High quality of SARS-CoV-2 molecular diagnostics in a diverse laboratory landscape through supported benchmark testing and External Quality Assessment

A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This strategy was successfully applied to 71 diagnostic laboratories in The Netherlands when upscaling the national diagnostic capacity during the SARS-CoV-2 pandemic. The availability of benchmark testing in combination with advice for improvement substantially enhanced the quality of the laboratory testing procedures for SARS-CoV-2 detection. The three subsequent EQA rounds demonstrated high quality testing with regard to specificity (99.6% correctly identified) and sensitivity (93.3% correctly identified). Even with the implementation of novel assays, changing workflows using diverse equipment and a high degree of assay heterogeneity, the overall high quality was maintained using this two-step strategy. We show that in contrast to the limited value of Cq value for absolute proxies of viral load, these Cq values can, in combination with metadata on strategies and techniques, provide valuable information for laboratories to improve their procedures. In conclusion, our two-step strategy (preparation phase followed by a series of EQAs) is a rapid and flexible system capable of scaling, improving, and maintaining high quality diagnostics even in a rapidly evolving (e.g. pandemic) situation.</p

High quality of SARS-CoV-2 molecular diagnostics in a diverse laboratory landscape through supported benchmark testing and External Quality Assessment

A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This strategy was successfully applied to 71 diagnostic laboratories in The Netherlands when upscaling the national diagnostic capacity during the SARS-CoV-2 pandemic. The availability of benchmark testing in combination with advice for improvement substantially enhanced the quality of the laboratory testing procedures for SARS-CoV-2 detection. The three subsequent EQA rounds demonstrated high quality testing with regard to specificity (99.6% correctly identified) and sensitivity (93.3% correctly identified). Even with the implementation of novel assays, changing workflows using diverse equipment and a high degree of assay heterogeneity, the overall high quality was maintained using this two-step strategy. We show that in contrast to the limited value of Cq value for absolute proxies of viral load, these Cq values can, in combination with metadata on strategies and techniques, provide valuable information for laboratories to improve their procedures. In conclusion, our two-step strategy (preparation phase followed by a series of EQAs) is a rapid and flexible system capable of scaling, improving, and maintaining high quality diagnostics even in a rapidly evolving (e.g. pandemic) situation.</p

Crystallisation kinetics of some archetypal ionic liquids: isothermal and non-isothermal determination of the Avrami exponent

The properties of ionic liquids give rise to applications in diverse technology areas including mechanical engineering, mining, aerospace and defence. The arbitrary physical property that defines an ionic liquid is a melting point below 100 degrees C, and as such, an understanding of crystallisation phenomena is extremely important. This is the first report dealing with the mechanism of crystallisation in ionic liquids. Assuming crystallisation of the ionic liquids is a thermal or mass diffusion-controlled process, the values of the isothermal Avrami exponent obtained from three different ionic liquids with three different anions and cations all indicate that growth occurs with a decreasing nucleation rate (n = 1.8-2.2). For one of the ionic liquids it was possible to avoid crystallisation by fast cooling and then observe a devitrification upon heating through the glass transition. The isothermal Avrami exponent of devitrification suggested growth with an increasing nucleating rate (n = 4.1), compared to a decreasing nucleation rate when crystallisation occurs on cooling from the melt (n = 2.0). Two non-isothermal methods were employed to determine the Avrami exponent of devitrification. Both non-isothermal Avrami exponents were in agreement with the isothermal case (n = 4.0-4.15). The applicability of JMAK theory suggests that the nucleation event in the ionic liquids selected is a random stochastic process in the volume of the material. Agreement between the isothermal and non-isothermal techniques for determining the Avrami exponent of devitrification suggests that the pre-exponential factor and the activation energy are independent of thermal history. The heating rate dependence of the glass transition enabled the calculation of the fragility index, which suggests that the ionic liquid is a "strong" glass former. This suggests that the temperature dependence of the rate constant could be close to Arrhenius, as assumed by JMAK theory. More generally, therefore, it can be concluded that there is nothing unusual about the crystallisation mechanism of the ionic liquids studied here

