Sarah Hill

This review discusses developments in elemental mass spectrometry, atomic absorption, emission and fluorescence, XRF and LIBS, as applied to the analysis of specimens of clinical interest, foods and beverages. Sample preparation procedures and quality assurance are also included.

There is an urgent need for reference methodologies to assign SI traceable values to quality control (QC) materials for protein biomarkers to validate biochemical tests currently used in disease diagnosis and patient-specific therapeutics. Here we describe a novel methodology specifically developed for the SI traceable quantification of human serum ferritin light chain (FTL), an established biomarker for the diagnosis of iron-related disorders such as hemochromatosis. Natural and ³⁴S isotopically enriched human FTL standards were recombinantly expressed using the HEK-293 mammalian cell system. Both standards were fully characterized for their total sulfur content, isotopic abundance, species distribution and primary sequence before using them for isotope dilution analysis (IDA). Treatment of serum spiked with FTL was optimized to selectively remove high abundant serum proteins without affecting significantly the integrity of the FTL. This was achieved by using methanol protein precipitation in combination with heat treatment and ultrafiltration. Complementary asymmetrical field-flow-fractionation (AF4) and anion-exchange high performance liquid chromatography (AE-HPLC) coupled to inductively coupled plasma mass spectrometry (ICP-MS) were used to monitor the impact of sample treatment on protein removal and FTL recovery. Both standards, natural and enriched, were used with the optimal sample treatment in a double species-specific isotope dilution analysis (SS-IDA) workflow for the determination of FTL in the WHO "4th International Standard for Ferritin" (NIBSC 19/118) resulting in a protein mass fraction of 11.0 with an expanded uncertainty (U, k = 2) of 1.0 μg mL^-1 (RSU of 9.4%). The method was validated by standard addition experiments, and a full uncertainty budget was established. For the first time sulfur SS-IDA has been used to assign an SI traceable value to a relatively low abundance serum protein biomarker at supraphysiological concentrations in a WHO standard. This methodology will be invaluable for adding SI traceability to existing QC materials and for the certification of new biomarker reference materials.

Quantitative MRI uses conventional clinical MRI hardware to make measurements of physical quantities. It also offers the opportunity to benchmark scanners in specific applications by characterising their measurement performance. This allows independent assessment of different scanners, products and services. Quantitation requires evaluation of the uncertainty and bias in the measurement process and as such requires a metrological framework. This process can be supported by the use of a reference object (phantom) that contains clinically relevant MRI quantities that are traceable to primary standards. Currently, there are very few traceable MRI standards available, and none cover all the forms of quantitative MRI that are being deployed clinically. The objective of this paper is to provide a metrological framework to build on and support the standardisation of qMRI through the provision of improved reference standards that are compatible with quantitative approaches. Here, we describe the design, construction, characterisation and measurement uncertainty of a traceable and metrologically quantified phantom. The phantom design is modular and comprises 30 distinct vials containing well-characterised, traceable solutions with reported uncertainty for the following MRI measurands: T ₁, T ₂, iron content and fat fraction.

This Update covers publications from the second half of 2023 to the middle of 2024, related to the analysis of clinical specimens, food and beverages and including reviews discussing specific aspects and future perspectives. The pursuit of lower detection capabilities continues to promote further research. Some works have focussed on vapour generating techniques for trapping and preconcentration prior to instrumental analysis and many more on the extraction and preconcentration of elements during the sample preparation step. The synthesis and application of nanomaterials play an important role for these developments. The interest in reagents for green chemistry was the subject of several reviews, and, increasingly, researchers are discussing the environmental impact and sustainability of new methods. In terms of analytical instrumentation, the performances of MICAP-OES were thoroughly assessed on various complex matrices, confirming the technique as highly robust to interferences and with detection capabilities similar to ICP-OES. The N₂-MICAP-MS, which is free from Ar-based polyatomic interferences, was applied to human serum and food samples, although with no significant advantage. There was continued interest in applications of scICP-TOF-MS for the evaluation of more than one characteristic of the same individual cell. The determination of isotope ratios in biological matrices was carried out by high precision MC-ICP-MS. The interest in single cell and single particle analysis and the determination of nanoparticles resulted in the publication of multiple papers specifically reviewing the development in these areas, from which the need emerged to apply multiple techniques and promote standardisation. Multielement techniques (LIBS and XRF) are increasingly applied both in the clinical and food area. Several papers reported new applications of LIBS for disease diagnosis, based on complex statistical modelling methods, whereas others have focussed on techniques to enhance its sensitivity and precision for the analysis of biological, food and water samples. Portable LIBS instrumentation offers potential for a wider application in forensic and food sciences, if calibration strategies and method validation could be improved. The indirect detection of low concentrations of molecules of clinical interest after element-tagging represents a rapidly expanding field. Applications of atomic spectrometry to food and beverages continue to grow, especially in relation to sustainable diets and food supplements. The trend of investigations of authenticity/provenance of foodstuffs using multielement profiles continues. The quality of analytical measurements should be of the utmost importance, however still too often such information is insufficient. We therefore highlight the analysis of CRMs in the papers discussed in this Update and report publications addressing interlaboratory comparisons and new CRMs.

