To understand biological processes, not only reliable identification, but quantification of constituents in biological processes play a pivotal role. This is especially true for the proteome: protein quantification must follow protein identification, since sometimes minute changes in abundance tell the real tale. To obtain quantitative data, many sophisticated strategies using electrospray and MALDI mass spectrometry (MS) have been developed in recent years. All of them have advantages and limitations. Several years ago, we started to work on strategies, which are principally capable to overcome some of these limits. The fundamental idea is to use elemental signals as a measure for quantities. We began by replacing the radioactive ³²P with the “cold” natural ³¹P to quantify modified nucleotides and phosphorylated peptides and proteins and later used tagging strategies for quantification of proteins more generally. To do this, we introduced Inductively Coupled Plasma Mass Spectrometry (ICP‐MS) into the bioanalytical workflows, allowing not only reliable and sensitive detection but also quantification based on isotope dilution absolute measurements using poly‐isotopic elements. The detection capability of ICP‐MS becomes particularly attractive with heavy metals. The covalently bound proteins tags developed in our group are based on the well‐known DOTA chelate complex (1,4,7,10‐tetraazacyclododecane‐N,N′,N″,N‴‐tetraacetic acid) carrying ions of lanthanoides as metal core. In this review, I will outline the development of this mutual assistance between molecular and elemental mass spectrometry and discuss the scope and limitations particularly of peptide and protein quantification. The lanthanoide tags provide low detection limits, but offer multiplexing capabilities due to the number of very similar lanthanoides and their isotopes. With isotope dilution comes previously unknown accuracy. Separation techniques such as electrophoresis and HPLC were used and just slightly adapted workflows, already in use for quantification in bioanalysis. Imaging mass spectrometry (MSI) with MALDI and laser ablation ICP‐MS complemented the range of application in recent years.

中文翻译：

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分子和元素进行定量生物分析：并排使用电喷雾，MALDI和ICP质谱法的魅力

要了解生物过程，不仅要可靠地进行识别，而且生物过程中成分的定量也起着关键作用。对于蛋白质组尤其如此：蛋白质定量必须紧随蛋白质鉴定之后，因为有时丰度的微小变化就能说明真实情况。为了获得定量数据，近年来已经开发出许多使用电喷雾和MALDI质谱（MS）的复杂策略。它们都有优势和局限性。几年前，我们开始研究策略，这些策略主要能够克服其中一些限制。基本思想是使用元素信号作为数量的度量。我们首先将放射性³² P替换为“冷”天然^31P。P用来量化修饰的核苷酸，磷酸化的肽和蛋白质，后来更普遍地使用标记策略来量化蛋白质。为此，我们在生物分析工作流程中引入了电感耦合等离子体质谱（ICP-MS），不仅可以进行可靠，灵敏的检测，还可以基于同位素稀释绝对测量（使用多同位素元素）进行定量分析。ICP‐MS的检测能力对于重金属尤为具有吸引力。我们小组开发的共价结合蛋白标签基于著名的DOTA螯合物（1,4,7,10-四氮杂环十二烷-N，N '，N '' ，Ntetra-四乙酸）携带镧系元素离子作为金属核。在这篇综述中，我将概述分子质谱和元素质谱之间这种互助的发展，并讨论范围和局限性，尤其是肽和蛋白质定量。镧系元素标签提供了低检测限，但由于非常相似的镧系元素及其同位素的数量，因此提供了多路复用功能。同位素稀释带来了前所未有的准确性。使用了电泳和HPLC等分离技术，只是略微调整了工作流程，这些工作流程已用于生物分析中的定量分析。具有MALDI和激光烧蚀ICP-MS的成像质谱（MSI）补充了近年来的应用范围。