Multi-collector ICP-mass Spectrometry Research Articles

Development and initial evaluation of a combustion-based sample introduction system for direct isotopic analysis of mercury in solid samples via multi-collector ICP-mass spectrometry

High-precision isotopic analysis of mercury (Hg) using multi-collector ICP-mass spectrometry (MC-ICP-MS) is a powerful method for obtaining insight into the sources, pathways and sinks of this toxic metal. Modification of a commercially available mercury analyzer (Teledyne Leeman Labs, Hydra IIc – originally designed for quantification of Hg through sample combustion, collection of the Hg vapor on a gold amalgamator, subsequent controlled release of Hg and detection using cold vapor atomic absorption spectrometry CVAAS) enabled the system to be used for the direct high-precision Hg isotopic analysis of solid samples using MC-ICP-MS – i.e., without previous sample digestion and subsequent dilution. The changes made to the mercury analyzer did not compromise its (simultaneous) use for Hg quantification via CVAAS. The Hg vapor was mixed with a Tl-containing aerosol produced via pneumatic nebulization, creating wet plasma conditions, and enabling the use of Tl as an internal standard for correction of instrumental mass discrimination. Accurate and precise (0.10 ‰ 2SD, δ202Hg, n = 5) results were obtained for an in-house standard solution of Hg (20 ng Hg sample intake). Initial validation relied on the successful analysis of two solid certified reference materials of biological origin (BCR CRM 464 Tuna fish and NRC-CNRC TORT-3 Lobster hepatopancreas). It was shown that instrumental mass discrimination can be adequately corrected for by relying on the use of an aqueous Hg standard solution (NIST SRM 3133), without the need of matrix-matching. The novel setup developed thus allows for direct high-precision isotopic analysis of Hg in solid samples, thus enhancing the sample throughput. It is also suited for samples for which low amounts are available only and/or that are characterized by low Hg concentrations.

Alzheimer's Disease and Age-Related Changes in the Cu Isotopic Composition of Blood Plasma and Brain Tissues of the APPNL-G-F Murine Model Revealed by Multi-Collector ICP-Mass Spectrometry.

Alzheimer's' disease (AD) is characterized by the formation of β-amyloid (Aβ) plaques and neurofibrillary tangles of tau protein in the brain. Aβ plaques are formed by the cleavage of the β-amyloid precursor protein (APP). In addition to protein aggregations, the metabolism of the essential mineral element Cu is also altered during the pathogenesis of AD. The concentration and the natural isotopic composition of Cu were investigated in blood plasma and multiple brain regions (brain stem, cerebellum, cortex, and hippocampus) of young (3-4 weeks) and aged (27-30 weeks) APPNL-G-F knock-in mice and wild-type controls to assess potential alterations associated with ageing and AD. Tandem inductively coupled plasma-mass spectrometry (ICP-MS/MS) was used for elemental analysis and multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for high-precision isotopic analysis. The blood plasma Cu concentration was significantly altered in response to both age- and AD-related effects, whereas the blood plasma Cu isotope ratio was only affected by the development of AD. Changes in the Cu isotopic signature of the cerebellum were significantly correlated with the changes observed in blood plasma. The brain stem showed a significant increase in Cu concentration for both young and aged AD transgenic mice compared with healthy controls, whereas the Cu isotopic signature became lighter as a result of age-related changes. In this work, ICP-MS/MS and MC-ICP-MS provided relevant and complementary information on the potential role of Cu in ageing and AD.

Petrochronological study of chloritoid schist from the Medvednica Mts. (Croatia, Zagorje Mid-Transdanubian zone)

A chloritoid schist from the Medvednica Mts. (Croatia, Zagorje-Mid-Transdanubian zone) is part of the metasedimentary succession of a Palaeozoic-Mesozoic Metamorphic Complex. The studied samples show the mineral association of chloritoid, chlorite, quartz and white mica. A P-T pseudosection, combined with modal and chemical isopleths, and classical thermobarometric calculations yield peak metamorphic conditions of 0.8 – 1.0 GPa at around 500 °C. Monazite in-situ dating with the electron microprobe results in an age of 156 ± 3 (2σ) Ma interpreted as dating monazite growth during prograde metamorphism. Laser ablation multicollector ICP mass spectrometry of U-Th-Pb isotope systematics in detrital zircon grains indicate a maximal deposition time of the sedimentary protolith in the Permian in accordance with published palaeontological records. The presented results are synchronous with the Late Jurassic obduction of a Neotethys-derived ophiolitic mélange onto a Permotriassic sedimentary sequence originated from the continental margin of Adria. This obduction caused regional collision metamorphism by thrusting Ophiolitic units (i.e. Neotethys) upon tectonic units of continental margin of Adria. Studied chloritoid schist is a part of the continental margin of Adria and is metamorphosed during collisional metamorphic event at upper greenschist-facies.

