Sensitive determination of biologically important transition metals by ICP-QMS using micro-ultrasonic single droplet nebulization

Abstract

The determination of trace transition metals in biological samples is often limited by extremely small sample volumes and complex matrix effects. In this work, a highly sensitive analytical method for the simultaneous determination of Mn, Co, Ni, Cu, and Zn in micro-volume samples was developed by coupling micro-ultrasonic single-droplet nebulization (MUSDN) with inductively coupled plasma quadrupole mass spectrometry (ICP-QMS). Key parameters were systematically optimized, with a particular focus on the evaluation of a Pt nebulizer sheet to reduce background equivalent concentrations (BECs). In addition, Ge was selected as the internal standard to effectively compensate for instrumental drift and matrix effects, thereby improving analytical stability. Under optimized conditions, the method exhibited excellent linearity (R² ≥ 0.999) and precision (RSDs ∼2%), while the achieved sensitivity enhancement (11.5–19.6-fold) was consistent with the previously reported advantages of MUSDN. The method exhibited good tolerance toward high-salt and organic matrices, thus enabling accurate analysis of diluted serum samples without digestion. Its feasibility and reliability were further validated through the analysis of certified serum reference materials and real samples. These results demonstrate that MUSDN-ICP-QMS is a robust and efficient approach for trace metal analysis in volume-limited biological samples.