质谱技术在中药小分子与生物大分子相互作用研究中的应用

中药发挥药理作用具有多组分,多靶点的重要特点。研究中药化学成分与生物大分子之间的相互作用不仅能够为阐明中药发挥药理作用的机理和物质基础提供科学依据,而且能够为新药设计提供理论指导。软电离质谱技术,尤其是电喷雾质谱(ESI-MS)和基质辅助激光解吸电离质谱(MALDI-MS)在一定条件下能够使药物与生物大分子形成的复合物完整地转移到气相中并被检测到,在中药小分子与生物大分子相互作用的研究中具有很大的优势。同时,色谱-质谱联用技术在中药复杂体系与生物大分子相互作用的研究中也显示出很大的应用潜力。本文介绍了质谱技术在药物与生物大分子相互作用研究中的应用原理,并总结了近年来软电离质谱技术在中药小分子与生物大分子相互作用研究中的应用。     

微流控芯片与电喷雾质谱联用接口的制作与应用

介绍了自制玻璃微流控芯片与电喷雾离子化质谱(ESI-MS)联用接口的制作方法。在芯片边缘直接将外接管路与管道相连，通过芯片上的旁路引入辅助液体，通过电场或压力驱动将样品送入质谱仪，实现稳定电喷雾。以芯片作为预进样平台，利用质谱检测了蛋白混合物、兴奋剂类药物混合物和中药提取物。在接口制作中，使用CB胶和保护性盖片，解决了机械加工步骤(切割、打磨和打孔等)中对微型结构的保护封装问题；在外接管路中的金属双通上施加高压电场地电势，实现了芯片管道中液体的电渗泵驱动。     

铀材料分析中的无机与同位素质谱法研究进展

综述了近年来中国工程物理研究院材料研究所应用无机与同位素质谱法进行铀材料分析的相关研究工作。在痕量铀同位素测量方面,发展了一种以氧化石墨烯作为电离增强剂的热电离质谱制样技术,显著增强了电离效率。在铀材料中杂质元素分析方面,开发了基于微流控芯片与电感耦合等离子体质谱联用的在线分离、分析方法,提高了分析的自动化程度。在金属铀中杂质元素的辉光放电质谱直接测定方面,基于相对灵敏度因子影响因素的研究基础,获得了一套普适性的相对灵敏度因子,实现了缺乏基体匹配标准物质时的准确测定。利用飞行时间-二次离子质谱法研究了铀及铀合金的偏析行为、夹杂物的表征、氢化/氧化腐蚀行为,为铀材料研究提供了表征手段。最后,对无机与同位素质谱法用于铀材料分析的发展前景进行了展望。     

GC8850气相色谱仪的高灵敏度微型热导池

毛细管柱色谱技术越来越被广泛应用.毛细管柱样品容量小,需要配用高灵敏度和小死体积检测器.目前绝大部分毛细管色谱分析都采用离子化检测器,其中以火焰电离检测器(FID)为最多.但FID-毛细柱系统不适合分析非烃类、惰性气体、H2O以及在火焰中难以电离的物质,应用有局限性,所以,美国惠普(HP)公司推出的微型热导池与毛细柱联用技术,引起了色谱工作者的极大兴趣.上海雷磁创益仪器仪表有限公司生产的GC8850气相色谱仪,除了FID外,还带有高灵敏度微型热导池,可与毛细柱联用,初步应用令人满意.     

用于离子迁移率谱仪的封闭式解吸电喷雾电离源研究

将解吸电喷雾电离(DESI)与离子迁移率谱(IMS)联用,快速检测农产品表面的有机磷农药残留。为减小干扰,设计并搭建了封闭式DESI电离源。对系统中电喷针与基底间距、鞘气流量、辅助电极电位、漂移管温度等参数进行优化。使用优化后的参数,实现对玻璃片和加标大白菜表面微量马拉硫磷的直接检测。系统对玻璃片和大白菜表面马拉硫磷的检测限分别为0.47 ng和8.2 ng,检测时间约10 s。     

敞开式离子源和微型气泵集成的微型针-柱放电结构芯片设计与实验分析

采用LIGA(Lithographie,Galvanoformung,Abformung)工艺设计加工了一种微型针-柱放电结构芯片,可实现敞开式离子源和微型气泵的系统集成。此微型放电结构由采用电镀铜加工而成的针电极、上圆柱电极和下圆柱电极组成,针-柱间距有1mm、2mm两种规格。在室温、大气压环境、无外界通入气流的条件下,通过在针-柱电极上加载负直流高压,可产生稳定的气体放电。利用风速计testo 405-V1测量芯片气体放电产生的离子风风速,结果表明针-柱间距为2mm时产生的离子风流速最大,可达0.79m/s。对针-柱间距2mm规格的微型芯片进行乙酸进样电离实验,当针-柱之间产生稳定的电晕放电后,可发现位于芯片出口处已被去离子水润湿的PH试纸变红。此时利用微弱电流检测系统采集电离产生的离子,当放电电压为-3300V时,通过微弱电流采集系统检测到的电流信号可达120pA。采用LTQ XL离子阱质谱仪,对芯片电离丙酮、无水乙醇和乙酸乙酯的离子产物进行检测,所得到的主要物质为质子化单体离子和二聚物离子。放电产生离子风风速以及乙酸的进样和电离实验表明,基于LIGA的微型针-柱结构芯片可实现大气压环境下敞开式离子源和微型气泵的双重功能。     

