Digital research data: from analysis of existing standards to a scientific foundation for a modular metadata schema in nanosafety.

BACKGROUND: Assessing the safety of engineered nanomaterials (ENMs) is an interdisciplinary and complex process producing huge amounts of information and data. To make such data and metadata reusable for researchers, manufacturers, and regulatory authorities, there is an urgent need to record and provide this information in a structured, harmonized, and digitized way. RESULTS: This study aimed to identify appropriate description standards and quality criteria for the special use in nanosafety. There are many existing standards and guidelines designed for collecting data and metadata, ranging from regulatory guidelines to specific databases. Most of them are incomplete or not specifically designed for ENM research. However, by merging the content of several existing standards and guidelines, a basic catalogue of descriptive information and quality criteria was generated. In an iterative process, our interdisciplinary team identified deficits and added missing information into a comprehensive schema. Subsequently, this overview was externally evaluated by a panel of experts during a workshop. This whole process resulted in a minimum information table (MIT), specifying necessary minimum information to be provided along with experimental results on effects of ENMs in the biological context in a flexible and modular manner. The MIT is divided into six modules: general information, material information, biological model information, exposure information, endpoint read out information and analysis and statistics. These modules are further partitioned into module subdivisions serving to include more detailed information. A comparison with existing ontologies, which also aim to electronically collect data and metadata on nanosafety studies, showed that the newly developed MIT exhibits a higher level of detail compared to those existing schemas, making it more usable to prevent gaps in the communication of information. CONCLUSION: Implementing the requirements of the MIT into e.g., electronic lab notebooks (ELNs) would make the collection of all necessary data and metadata a daily routine and thereby would improve the reproducibility and reusability of experiments. Furthermore, this approach is particularly beneficial regarding the rapidly expanding developments and applications of novel non-animal alternative testing methods.

How Structured Metadata Acquisition Contributes to the Reproducibility of Nanosafety Studies: Evaluation by a Round-Robin Test.

It has been widely recognized that nanosafety studies are limited in reproducibility, caused by missing or inadequate information and data gaps. Reliable and comprehensive studies should be performed supported by standards or guidelines, which need to be harmonized and usable for the multidisciplinary field of nanosafety research. The previously described minimal information table (MIT), based on existing standards or guidelines, represents one approach towards harmonization. Here, we demonstrate the applicability and advantages of the MIT by a round-robin test. Its modular structure enables describing individual studies comprehensively by a combination of various relevant aspects. Three laboratories conducted a WST-1 cell viability assay using A549 cells to analyze the effects of the reference nanomaterials NM101 and NM110 according to predefined (S)OPs. The MIT contains relevant and defined descriptive information and quality criteria and thus supported the implementation of the round-robin test from planning, investigation to analysis and data interpretation. As a result, we could identify sources of variability and justify deviating results attributed to differences in specific procedures. Consequently, the use of the MIT contributes to the acquisition of reliable and comprehensive datasets and therefore improves the significance and reusability of nanosafety studies.

Experimental verification of an exact evanescent light scattering model for TIRM.

Total internal reflection microscopy (TIRM) is a method for the precise measurement of interaction potentials between a spherical colloidal particle and a wall. The method is based on single-particle evanescent wave light scattering. The well-established model used to interpret TIRM data is based on an exponential relation between scattering intensity and particle wall distance. However, applying this model for a certain range of experimental parameters leads to significant distortions of the measured potentials. Using a TIRM setup based on a two-wavelength illumination technique, we were able to directly measure the intensity distance relation revealing deviations from an exponential decay. The intensity-distance relations could be compared to scattering simulations taking into account exact experimental parameters and multiple reflections between a particle and the wall. Converging simulation results were independently obtained by the T-matrix method and the discrete sources method (DSM) and show excellent agreement with experiments. Using the new scattering model for data evaluation, we could reconstruct the correct potential shape for distorted interaction potentials as we demonstrate. The comparison of simulations to experiment intrinsically yields a new method to determine absolute particle-wall distances, a highly desired quantity in TIRM experiments.

Single-particle evanescent light scattering simulations for total internal reflection microscopy.

We simulate and measure light scattering of a micrometer-sized spherical particle suspended in solution close to a glass substrate. The model, based on the discrete sources method, is developed to describe the experimental situation of total internal reflection microscopy experiments; i.e., the particle is illuminated by an evanescent light field originating from the glass-solvent interface. In contrast to the well-established assumption of a simple exponential decay of the scattering intensity with distance, we demonstrate significant deviations for a certain range of penetration depths and polarization states of the incident light.