Molecules and elements for quantitative bioanalysis: The allure of using electrospray, MALDI, and ICP mass spectrometry side‐by‐side. Issue 2 (30th March 2018)

• Record Type: Journal Article
• Authors: Linscheid, Michael W.
• Other Names: Kuck Dietmar guestEditor.; Grotemeyer Jürgen guestEditor.
• Is Part Of: Mass spectrometry reviews. Volume 38:Issue 2(2019)
• Page Start: 169
• Page End: 186
• Publication Date: 2018-03-30
• Subjects: chemical labeling -- elemental mass spectrometry -- mass spectrometric imaging -- mass spectrometry -- molecular mass spectrometry -- quantitative mass spectrometry; Mass spectrometry -- Periodicals; 543
• DOI: 10.1002/mas.21567
• Languages: English
• ISSNs: 0277-7037

Abstract

Abstract : 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 32 P with the "cold" natural 31 P 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.