ICP-MS and trace element analysis as tools for better understanding medical conditions
Graphical abstract
Introduction
Paraphrasing Philippus Aureolus Theophrastus Bombastus von Hohenheim, better known as Paracelsus, “Dosis sola facit venenum” (Only the dose makes the poison) [1,2], which, in fact, means that all substances may be poisons; it all depends on the dose administered. Looking from another perspective, the right dose differentiates a poison from a nutrient. When considering metals and metalloids in human health, several elements are required to keep the human body in good health. Those are divided into essential and non-essential elements (among which some may be toxic even at trace levels) [2]. Going back to Paracelsus, even those elements considered essential, such as calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), potassium (K), sodium (Na) and zinc (Zn), among others, could become poisonous depending on their concentration in the organism. In fact, it is well known that Fe is involved in many functions of the human body, being considered a crucial element for survival. When Fe is absorbed at a lower rate by the body, problems such as anemia may occur. On the other hand, when it is absorbed in excess, due to hemochromatosis disease, high levels of Fe accumulate especially in the liver, heart and pancreas, which can result in liver disease, heart problems, and diabetes. Additionally, and taken as an example of a metalloid, selenium (Se) excess may produce selenosis, a disease caused by high levels of bioavailable Se interfering with cellular oxidation and reduction reactions [3]. Alternatively, Se at balanced levels plays a role in human growth and reproduction, and its deficiency is associated with depressed mood, anxiety, and confusion [4]. Similar health problems are caused by excess or deficiency of other elements, which corroborates Paracelsus’ statement.
In addition to their role as nutrients, a diversity of metals is also associated with the function of many enzymes, as they modify the electron flux in substrates and enzymes, thus controlling enzyme-catalyzed reactions [5]. Metalloproteins can be exemplified, such as carbonic anhydrase, which has a zinc-containing active site that catalyzes the conversion of CO2 into bicarbonate [6]. Thus, any problem in the exact homeostasis of zinc in such protein may affect the processes associated with breathing. As previously demonstrated, this dynamic shows that an exact regulation of metals/metalloids in the human body may indicate if an individual is healthy or not. Based on this principle, modern bioinorganic chemistry-focused medicine studies the imbalance of metals/metalloids in the body, which could be used for understanding a diversity of diseases, and even for prognosis or diagnosis [7].
In this context, and considering a multitude of diseases associated with dysregulation of metal homeostasis, this review manuscript discusses some important aspects regarding the role of trace element analysis as an effective tool for better comprehending medical conditions and health outcomes. We guide our discussion based on the following questions: (1) What are the most important strategies involving the broadly used inductively coupled plasma mass spectrometry (ICP-MS) method for accurately determining metal/metalloids in tissues and body fluids? (2) What advanced statistical tools/machine learning techniques have been used to take advantage of trace element information for the study of different diseases? (3) What types of element alterations in tissues and body fluids are associated with medical conditions? (4) What are the most important trace elements associated with medical conditions that may be eventually used for diagnosis/prognosis? The topics associated with these questions are exemplified through several applications described in the literature. Finally, as a large avenue is visualized for future developments, we point out possible trends in this field, focusing on the analytical, biochemical, and medical aspects involved with using trace elements for better understanding medical conditions.