Thermal and physical properties of an archetypal organic ionic plastic crystal electrolyte

The thermal and mechanical properties of the ionic plastic crystal N-methyl-N-propylpyrrolidinium hexafluorophosphate have been investigated and the effect of adding a miscible polymer on the mechanical properties is reported. The physical properties of the pure plastic crystal are discussed in detail and for the first time the change in volume with temperature for an organic ionic plastic crystal is reported. An increase in volume in conjunction with increased conductivity supports the hypothesis that ion conduction within the plastic crystal proceeds via defects. For phase I and melting, the magnitude of the volume increase does not appear to be in accord with the subtle change in conductivity. This is suggested to be due to the presence of layer defects, which allow for correlated ionic motion, which does not increase the conductivity. Addition of polymer to the plastic crystal significantly increases the mechanical strength, decreases the conductivity, but has little effect on the phase behaviour, further supporting the hypothesis of vacancy-mediated conduction.<br /

Advanced fitting algorithms for analysing positron annihilation lifetime spectra

Abstract 2 The most common way to analyse PALS spectra involves fitting a parameter-dependent model to the experimental data. Traditionally, this fit involves local nonlinear optimisation routines that depend on a reasonable initial guess for the searched parameters. This, together with the fact that very different sets of parameters may yield indistinguishably good fits for a given experimental spectrum, gives rise to ambiguities in the data analysis in most but the simplest cases. In order to alleviate these difficulties, a computer program named PAScual was developed that incorporates two advanced algorithms to provide a robust fitting tool: on the one hand, it incorporates a global nonlinear optimisation routine based on the Simulated Annealing algorithm and, on the other hand, it yields information on the reliability of the results by means of a Markov Chain Monte-Carlo Bayesian Inference method. In this work the methods used in PAScual are described and tested against both simulated and experimental spectra, comparing the results with those from the well established program LTv9. The examples focus on the type of complex data that results from the study of self-assembled amphiphile materials containing co-existing aqueous and hydrocarbon regions

Supercritical CO2 modified organic ionic plastic crystals

The treatment of an organic ionic plastic crystal electrolyte N-methyl-N-ethylpyrrolidinium tetrafluoroborate (P1,2BF4) with supercritical CO2 resulted in a substantial increase in ionic conductivity, especially in the more highly ordered solid phases of the material, and also stabilised the most ordered phase to lower temperatures. <br /

Exposing the molecular sieving architecture of amorphous silica using positron annihilation spectroscopy

Despite extensive research into silica gels, little exists that describes the porous properties of the fundamental molecular sieving framework due to limitations of current characterization techniques. This paper describes the novel use of positron annihilation lifetime spectroscopy (PALS) for rapid quantitative measurement of sub-nanometer pores in amorphous molecular sieving silicas. The well-established N2 adsorption technique was also used, but most materials appeared nonporous as adsorption cannot detect pores less than the size of the N2 molecule. PALS, on the other hand, detected hierarchical trimodal porosity in all silicas, peaking at around 3, 8, and 12A ° . Gas permeation probing through membranes made using the same silicas verified the 3A° size cutoff and provided strong evidence that the intermediate and larger pores are not continuously connected for large molecule diffusion. For these ‘‘sponge-like’’ silicas, all molecules must pass through the fundamental silica framework that provides the selectivity. The quantity and size of intermediate and large pores was in turn found to contribute to the permeation performance. A hydrostabilized templated silica had more intermediate and larger pore interconnection evident by high N2 adsorption and slightly lower selectivity than the same non-templated material. A material tailored for improved H2/CO2 separation had a reduced size of the smaller pores, which gave it better selectivity. Studies of temperature evolution of silica gels from 200–600 8C using PALS conclusively showed that temperature increases the pore size of the fundamental silica framework. This observation fits well with widely reported progressive network assembling via formation of siloxane groups causing the silica to ‘‘inflate’’, which now describes in better detail the porous features of the fundamental silica network