Review about Powerful Combinations of Advanced and Hyphenated Sample Introduction Techniques with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for Elucidating Trace Element Species in Pathologic Conditions on a Molecular Level

Abstract

Element analysis in clinical or biological samples is important due to the essential role in clinical diagnostics, drug development, and drug-effect monitoring. Particularly, the specific forms of element binding, actual redox state, or their spatial distribution in tissue or in single cells are of interest in medical research. This review summarized exciting combinations of sophisticated sample delivery systems hyphenated to inductively coupled plasma-mass spectrometry (ICP-MS), enabling a broadening of information beyond the well-established outstanding detection capability. Deeper insights into pathological disease processes or intracellular distribution of active substances were provided, enabling a better understanding of biological processes and their dynamics. Examples were presented from spatial elemental mapping in tissue, cells, or spheroids, also considering elemental tagging. The use of natural or artificial tags for drug monitoring was shown. In the context of oxidative stress and ferroptosis iron, redox speciation gained importance. Quantification methods for Fe²⁺, Fe³⁺, and ferritin-bound iron were introduced. In Wilson's disease, free and exchangeable copper play decisive roles; the respective paragraph provided information about hyphenated Cu speciation techniques, which provide their fast and reliable quantification. Finally, single cell ICP-MS provides highly valuable information on cell-to-cell variance, insights into uptake of metal-containing drugs, and their accumulation and release on the single-cell level.

Keywords: LA-ICP-MS; copper speciation; elemental tagging; iron redox speciation; single cell ICP-MS (SC-ICP-MS); spatial element mapping.

Figure 1

Platinum distribution in cryo-sections of HCT116 and CH1/PA-1 tumor spheroids after treatment with Pt-complexes (1–5 µM) measured by LA-ICP-MS. Reprinted with permission from Ref. [21], Copy right year: 2016, copyright owner: Oxford University Press, (A) HCT116 tumor spheroids treated with satraplatin, (B) CH1/PA1 spheroids treated with satraplatin, (C) HCT116 tumor spheroids treated with new “Pt-compound 1”, (D) CH1/PA1 spheroids treated with new “Pt-compound 1”, (E) HCT116 tumor spheroids treated with new “Pt-compound 2”, (F) CH1/PA1 spheroids treated with new “Pt-compound 2”.

Figure 2

Signal intensity maps of (A) Mg, (B) P, (C) S, (D) Ca, (E) Fe, (F) Cu, (G) Zn, (H) Gd, and (I) Pt in a germ cell tumor tissue section of a patient obtained by LA-ICP-TOFMS imaging. The parallel line scans overlap one another by 10 µm. Reprinted with permission from [22]. Copy right year: 2020, copyright owner: Oxford University Press.

Figure 3

Intracellular total iron content (left) and Fe^2+/Fe³⁺ ratios (right), measured by CE-ICP-DRC-MS in normoxic B16-F10 cells (n = 3). The data are analyzed using a one-way ANOVA with Tukey’s multiple comparisons test. ** p < 0.01 shBNIP3 compared against shCntl, ## p < 0.01 shBNIP3 compared against shATG5.Reprinted, [76]. Copy right year: 2021, copyright owner: John Wiley and Sons.