Prenormative verification and validation of a protocol for measuring magnetite–maghemite ratios in magnetic nanoparticles

Lara K Bogart,Marcin Sikora,Kerstin Witte,Mikkel Fougt Hansen,Quentin A Pankhurst,Geraldo M Da Costa,Drew E Latta,Cathrine Frandsen,Jan Zukrowski,Michelle M Scherer,Jean-Marc Greneche,Jeppe Fock

doi:10.1088/1681-7575/ac36b6

Abstract

An important step in establishing any new metrological method is a prenormative interlaboratory study, designed to verify and validate the method against its stated aims. Here, the 57Fe Mössbauer spectrometric ‘centre of gravity’ (COG) method was tested as a means of quantifying the magnetite/maghemite (Fe3O4/γ-Fe2O3) composition ratio in biphasic magnetic nanoparticles. The study involved seven laboratories across Europe and North and South America, and six samples—a verification set of three microcrystalline mixtures of known composition, and a validation set of three nanoparticle samples of unknown composition. The spectra were analysed by each participant using in-house fitting packages, and ex post facto by a single operator using an independent package. Repeatability analysis was performed using Mandel’s h statistic and modified Youden plots. It is shown that almost all (83/84) of the Mandel h statistic values fall within the 0.5% significance level, with the one exception being borderline. Youden-based pairwise analysis indicates the dominance of random uncertainties; and in almost all cases the data analysis phase is only a minor contributor to the overall measurement uncertainty. It is concluded that the COG method is a robust and promising candidate for its intended purpose.

Highlights

Magnetic nanoparticles comprising mixtures of the iron oxides magnetite (Fe3O4) and maghemite (γ-Fe2O3) have been the subject of sustained and significant R & D interest for many years, with ca 25 000 publications to date, including ca 200 per month in the last 5 years [1]
The 57Fe Mössbauer spectrometric ‘centre of gravity’ (COG) method was tested as a means of quantifying the magnetite/maghemite (Fe3O4/γ-Fe2O3) composition ratio in biphasic magnetic nanoparticles
Figure 1. 57Fe Mössbauer spectra, recorded at room temperature (T = 295 K ± 5 K), of six representative iron oxide samples chosen for the interlaboratory study, viz three microcrystalline mixtures of magnetite and maghemite (NM-A to -C) and three nanoparticulate iron oxide samples (NM-D to -F). mixtures

Summary

Introduction

Magnetic nanoparticles comprising mixtures of the iron oxides magnetite (Fe3O4) and maghemite (γ-Fe2O3) have been the subject of sustained and significant R & D interest for many years, with ca 25 000 publications to date, including ca 200 per month in the last 5 years [1]. Almost all of these biological applications rely on the nanoscale form, where the absence of remanent magnetisation—due to the size-dependent phenomenon of superparamagnetism [2]—removes the risk of agglomeration and embolism in vivo This is beneficial for their intended use, but it makes their characterisation much more difficult than it is for bulk materials. The bulk magnetisations of magnetite and maghemite differ by only a few percent, so that distinguishing them magnetically is difficult even in single-phase samples, let alone in mixtures, where the component masses are themselves hard to assess This is a longstanding problem in the field, which has led to a tendency for researchers to report their findings with reference to an unspecified ‘magnetite/maghemite’ material, rather than attempt to interrogate the actual composition

Methods

Results

Conclusion