Revolutionizing Blood Collection: Innovations, Applications, and the Potential of Microsampling Technologies for Monitoring Metabolites and Lipids

Abstract

Blood serves as the primary global biological matrix for health surveillance, disease diagnosis, and response to drug treatment, holding significant promise for personalized medicine. The diverse array of lipids and metabolites in the blood provides a snapshot of both physiological and pathological processes, with many routinely monitored during conventional wellness checks. The conventional method involves intravenous blood collection, extracting a few milliliters via venipuncture, a technique limited to clinical settings due to its dependence on trained personnel. Microsampling methods have evolved to be less invasive (collecting ≤150 µL of capillary blood), user-friendly (enabling self-collection), and suitable for remote collection in longitudinal studies. Dried blood spot (DBS), a pioneering microsampling technique, dominates clinical and research domains. Recent advancements in device technology address critical limitations of classical DBS, specifically variations in hematocrit and volume. This review presents a comprehensive overview of state-of-the-art microsampling devices, emphasizing their applications and potential for monitoring metabolites and lipids in blood. The scope extends to diverse areas, encompassing population studies, nutritional investigations, drug discovery, sports medicine, and multi-omics research.

Keywords: dried blood spot; drug discovery; lipidomics; metabolomics; microsampling; personalized medicine.

Figure 1

Graphical summary of microsampling technologies. Blood microsampling has various applications and offers several advantages compared to traditional venous blood sampling. DBS: dried blood spot; DPS: dried plasma spots; DSS: dried serum spots; TAP: touch-activated phlebotomy; VAMS: volumetric absorptive microsampling.

Figure 2

Microsampling devices. (A) DBS sample cards. (B) Capitainer^® B (Capitainer AB, Stockholm, Sweden) (qDBS) with cross-sectional view. It involves a microfluidic system that allows the collection of an exact volume of 10 µL of whole blood. 1B—a single drop of blood is collected and fills the capillary microchannel; 2B—the thin film located at the inlet dissolves and the blood in excess is absorbed by a paper substrate; 3B—the thin film at the outlet is dissolved, the capillary channel is emptied thanks to capillary forces, and 10 µL of blood is absorbed on a pre-cut paper disk. (C) HemaSpot^TM (Spot On Sciences, San Francisco, CA, USA) HF cross-sectional view for the quantitative collection of whole blood. (D) HemaSpot^TM (Spot On Sciences, San Francisco, CA, USA) SE cross-sectional view. It allows the serum separation from whole blood by lateral flow. (E) Telimmune DUO (Telimmune, West Lafayette, IN, USA) cross-sectional view for the plasma separation from whole blood without centrifugation. (F) Mitra^® device (Trajan Scientific and Medical, Melbourne, VIC, Australia) using VAMS tips to collect whole blood. (G) TASSO (Tasso Inc., Seattle, WA, USA) M-20 for whole blood collection. (H) TAP device (YourBio Health, Medford, MA, USA) to collect capillary blood samples by deploying and withdrawing a microneedle array, generating a vacuum pressure that allows the collection. 1H—the button at the top of the device is pushed and the microneedle array is deployed and then withdrawn; 2H—the vacuum draws blood into the sample container. 3H—the visual indicator turns red when the collection is completed. 4H—The device is removed and sampling is completed (I) hemaPEN^® (Trajan Scientific and Medical, Melbourne, VIC, Australia) for the collection of whole blood on 4 pre-punched DBS through capillary action.