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Dried blood spots in clinical lipidomics: optimization and recent findings

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Abstract

Dried 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.

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Abbreviations

AA:

Arachidonic acid

ACN:

Acetonitrile

BHT:

Butylated hydroxytoluene

CE:

Cholesteryl esters

Chol:

Cholesterol

CH2Cl2 :

Dichloromethane

DBS:

Dried blood spots

DHA:

Docosahexaenoic acid

DI-MS:

Direct injection mass spectrometry

EPA:

Eicosapentaenoic acid

FA:

Fatty acids

GC-FID:

Gas chromatography with flame ionization detection

GC-MS:

Gas chromatography coupled with mass spectrometry

Hct:

Haematocrit

HDL:

High density lipoproteins

HPLC:

High-performance liquid chromatography

IPA:

Isopropyl alcohol

LC-MS:

Liquid chromatography coupled with mass spectrometry

LDL:

Low density lipoprotein

MeOH:

Methanol

MS:

Mass spectrometry

MTBE:

Methyl tert-butyl ether

MS/MS:

Tandem mass spectrometry

P:

Plasmenyl

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PG:

Phosphatidylglycerol

PI:

Phosphatidylinositol

PL:

Phospholipids

PS:

Phosphatidylserine

PUFA:

Polyunsaturated fatty acids

RP:

Reverse phase

SFC-MS:

Supercritical fluids chromatography coupled with mass spectrometry

SM:

Sphingomyelins

SPME:

Solid-phase microextraction

TG:

Triacylglycerols

TLC-GC-FID:

Thin layer chromatography followed by gas chromatography with flame ionization detection

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Acknowledgements

Thanks are due for the financial support to the University of Aveiro and FCT/MCT for the financial 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-financed 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 Scientific Employment Stimulus 2020 (CEECIND/01578/2020). The authors are thankful to the COST Action EpiLipidNET, CA19105-Pan-European Network in Lipidomics and EpiLipidomics.

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Authors and Affiliations

  1. Mass Spectrometry Center & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    Helena Beatriz Ferreira, Tânia Melo, Ana S. P. Moreira & M. Rosário Domingues

  2. CESAM–Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    Helena Beatriz Ferreira, Inês M. S. Guerra, Tânia Melo & M. Rosário Domingues

  3. CICECO-Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    Inês M. S. Guerra & Ana S. P. Moreira

  4. Newborn Screening, Metabolism and Genetics Unit, Human Genetics Department, National Institute of Heath Doutor Ricardo Jorge, 4000-053, Porto, Portugal

    Hugo Rocha

  5. Superior School of Heath, Polytechnic Institute of Porto, 4200-072, Porto, Portugal

    Hugo Rocha

  6. Unidade de Gestão Operacional Em Citometria, Centro Hospitalar e Universitário de Coimbra (CHUC), 3004-561, Coimbra, Portugal

    Artur Paiva

  7. Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-370, Coimbra, Portugal

    Artur Paiva

  8. Instituto Politécnico de Coimbra, ESTESC-Coimbra Health School, Ciências Biomédicas Laboratoriais, 3046-854, Coimbra, Portugal

    Artur Paiva

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  1. Helena Beatriz Ferreira
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  6. Artur Paiva
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  7. M. Rosário Domingues
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Correspondence to Helena Beatriz Ferreira or M. Rosário Domingues.

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Ferreira, H.B., Guerra, I.M.S., Melo, T. et al. Dried blood spots in clinical lipidomics: optimization and recent findings. Anal Bioanal Chem 414, 7085–7101 (2022). https://doi.org/10.1007/s00216-022-04221-1

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