ICP-MS and trace element analysis as tools for better understanding medical conditions

Highlights

• The state-of-the-art of trace elemental analysis in tissues and body fluids is reviewed.

• The most recent developments in ICP-MS instrumentation are discussed.

• Single-cell and single-particle ICP-MS methods enable analysis at cell level.

• Advances in elemental distribution imaging enhance medical research.

• Statistical tools combined with elemental composition used for disease modeling.

Abstract

Element constitution and distribution in tissues and body fluids have increasingly become key pieces of information in life sciences and medicine, and trace elements may be successfully used as disease biomarkers. Here, we review the most recent advances in inductively coupled plasma mass spectrometry (ICP-MS) and the related state-of-the-art instrumentation and methods (e.g. single-particle and single-cell determination capabilities) used to expand the application of trace element information to the study of diseases. Advanced statistical tools and machine learning used for evaluating, diagnosing, and treating different diseases has highlighted the importance of trace elements in clinical research. In this manuscript, we review recently published studies involving trace element analysis and machine learning applied to better understanding clinical conditions and pathologies, and discuss some perspectives for this field.

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.