Advanced Microsamples: Current Applications and Considerations for Mass Spectrometry-Based Metabolic Phenotyping Pipelines

Microsamples are collections usually less than 50 µL, although all devices that we have captured as part of this review do not fit within this definition (as some can perform collections of up to 600 µL); however, they are considered microsamples that can be self-administered. These microsamples have been introduced in pre-clinical, clinical, and research settings to overcome obstacles in sampling via traditional venepuncture. However, venepuncture remains the sampling gold standard for the metabolic phenotyping of blood. This presents several challenges in metabolic phenotyping workflows: accessibility for individuals in rural and remote areas (due to the need for trained personnel), the unamenable nature to frequent sampling protocols in longitudinal research (for its invasive nature), and sample collection difficulty in the young and elderly. Furthermore, venous sample stability may be compromised when the temperate conditions necessary for cold-chain transport are beyond control. Alternatively, research utilising microsamples extends phenotyping possibilities to inborn errors of metabolism, therapeutic drug monitoring, nutrition, as well as sport and anti-doping. Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. Research into the metabolic phenotyping of microsamples is limited; however, with advances in commercially available microsampling devices, common barriers such as volumetric inaccuracies and the ‘haematocrit effect’ in dried blood spot microsampling can be overcome. In this review, we provide an overview of the common uses and workflows for microsampling in metabolic phenotyping research. We discuss the advancements in technologies, highlighting key considerations and remaining knowledge gaps for the employment of microsamples in metabolic phenotyping research. This review supports the translation of research from the ‘bench to the community’

Rapid and Self-Administrable Capillary Blood Microsampling Demonstrates Statistical Equivalence with Standard Venous Collections in NMR-Based Lipoprotein Analysis

We investigated plasma and serum blood derivatives from capillary blood microsamples (500 μL, MiniCollect® tubes) and corresponding venous blood (10 mL vacutainers). Samples from twenty healthy participants were analysed by 1H-NMR and 112 lipoprotein subfraction parameters; 3 supramolecular phospholipid composite (SPC) parameters from SPC1, SPC2, and SPC3 subfractions; 2 N-acetyl signals from α-1-acid glycoprotein (Glyc), GlycA and GlycB; and 3 calculated parameters, SPC (total), SPC3/SPC2, Glyc (total)—were assessed. Using linear regression between capillary and venous collection sites, explained variance (Adj. R2 ≥ 0.8, p < 0.001) was witnessed for 86% of plasma parameters (103/120), and 88% of serum parameters (106/120), indicating capillary lipoprotein, SPC, and Glyc concentration follows changes in venous concentra-tions. These results indicate capillary blood microsamples are suitable for sampling in remote areas and for high-frequency longitudinal sampling of the majority of lipoproteins, SPCs, and Glycs

Rapid and Self-Administrable Capillary Blood Microsampling Demonstrates Statistical Equivalence with Standard Venous Collections in NMR-Based Lipoprotein Analysis

We investigated plasma and serum blood derivatives from capillary blood microsamples (500 μL, MiniCollect tubes) and corresponding venous blood (10 mL vacutainers). Samples from 20 healthy participants were analyzed by 1H NMR, and 112 lipoprotein subfraction parameters; 3 supramolecular phospholipid composite (SPC) parameters from SPC1, SPC2, and SPC3 subfractions; 2 N-acetyl signals from α-1-acid glycoprotein (Glyc), GlycA, and GlycB; and 3 calculated parameters, SPC (total), SPC3/SPC2, and Glyc (total) were assessed. Using linear regression between capillary and venous collection sites, we explained that agreement (Adj. R2 ≥ 0.8, p < 0.001) was witnessed for 86% of plasma parameters (103/120) and 88% of serum parameters (106/120), indicating that capillary lipoprotein, SPC, and Glyc concentrations follow changes in venous concentrations. These results indicate that capillary blood microsamples are suitable for sampling in remote areas and for high-frequency longitudinal sampling of the majority of lipoproteins, SPCs, and Glycs