In future, measurements of extracellular vesicles in body fluids could become a standard diagnostic tool in medicine. For this purpose, reliable and traceable methods, which can be easily applied in hospitals, have to be established. Within the European Metrological Research Project (EMRP) 'Metrological characterization of micro-vesicles from body fluids as noninvasive diagnostic biomarkers' (www.metves.eu), various nanoparticle reference materials were developed and characterized. We present results of an international comparison among four national metrology institutes and a university hospital. The size distributions of five monodisperse and two bimodal spherical particle samples with diameters ranging from 50 nm to 315 nm made out of silica and polystyrene were compared. Furthermore, the stability of the samples was verified over a period of 18 months. While monodisperse reference particle samples above a certain size level lead to good agreements of the size measurements among the different methods, small and bimodal samples show the limitations of current 'clinical' methods. All samples proved to be stable within the uncertainty of the applied methods.

The accuracy of today’s coordinate measuring machines (CMM) has reached a level at which the exact knowledge of each component is required. The role of the probe tip is particularly crucial because it is in contact with the sample surface. Understanding how the probe tip wears off will help to narrow the measurement errors. Today, diamond-coated probes of excellent quality are becoming commercially available. In the present work, the wear of those probes was studied when scanning on different sample materials and under different measuring conditions. The wear rate was quantified in terms of the rate of the removed diamond volume per meter scan length. It cannot be simply derived from material properties or scanning conditions. A simple calculation also shows that only a very small fraction of the friction energy is devoted to the removal of atoms from the diamond crystal. The wear rate of diamond-coated probes was found to be orders of magnitude smaller compared with the wear of traditional sapphire probes.

The accuracy of today's coordinate measuring machines (CMM) has reached a level at which exact knowledge of each component is required. The role of the probe tip is particularly crucial as it is in contact with the sample surface. Understanding how the probe tip wears off will help to narrow the measurement errors. In this work, wear of a sapphire sphere was studied for different scanning conditions and with different sample materials. Wear depth on the probe was investigated using an automated process in situ on the METAS micro-CMM and completed by measurements with an atomic force microscope. We often found a linear dependence between the wear depth and the scan length ranging from 0.5 to 9 nm m−1, due to variations in scan speed, contact force or sample material. In the case of steel, the wear rate is proportional to the scan speed, while for aluminum several processes seem to interact. A large amount of debris was visible after the tests. Except for aluminum, wear was visible only on the sphere and not on the sample. Sapphire/steel is the worst combination in terms of wear, whereas the combination sapphire/ceramic exhibits almost no wear.

Tactile ultra-precise coordinate measuring machines (CMMs) are very attractive for accurately measuring optical components with high slopes, such as aspheres. The METAS µ-CMM, which exhibits a single point measurement repeatability of a few nanometres, is routinely used for measurement services of microparts, including optical lenses. However, estimating the measurement uncertainty is very demanding. Because of the many combined influencing factors, an analytic determination of the uncertainty of parameters that are obtained by numerical fitting of the measured surface points is almost impossible. The application of numerical simulation (Monte Carlo methods) using a parametric fitting algorithm coupled with a virtual CMM based on a realistic model of the machine errors offers an ideal solution to this complex problem: to each measurement data point, a simulated measurement variation calculated from the numerical model of the METAS µ-CMM is added. Repeated several hundred times, these virtual measurements deliver the statistical data for calculating the probability density function, and thus the measurement uncertainty for each parameter. Additionally, the eventual cross-correlation between parameters can be analyzed. This method can be applied for the calibration and uncertainty estimation of any parameter of the equation representing a geometric element. In this article, we present the numerical simulation model of the METAS µ-CMM and the application of a Monte Carlo method for the uncertainty estimation of measured asphere parameters.

Size measurements of sub-micrometre spherical particles are quite easily performed with an atomic force microscope. The diameter is typically evaluated as the apex of the particle relative to a flat surface. However, some interaction effects may modify the expected results, such as the adhesive forces between the particle and the substrate or the tip–particle interface. In this paper, both effects were experimentally investigated for polystyrene particles with sizes ranging from 150 nm to 700 nm deposited on mica. Additionally, the experimental findings were compared with theoretical models of adhesion, describing both elastic and plastic deformation at the particle–substrate interface. While no clear indication of particle deformation due to the tip–particle interaction was obtained, the deformation due to adhesive forces between the particle and the substrate could be quantified. Contrary to certain theoretical models, the deformation was found to be proportional to the particle size.