A Simple Online Internal Standard Calibration Strategy for Single-Particle Inductively Coupled Plasma Mass Spectrometry Based on Multielement Analysis

Single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) is a powerful tool for resolving particle heterogeneity. However, in real environmental and biological samples, matrix effects pose significant challenges to accurate mass/size determination. Herein, we first systematically investigated the specific matrix effects on each stage of SP-ICP-MS analysis. Results showed that the sizes of Ag nanoparticles in the typical matrices were underestimated by nearly 10 nm due to 30-50% signal attenuation. To address this issue, we developed an online internal standard calibration strategy based on multielement detection and nonanalyte elements as internal standards. The theory of a novel calibration approach involving the use of nonanalyte elements as internal standards for signal response calibration was proposed and experimentally validated. The multielement detection mode was employed to measure the analyte (Ag) and internal standard elements (Pd and Au) within a single analytical run, enabling simultaneous correction of matrix-induced variations in signal response and nebulization efficiency. Under optimized time-resolution conditions (dwell time of 5 ms), the measured sizes of the particles in both simulated and real matrices showed good agreement with the true values. Overall, the proposed method provides a simple, reliable, and flexible solution for extending the applicability of SP-ICP-MS to the analysis of complex environmental and biological samples.