Section snippets
ICP-MS capabilities for obtaining trace element information from biological samples
Recent advances in ICP-MS technology have allowed for the determination of difficult analytes, at the trace and ultra-trace levels, in tissues and biological fluids. New strategies include spatially resolved analysis of solid samples, isotope fractionation, single-particle and single-cell analysis. These developments have contributed for improving the understanding of the role of trace elements in biological processes, as well as other important mechanisms such as metabolic isotope mass bias
Data visualization and dimensionality reduction
Multi-element information based on a large number of samples may be a powerful tool for better understanding biological systems and processes. However, the more data the more difficult it is to extract useful information from an experiment. One of the most common approaches to deal with large datasets is to apply a dimensionality reduction (DR) method, which contributes to both facilitating interpretation and minimizing noise. Principal component analysis (PCA) is probably the simplest and most
Element alterations in tissues and body fluids associated with medical conditions
Many of the recent applications of trace element analysis are focused on the search for alterations in element composition, concentration, isotopic fractionation, and distribution in human tissues and body fluids due to different pathogenesis. The overarching goal of such efforts is to identify signatures of the evolution of a disease caused by metabolic imbalances, biochemical abnormalities and tissue injuries [92]. It is worth noting that ions in the human body keep a dynamic equilibrium. The
Machine learning for trace element biomarker identification and disease modeling
Trace element analysis combined with machine learning techniques may be used for biomarker identification and for studying the onset and evolution of a disease, which could eventually be used to develop new diagnostic methods. For diabetes mellitus, for example, Chen et al. used Li, Cr, Fe, Zn, Cu, Mn, Ni and V concentrations in hair, determined by ICP optical emission spectrometry (ICP OES), and ensemble support vector machine (SVM) for classification and potentially as a supplementary
Conclusions and perspectives
This review manuscript presented an overview of the state of evaluation of trace elements as indicators of medical conditions using a consolidated analytical platform known for its high sensitivity, i.e. ICP-MS. Our focus was not on discussing the role of specific trace elements on disease onset or on new diagnosis methods. It was rather an examination of the potential benefits of including elemental information in the study of medical conditions, and how new developments in instrumentation,
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
The authors (RSA and MAZA) thank the São Paulo Research Foundation (FAPESP, São Paulo, Brazil, 2018/25207-0, 2017/50085-3, 2018/23478-7), the Brazilian National Council of Scientific and Technological Development (CNPq, Brasília, Brazil, 401170/2016-0), the Coordination for the Improvement of Higher Education Personnel (CAPES, Brasília, Brazil, 88887.115406/2015) and INCTBio (FAPESP, São Paulo, Brazil, 2014/50867-3) for the financial support and fellowships. GLD thanks the Graduate School of
References (142)
- et al.
Selenium, Reference Module in Biomedical Sciences Encyclopedia of Toxicology
(2014) - et al.
Recent developments in trace element analysis in the prevention, diagnosis, and treatment of diseases
Microchem. J.
(1998) - et al.
Inductively coupled plasma – tandem mass spectrometry (ICP-MS/MS): a powerful and universal tool for the interference-free determination of (ultra)trace elements – a tutorial review
Anal. Chim. Acta
(2015) - et al.
Reactivity and analytical performance of oxygen as cell gas in inductively coupled plasma tandem mass spectrometry
Spectrochim. Acta, Part B
(2016) - et al.
Opportunities and challenges of isotopic analysis by laser ablation ICP-MS in biological studies
Trac. Trends Anal. Chem.
(2018) - et al.
87Sr/86Sr isotope ratio measurements by laser ablation multicollector inductively coupled plasma mass spectrometry: reconsidering matrix interferences in bioapatites and biogenic carbonates
Spectrochim. Acta, Part B
(2016) - et al.
Down-regulation of SLC8A1 as a putative apoptosis evasion mechanism by modulation of calcium levels in penile carcinoma
J. Urol.
(2015) - et al.
Metrological approach to quantitative analysis of clinical samples by LA-ICP-MS: a critical review of recent studies
Talanta
(2018) - et al.
Laser ablation ICP-MS for simultaneous quantitative imaging of iron and ferroportin in hippocampus of human brain tissues with Alzheimer's disease
Talanta
(2019) - et al.
High-resolution imaging and single-cell analysis via laser ablation-inductively coupled plasma-mass spectrometry for the determination of membranous receptor expression levels in breast cancer cell lines using receptor-specific hybrid tracers
Anal. Chim. Acta
(2019)
High-precision isotopic analysis of essential mineral elements in biomedicine: natural isotope ratio variations as potential diagnostic and/or prognostic markers
Trac. Trends Anal. Chem.
On the effect of using collision/reaction cell (CRC) technology in single-particle ICP-mass spectrometry (SP-ICP-MS)
Anal. Chim. Acta
Trends on (elemental and molecular) mass spectrometry based strategies for speciation and metallomics
Trac. Trends Anal. Chem.
Mass cytometry: single cells, many features
Cell
Principal component analysis
Chemometr. Intell. Lab.
Independent component analysis, a new concept
Signal Process.
The kernel PCA algorithms for wide data, 1. Theory and algorithms
Chemometr. Intell. Lab.
Diffusion maps
Appl. Comput. Harmon. Anal.
A review of feature selection methods in medical applications
Comput. Biol. Med.