质谱在新药研究中应用的回顾

回顾了质谱在新药研究中的一些应用 ,包括新药合成、化学结构确证、质量控制以及药物代谢物的鉴定等。综述了基质辅助激光解吸电离 \飞行时间质谱 ( Matrix-assistant laser desorption ionization time-of-flight mass spectrometry,MALDI/ TOFMS)、电喷雾电离质谱 ( Electrode spray ionization m ass spectrome-try,ESI-MS)等仪器及其联用技术在生物大分子药物研究 ,包括蛋白质组学、肽图谱、氨基酸序列、核苷酸分析等方面的进展 ,展望了质谱在未来生命科学中广阔的应用前景。     

混杂样品各组分顺次电离装置的研制与应用

本工作研发了能与质谱联用的混杂样品顺次电离装置,用于在分子层次获取样品中不同组分的分子结构、丰度以及空间分布等信息。本装置设计了包括试剂选择与混配、形貌显微分析、微量样品电解与电离等多个模块。在微型反应池内,不同溶剂选择性地溶出样品中物理化学性质各异的组分,在时序触发与智能控制模块的调控下实现混杂样品的顺次电离与质谱分析。利用该装置实现了对合金、矿石、生物样品中有机及无机组分的顺次检测,获得了丰富的组分信息,在材料、能源、地球、生命等科学领域具有良好的应用前景。     

啤酒中氨基酸衍生物的GC／MS分析

本文利用色谱—质谱联用技术及电子轰击电离和化学电离方法,对啤酒中十一种主要氨基酸衍生物进行了分析鉴定,为气相色谱法分析氨基酸提供了定性依据。     

电喷雾电离质谱及其在蛋白质化学研究中的应用

本文介绍了电喷雾电离质谱并综述其在蛋白质化学研究中的应用.由于电喷雾电离质谱可产生多电荷峰,因此扩大了检测的分子质量范围,同时灵敏度较高,另外它可与HPLC及高效毛细管电泳分离技术联用,扩大了质谱在蛋白质化学研究中的应用.     

Microchip technology in mass spectrometry

Microfabrication of analytical devices is currently of growing interest and many microfabricated instruments have also entered the field of mass spectrometry (MS). Various (atmospheric pressure) ion sources as well as mass analyzers have been developed exploiting microfabrication techniques. The most common approach thus far has been the miniaturization of the electrospray ion source and its integration with various separation and sampling units. Other ionization techniques, mainly atmospheric pressure chemical ionization and photoionization, have also been subject to miniaturization, though they have not attracted as much attention. Likewise, all common types of mass analyzers have been realized by microfabrication and, in most cases, successfully applied to MS analysis in conjunction with on‐chip ionization. This review summarizes the latest achievements in the field of microfabricated ion sources and mass analyzers. Representative applications are reviewed focusing on the development of fully microfabricated systems where ion sources or analyzers are integrated with microfluidic separation devices or microfabricated pums and detectors, respectively. Also the main microfabrication methods, with their possibilities and constraints, are briefly discussed together with the most commonly used materials. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:351‐391, 2010     

KYKY-QP1000AG/CMS毛细管连接技术研究

作者在多年GS MS应用实践中 ,摸索出十分有用的毛细管连接技术 ,显著地提高了KYKY -QP10 0 0AGC MS的检出灵敏度 ,扩展了仪器的适应范围 ,为拥有同类仪器的同行提供了很好的帮助     

Chip‐mass spectrometry for glycomic studies

The introduction of micro‐ and nanochip front end technologies for electrospray mass spectrometry addressed a major challenge in carbohydrate analysis: high sensitivity structural determination and heterogeneity assessment in high dynamic range mixtures of biological origin. Chip‐enhanced electrospray ionization was demonstrated to provide reproducible performance irrespective of the type of carbohydrate, while the amenability of chip systems for coupling with different mass spectrometers greatly advance the chip/MS technique as a versatile key tool in glycomic studies. A more accurate representation of the glycan repertoire to include novel biologically‐relevant information was achieved in different biological sources, asserting this technique as a valuable tool in glycan biomarker discovery and monitoring. Additionally, the integration of various analytical functions onto chip devices and direct hyphenation to MS proved its potential for glycan analysis during the recent years, whereby a new analytical tool is on the verge of maturation: lab‐on‐chip MS glycomics. The achievements until early beginning of 2007 on the implementation of chip‐ and functional integrated chip/MS in systems glycobiology studies are reviewed here. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:223–253, 2009     