Main text: KRISS and NMIJ jointly coordinated the CCQM-K158 comparison on elements and inorganic As in polished rice flour. The study comprised two parts, Part A and Part B. Successful participation in formal international comparisons is essential for documenting calibration and measurement capability claims (CMCs) by national metrology institutes (NMIs) and designated institutes (DIs). CCQM-K158 specifically supports CMCs within the food category, corresponding to the sample matrix labeled "High organic content" in the new CC table for broad claims. Simultaneously, the CCQM-P200 comparison ran in parallel with the key comparison CCQM-K158. In Part A, sixteen NMIs/DIs participated. Participants were requested to measure the mass fractions of Cu, Hg, K, Na, Pb, and Sb in rice flour, expressed in mg·kg-1, on a dry mass basis. Most NMIs/DIs adopted microwave-assisted acid digestion in a closed vessel for sample pretreatment, except for NIS, which used open vessel acid digestion with heating. Majority of the participants used isotope dilution (ID) ICP-MS, except for K and Na. ICP-MS or ICP-OES with standard addition calibration and k0 INAA were also applied specially for elements of which ID is impossible or difficult to access. ICP-MS, ICP-OES, AAS methods were also used with external calibration. In Part B, fifteen NMIs/DIs participated. Participants were requested to evaluate the mass fractions, expressed in mg·kg-1, of total arsenic and inorganic arsenic (the sum of As (III) and As (V)) in polished rice flour. For total As, thirteen NMIs/DIs reported their analytical results, where all the NMIs/DIs, except for JSI, adopted ICP-MS with a microwave acid digestion. JSI adopted k0-INAA after pelletizing the sample. For inorganic As, seven NMIs/DIs reported their analytical results, where all the NMIs/DIs adopted liquid chromatography-ICP-MS with a thermostatically controlled extraction using diluted acids. The results of all the participating NMIs/DIs were evaluated against the key comparison reference value (KCRV). The KCRV and associated uncertainty were estimated from reported results, excluding outliers, using NIST decision tree (NDT) as an estimator of the KCRVs. Successful participation in CCQM-K158 Part A demonstrates measurement capabilities for determining mass fractions of alkali and alkaline earth (K, Na), transition (Cu, Hg, Pb), and metalloid/semi-metal (Sb) elements in mass fraction range above 0.05 mg kg-1, in high organic content matrices such as grains, beans, and related samples. Similarly, successful participation in CCQM-K158 Part B demonstrates measurement capabilities to determine mass fractions of total arsenic and water-soluble arsenic species such as inorganic arsenic (the sum of As (III) and As (V)), mono-, di-, tri-, and tetra-methyl arsenic compounds (MAA, DMAA, TMAO, TeMA), arsenocholine (AsC), and arsenobetaine (AsB), in mass fraction range above 0.05 mg·kg-1 in grains, beans, and related samples. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

A methodology based on the use of asymmetrical flow field-flow fractionation (AF4) coupled to ICP-MS with size fraction-targeted isotope dilution analysis (IDA) has been developed, validated, and applied for the first time to determine the mass fraction of nanoscale silica (SiO₂). For this purpose, ²⁹Si-enriched SiO₂ nanoparticles, to be used as an IDA spike/internal standard, were synthesized and characterized in-house. Double IDA was used to quantify an aqueous suspension of Stöber silica particles of similar characteristics to those of the ²⁹SiO₂ nanoparticle (NP) spike using a representative test material of natural Si isotopic composition as the calibrant. For fumed SiO₂ NP in a highly complex food matrix, a methodology based on single IDA with AF4/ICP-MS using the same ²⁹SiO₂ NP spike was developed and validated. Relative expanded measurement uncertainties (k = 2) of 4% (double IDA) and 8% (single IDA) were achieved for nanoscale silica mass fractions of 5143 and 107 mg kg^-1 in water suspension and food matrix, respectively. To assess the accuracy of AF4/ICP-IDMS for the characterization of SiO₂ NP in a food matrix, standard addition measurements on samples spiked with Aerosil AF200, also in-house characterized for Si mass fraction, were undertaken, with an average recovery of 95.6 ± 4.1% (RSD, n = 3) obtained. The particle-specific IDA data obtained for both SiO₂ NP-containing samples were also compared with that of post-AF4 channel external calibration using inorganic Si standards. The mass fractions obtained by IDA agreed well with those obtained by external calibration within their associated measurement uncertainties.

This review discusses developments in elemental mass spectrometry, atomic absorption, emission and fluorescence, XRF and LIBS, as applied to the analysis of specimens of clinical interest, foods and beverages. Sample preparation procedures and quality assurance are also included.

