ICP‐MS‐Based strategies for protein quantification

In the post‐genomics era, proteomics has become a central branch in life sciences. An understanding of biological functions will not only rely on protein identification, but also on protein quantification in a living organism. Most of the existing methods for quantitative proteomics are based on isotope labeling combined with molecular mass spectrometry. Recently, a remarkable progress that utilizes inductively coupled plasma‐mass spectrometry (ICP‐MS) as an attractive complement to electrospray MS and MALDI MS for protein quantification, especially for absolute quantification, has been achieved. This review will selectively discuss the recent advances of ICP‐MS‐based technique, which will be expected to further mature and to become one of the key methods in quantitative proteomics. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:326–348, 2010     

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     

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     

改良全蒸发技术测量铀同位素比

全蒸发热表面电离质谱(TE-TIMS)是测定铀主同位素比(²³⁵U/²³⁸U)最经典的方法,但受限于强峰拖尾等因素影响,次同位素比(²³⁴U/²³⁸U、²³⁶U/²³⁸U)的测量精密度不高,存在偏差。本工作研究目标动态加热程序、动态和静态相结合的接收程序、强峰拖尾校正、不同接收器效率校正、质量歧视校正等,建立了改良全蒸发-热表面电离质谱技术(MTE-TIMS)高精度测定铀同位素比的方法,通过测试标准物质验证方法的准确性和可靠性。结果表明：采用MTE-TIMS法测量²³⁵U丰度为2%的铀样品,其²³⁵U/²³⁸U、²³⁴U/²³⁸U和²³⁶U/²³⁸U的方法精密度分别为0.024%、0.06%和0.19%,测量值与参考值的偏差分别为0.025%、0.19%和0.38%。     

Neptune多接收器等离子体质谱精确测定锶同位素组成

报道了近两年来在Neptune多接收器等离子体质谱(MC-ICP-MS)上对NIST SRM987的测试结果。针对实际地质样品,Neptune MC-ICP-MS和热电离质谱(TIMS)进行了平行测定。Neptune MC-ICP-MS可以精确测定锶同位素组成,与传统的TIMS相比,MC-ICP-MS可以获得与TIMS相媲美的数据精度,而且分析时间短,效率高。对于等离子体载气———氩气中少量氪的干扰,可以直接扣除;对于样品中少量铷(Rb/Sr<0.01)的干扰,同样可以直接扣除,从而获得准确的锶同位素组成。     

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     

同位素稀释电感耦合等离子体质谱法测定高纯石英中痕量硼

应用同位素稀释电感耦合等离子体质谱法 ( ID-ICP-MS)测定地质标样 ( GSD-4和 GSD-8)和高纯石英中的痕量硼。样品处理采用低温密封焖罐酸溶样技术 ,将样品与稀释剂充分混匀 ,硼损失较小。硼元素在碱性条件下主要以 B( OH) 4 -形式存在于溶液中 ,可被硼特效离子交换树脂所交换吸附 ,故能很好地与大部分基体元素分离 ,从而减少基体效应。测定结果表明 :该方法测定痕量硼具有较高的准确度和精密度 ,且方法的检出限低 ,可达 5 1 .7ng/g,是准确定量测定痕量硼的理想方法     

Liquid chromatography–tandem mass spectrometry applications in endocrinology

Liquid chromatography–tandem mass spectrometry (LC–MS/MS) has been recognized as a primary methodology for the accurate analysis of endogenous steroid hormones in biological samples. This review focuses on the use of LC–MS/MS in clinical laboratories to assist with the diagnosis of diverse groups of endocrine and metabolic diseases. Described analytical methods use on‐line and off‐line sample preparation and analytical derivatization to enhance analytical sensitivity, specificity, and clinical utility. Advantages of LC–MS/MS as an analytical technique include high specificity, possibility to simultaneously measure multiple analytes, and the ability to assess the specificity of the analysis in every sample. All described analytical methods were extensively validated, utilized in routine diagnostic practice, and were applied in a number of clinical and epidemiological studies, including a study of the steroidogenesis in ovarian follicles. © 2009 Wiley Periodicals, Inc. Mass Spec Rev 29:480‐502, 2010     

表面热电离同位素稀释质谱法的计算及质量分馏效应校正

表面热电离同位素稀释质谱法(ID-TIMS)是国际公认的基准方法之一。本文以稀释分析锶同位素为例,详细介绍了其计算和推导过程,提出基于指数近似模式的稀释分析同位素分馏校正的方法。该方法适用于校正含有两对参考比值的元素静态多接收稀释分析同位素比值的质量分馏,与指数校正方法和对数校正方法相比,计算过程更简单。还讨论了稀释剂同位素比值准确度对稀释分析同位素比值的影响及其质量分馏的校正方法,通过数学迭代计算质量分馏系数,得到稀释剂测量的质量分馏系数和准确的同位素比值。采用建立的质量分馏校正方法稀释分析NBS987,结果表明,在误差范围内与其参考值（⁸⁷Sr/⁸⁶Sr=0.710237±8（1σ））一致。     

High‐precision mass spectrometric analysis using stable isotopes in studies of children

