Multicollector Inductively Coupled Plasma–Mass Spectrometry with 10¹³ Ω Faraday Cup Amplifiers for Ultrasensitive Mg Isotopic Analysis of Cerebrospinal Fluid Microsamples

Abstract

Magnesium isotopic analysis of cerebrospinal fluid (CSF) is a potentially interesting approach for studies on neurodegeneration. However, this type of analysis is challenging because of the invasiveness of the sampling and small sample volume. In this work, a novel analytical method was developed for ultrasensitive Mg isotopic analysis of CSF microsamples via multicollector inductively coupled plasma−mass spectrometry (MC-ICP-MS) using high-gain 10 13 Ω Faraday cup amplifiers. The intermediate and internal errors on the δ 26 Mg value were improved up to fourfold using 10 13 Ω resistors for the monitoring of both the 24 Mg and 26 Mg isotopes and up to twofold using a 10 11 Ω resistor for the most abundant 24 Mg isotope and a 10 13 Ω resistor for the 26 Mg isotope. Magnesium isotope ratios measured at a concentration level of 7−10 μg L −1 were in good agreement with those obtained using the conventional method at a concentration level of 150 μg L −1. The expanded uncertainty for the quality control CSF material obtained at the ultratrace level was ±0.16‰. Ultrasensitive Mg isotopic analysis was carried out for CSF from hydrocephalus patients using only 5 μL of sample. δMg values thus obtained were not significantly different from those obtained using the conventional method using a sample volume of 400 μL instead (p ≤ 0.05). The Mg isotopic composition of the CSF from hydrocephalus patients ranged between −0.65 and 0.30‰, with a mean δ 26 Mg value of −0.14 ± 0.27‰.

Atomic spectrometry update: review of advances in atomic spectrometry and related techniques

“…Measurement of Mg isotopes in cerebrospinal fluid is challenging due to the invasive nature of the procedure, but has potential uses in studies of neurodegeneration. Grigoryan et al 176 used 10 13 Ω amplifiers with MC-ICP-MS to reduce errors on the micro sample determinations of small amounts of Mg (between 7 and 10 μg L −1 ). The ∂Mg values were found to be similar to the ratios determined for 150 μg L −1 samples.…”

Microsampling of biological fluids for elemental and isotopic analysis by ICP-MS: strategies and applications for disease diagnosis

“…Accurate and precise Mg isotope ratios could be achieved using about 5 mL of human CSF. 12 The method was applied for CSF collection from hydrocephalus patients. The other publication refers to the isotopic determination of Cu and Zn in patients with amyotrophic lateral sclerosis or Alzheimer's disease.…”

“…It is well known that a low amount of sample and/or a low target isotope concentration can strongly compromise applications focused on high-precision isotopic analysis of biouids by MC-ICP-MS. 11 The use of aerosol desolvating systems, high-efficiency jet interfaces, high gain Faraday cup ampliers (10 13 U with respect to the 10 11 U conventional ones) and ion counter devices has proved to enhance instrument sensitivity. 12,13 Methods based on sample mixing of the analyte with a non-enriched in-house standard, 11 the use of droplets of serum deposited on silicon, 14 or preconcentration procedures, 15 have been proposed to extend the applications of MC-ICP-MS within a clinical context.…”

Longitudinal isotope ratio variations in human hair and nails

“…Magnesium isotopic analysis of human tissues is a fledging field with the Mg isotopic composition showing potential to be applied as a biomarker in clinical settings (Grigoryan et al, 2019(Grigoryan et al, , 2020b(Grigoryan et al, , 2021. To the best of the authors' knowledge, no studies have reported δ 26 Mg values for hair or nails.…”