Towards improved workflows for the production and metrological characterization of LA-ICP-MS calibration standards for quantitative bioimaging

Abstract

The lack of suitable calibration standards is a persistent bottleneck for quantitative bioimaging by LA-ICP-MS. Widespread use of in-house calibration approaches has led to a lack of harmonisation limiting the potential of LA-ICP-MS in clinical or biomedical fields. This work addresses this challenge by utilising automation via a bioprinting approach to produce re-usable gelatin-droplet standards, doped with multiple elements for both instrument tuning and quantitative analysis. The resulting standards were systematically characterized in terms of thickness, elemental homogeneity, and long-term stability. Droplets were doped with Ti, Ce, Au, Th and U (used for instrument tuning) as well as increasing concentrations of lanthanides such as Gd and Yb (typically used in bio-clinical applications). Variation of thickness (measured by ellipsometry) between droplets, after printing and dehydration, was 5% (RSD, n = 12). Intra- and inter-droplet elemental homogeneity were less than 6% (RSD, n = 10) and 8% (RSD, n = 9), respectively for all elements. Due to the reproducibility of both physical characteristics (thickness and size) and elemental distribution, there is no need of ablating the entire droplet. Instead, ablation of an area as small as 1 line across a droplet produced elemental data which is representative of the entire droplet. This feature enables the same droplet to be used across multiple batches or multiple times within a batch, the latter for quality control purposes. Data from long-term stability and shipping tests highlight the usability of these standards and a potential route towards harmonisation.