Performance of a web-based application measuring spot quality in dried blood spot sampling

Background The dried blood spot (DBS) method allows patients and researchers to collect blood on a sampling card using a skin-prick. An important issue in the application of DBSs is that samples for therapeutic drug monitoring are frequently rejected because of poor spot quality, leading to delayed monitoring or missing data. We describe the development and performance of a web-based application (app), accessible on smartphones, tablets or desktops, capable of assessing DBS quality at the time of sampling by means of analyzing a picture of the DBS. Methods The performance of the app was compared to the judgment of experienced laboratory technicians for samples obtained in a trained and untrained setting. A robustness- and user test were performed. Results In a trained setting the app yielded an adequate decision in 90.0% of the cases with 4.1% false negatives (insufficient quality DBSs incorrectly not rejected) and 5.9% false positives (sufficient quality DBSs incorrectly rejected). In an untrained setting this was 87.4% with 5.5% false negatives and 7.1% false positives. A patient user test resulted in a system usability score of 74 out of 100 with a median time of 1 min and 45 s to use the app. Robustness testing showed a repeatability of 84%. Using the app in a trained and untrained setting improves the amount of sufficient quality samples from 80% to 95.9% and 42.2% to 87.9%, respectively. Conclusions The app can be used in trained and untrained setting to decrease the amount of insufficient quality DBS samples.

Analysis of wavefront effects for large-aperture tiled-grating compressor

Monolithic large-aperture diffraction grating tiling is desired to increase the output capability of multi-kilojoule petawatt laser facilities. However, the wavefront errors of input pulse and gratings will degrade the focal spot quality and the compressibility of the output pulse. In this work, the effects of wavefront error of input pulse, deformation and wave aberration of the grating for the large-aperture tiled-grating compressor are investigated theoretically. A series of numerical simulations are presented to discuss the changing trends of focal spot energy caused by wavefront error of input pulse and obtain the error tolerance for specific goals. The influences of coating stress and the wave aberration of holographic exposure gratings on the diffraction wavefront are also discussed. Some advice is proposed for improving the performance of large-aperture tiled-grating. This work paves the way for the design of practical large-aperture tiled-grating compressor for ultrahigh intensity laser facilities in the future.

Effect of Dried Blood Spot Quality on Newborn Screening Analyte Concentrations and Recommendations for Minimum Acceptance Criteria for Sample Analysis

BACKGROUND The analysis of dried blood spots has been used routinely for newborn screening since the early 1970s, and the number of disorders screened has expanded substantially in recent years. However, there is a lack of evidence regarding minimum blood spot quality acceptance criteria for sample analysis. METHODS Blood pools were spiked with phenylalanine, tyrosine, leucine, methionine, octanoylcarnitine, decanoylcarnitine, isovalerylcarnitine, glutarylcarnitine, thyroid-stimulating hormone, and immunoreactive trypsinogen to concentrations at the analytical cutoffs used in UK screening protocols. We evaluated the effect of sample volume applied to the card (10, 20, 50, 75, and 100 μL), punch location (central vs peripheral), and sample quality (double layering, applying blood to both sides of the filter paper, multispotting, applying insufficient sample, and compressing the sample after application). RESULTS Compression of blood spots produced significantly lower results (14%–44%) for all analytes measured (P < 0.001). Smaller blood spots produced significantly lower results (15%–24% for 10-μL vs 50-μL sample size) for all analytes at all concentrations measured (P < 0.001). Results obtained from peripheral punches were higher than those from a central punch, although this did not reach statistical significance for all analytes. Insufficient and multispotted samples demonstrated heterogeneous results. CONCLUSIONS All blood spots containing ≤20 μL (blood spot diameter <8 mm), those in which blood has not fully penetrated the filter paper, and all samples with evidence of compression should be rejected, since there is a risk of producing false-negative results.