Study of the protective role of Zn in cultured retinal pigment epithelial cells subjected to pro-inflammatory conditions using transcriptomics and mass spectrometry

The present work aimed at investigating Zn alterations as a response to an inflammatory process in an in vitro human retinal pigment epithelial (RPE) cell model mimicking aging process. Cells were subjected to acute inflammatory stress with and without Zn supplementation and the effects of such exposure were evaluated by studying alterations at the transcriptome level and in the Zn concentration and its isotopic composition using single-collector and multi-collector ICP-mass spectrometry, respectively. The in vitro RPE model strongly responded to pro-inflammatory events (caused using 100 U/mL Interleukin-1α) at the RNA level by inducing immune and cytokine responses, while Zn supplementation (100 µM Zn) partially attenuated the aforementioned inflammatory effects. Interestingly, the Zn isotope ratios were correlated with the transcriptome, as inflammation was demonstrated to lead to a lighter Zn isotopic composition. This change in the isotopic composition of Zn signaling inflammation, which could also be avoided by short-term zinc supplementation, is probably indicating the modulation of the cellular immune function via cytokine signaling.

(U,Th)-He dating of Pleistocene carbonates: Analytical methods and age calculations

The uranium-thorium-helium ((U,Th)-He) dating method applied to calcium carbonate speleothems holds much promise for constraining the timeline of hominin evolution, as well as for palaeoclimatology research beyond the range of U/Th disequilibrium dating. Technical problems are posed by often low U concentrations and the requirement that samples need to be individually removed from the ultrahigh vacuum (UHV) system after helium is extracted from them, to be then analyzed for U, Th content and U series disequilibrium. We describe a low-cost furnace with this capability, constructed from standard UHV components, as well as the methods for subsequent U/Th disequilibrium analysis using multicollector ICP mass spectrometry. We present analytical and numerical solutions to determine (U,Th)-He ages for four conditions that have been encountered: (1) for an age range in which the residual activity ratio (234U/238U) can still be resolved but not that of (230Th/234U) (up to about 3000 ka), (2) for an age range where neither can be resolved (unlimited), (3) for ages up to 1000 ka where both activity ratios may be resolvable, and (4) for cases where (234U/238U) and (230Th/234U) indicate ages < 200 ka but (U,Th)-He systematics point to much older ages.•Helium extraction is carried out using an in-house built vacuum furnace that allows for large sample sizes (20 to 100 mg) of powdered carbonate material wrapped in Cu foil.•U and Th are separated together using Eichrom UTEVAⓇ resin and their isotope abundances are measured together in a single 2-cycle dynamic run using the multicollector inductively coupled plasma mass spectrometer (MC-ICP-MS).•(U,Th)-He ages are calculated using four methods that take into account the U/Th disequilibria.

Frontispiece: High‐precision isotopic analysis of essential mineral elements: capabilities as a diagnostic/prognostic tool (View 1/2021)

For several essential mineral elements (metals such as Ca, Mg, Fe, Cu, Zn), it has been demonstrated in article number 20200094 by Frank Vanhaecke and his colleague that different body compartments may display different isotopic compositions and that disease conditions may alter the isotopic composition of that element in a biofluid and/or tissue. Multi-collector ICP-mass spectrometry (MC-ICP-MS) offers the precision required to reveal and quantify such differences in isotope ratios. As a result, high-precision isotopic analysis shows promise as a diagnostic or prognostic tool. This review paper provides the background of such approach and sketches the state-of-the-art.

Source Identification Analysis of Lead in the Blood of Japanese Children by Stable Isotope Analysis.

Considering the negative effect of lead (Pb) on children’s neurodevelopment, Pb exposure should be minimized to the lowest extent possible, though the blood Pb (BPb) concentrations in Japanese children are among the lowest in the world. To identify the sources of Pb in blood, isotope ratios (IRs: 207Pb/206Pb and 208Pb/206Pb) of Pb (PbIR) in whole blood from eight Japanese children were measured by multi-collector ICP mass spectrometry. Further, samples of house dust, soil, duplicate diet, and tobacco, collected from home environments, were also measured and were compared with PbIR of blood case by case. The relative contribution of Pb in the home environment to BPb were estimated by linear programming (finding an optimal solution which satisfy the combination of IRs and intakes from various sources) when appropriate. Source apportionment for three children could be estimated, and contributions of diet, soil, and house dust were 19–34%, 0–55%, and 20–76%, respectively. PbIR for the remaining five children also suggested that non-dietary sources also contributed to Pb exposure, though quantitative contributions could not be estimated. Non-dietary sources such as soil, house dust, and passive tobacco smoke are also important contributors to Pb exposure for Japanese children based on PbIR results.

