Laser ablation of microdroplets for copper isotopic analysis via MC-ICP-MS. Analysis of serum microsamples for the diagnosis and follow-up treatment of Wilson's disease

Abstract

Cu isotopic analysis can provide valuable insight when investigating Wilson's disease (WD), but one of the problems related to this type of study is that usually low sample volumes are available and/or low Cu concentrations are found in these samples. This paper presents a new approach for Cu isotope ratio determination that requires only 1 μL of pre-treated serum sample per replicate (after Cu separation and preconcentration to a Cu concentration range between 0.3 and 4 mg L⁻¹). Cu determination was carried out by direct μ-injection of 1 μL of pretreated serum samples into an ICP-MS, offering a LOD of 3 μg L⁻¹. For Cu isotopic analysis, the method presented is based on micro-volume deposition on a pure silicon wafer and subsequent ablation analysis by fsLA-MC-ICP-MS. Cu isotopic analysis of NIST 3114 at 1 mg L⁻¹ Cu concentration with the self-bracketing method provided average δ⁶⁵Cu values of −0.01 ± 0.19‰ (2SD) and an internal precision value of 517 ppm. This method was deployed for the analysis of serum samples from WD patients under different treatments, as well as healthy newborns and patients with other liver disorders. The results seem to link decreased δ⁶⁵Cu values to Cu release from the liver, further demonstrating the potential of this type of analysis in the biomedical context.