Abstract

AbstractAll elements with two or more isotopes show natural variation in their isotopic composition as a result of the isotope fractionation that accompanies (bio)chemical reactions and (bio)physical processes. Multicollector inductively coupled plasma‐mass spectrometry (MC‐ICP‐MS) offers the precision required to reveal and quantify the differences in isotope ratios thus caused, although they are often of sub‐permil magnitude only. Using MC‐ICP‐MS, it has been shown that (a) in different body compartments, essential mineral elements may display different isotopic compositions, and (b) disease conditions may alter the isotopic composition of an essential mineral element in a biofluid and/or tissue. As a result, high‐precision isotopic analysis of these elements is a powerful way to unravel the actual role these essential mineral elements play in specific biochemical processes. Moreover, isotope ratio shifts also show promise as a diagnostic or prognostic tool. Despite the intensive sample pretreatment preceding MC‐ICP‐MS isotopic analysis and the high purchase and running costs of the instrumentation, this approach may be valuable, especially for diseases that can otherwise only be established at a later stage and/or via a more invasive approach. This review paper describes the basics of “biomedical isotopic analysis” and uses selected cases from the literature to sketch the state‐of‐art and illustrate in which context isotope ratio markers could be exploited in a clinical context.

Highlights

  • All elements with two or more isotopes show natural variation in their isotopic composition as a result of the isotope fractionation that accompanieschemical reactions andphysical processes

  • Despite the fact that the concept of isotopes was already introduced more than a century ago, many chemistry courses still barely touch upon the subject, at best

  • This situation changed with the introduction of MCICP-mass spectrometry (MS) in 1992.5 In MC-ICP-MS, an inductively coupled plasma or ICP is used as ion source

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Summary

ISOTOPES: A HISTORICAL BACKGROUND

Isotopes of a given element show the same number of protons in their nuclei and the same number of electrons in their electron cloud. Despite the fact that the concept of isotopes was already introduced more than a century ago, many chemistry courses still barely touch upon the subject, at best The reason for this is that chemical reactions involve the valence (outer) electrons only and the isotopes of an element should show exactly the same chemical behavior. For the lightest elements (H, C, N, O, and S), it was realized that as a result of the large relative difference in mass, the isotopes may behave to some extent differently in physicochemical processes. Basic rule of thumb in this context is that the lighter of any two isotopes reacts slightly faster (lower activation energy), whereas the heavier of any two isotopes shows a slight preference for strong and hard chemical bonds at chemical equilibrium

INSTRUMENTATION FOR ISOTOPIC ANALYSIS OF ESSENTIAL MINERAL ELEMENTS
IRON STATUS AND DISORDERS AFFECTING IRON HOMEOSTASIS
BONE FORMATION AND DESORPTION
LIVER DISEASE
CANCER
NEURODEGENERATIVE DISORDERS
DIABETES MELLITUS
Findings
10 OUTLOOK

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