocols by the adoption of internationally accepted reference materials for the light elements, to which measurements from various laboratories could be compared. Subsequently, a number of heavy elements such as iron, molybdenum and cadmium have been shown to exhibit isotope fractionation. The magnitude of such isotope fractionation in nature is less than for the light elements, but technological developments, such as multiple collector-inductively coupled plasma-mass spectrometry, have enabled such fractionation effects to be determined. Measurements of the atomic weights of certain elements affect the determination of important fundamental constants such as the Avogadro Constant, the Faraday Constant and the Universal Gas Constant. Heroic efforts have been made to refine the accuracy of the atomic weight of silicon, with the objective of replacing the SI standard of mass--the kilogram--with the Avogadro Constant. Improvements in these fundamental constants in turn affect the set of self-consistent values of other basic constants through a least-squares adjustment methodology. Absolute isotope abundances also enable the Solar System abundances of the s-, r-, and p-process of nucleosynthesis to be accurately determined, thus placing constraints on theories of heavy element nucleosynthesis. Future developments in the science of atomic weight determinations are also examined.     

气相色谱-质谱法测定化妆品中的苯甲醇

本文采用气相色谱/质谱法测定了化妆品中苯甲醇。实验主要优化了仪器条件,获得固体和液体样品中苯甲醇添加回收率在96%～101%之间。该方法具有稳定性好、不易受干扰灵敏度高等特点,可简单、快速地测定化妆品中的苯甲醇。     

Analysis of boron-10 in soft tissue by dynamic secondary ion mass spectrometry

We report here a preliminary study in which dynamic secondary ion mass spectrometry (SIMS) has provided images of boron‐10 (¹⁰B) in biological tissue as used in research into boron neutron capture therapy. Cultured tumour cells incubated in media containing known concentrations of a ¹⁰B‐containing compound, p‐boronophenylalanine (BPA), and intracranial tumour tissue from animals previously injected with BPA were analysed by an in‐house constructed SIMS. Investigations were conducted in positive secondary ion detection mode using a 25‐keV, 5‐nA gallium primary ion source. For calibration purposes, tissue standards were also analysed and their boron‐to‐carbon signal ratios correlated to bulk boron concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP‐AES). Ion maps of ¹⁰B, ¹²C, ²³Na and ³⁹K showing gross tissue and cell features were acquired. SIMS and ICP‐AES standard measurements were in good agreement. Tissue regions with high or low ¹⁰B concentrations were identified along with ¹⁰B hotspots in normal brain areas. Cultured cells revealed the intracellular localization of ¹⁰B. SIMS is capable of producing images showing the distribution of ¹⁰B at p.p.m. levels in cells and in normal and tumour‐bearing brain tissue.     

Advances in mass spectrometry for the identification of pathogens

Mass spectrometry (MS) has become an important technique to identify microbial biomarkers. The rapid and accurate MS identification of microorganisms without any extensive pretreatment of samples is now possible. This review summarizes MS methods that are currently utilized in microbial analyses. Affinity methods are effective to clean, enrich, and investigate microorganisms from complex matrices. Functionalized magnetic nanoparticles might concentrate traces of target microorganisms from sample solutions. Therefore, nanoparticle-based techniques have a favorable detection limit. MS coupled with various chromatographic techniques, such as liquid chromatography and capillary electrophoresis, reduces the complexity of microbial biomarkers and yields reliable results. The direct analysis of whole pathogenic microbial cells with matrix-assisted laser desorption/ionization MS without sample separation reveals specific biomarkers for taxonomy, and has the advantages of simplicity, rapidity, and high-throughput measurements. The MS detection of polymerase chain reaction (PCR)-amplified microbial nucleic acids provides an alternative to biomarker analysis. This review will conclude with some current applications of MS in the identification of pathogens.     