High-precision isotopic analysis of Mg and Ca in biological samples using multi-collector ICP-mass spectrometry after their sequential chromatographic isolation – Application to the characterization of the body distribution of Mg and Ca isotopes in mice

A sequential chromatographic separation procedure for subsequent high-precision isotopic analysis of Mg and Ca via multi-collector ICP-mass spectrometry (MC-ICP-MS) from a single aliquot of sample was developed and used for a variety of animal/human biofluids and tissues. The procedure consists of a one-stage Mg isolation protocol (for most of the sample types) and a three-stage isolation protocol for Ca. AG50W-X8 strong cation exchange resin was used for the isolation of Mg and Ca, while Sr-resin was used to additionally purify the Ca fraction from Sr. Potential effects on the Mg isotope ratio measurement results caused by the possible presence of concomitant matrix elements (Cu, Fe, Zn, Ca) were systematically evaluated. δ26Mg values were biased for a Fe/Mg ratio > 0.13 and a Ca/Mg ratio > 1.5, resulting in a shift towards a lighter Mg isotopic composition. It was shown that the Mg isotope ratio data for Mg standards, the isotopic reference materials ERM-AE143 and IRMM 009 and the biological samples investigated are located on a mass-dependent fractionation line. Biological reference materials and commercially available serum samples were analyzed for both their Mg and Ca isotope ratios. For some of the biomaterials analyzed, the Ca isotope ratio data as obtained using MC-ICP-MS were further validated via their determination using double-spike thermal ionization mass spectrometry (DS-TIMS). The expanded uncertainty for δ26Mg was ≤ 0.12‰ and for δ44/42Ca ≤ 0.29‰. Biological fluids and tissues of mice were analyzed to characterize the body distribution of the stable isotopes of Mg and Ca. The isotopic variability among the body compartments was about 1.5‰ for Mg and 1.0‰ for Ca. Among the tissues explored, muscle tissue shows the lightest Mg and Ca isotopic compositions and liver the heaviest Mg and Ca isotopic compositions, respectively.

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

Age-related macular degeneration (AMD), the main cause of irreversible blindness in people over 60 years of age, is an eye disease that evolves with loss of central vision. Although AMD manifests itself in the eye, blood is continuously flowing through the macular region, such that potential alterations in this region could be reflected in the composition of whole blood or plasma/serum. Therefore, the potential clinical relevance of analysis of serum samples was assessed because of the low degree of invasiveness of blood sampling. 40 initial samples (20 from controls and 20 from patients with the dry form of AMD) have been analysed in this work to investigate the possible occurrence of homeostatic alterations of essential mineral elements caused by the disease. Both major (Na, Mg, P and K) and trace (Fe, Cu and Zn) essential mineral elements were determined in blood serum using single-collector ICP-mass spectrometry. Also, the isotopic composition of Cu (an element proposed to be directly involved in the onset of AMD) was determined using multi-collector ICP-mass spectrometry. Unexpected light Cu isotopic compositions in three individuals assumed as controls, resulted in a re-evaluation of their clinical information and a later exclusion due to pathologies initially not accounted for. In this pilot study, a significant alteration in the δ65Cu value has been found between the two final cohorts (AMD patients: n = 20; controls n = 17), with lower δ65Cu values (i.e. an enrichment in the light 63Cu isotope) in the case of AMD. Also, higher serum concentrations of the elements P and Zn were established in AMD at a systemic level.

Speciation and isotopic characterization of mercury detected at high concentration in Pakistani hair samples

Speciation and isotopic analyses of mercury (Hg) detected at high concentration (11–107 mg total Hg/kg) in the hair samples of Pakistani subjects were carried out to analyze whether the source of Hg was the skin cream or the soap they used. Liquid chromatography-ICP mass spectrometric speciation analysis revealed that the Hg in the hair was primarily inorganic. This result supported our assumption that skin care products were the source of the high concentration of Hg in hair, which was based on the statistical association found in our previous study because it is known that inorganic Hg compounds are added to some skin care products sold in some countries. Stable isotope ratios of the Hg in the hair samples of 6 subjects and 3 skin cream samples, which were reported to be used by the subjects, were measured by multi-collector ICP mass spectrometry after acid digestion. A comparison of the isotopic compositions of Hg in hair and skin cream in two subjects revealed that the composition in both samples matched in one subject, hence confirming that the products were the source of high Hg concentration in hair. However, the isotopic compositions of Hg in hair and skin cream did not match in the other subject demonstrating the presence of other exposure source(s).