The role of chemometrics in single and sequential extraction assays: a Review. Part II. Cluster analysis, multiple linear regression, mixture resolution, experimental design and other techniques
Anal. Chim. Acta
Differential diagnosis of multielements in cancerous and non-cancerous esophageal tissues
Talanta
Pilot study of homeostatic alterations of mineral elements in serum of patients with age-related macular degeneration via elemental and isotopic analysis using ICP-mass spectrometry
J. Pharmaceut. Biomed. Anal.
Paracelsus revisited: the dose concept in a complex world
Basic Clin. Pharmacol. Toxicol.
The essential metals for humans: a brief overview
J. Inorg. Biochem.
The importance of selenium to human health
Lancet
Metal ions in biological catalysis: from enzyme databases to general principles
J. Biol. Inorg. Chem.
The catalytic mechanism of carbonic anhydrase: implications of a rate-limiting protolysis of water
Acc. Chem. Res.
Overcoming spectral overlap via inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS). A tutorial review
J. Anal. At. Spectrom.
Expanding beyond ICP-MS to better understand selenium biochemistry
Metallomics
Development of a UPLC-IDA-ICP-MS/MS method for peptide quantitation in plasma by Se-labelling, and comparison to S-detection of the native peptide
J. Anal. At. Spectrom.
Developing ICP-MS/MS for the detection and determination of synthetic DNA-protein crosslink models via phosphorus and sulfur detection
Anal. Bioanal. Chem.
ICP-MS/MS-based ionomics: a validated methodology to investigate the biological variability of the human ionome
J. Proteome Res.
Review of the applications of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to the analysis of biological samples
J. Anal. At. Spectrom.
Calibration strategies for elemental analysis of biological samples by LA-ICP-MS and LIBS – a review
Anal. Bioanal. Chem.
Study on aerosol characteristics and fractionation effects of organic standard materials for bioimaging by means of LA-ICP-MS
J. Anal. At. Spectrom.
Zinc isotope ratio imaging of rat brain thin sections from stable isotope tracer studies by LA-MC-ICP-MS
Metallomics
Software solutions for evaluation and visualization of laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) data: a short overview
J. Cheminf.
Recent developments in the design of rapid response cells for laser ablation-inductively coupled plasma-mass spectrometry and their impact on bioimaging applications
J. Anal. At. Spectrom.
The enigma of aluminum deposition in bone tissue from a patient with chronic kidney disease: a case report
Braz. J. Nephrol.
Quantitative bioimaging of platinum in polymer embedded mouse organs using laser ablation ICP-MS
Metallomics
Internal standardization of LA-ICP-MS immuno imaging via printing of universal metal spiked inks onto tissue sections
J. Anal. At. Spectrom.
Calibration of LA-ICP-MS via standard addition using dried picoliter droplets
J. Anal. At. Spectrom.
A novel calibration strategy based on internal standard–spiked gelatine for quantitative bio-imaging by LA-ICP-MS: application to renal localization and quantification of uranium
Anal. Bioanal. Chem.
Multiplex LA-ICP-MS bio-imaging of brain tissue of a parkinsonian mouse model stained with metal-coded affinity-tagged antibodies and coated with indium-spiked commercial inks as internal standards
J. Neurosci. Methods
Quantitative bioimaging of platinum via online isotope dilution-laser ablation-inductively coupled plasma mass spectrometry
Anal. Chem.
Diagnosis of nephrogenic systemic fibrosis by means of elemental bioimaging and speciation analysis
Anal. Chem.
Quantitative mapping of specific proteins in biological tissues by laser ablation–ICP-MS using exogenous labels: aspects to be considered
Anal. Bioanal. Chem.
Critical evaluation of fast and highly resolved elemental distribution in single cells using LA-ICP-SFMS
J. Anal. At. Spectrom.
Fast chemical imaging at high spatial resolution by laser ablation inductively coupled plasma mass spectrometry
Anal. Chem.
Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry
Nat. Methods
Cited by (40)
Influence of haemolysis on blood biochemistry profiles in cattle
2024, Research in Veterinary ScienceAnthropogenic trace metals in Setiu Wetland: Spatial and seasonal distribution and implications for environmental health
2023, Journal of Water Process EngineeringSingle-cell ICP-MS to address the role of trace elements at a cellular level
2023, Journal of Trace Elements in Medicine and Biology