A Single-Step Digestion for the Quantification and Characterization of Trace Particulate Silica Content in Biological Matrices Using Single Particle Inductively Coupled Plasma-Mass Spectrometry

The increased use of amorphous silica nanoparticles (SiNPs) in food products, materials science, cosmetics, and pharmaceuticals has raised questions about potential hazards in the environment and in human health. Although SiNPs are generally thought to be benign, recent studies have demonstrated toxicity in different cell and animal models. Despite their ubiquitous use, SiNPs are rarely analyzed quantitatively. Often, the methods used to analyze silicon and SiNPs are difficult, costly, require the use of dangerous reagents, and are prone to interferences. Additionally, characterization of SiNPs in complex matrices requires extensive sample preparation. To address this, we propose a single-step digestion method for the determination of trace SiNP content in biological matrices. For conventional inductively coupled plasma-mass spectrometry (ICP-MS) analysis, biological samples are often digested with concentrated HNO₃. We found that with conventional ICP-MS, lower limits of detection (LLOD) of silicon are too high for trace analysis. However, we found that SiNPs are stable at a strong acidic pH; thus, concentrated HNO₃ could be used to digest biological samples leaving SiNPs intact. Then, by analysis with single particle ICP-MS, we found that the smallest SiNP that could be read was 185 nm in size. The concentration for the LLOD was found to be 0.032 ppb with interday variability in sizing and concentration at 2.5% and 6.8% respectively. Utilizing this method, SiNPs were accurately sized and counted in cell pellets and media. Our proposed method can be used to accurately quantify and characterize SiNPs (or agglomerated SiNPs) larger than the derived LLOD in a variety of biological matrices and will assist in determining relationships between exposures of SiNPs and toxicity in humans and the environment.