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

Abstract

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.

Cu and Zn isotope ratio variations in plasma for survival prediction in hematological malignancy cases

“…Fe, Cu and Zn standard solutions (Inorganic Ventures) that were previously characterized isotopically were measured every five samples for quality assurance/quality control (QA/QC) of the measurements. The δ-values (mean ± 2SE) obtained along this work were 0.23 ± 0.01‰ for δ 65 Cu (N = 53), 0.46 ± 0.02‰ for δ 56 Fe (N = 53), and − 7.04 ± 0.01‰ for δ 66 Zn (N = 40), which all agreed well with the data from previous studies 17,21,22 .…”

“…The Cu fraction was eluted using 9 mL of 5 M HCl + ~ 0.001% H 2 O 2 , the Fe fraction using 7 mL of 0.6 M HCl and the Zn fraction using 7 mL of 0.7 M HNO 3 . The Cu fractions were subjected to a second column pass to ensure a Na/Cu ratio < 2 in all solutions 17,22 . The pure fractions thus obtained were subjected to two steps of drying and re-dissolution in 14 M HNO 3 to remove residual chlorides and, were finally re-dissolved in 0.5 mL of 0.42 M HNO 3 for high-precision isotope ratio measurements using MC-ICP-MS. For elemental analysis, plasma samples were digested with 0.5 mL of 14 M HNO 3 (Tamapure-AA-100, Tama Chemical Co. Ltd., Kanagawa, Japan) at 180 °C for 20 min using an ETHOS 1 microwave dissolution unit (Milestone, Shelton, CT, USA) and then diluted with Milli-Q water (Nihon Millipore, Tokyo, Japan) to a final volume of 5 mL.…”

Lighter serum copper isotopic composition in patients with early non-alcoholic fatty liver disease

“…A Cu in-house standard (Inorganic Ventures, the Netherlands) was measured every five samples to monitor the quality of the isotope ratio data. The Cu isotope ratio obtained for the in-house QC sample in this work was δ 65 Cu = 0.223 ± 0.009 (sd, n = 9), which corresponds well with the value obtained in our previous study [12].…”

“…A larger patient cohort could have also allowed to evaluate assay reproducibility and sensitivity. Nevertheless, serum δ 65 Cu values have previously been shown to be reproducible in healthy controls [11][12][13], so that these results seem highly reliable.…”

“…Cu was isolated by anion exchange chromatography using 1 mL of AG-MP-1 resin (Bio-Rad Laboratories, CA, USA) [12]. Two column passes ensure sufficient purity, while a quantitative recovery avoids potential on-column isotope fractionation effects from affecting the final Cu isotope ratio results.…”