A review of current applications of mass spectrometry for neuroproteomics in epilepsy

The brain is unquestionably the most fascinating organ, and the hippocampus is crucial in memory storage and retrieval and plays an important role in stress response. In temporal lobe epilepsy (TLE), the seizure origin typically involves the hippocampal formation. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward an improved understanding of the complex molecular mechanisms that underlie functions of the brain and hippocampus is neuroproteomics. Mass spectrometry has been widely used to analyze biological samples, and has evolved into an indispensable tool for proteomics research. In this review, we present a general overview of the application of mass spectrometry in proteomics, summarize neuroproteomics and systems biology‐based discovery of protein biomarkers for epilepsy, discuss the methodology needed to explore the epileptic hippocampus proteome, and also focus on applications of ingenuity pathway analysis (IPA) in disease research. This neuroproteomics survey presents a framework for large‐scale protein research in epilepsy that can be applied for immediate epileptic biomarker discovery and the far‐reaching systems biology understanding of the protein regulatory networks. Ultimately, knowledge attained through neuroproteomics could lead to clinical diagnostics and therapeutics to lessen the burden of epilepsy on society. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:197–246, 2010     

Structure elucidation of native N- and O-linked glycans by tandem mass spectrometry (tutorial)

Oligosaccharides play important roles in many biological processes. However, the structural elucidation of oligosaccharides remains a major challenge due to the complexities of their structures. Mass spectrometry provides a powerful method for determining oligosaccharide composition. Tandem mass spectrometry (MS) provides structural information with high sensitivity. Oligosaccharide structures differ from other polymers such as peptides because of the large number of linkage combinations and branching. This complexity makes the analysis of oligosaccharide unique from that of peptides. This tutorial addresses the issue of spectral interpretation of tandem MS under conditions of collision-induced dissociation (CID) and infrared multiphoton dissociation (IRMPD). The proper interpretation of tandem MS data can provide important structural information on different types of oligosaccharides including O- and N-linked.     

吸附管/气相色谱/质谱法分析纵火案的纵火剂残留物

用吸附管(AT)/气相色谱(GC)/质谱(MS)法检测纵火残留物中轻质矿物油是通过吸附管动态吸附检材中可挥发的有机物,然后通过热脱附将挥发物送至GC及GC/MS中检测。它既适用于轻组分的碳氢化合物,如汽油,也适用于较高分子的碳氢化合物,如柴油和煤油。用沸石预处理样品克服了样品中水分对鉴定的干扰。用本方法能够得到比过去所使用的溶剂提取法或顶空法(HS)更高的吸附效率和灵敏度,解决以往由于残留物中热解产物干扰所造成的GC图形混乱复杂,难以准确分析鉴定的问题。用本方法分析纵火或火灾案件中常见的残留物——轻质矿物油,具有快速、灵敏、准确和简便等特点,可广泛用于公安、司法和保险等各个领域。     

Detection and characterization of variant and modified structures of proteins in blood and tissues by mass spectrometry

Some variant proteins cause diseases, and some diseases result in increases of proteins with abnormally modified structures. The detection, characterization, and estimation of the relative amounts of protein variants and abnormally modified proteins are important for clinical diagnosis and for elucidation of the mechanisms of the pathogenesis of diseases. Analysis of the covalent structures of proteins using matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) and liquid chromatography-electrospray ionization MS (LC-ESI-MS), which had been developed by the early 1990s, have largely replaced analyses by conventional protein chemistry. Here, we review the detection and characterization of hemoglobin variants, HbA1c measurement, detection of carbohydrate-deficient transferrin, and identification of variants of transthyretin (TTR) and Cu/Zn-superoxide dismutase (SOD-1) using soft ionization MS. We also propose the diagnostic application of the signals of modified forms of TTR, that is, S-sulfonated TTR and S-homocysteinyl TTR. The relative peak height ratio of the abnormal/normal components gives valuable information about the instability of variants and enables the detection of unstable Hb subunits or thalassemia heterozygotes. We found unique modified structures of TTR that suggested changes in amyloid fibrils.     

Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular‐scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS)

Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron‐10 (¹⁰B) atoms to individual tumour cells. Cell killing results from the ¹⁰B (n, α)⁷Li neutron capture and fission reactions that occur if a sufficient number of ¹⁰B atoms are localized in the tumour cells. Intranuclear ¹⁰B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of ¹⁰B atoms reflects both bound and free pools of boron in individual tumour cells. The assessment of these pools, delivered by a boron delivery agent, currently cannot be made at subcellular‐scale resolution by clinically applicable techniques such as positron emission tomography and magnetic resonance imaging. In this study, a secondary ion mass spectrometry based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G glioblastoma cells were evaluated for boron uptake and retention of two delivery agents. The first, L‐p‐boronophenylalanine (BPA), has been used clinically for BNCT of high‐grade gliomas, recurrent tumours of the head and neck region and melanomas. The second, a boron analogue of an unnatural amino acid, 1‐amino‐3‐borono‐cyclopentanecarboxylic acid (cis‐ABCPC), has been studied in rodent glioma and melanoma models by quantification of boron in the nucleus and cytoplasm of individual tumour cells. The bound and free pools of boron were assessed by exposure of cells to boron‐free nutrient medium. Both BPA and cis‐ABCPC delivered almost 70% of the pool of boron in the free or loosely bound form to the nucleus and cytoplasm of human glioblastoma cells. This free pool of boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular boron. In the case of BPA, the intracellular free pool of boron also was affected by the presence of phenylalanine in the nutrient medium. This suggests that it might be advantageous if patients were placed on a low phenylalanine diet prior to the initiation of BNCT. Since BPA currently is used clinically for BNCT, our observations may have direct relevance to future clinical studies utilizing this agent and provides support for individualized treatment planning regimens rather than the use of fixed BPA infusion protocols.     

Ion mobility spectrometry‐mass spectrometry (IMS‐MS) of small molecules: Separating and assigning structures to ions

The phenomenon of ion mobility (IM), the movement/transport of charged particles under the influence of an electric field, was first observed in the early 20th Century and harnessed later in ion mobility spectrometry (IMS). There have been rapid advances in instrumental design, experimental methods, and theory together with contributions from computational chemistry and gas‐phase ion chemistry, which have diversified the range of potential applications of contemporary IMS techniques. Whilst IMS‐mass spectrometry (IMS‐MS) has recently been recognized for having significant research/applied industrial potential and encompasses multi‐/cross‐disciplinary areas of science, the applications and impact from decades of research are only now beginning to be utilized for “small molecule” species. This review focuses on the application of IMS‐MS to “small molecule” species typically used in drug discovery (100–500 Da) including an assessment of the limitations and possibilities of the technique. Potential future developments in instrumental design, experimental methods, and applications are addressed. The typical application of IMS‐MS in relation to small molecules has been to separate species in fairly uniform molecular classes such as mixture analysis, including metabolites. Separation of similar species has historically been challenging using IMS as the resolving power, R, has been low (3–100) and the differences in collision cross‐sections that could be measured have been relatively small, so instrument and method development has often focused on increasing resolving power. However, IMS‐MS has a range of other potential applications that are examined in this review where it displays unique advantages, including: determination of small molecule structure from drift time, “small molecule” separation in achiral and chiral mixtures, improvement in selectivity, identification of carbohydrate isomers, metabonomics, and for understanding the size and shape of small molecules. This review provides a broad but selective overview of current literature, concentrating on IMS‐MS, not solely IMS, and small molecule applications. © 2012 Wiley Periodicals, Inc., Mass Spec Rev 32:43–71, 2013     

Recent developments of proton‐transfer reaction mass spectrometry (PTR‐MS) and its applications in medical research

Proton‐transfer reaction mass spectrometry (PTR‐MS) allows for real‐time, on‐line determination of absolute concentrations of volatile organic compounds (VOCs) with a high sensitivity and low detection limits (in the pptv range). The technique utilizes H₃O⁺ ions for proton‐transfer reactions with many common VOCs while having little to no reaction with any constituents commonly present in air. Over the past decades, research has greatly improved the applications and instrumental design of PTR‐MS. In this article, we give an overview of the development of PTR‐MS in recent years and its application in medical research. The theory of PTR‐MS and various methods for discriminating isobaric VOCs are also described. We also show several specialized designs of sample inlet system, some of those may make PTR‐MS suitable for the detection of aqueous solution and/or non‐volatile samples. © 2012 Wiley Periodicals, Inc., Mass Spec Rev 32:143–165, 2013     

Bioimaging of metals by laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS)

