High-precision K isotopic analysis of cerebrospinal fluid and blood serum microsamples via multicollector inductively coupled plasma-mass spectrometry equipped with 1013 Ω faraday cup amplifier resistors.

BACKGROUND: Potassium isotopic analysis is increasingly performed in both geological and biological contexts as a result of the introduction of MC-ICP-MS instrumentation either equipped with a collision/reaction cell or having the capability of working at "extra-high" mass resolution in order to deal with spectral interference caused by argon hydride (ArH+) ions. Potassium plays an important role in the central nervous system, and its isotopic analysis could provide an enhanced insight into the corresponding processes, but K isotopic analysis of cerebrospinal fluid is challenging due to the small volume, a few microliter only, typically available. This work aimed at developing a method for determining the K isotopic signature of serum and cerebrospinal fluid at a final K concentration of 25 ng mL-1 using Faraday cup amplifiers equipped with a 1013 Ω resistor. RESULTS: Potassium isotope ratios obtained for reference materials measured at a final K concentration of 25 ng mL-1 were in excellent agreement with the corresponding reference values and the internal and external precision for the δ41K value was 0.11 ‰ (2SE, N = 50) and 0.10 ‰ (2SD, N = 6), respectively. The robustness against the presence of matrix elements and the concentration mismatch between sample and standard observed at higher K concentrations is preserved at low K concentration. Finally, K isotopic analysis of serum and cerebrospinal fluid (3-12 µL of sample) of healthy mice of both sexes was performed, revealing a trend towards an isotopically lighter signature for serum and cerebrospinal fluid from female individuals, however being significant for serum only. SIGNIFICANCE: This work provides a robust method for high-precision K isotopic analysis at a concentration of 25 ng mL-1. By monitoring both K isotopes, 39K and 41K, with Faraday cups connected to amplifiers with 1013 Ω resistors, accurate K isotope ratio results are obtained with a two-fold improvement in internal and external precision compared to those obtained with the set-up with traditional 1011 Ω resistors. The difference in the K isotope ratio in CSF and serum between the sexes, is possibly indicating an influence of the sex or hormones on the fractionation effects accompanying cellular uptake/release.

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 ß-amyloid (Aß) plaques and neurofibrillary tangles of tau protein in the brain. Aß plaques are formed by the cleavage of the ß-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.

First insights into human mobility in Neolithic Belgium using strontium isotopic analysis and proteomics: A case study of Grotte de La Faucille (Sclayn, province of Namur).

OBJECTIVES: So far, no 87 Sr/86 Sr mobility studies have been done for Neolithic remains from Belgium and information on the Sr isotopic variability in the region is scarce. This study aims to explore mobility in a Final Neolithic population from the funerary cave 'Grotte de La Faucille', contribute to the understanding of the isotopic composition of bioavailable Sr in Belgium, assess evidence for male mobility using proteomic analysis, and explore possible places of origin for nonlocal individuals. MATERIALS AND METHODS: The 87 Sr/86 Sr isotope ratio of dental enamel from six adults and six juveniles was determined. Liquid chromatography mass spectrometry-based protein analysis was employed to identify individuals of male biological sex. 87 Sr/86 Sr of micromammal teeth, snail shells, and modern plants from three geological areas in Belgium were measured to establish isotopic signatures for bioavailable strontium. Nonlocality was assessed by comparing human 87 Sr/86 Sr isotope ratios to the 87 Sr/86 Sr range for bioavailable Sr. RESULTS: Four individuals yielded 87 Sr/86 Sr isotope ratios consistent with a nonlocal origin. No statistical differences were found between adults and juveniles. Three males were detected in the sample set, of which two show nonlocal 87 Sr/86 Sr values. DISCUSSION: This study provides evidence for mobility in Final Neolithic Belgium. The four nonlocal 87 Sr/86 Sr signatures correspond with the 87 Sr/86 Sr of bio-available Sr in Dutch South Limburg, the Black Forest in Southwest Germany, and regions of France, such as parts of the Paris Basin and the Vosges. The results support the ruling hypothesis of connections with Northern France, brought to light by archeological research.

High-Precision Isotopic Analysis of Cu and Fe via Multi-Collector Inductively Coupled Plasma-Mass Spectrometry Reveals Lipopolysaccharide-Induced Inflammatory Effects in Blood Plasma and Brain Tissues.

The concentration and the isotopic composition of the redox-active essential elements Cu and Fe were investigated in blood plasma and specific brain regions (hippocampus, cortex, brain stem and cerebellum) of mice to assess potential alterations associated with sepsis-associated encephalopathy induced by lipopolysaccharide (LPS) administration. Samples were collected from young (16-22 weeks) and aged (44-65 weeks) mice after intraperitoneal injection of the LPS, an endotoxin inducing neuroinflammation, and from age- and sex-matched controls, injected with phosphate-buffered saline solution. Sector-field single-collector inductively coupled plasma-mass spectrometry was relied upon for elemental analysis and multi-collector inductively coupled plasma-mass spectrometry for isotopic analysis. Significant variations were observed for the Cu concentration and for the Cu and Fe isotope ratios in the blood plasma. Concentrations and isotope ratios of Cu and Fe also varied across the brain tissues. An age- and an inflammatory-related effect was found affecting the isotopic compositions of blood plasma Cu and cerebellum Fe, whereas a regional Cu isotopic redistribution was found within the brain tissues. These findings demonstrate that isotopic analysis of essential mineral elements picks up metabolic changes not revealed by element quantification, making the two approaches complementary.

Robust Potassium Isotopic Analysis of Geological and Biological Samples via Multicollector ICP-Mass Spectrometry Using the "Extra-High Resolution Mode".

Potassium isotopic analysis is arousing increasing interest, not only in geochemistry, but also in biomedicine. However, real-life applications are still hindered by the lack of robustness of the methods used. In this work, a novel and robust method for high-precision K isotopic analysis of geological and biological samples was developed, based on the use of a multicollector ICP-mass spectrometer providing a mass resolving power of 15,000 (extra-high resolution mode, XHR). After evaluation of different measurement conditions, i.e., hot vs cold plasma conditions, standard-type vs jet-type sampling cone, and high resolution (HR) vs XHR, a combination of hot plasma conditions, use of the high-transmission jet-type sampling cone, and the XHR mode allowed for high-precision and interference-free K isotopic analysis. Potassium signal monitoring was performed in the ArH+ interference-free 0.006-0.007 amu wide peak shoulder using the XHR mode. The within-run, short-term external, and long-term external precisions for the δ41K value were 0.02‰ (2se, N = 50), 0.03‰ (2SD, N = 7), and 0.06‰ (2SD, N = 163), respectively. A two-stage chromatographic procedure was developed for the isolation of K from both geological and biological samples, and potential matrix effects affecting the K isotope ratio were systematically evaluated. The method was first applied to geological reference materials (RMs) for validation purposes, and the K isotope ratio results were in good agreement with those previously reported. Subsequently, a series of biological RMs, including serum, whole blood, cerebrospinal fluid, bovine muscle, and lobster hepatopancreas, were characterized for their K isotopic composition.