Laser ablation-tandem ICP-mass spectrometry (LA-ICP-MS/MS) imaging of iron oxide nanoparticles in Ca-rich gelatin microspheres

Abstract

This work describes the development of an analytical method for quantitative laser ablation tandem ICP-mass spectrometry (LA-ICP-MS/MS) imaging of iron oxide nanoparticles (FeO_x NPs) in gelatin microspheres containing CaCO₃ crystals (≤30 μm diameter). The strong spectral overlap between the signal of ⁵⁶Fe⁺ and those of ⁴⁰Ar¹⁶O⁺, ³⁸Ar¹⁸O⁺, ⁴⁰Ar¹⁵NH⁺ and ⁴⁰Ca¹⁶O⁺ and between those of ⁴⁰Ca⁺ and ⁴⁰Ar⁺ was overcome by relying on chemical resolution using a mixture of NH₃/He (1 : 9) in a mass-shift approach. Product ion scanning allowed Fe(NH₃)₂⁺ and CaNH₃⁺ to be identified as the best suited reaction product ions, formed upon reaction of NH₃ with Fe⁺ and Ca⁺, respectively. The method was validated by using two certified reference materials, i.e. NIST SRM 1577 and 1577a bovine liver, which were solubilized by acidic digestion. Fe-spiked gelatin droplet standards were prepared on a high-purity single-side polished silicon wafer and used as external calibration standards for LA-ICP-MS/MS analysis and a priori, their corresponding Fe concentrations were determined via pneumatic nebulization tandem ICP-MS (PN-ICP-MS/MS) after acidic digestion. High-resolution LA-ICP-MS/MS imaging revealed the mixed structure of the gelatin microspheres containing a high loading of FeO_x NPs (2.69 ± 0.91 wt% Fe) in the gelatin phase. The high FeO_x NP concentrations are required for magnetic removal after peritoneal injection and are accompanied by numerous CaCO₃ crystals that provide an indication about the final porosity of the microspheres.