After 40 years of development, inductively coupled plasma-mass spectrometry (ICP-MS) can hardly be considered as a novel technique anymore. ICP-MS has become the reference when it comes to multi-element bulk analysis at (ultra)trace levels, as well as to isotope ratio determination for metal(loid)s. However, over the last decade, this technique has managed to uncover an entirely new application field, providing information in a variety of contexts related to the individual analysis of single entities (e.g., nanoparticles, cells, or micro/nanoplastics), thus addressing new societal challenges. And this profound expansion of its application range becomes even more remarkable when considering that it has been made possible in an a priori simple way: by providing faster data acquisition and developing the corresponding theoretical substrate to relate the time-resolved signals thus obtained with the elemental composition of the target entities. This review presents the underlying concepts behind single event-ICP-MS, which are needed to fully understand its potential, highlighting key areas of application (e.g., single particle-ICP-MS or single cell-ICP-MS) as well as of future development (e.g., micro/nanoplastics).

This work tries to provide guidance for the development of new methods aiming at the direct analysis of solid samples or complex liquid materials using HR CS GFAAS.

Wilson's disease (WD) is a genetic disorder affecting Cu metabolism, which can lead to severe physiological and neurological symptoms, and even death if untreated. Based on the fact that WD patients show low Cu levels in serum, implementation of screening programs for diagnosis of this condition at the moment of birth, when progression of the disease can be still arrested, has been attempted in the past. These attempts, however, have been unsuccessful, as healthy new-borns often show low Cu levels in serum due to liver immaturity. In this work, the potential use of isotopic analysis of Cu in serum samples as an alternative diagnostic parameter for Wilson's disease has been investigated. For this purpose, the Cu isotopic composition of a set of serum samples from different groups showing either low (i.e. WD patients, patients who had undergone bariatric surgery, infants) or normal (supposedly healthy adults) Cu concentration levels was determined by means of multi-collector ICP-mass spectrometry (MC-ICP-MS), after chromatographic isolation of Cu. For this purpose, AG-MP-1 strong anion exchange resin was relied upon, enabling quantitative recovery of Cu in pure form from the serum samples. MC-ICP-MS measuring conditions were optimized to avoid the influence of spectral overlap, and Ni was admixed as an internal standard for correction of instrumental mass discrimination. The use of this optimized method provided δ⁶⁵Cu for the serum samples with a typical analytical uncertainty of ±0.20‰ (k = 2). Our results show that, for the population considered in this study, combination of Cu concentration values and Cu isotopic information allows classification of WD patients, infants and controls into different groups, while the use of concentration values only is not sufficient for this purpose. Although further studies with a larger number of samples are needed, results are encouraging as far as the use of Cu isotopic analysis for early diagnosis of Wilson's disease is concerned.