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Background: Capillary blood collection is minimally invasive, easy to perform, and when dried, is more stable at higher temperatures than liquid blood, making dried capillary blood microsamplers a promising alternative to venous blood for epidemiological research, particularly for vulnerable populations. Newly developed microsampler technologies are making headway as replacements to venous blood sampling in nonclinical pharmaceutical research, suggesting their potential for use in epidemiological research. However, their compatibility with untargeted metabolomics assays has not been fully evaluated.
Methods: Using commercially purchased whole blood, we performed untargeted metabolomics profiling of 5-mm Guthrie card punches (~8-10 µL of whole blood), Volumetric Absorptive Microsampling (VAMS®) tips (10 µL of whole blood), HemaXis^TM whole spots (10 µL of whole blood), and a Noviplex™ plasma discs (2.74 µL of plasma). Samples were analyzed using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) for measurement of polar compounds (ZHP) and semi- and non-polar compounds (RPN). Molecular features with a fold-change > 3, compared to equivalent matrix blank were retained for analysis.
Results: Endogenous and exogenous metabolites, environmental chemicals, and contaminants were measured in all four samplers. 4690 and 1605 peaks were measured in all four methods for ZHP and RPN analysis, respectively. An additional 3669 and 1848 peaks were shared by VAMS, Guthrie and HemaXis, but not found in Noviplex for ZPH and RPN analysis, respectively. Coefficients of variation calculated in replicate samples indicated higher reproducibility in VAMS and Guthrie card punches, than from HemaXis^TM and Noviplex™. Furthermore, Noviplex™ extracts contained large contamination peaks not found in other devices.
Conclusions: While we found that all microsamplers were amenable to untargeted metabolomics, differences were observed in the total number of metabolites measured, reproducibility of features, and background contamination levels. VAMS and Guthrie cards are the most promising devices for further untargeted metabolomics development for use in epidemiological research.