Multi-collector ICP-mass spectrometry reveals changes in the serum Mg isotopic composition in diabetes type I patients

Serum Mg shows a lighter isotopic composition in diabetes type-1 patients than in an age- and gender-matched reference population.

Quantification and isotopic analysis of bulk and of exchangeable and ultrafiltrable serum copper in healthy and alcoholic cirrhosis subjects

Information on the Cu speciation in blood serum can be valuable for a better understanding of the metabolism of this essential transition metal, but Cu speciation analysis and, to an even larger extent, compound-specific high-precision Cu isotopic analysis are challenging. In this work, quantification and isotopic analysis of Cu were carried out in bulk serum and in both its exchangeable + ultrafiltrable (EXCH + UF) Cu fraction and its non-exchangeable + non-ultrafiltrable (NEXCH + NUF) fraction using quadrupole and multi-collector ICP-mass spectrometry, respectively. The EXCH + UF serum Cu represents the labile Cu pool, i.e. Cu loosely bound to proteins, such as albumin, alpha-2 macroglobulin and other low molecular weight compounds, while the NEXCH + NUF serum Cu contains the Cu firmly bound to ceruloplasmin (Cp). The method was evaluated using human, goat and fetal bovine serum and applied to serum samples from assumed healthy subjects and from patients with alcoholic liver cirrhosis (AC). The healthy subjects showed an isotopic composition of EXCH + UF serum Cu heavier (by on average + 0.4‰) than that of their total serum Cu. In general, patients with AC showed higher EXCH + UF serum Cu concentrations and significantly lower δ65CuEXCH+UF and δ65Cuserum values than did healthy subjects. Within the AC population, δ65CuEXCH+UF values were comparable to or lower than the corresponding δ65Cuserum values, potentially reflecting the extent of labile Cu deregulation. As to be expected, the NEXCH + NUF serum Cu isotopic composition was similar to that of the total serum Cu, as most of the serum Cu is firmly bound to Cp.

Ultra-trace Cu isotope ratio measurements via multi-collector ICP-mass spectrometry using Ga as internal standard: an approach applicable to micro-samples

The capabilities of Cu isotope ratio measurements are often restricted by the small volumes of sample available and/or their low Cu concentration. In this work, an analytical approach was developed for performing Cu isotopic analysis via multi-collector ICP-mass spectrometry (MC-ICP-MS) at ultra-trace level using Ga as an internal standard for mass bias correction. The minimum concentration of Cu required for accurate and precise isotope ratio measurements was established to be 20 μg L−1 with wet plasma conditions and 5 μg L−1 with dry plasma conditions. The use of Ga as an internal standard for mass bias correction provided several advantages compared to Ni, i.e. improved internal precision on δ65Cu values and lower blank levels. Ga can also be used at a 4-fold lower concentration level than Ni. However, in wet plasma conditions, the signals of 36Ar16O21H+ and 40Ar15N16O+ interfered with the signals of 69Ga+ and 71Ga+, respectively, while in dry plasma conditions, realized by the use of a desolvation unit, 69Ga+ suffered from spectral interference from 40Ar14N21H+. These interferences were resolved by using medium mass resolution. For validation purposes, the approach was applied to commercially available blood and serum samples. The δ65Cu values for the samples measured at a concentration level of 5 μg L−1 Cu and 5 μg L−1 Ga using dry plasma conditions were in good agreement with those obtained for isotope ratio measurements at the “standard” concentration level of 200 μg L−1 Cu and 200 μg L−1 Ni using wet plasma conditions. In addition, the δ65Cu values obtained for micro-samples of serum/blood (volume of 100 µL) were in good agreement with the corresponding ones obtained using the “standard” volume for isotopic analysis (500 μL).

Cu isotope fractionation response to oxidative stress in a hepatic cell line studied using multi-collector ICP-mass spectrometry.

