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 microvolume samples was developed by coupling micro-ultrasonic single-droplet nebulization (MUSDN) with inductively coupled plasma quadrupole mass spectrometry (ICP-QMS). Key parameters, including nebulizer sheet material, droplet volume, and internal standard selection, were systematically optimized. Compared with conventional pneumatic nebulization, MUSDN-ICP-QMS achieved sensitivity enhancements of 11.5-19.6-fold and improvements in absolute limits of detection by 1-2 orders of magnitude, while requiring only 4 μL of sample.The use of a platinum nebulizer sheet effectively reduced background equivalent concentrations, and germanium was identified as the optimal internal standard, providing effective compensation for instrumental drift and matrix effects. 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.