The use of stable isotopes combined with mass spectrometry (MS) provides insight into metabolic processes within the body. Herein, an overview on the relevance of stable isotope methodology in pediatric research is presented. Applications for the use of stable isotopes with MS cover carbohydrate, fat, and amino acid metabolism as well as body composition, energy expenditure, and the synthesis of specific peptides and proteins, such as glutathione and albumin. The main focus of these studies is on the interactions between nutrients and the endogenous metabolism within the body and how these factors affect the health of a growing infant. Considering that the early imprinting of metabolic processes hugely impacts metabolism (and thus functional outcome) later in life, research in this area is important and is advancing rapidly. The major fluxes on a metabolic level are the synthesis and breakdown rates. They can be quantified using kinetic tracer analysis and mathematical modeling. Organic MS and isotope ratio mass spectrometry (IRMS) are the two most mature techniques for the isotopic analysis of compounds. Introduction of the samples is usually done by coupling gas chromatography (GC) to either IRMS or MS because it is the most robust technique for specific isotopic analysis of volatile compounds. In addition, liquid chromatography (LC) is now being used more often as a tool for sample introduction of both volatile and non‐volatile compounds into IRMS or MS for ¹³C isotopic analyses at natural abundances and for ¹³C‐labeled enriched compounds. The availability of samples is often limited in pediatric patients. Therefore, sample size restriction is important when developing new methods. Also, the availability of stable isotope‐labeled substrates is necessary for measurements of the kinetics and concentrations in metabolic studies, which can be a limiting factor. During the last decade, the availability of these substrates has increased. Furthermore, improvements in the accuracy, precision, and sensitivity of existing techniques (such as GC/IRMS) and the development of new techniques (such as LC/IRMS) have opened up new avenues for tackling these limitations. © 2011 Wiley Periodicals, Inc. Mass Spec Rev 31:312–330, 2012     

地球科学中热电离质谱法的进展

对应用于地球科学领域的几种热电离质谱新方法的进展进行了综述,包括Sr、Nd同位素稀释分析的分馏校正、Re—Os负离子质谱法、热电离质谱铀系法、B、Cl稳定同位素测定及La—Ce法。     

LABEL‐FREE BIO‐AFFINITY MASS SPECTROMETRY FOR SCREENING AND LOCATING BIOACTIVE MOLECULES

Despite the recent increase in the development of bioactive molecules in the drug industry, the enormous chemical space and lack of productivity are still important issues. Additional alternative approaches to screen and locate bioactive molecules are urgently needed. Label‐free bio‐affinity mass spectrometry (BA‐MS) provides opportunities for the discovery and development of innovative drugs. This review provides a comprehensive portrayal of BA‐MS techniques and of their applications in screening and locating bioactive molecules. After introducing the basic principles, alongside some application notes, the current state‐of‐the‐art of BA‐MS‐assisted drug discovery is discussed, including native MS, size‐exclusion chromatography‐MS, ultrafiltration‐MS, solid‐phase micro‐extraction‐MS, and cell membrane chromatography‐MS. Finally, several challenges and limitations of the current methods are summarized, with a view to potential future directions for BA‐MS‐assisted drug discovery. © 2019 John Wiley & Sons Ltd. Mass Spec Rev     

Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research

Progress in proteomics research has led to a demand for powerful analytical tools with high separation efficiency and sensitivity for confident identification and quantification of proteins, posttranslational modifications, and protein complexes expressed in cells and tissues. This demand has significantly increased interest in capillary electrophoresis‐mass spectrometry (CE‐MS) in the past few years. This review provides highlights of recent advances in CE‐MS for proteomics research, including a short introduction to top‐down mass spectrometry and native mass spectrometry (native MS), as well as a detailed overview of CE methods. Both the potential and limitations of these methods for the analysis of proteins and peptides in synthetic and biological samples and the challenges of CE methods are discussed, along with perspectives about the future direction of CE‐MS. @ 2019 Wiley Periodicals, Inc. Mass Spec Rev 00:1–16, 2019.     

Advances in analysis of microbial metabolic fluxes via 13C isotopic labeling

Metabolic flux analysis via ¹³C labeling (¹³C MFA) quantitatively tracks metabolic pathway activity and determines overall enzymatic function in cells. Three core techniques are necessary for ¹³C MFA: (1) a steady state cell culture in a defined medium with labeled‐carbon substrates; (2) precise measurements of the labeling pattern of targeted metabolites; and (3) evaluation of the data sets obtained from mass spectrometry measurements with a computer model to calculate the metabolic fluxes. In this review, we summarize recent advances in the ¹³C‐flux analysis technologies, including mini‐bioreactor usage for tracer experiments, isotopomer analysis of metabolites via high resolution mass spectrometry (such as GC‐MS, LC‐MS, or FT‐ICR), high performance and large‐scale isotopomer modeling programs for flux analysis, and the integration of fluxomics with other functional genomics studies. It will be shown that there is a significant value for ¹³C‐based metabolic flux analysis in many biological research fields. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:362–375, 2009     

Advances on the compositional analysis of glycosphingolipids combining thin‐layer chromatography with mass spectrometry

