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

Abstract

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

“…However, frequent vein puncture must also be avoided, and although a cannula can be used for repeated sampling, it must remain clean and dry, making it ill-suited beyond controlled settings. In contrast, capillary blood microsamples have a collection volumes (typically less than 50 μL, although volumes can extend up to 600 μL) that offer a minimally invasive alternative to traditional intravenous sampling, which supports the evolving nature of healthcare from reactive disease care to care that is predictive, preventive, personalized, and participatory (P4 medicine). ,, Capillary microsampling is performed by lancing the fingertip for collection of blood drops into a small container or blood collection card, making increased sampling frequencies possible. Many advanced devices are also commercially available with volumes that are suitable for standard metabolic profiling protocols …”

“…LISA, version PL-5009-01/ 001) method was performed. 11 The platform applied a regression model to 1 H NMR spectra with solvent suppression to compute the concentration of triglycerides (-TG), cholesterol (-CH), free cholesterol (-FC), phospholipids (-PL), Apo A1 (-A1), Apo-A2 (-A2), and Apo B100 (-AB) of the main very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), LDL, and HDL classes. 11 The full B.I.…”

“…Many advanced devices are also commercially available with volumes that are suitable for standard metabolic profiling protocols. 1 1 H NMR spectroscopy has long been used for the measurement of variable biochemical signatures of blood plasma and serum to understand health and disease. 5−9 This includes analysis of panels of lipoproteins, supramolecular phospholipid composites (SPCs), and glycoprotein acetyls (α-1-acid glycoproteins) and others, which offer a diagnostic tool that extends beyond the standard clinical assays for low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol.…”

Blood microsampling technologies: Innovations and applications in 2022

“…About 75% of samples require centrifugation to obtain plasma or serum for analysis, which increases economic costs and is a substantial factor for delays in a laboratory workflow 9 . Wet blood samples require cold‐chain storage and shipping to prevent sample degradation and bacterial growth 10 …”

“…Blood microsampling, the process of capturing small volumes of capillary blood (typically <100 µL), often in a minimally‐invasive manner, presents a viable alternative to vascular puncture and is a significant contributor in the revolutionization of human healthcare towards preventive, participative and personalised approaches in disease management. The minimal invasiveness of a low‐volume blood draw provides benefits over conventional blood sampling by enabling amenable self‐sampling without the need for trained personnel or hospital visits, which can advance primary healthcare in rural and remote geographical areas, 11 and improve patient recruitment and retention, thereby increasing statistical power in clinical studies 10 . Reduced blood volumes enhance the feasibility of sampling volume‐limited candidates and serial sampling, which can facilitate longitudinal investigations with fewer participants 12 .…”