A novel and selective method has been developed for high-accuracy determination of Pd, Pt and Rh in complex autocatalyst matrices using isotope dilution (ID) analysis (for Pt and Pd) and internal standard (IS) matching (for Rh) with ICP-time-of-flight mass spectrometry (ICP-TOFMS). By using a desolvating inlet interface and He collision gas, spectral interferences on selected isotopes (e.g., ¹⁰⁵Pd, ¹⁹⁵Pt, ¹⁹⁶Pt) were successfully removed. Calibration is performed by exact-matching ID analysis for Pd (¹⁰⁴Pd/¹⁰⁵Pd) and Pt (¹⁹⁶Pt/¹⁹⁵Pt) and IS matching with ¹⁰¹Ru for monoisotopic ¹⁰³Rh. Due to the quasi-simultaneous determination of all the isotopes of interest by ICP-TOFMS, isotope ratio precision was improved in comparison with that of sequential instrumentation, thus leading to reduced measurement uncertainties of k = 2), as required by autocatalyst manufacturers. This represents an approximately 2–3-fold improvement for Rh and Pd and 6-fold improvement for Pt in comparison to the uncertainties achieved using the same measurement strategy for sequential ICP-MS instrumentation. The method has been applied to the characterisation of a candidate CRM LGC3101 (unused automobile catalyst) containing high levels of Zr and Hf and validated by the analysis of similar matrix CRMs and by participation in an interlaboratory exercise.

Main text: The platinum group elements (PGEs) play an important role in reducing emissions from automotive vehicles through their use in catalytic convertors but also for catalysis in the pharmaceutical industry. The immense economic value of platinum (Pt), palladium (Pd) and rhodium (Rh) highlights the importance of highly accurate measurements. Therefore, there is a need for National Metrology Institutes (NMIs) and Designated Institutes (DIs) to demonstrate measurement capability in this space. A pilot comparison (CCQM-P63) for precious metals in automotive catalyst took place in 2006, but with a limited number of institutes participating. Furthermore, this study was performed over 17 years ago. Therefore, there was a need to maintain existing capability and demonstrate new capability in a key comparison, in order to claim calibration and measurement capability claims (CMCs). With the core capability matrix, this study falls into the "Difficult to dissolve metals/metal oxides" which will support CMC categories 8 (Metal and metal alloys), 9 (Advanced materials) and 14 (Other materials). Eleven NMIs and DIs participated in the Key Comparison CCQM-K160 Platinum Group Elements in Automotive Catalyst. Participants were requested to evaluate the mass fractions of Pt, Pd and Rh in mg/kg in an unused autocatalyst material (cordierite ceramic base). The Key Comparison Reference Values (KCRVs) and Degrees of Equivalence (DoEs) were calculated utilising the NIST Decision Tree for the measurands. The participants utilised a number of sample preparation and analytical methods including hot plate digestion, microwave digestion and sodium fusion, followed by either atomic absorption spectroscopy (AAS), inductively coupled plasma optical emission spectroscopy (ICP-OES) or inductively coupled plasma mass spectrometry (ICP-MS) detection. Several calibration techniques were used, namely external calibration, standard addition, isotope dilution mass spectrometry (IDMS) and an exact matching procedure. Additionally, one participant employed instrumental neutron activation analysis (INAA) with k0 standardisation which is a direct solid analysis method. The majority of participants claimed traceability to NIST primary calibrants or their own CRMs. Furthermore, several matrix CRMs were included or spiked samples for quality control. All institutes were required to determine the dry mass fraction using the stipulated protocol. The NIST decision tree was implemented for the calculation of the KCRVs and DoEs. The participant results overall showed good agreement with the KCRV, despite the variety of dissolution procedures and measurement techniques for this highly complex matrix and challenging measurands. Successful participation in CCQM-K160 demonstrated measurement capabilities for the determination of mass fraction of Pt, Pd and Rh in the mg/kg range and will support broad scope CMC claims for a wide range of challenging matrices. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

This update covers publications from the second half of 2021 to the middle of 2022. Advances in the application of atomic spectrometry techniques to clinical and biological materials, foods and beverages are reviewed in the text, highlighting their key features. Technical details of sample collection and preparation, as well as progresses with analytical techniques are considered and three tables complement the text, summarising details of a larger spectrum of publications. During this period, the trend toward the application of multi-element techniques, such as EDXRFS, ICP-MS and LIBS continued, in particular for food authenticity studies. Triple quadrupole ICP-MS is becoming increasing popular, as it is less affected by interferences, as well as LIBS and XRF, that require minimal sample preparation. However, AAS is still considered a valid alternative for single or a limited number of elements: as in previous years, numerous pre-concentration techniques were presented, some of which explored “greener” reagents. The interest in NPs continued, both as a potential exposure risk and for their application as tags of biological materials, and led to a wider application of spICP-MS. Chromium speciation in food received more attention than usual during this period, providing evidence that the carcinogenic species Cr^VI was not present. A number of studies covered the application of atomic spectrometry techniques for the indirect determination of biological macromolecules, including an interesting application of LIBS for the rapid detection of the immune response to SARS-CoV-2.