Glycosphingolipids (GSLs), composed of a hydrophilic carbohydrate chain and a lipophilic ceramide anchor, play pivotal roles in countless biological processes, including infectious diseases and the development of cancer. Knowledge of the number and sequence of monosaccharides and their anomeric configuration and linkage type, which make up the principal items of the glyco code of biologically active carbohydrate chains, is essential for exploring the function of GSLs. As part of the investigation of the vertebrate glycome, GSL analysis is undergoing rapid expansion owing to the application of novel biochemical and biophysical technologies. Mass spectrometry (MS) takes part in the network of collaborations to further unravel structural and functional aspects within the fascinating world of GSLs with the ultimate aim to better define their role in human health and disease. However, a single‐method analytical MS technique without supporting tools is limited yielding only partial structural information. Because of its superior resolving power, robustness, and easy handling, high‐performance thin‐layer chromatography (TLC) is widely used as an invaluable tool in GSL analysis. The intention of this review is to give an insight into current advances obtained by coupling supplementary techniques such as TLC and mass spectrometry. A retrospective view of the development of this concept and the recent improvements by merging (1) TLC separation of GSLs, (2) their detection with oligosaccharide‐specific proteins, and (3) in situ MS analysis of protein‐detected GSLs directly on the TLC plate, are provided. The procedure works on a nanogram scale and was successfully applied to the identification of cancer‐associated GSLs in several types of human tumors. The combination of these two supplementary techniques opens new doors by delivering specific structural information of trace quantities of GSLs with only limited investment in sample preparation. © 2009 Wiley Periodicals, Inc. Mass Spec Rev 29:425‐479, 2010     

痕量铱同位素的负离子质谱分析方法研究

铱（Ir）同位素组成可作为理想的核燃料燃耗指示信息。提高Ir待测离子的电离效率,以获得足够强度且稳定的离子流是精确测量痕量Ir同位素组成的关键。因Ir电离电位较高,极难形成稳定的正离子,因此需采用负离子模式。本研究通过对比不同的灯丝材料、灯丝结构、涂样条件、电离温度等因素,建立并优化了Ir的负离子转化条件。通过采用Pt单带、Ba(OH)₂为发射剂涂样,并缓慢提高灯丝电流,50 ng的Ir电离效率可达9.8×10^-4。经氧同位素校正后,Ir涂样量10 ng以上的n(¹⁹¹Ir)/n(¹⁹³Ir)同位素比值与标准溶液的参考值在误差范围内一致,且相对标准偏差优于0.2%,能够满足痕量Ir同位素组成的测量精度要求。     

Structural characterization of bacterial lipopolysaccharides with mass spectrometry and on‐ and off‐line separation techniques

The focus of this review is the application of mass spectrometry to the structural characterization of bacterial lipopolysaccharides (LPSs), also referred to as “endotoxins,” because they elicit the strong immune response in infected organisms. Recently, a wide variety of MS‐based applications have been implemented to the structure elucidation of LPS. Methodological improvements, as well as on‐ and off‐line separation procedures, proved the versatility of mass spectrometry to study complex LPS mixtures. Special attention is given in the review to the tandem mass spectrometric methods and protocols for the analyses of lipid A, the endotoxic principle of LPS. We compare and evaluate the different ionization techniques (MALDI, ESI) in view of their use in intact R‐ and S‐type LPS and lipid A studies. Methods for sample preparation of LPS prior to mass spectrometric analysis are also described. The direct identification of intrinsic heterogeneities of most intact LPS and lipid A preparations is a particular challenge, for which separation techniques (e.g., TLC, slab‐PAGE, CE, GC, HPLC) combined with mass spectrometry are often necessary. A brief summary of these combined methodologies to profile LPS molecular species is provided. © 2012 Wiley Periodicals, Inc., Mass Spec Rev 32:90–117, 2013     

Utilization of laser‐assisted analytical methods for monitoring of lead and nutrition elements distribution in fresh and dried Capsicum annuum l. leaves

Laser induced breakdown spectroscopy (LIBS) and laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) have been applied for high‐resolution mapping of accumulation and distribution of heavy metal (lead) and nutrition elements (potassium, manganese) in leaves of Capsicum annuum L. samples. Lead was added in a form of Pb(NO₃)₂ at concentration up to 10 mmol L^?1 into the vessels that contained tap water and where the 2‐months old Capsicum annuum L. plants were grown another seven days. Two dimensional maps of the elements are presented for both laser‐assisted analytical methods. Elemental mapping performed on fresh (frozen) and dried Capsicum annuum L. leaves are compared. Microsc. Res. Tech., 2011. © 2010 Wiley‐Liss, Inc.     

质谱直接定量分析技术的应用进展

质谱直接定量分析指待测样品在引入质谱离子源之前,不经色谱分离,直接利用质谱信号对分析物进行含量测定的分析技术。该技术在很大程度上缩短了样品的检测周期,能够满足快速在线、原位分析的需求,目前已在质谱成像、单细胞分析以及在线反应监测等领域展现出广阔的应用前景。本工作综述了与质谱直接定量分析有关的质谱技术、样品处理方法以及相关应用,并展望质谱定量分析的发展趋势。