Reactive oxygen species (ROS) are generated in biological processes involving electron transfer reactions and can act in a beneficial or deleterious way. When intracellular ROS levels exceed the cell's anti-oxidant capacity, oxidative stress occurs. In this work, Cu isotope fractionation was evaluated in HepG2 cells under oxidative stress conditions attained in various ways. HepG2 is a well-characterised human hepatoblastoma cell line adapted to grow under high oxidative stress conditions. During a pre-incubation stage, cells were exposed to a non-toxic concentration of Cu for 24h. Subsequently, the medium was replaced and cells were exposed to one of three different external stressors: H2O2, tumour necrosis factor α (TNFα) or UV radiation. The isotopic composition of the intracellular Cu was determined by multi-collector ICP-mass spectrometry to evaluate the isotope fractionation accompanying Cu fluxes between cells and culture medium. For half of these setups, the pre-incubation solution also contained N-acetyl-cysteine (NAC) as an anti-oxidant to evaluate its protective effect against oxidative stress via its influence on the extent of Cu isotope fractionation. Oxidative stress caused the intracellular Cu isotopic composition to be heavier compared to that in untreated control cells. The H2O2 and TNFα exposures rendered similar results, comparable to those obtained after mild UV exposure. The heaviest Cu isotopic composition was observed under the strongest oxidative conditions tested, i.e., when the cell surfaces were directly exposed to UV radiation without apical medium and in absence of NAC. NAC mitigated the extent of isotope fractionation in all cases.

Direct lead isotopic analysis of bioethanol by means of multi-collector ICP-mass spectrometry with a total consumption sample introduction system

A method has been developed for the direct (no sample pretreatment and/or isolation of the target element from the sample matrix) Pb isotopic analysis of bioethanol via multi-collector ICP-mass spectrometry (MC-ICP-MS).

Evaluation of the use of cold plasma conditions for Fe isotopic analysis via multi-collector ICP-mass spectrometry: effect on spectral interferences and instrumental mass discrimination

The application of cold plasma conditions for isotopic analysis of Fe via MC-ICP-MS was evaluated in combination with the standard and the ‘jet’ interface and with dry and wet plasma conditions.

Determination of the isotopic composition of sub-ng amounts of Sr in Antarctic snow by multi-collector ICP-mass spectrometry

Determination of the87Sr/86Sr isotope ratio in Antarctic snow by multi-collector ICP-MS can provide useful information on the sources of the atmospheric particulates in present and ancient times.

High-precision isotopic analysis of Cu in blood serum via multi-collector ICP-mass spectrometry for clinical investigation: steps towards improved robustness and higher sample throughput

A procedure for Cu isolation from serum prior to MC-ICP-MS measurements was developed and applied in a clinical context. The serum Cu isotopic composition does not show diurnal variation.

Elemental and isotopic analysis of oral squamous cell carcinoma tissues using sector-field and multi-collector ICP-mass spectrometry

Elemental and isotopic analysis via single-collector and multi-collector ICP-mass spectrometry, respectively, have been explored as a tool for identifying potential differences between non-tumor and oral squamous cell carcinoma tissues. Elemental concentrations of major and minor elements, known to be essential for different processes in the cell (i.e. Na, Ca, Mg, K, P, Fe, Cu and Zn), have been determined and results for cancerous and non-cancerous tissues collected from the same individual have been compared. Among the elements studied, only Mg, K and P turned out to be significantly higher in concentration in the tumor tissues. However, a shift towards higher and wider concentration ranges has also been observed for Cu and Zn in the tumor samples, whereas for Ca lower concentrations were established. Possible isotope ratio variations for Cu and Zn in both biological tissues have also been evaluated with the same goal. δ66Zn results did not provide an obvious trend, but in the case of Cu, a clear distinction between the tumor and non-tumor tissues was observed: δ65Cu values ranged between −0.68% and 0.03% in the non-tumor tissues, whereas tumor samples turned out to be enriched in 65Cu, with δ65Cu values between 0.10% and 0.93%. These results confirm the considerable potential of isotopic and elemental studies for biomedical purposes.

Cu isotopic signature in blood serum of liver transplant patients: a follow-up study.

End-stage liver disease (ESLD) is life-threatening and liver transplantation (LTx) is the definitive treatment with good outcomes. Given the essential role of hepatocytes in Cu homeostasis, the potential of the serum Cu isotopic composition for monitoring a patient’s condition post-LTx was evaluated. For this purpose, high-precision Cu isotopic analysis of blood serum of ESLD patients pre- and post-LTx was accomplished via multi-collector ICP-mass spectrometry (MC-ICP-MS). The Cu isotopic composition of the ESLD patients was fractionated in favour of the lighter isotope (by about −0.50‰). Post-LTx, a generalized normalization of the Cu isotopic composition was observed for the patients with normal liver function, while it remained light when this condition was not reached. A strong decrease in the δ65Cu value a longer term post-LTx seems to indicate the recurrence of liver failure or cancer. The observed trend in favour of the heavier Cu isotopic composition post-LTx seems to be related with the restored biosynthetic capacity of the liver, the restored hepatic metabolism and/or the restored biliary secretion pathways. Thus, Cu isotopic analysis could be a valuable tool for the follow-up of liver transplant patients and for establishing the potential recurrence of liver failure.