面向工程振动环境监测需求的MEMS加速度计及其应用

要:随着我国重大建设项目的日益增多,核电设施、大型桥梁、大科学装置等重要建筑工程对其所处环境的振动控制要求愈发苛刻,对工程振动的监测需求也日益强烈.基于硅微加工和超精密制造的MEMS加速度计集成度更高、尺寸更小、功耗和成本更低,高度契合需要使用极多加速度计的振动环境监测的应用需求.文中介绍了压电式和电容式MEMS加速度...     

环境荷尔蒙研究的现状及其监测分析

本文较为详细地介绍了环境荷尔蒙物质对野生动物和人类造成的危害,日本及ＷＷＦ提出的环境荷乐南分类及有关污染来源,并对ＷＨＯ,ＯＥＣＰ,ＩＰＣＳ及美国ＥＰＡ,日本等对一重大环境问题的研究现状及研究动向进行了介绍。２０００－２００３年是关于“环境荷尔蒙问题”研究的关键阶段,应引起我国政府及人民的高度重视。     

Mass spectrometric approaches for the investigation of dynamic processes in condensed phase

Mass spectrometry (MS) offers many advantages over other established spectroscopic techniques employed for the investigation of processes in condensed phase. The sensitivity, specificity, and speed afforded by MS-based methods enable to obtain very valuable insights into the mechanism of complex dynamic processes. Off-line methods rely on quenching to halt the progress of the reaction of interest and allow for the implementation of a broad range of analytical procedures for sample fractionation, isolation, or desalting. On the contrary, on-line methods are designed to carry out the real-time monitoring of dynamic processes through a continuous uninterrupted analysis of reaction mixtures, with the only caveat that the sample solutions be directly amenable to the available ionization technique. The utilization of rapid mixing devices in direct connection with a mass spectrometer or included in off-line schemes provides access to the initial moments of a reaction, which can offer very important information about the reaction mechanism. This report summarizes the different off- and on-line strategies developed to study chemical and biochemical reactions in solution and obtain kinetic/mechanistic information. The merits of the various experimental designs, the characteristics of the different instrumental setups, and the factors affecting time resolution are discussed with the aid of specific examples, which highlight the contributions of MS to the different facets of the investigation of dynamic processes in condensed phase.     

运用GC／MS（EI,PCI）技术鉴定尿中MDMA及其代谢物

本文运用GC／MS的EI、PCI技术，对尿中MDMA及其代谢物进行研究，鉴定了4种MDMA的代谢物，并为MDMA滥用者的尿样鉴定提供了方法。     

Discovering new invertebrate neuropeptides using mass spectrometry

Neuropeptides are a complex set of messenger molecules controlling a wide array of regulatory functions and behaviors within an organism. These neuromodulators are cleaved from longer protein molecules and often experience numerous post-translational modifications to achieve their bioactive form. As a result of this complexity, sensitive and versatile analysis schemes are needed to characterize neuropeptides. Mass spectrometry (MS) through a variety of approaches has fueled the discovery of hundreds of neuropeptides in invertebrate species in the last decade. Particularly successful are direct tissue and single neuron analyses by matrix-assisted laser desorption/ionization (MALDI) MS, which has been used to elucidate approximately 440 neuropeptides, and examination of neuronal homogenates by electrospray ionization techniques (ESI), also leading to the characterization of over 450 peptides. Additional MS methods with great promise for the discovery of neuropeptides are MS imaging and large-scale peptidomics studies in combination with a sequenced genome.     

Mass spectrometry‐based holistic analytical approaches for metabolite profiling in systems biology studies

Metabonomics and metabolomics represent one of the three major platforms in systems biology. To perform metabolomics it is necessary to generate comprehensive “global” metabolite profiles from complex samples, for example, biological fluids or tissue extracts. Analytical technologies based on mass spectrometry (MS), and in particular on liquid chromatography–MS (LC–MS), have become a major tool providing a significant source of global metabolite profiling data. In the present review we describe and compare the utility of the different analytical strategies and technologies used for MS‐based metabolomics with a particular focus on LC–MS. Both the advantages offered by the technology and also the challenges and limitations that need to be addressed for the successful application of LC–MS in metabolite analysis are described. Data treatment and approaches resulting in the detection and identification of biomarkers are considered. Special emphasis is given to validation issues, instrument stability, and QA/quality control (QC) procedures. © 2011 Wiley Periodicals, Inc., Mass Spec Rev 30:884–906, 2011     

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