Dried blood spots in clinical lipidomics: optimization and recent findings

ReviewDried blood spots (DBS) are being considered as an alternative sampling method of blood collection that can be used in combination with lipidomic and other omic analysis. DBS are successfully used in the clinical context to collect samples for newborn screening for the measurement of specific fatty acid derivatives, such as acylcarnitines, and lipids from whole blood for diagnostic purposes. However, DBS are scarcely used for lipidomic analysis and investigations. Lipidomic studies using DBS are starting to emerge as a powerful method for sampling and storage in clinical lipidomic analysis, but the major research work is being done in the pre- and analytical steps and procedures, and few in clinical applications. This review presents a description of the impact factors and variables that can affect DBS lipidomic analysis, such as the type of DBS card, haematocrit, homogeneity of the blood drop, matrix/chromatographic effects, and the chemical and physical properties of the analyte. Additionally, a brief overview of lipidomic studies using DBS to unveil their application in clinical scenarios is also presented, considering the studies of method development and validation and, to a less extent, for clinical diagnosis using clinical lipidomics. DBS combined with lipidomic approaches proved to be as effective as whole blood samples, achieving high levels of sensitivity and specificity during MS and MS/MS analysis, which could be a useful tool for biomarker identification. Lipidomic profiling using MS/MS platforms enables significant insights into physiological changes, which could be useful in precision medicine.Thanks are due for the financial support to the University of Aveiro and FCT/MCT for the fnancial support to research units CESAM (UIDB/50017/2020, UIDP/50017/2020 & LA/P/0094/2020), LAQV-REQUIMTE (UIDB/50006/2020), and CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020), and to RNEM, Portuguese Mass Spectrometry Network (LISBOA-01-0145-FEDER-402-022125) through national funds and, where applicable, co-fnanced by the FEDER, within the PT2020. Helena Beatriz Ferreira is grateful to FCT for her PhD Grant (2020.04611.BD). Inês M. S. Guerra is grateful to FCT for her PhD Grant (2021.04754.BD). Ana S. P. Moreira thanks the contract in the scope of the project ‘Coccolitho4BioMat’ (POCI 01-0145-FEDER-031032). Tânia Melo thanks the Junior Researcher contract in the scope of the Individual Call to Scientifc Employment Stimulus 2020 (CEECIND/01578/2020). The authors are thankful to the COST Action EpiLipidNET, CA19105-Pan-European Network in Lipidomics and EpiLipidomics.