The distribution analysis of (essential, beneficial, or toxic) metals (e.g., Cu, Fe, Zn, Pb, and others), metalloids, and non‐metals in biological tissues is of key interest in life science. Over the past few years, the development and application of several imaging mass spectrometric techniques has been rapidly growing in biology and medicine. Especially, in brain research metalloproteins are in the focus of targeted therapy approaches of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, or stroke, or tumor growth. Laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) using double‐focusing sector field (LA‐ICP‐SFMS) or quadrupole‐based mass spectrometers (LA‐ICP‐QMS) has been successfully applied as a powerful imaging (mapping) technique to produce quantitative images of detailed regionally specific element distributions in thin tissue sections of human or rodent brain. Imaging LA‐ICP‐QMS was also applied to investigate metal distributions in plant and animal sections to study, for example, the uptake and transport of nutrient and toxic elements or environmental contamination. The combination of imaging LA‐ICP‐MS of metals with proteomic studies using biomolecular mass spectrometry identifies metal‐containing proteins and also phosphoproteins. Metal‐containing proteins were imaged in a two‐dimensional gel after electrophoretic separation of proteins (SDS or Blue Native PAGE). Recent progress in LA‐ICP‐MS imaging as a stand‐alone technique and in combination with MALDI/ESI‐MS for selected life science applications is summarized. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:156–175, 2010     

Current mass spectrometry strategies for the analysis of pesticides and their metabolites in food and water matrices

Analysis of pesticides and their metabolites in food and water matrices continues to be an active research area closely related to food safety and environmental issues. This review discusses the most widely applied mass spectrometric (MS) approaches to pesticide residues analysis over the last few years. The main techniques for sample preparation remain solvent extraction and solid‐phase extraction. The QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) approach is being increasingly used for the development of multi‐class pesticide residues methods in various sample matrices. MS detectors—triple quadrupole (QqQ), ion‐trap (IT), quadrupole linear ion trap (QqLIT), time‐of‐flight (TOF), and quadrupole time‐of‐flight (QqTOF)—have been established as powerful analytical tools sharing a primary role in the detection/quantification and/or identification/confirmation of pesticides and their metabolites. Recent developments in analytical instrumentation have enabled coupling of ultra‐performance liquid chromatography (UPLC) and fast gas chromatography (GC) with MS detectors, and faster analysis for a greater number of pesticides. The newly developed “ambient‐ionization” MS techniques (e.g., desorption electrospray ionization, DESI, and direct analysis in real time, DART) hyphenated with high‐resolution MS platforms without liquid chromatography separation, and sometimes with minimum pre‐treatment, have shown potential for pesticide residue screening. The recently introduced Orbitrap mass spectrometers can provide high resolving power and mass accuracy, to tackle complex analytical problems involved in pesticide residue analysis. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:907–939, 2011     

原子吸收光谱法测定化学原料药中的钌

醋酸艾司利卡西平是一种抗癫痫药物。在原料药合成中需要使用钌炭催化剂,这是一种重要的金属催化剂,广泛应用于化工及医药合成等领域中。在原料药中钌的含量限值控制是一个非常关键的指标。本文建立了石墨炉原子吸收光谱法测定原料药(醋酸艾司利卡西平)中的催化剂钌残留的分析方法。通过配制钌系列标准溶液,验证标准曲线方程和相关系数,确定该方法的相关系数均为0.998以上,钌回收率较好,在84%~92%之间。方法检出限为0.0204mg/kg,RSD值为0.365%。该方法可用于原料药(醋酸艾司利卡西平)中的催化剂钌残留的测定。     

Electrospray mass spectrometry (ESI-MS) in the study of metal-ligand solution equilibria

In the 20 years, since the introduction of electrospray mass spectrometry (ESI-MS), the use of this technique in various fields of inorganic, organometallic, and analytical chemistry has been steadily increasing. In this study, the application of ESI-MS to the study of metal-ligand solution equilibria is reviewed (till 2004 included). In a first section, advantages and drawbacks of ESI-MS in this type of application are described. Subsequently, a list of ca. 300 studies is reported, in which ESI-MS was used to give number and stoichiometry of the species at equilibrium, or also to estimate their stability constants. All studies are classified according to the metal ions under examination. Other related applications, such as host-guest interactions and metal ion-protein binding studies, are briefly reviewed as well.     

土豆泥中痕量可卡因的表面解吸常压化学电离质谱直接检测

采用纳升取样表而解吸常压化学电离质谱法(nanoSDAPCI-MS),无需任何样品预处理,直接对肯德幕生产的糊状土豆泥样品进行快速质谱检测.实验结果表明.nanoSDAPCI可以承受粘稠土豆泥样品中的大量基体,直接检测土豆泥中痕量的可卡因等成分.本方法操作简单,取样品量少,对含有复杂基体的粘稠样品的直接质谱检测具有借鉴意义.