Cutting-Edge Triple Quad ICP-MS for Clinical Trace Element Analysis

Unlocking the power of triple quadrupole ICP-MS for clinical research: A focus on trace element analysis

Trace elements play a crucial role in various physiological and pathological processes, influencing everything from metabolic function to disease progression. The ability to accurately quantify these elements in biological matrices such as blood, serum, and urine is essential for advancing clinical diagnostics, nutritional studies, and toxicology research. As clinical researchers push the boundaries of precision medicine, the ability to accurately measure trace elements in biological samples has become increasingly critical.

Traditional techniques often face limitations in sensitivity or may offer access to a limited set of analytes only, but Inductively Coupled Plasma Mass Spectrometry (ICP-MS) overcomes these challenges and offers full multi-element detection with unmatched detection power. It is known as the gold standard for trace element analysis in a variety of other applications, offering unmatched sensitivity, precision, and throughput. Our latest technical note explores how the Thermo Scientific iCAP MTX ICP-MS system empowers laboratories to achieve superior analytical performance in clinical research applications

The role of ICP-MS in clinical research

Essential and trace element analysis of biological samples provides significant information to support clinical research and forensic toxicology. For example, the exposure to toxic metals is a known risk factor for several diseases, whereas other elements, when present at appropriate levels, support regular biological function. Concentrations of elements within the blood of a population of subjects can correlate elemental exposure to geographical area, lifestyle, and socio-demographic factors.¹

Addressing analytical challenges with the iCAP MTX ICP-MS

However, the analysis of samples containing higher levels of salts and biomolecules, such as proteins or metabolites is a known challenge in ICP-MS analytical techniques. The complexity of the sample matrix can significantly affect the sensitivity of the instrument, cause intensity fluctuation of the internal standard (suppression and drift), and lead to increased system maintenance with unwanted downtime due to obstruction of the interface cones, torch, and injector, or the nebulizer. In addition, the development of a multi-element method is challenging due to the wide concentration ranges that need to be covered across essential and toxic elements and the wide range of potential interferences from the sample matrix. These complex prerequisites often mean that triple quadrupole ICP-MS instruments are the best choice for analysis. The iCAP MTX ICP-MS system addresses key challenges in trace element analysis, including:

• Enhanced sensitivity and accuracy: The triple quadrupole design improves detection limits, ensuring reliable quantification of even ultra-trace elements.
• Matrix interference elimination: The system employs advanced interference removal techniques, delivering high-quality data even in complex biological samples.
• Workflow efficiency: Designed for high-throughput laboratories, the system enhances productivity by streamlining sample preparation and data processing.

The iCAP MTX ICP-MS was employed to analyze 43 elements in whole blood samples. Among the analytes, several critical interferences can cause unexpected bias, which were investigated closely for effective and complete removal by means of selective collision / reaction cell reactions with oxygen. This analytical method was rigorously tested, and the results obtained clearly demonstrated analytical advantages:

• The combination of He KED and TQ-O₂ mode allows for effective suppression of typical interferences, which enables high sensitivity required for the accurate determination of the entire mass range (lithium to uranium) and a linear response for all analytes, which cover a concentration range of 8 orders of magnitude (Table 1).

• The Thermo Scientific iSC-65 Autosampler equipped with the Step Ahead feature allowed for a reduction of the total analysis time, and in combination with intelligent Matrix Handling, the analysis of whole blood could be carried out with improved productivity.

• The use of TQ-O₂ mode allowed removal of interferences of any kind, especially on key analytes such as common transition metals, and toxic/essential elements such as arsenic or selenium in the 50-fold diluted whole blood samples. Figure 1 shows the TQ-O₂ mode and a mass shift reaction for interference free detection of As and Ti.

Table 1. Summary of analysis mode, and calibration results, R², LODs, and MDLs for all analytes. All numbers are shown in μg·L-1.

Figure 1. Schematic showing the use of TQ-O 2 mode and a mass shift reaction for interference free detection of arsenic (As) and titanium (Ti)

• The total analysis time was 3 min 14 s per sample (including uptake and wash time) for 43 elements. This is specifically for large cohort studies, for example to screen exposure in a representative population.

• Robust and stable analytical performance was demonstrated over 15 hours of continuous acquisition of 287 samples by the iCAP MTX ICP-MS with excellent CCV results. Figure 2 shows the highly reproducible internal standard responses over the entire batch, demonstrating robust analytical performance.

Figure 2. Response of the internal standards in a batch covering about ~15 hours of uninterrupted analysis of 287 samples

Literature Reference

1. Simic, A. et al. Trace elements in whole blood in the general population in Trøndelag County, Norway: The HUNT3 Survey. Science of the Total Environment, 2022, 806, 150875.

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