Dried blood spot analysis with liquid chromatography and mass spectrometry: Trends in clinical chemistry

Abstract

Dried blood spot samples are simple to prepare and transport, enabling safe and accessible diagnostics, both locally and globally. We review dried blood spot samples for clinical analysis, focusing on liquid chromatography‐mass spectrometry as a versatile measurement tool for these samples. Dried blood spot samples can provide information for, for example, metabolomics, xenobiotic analysis, and proteomics. Targeted analyses of small molecules are the main application of dried blood spot samples and liquid chromatography‐mass spectrometry, but emerging applications include untargeted metabolomics and proteomics. Applications are highly varied, including analyses related to newborn screening, diagnostics and monitoring of disease progression and treatment effects of virtually any disease, as well as studies into the physiology and effects of diet, exercise, xenobiotics, and doping. A range of dried blood spot products and methods are available, and applied liquid chromatography‐mass spectrometry instrumentation is varied with regard to liquid chromatography column formats and selectivity. In addition, novel approaches such as on‐paper sample preparation (e.g., selective trapping of analytes with paper‐immobilized antibodies) are described. We focus on research papers published in the last 5 years.

One‐step functionalization of paper and simplified antibody immobilization for on‐the‐spot immunocapture from dried serum in liquid chromatography‐tandem mass spectrometry based targeted protein determination

“…mAbs E27 selective against several variants of hCG 25 were supplied by Central Laboratory, Norwegian Radium Hospital, Oslo University Hospital (Oslo, Norway). Isotopically labelled peptide internal standard for hCG β peptide sequence, VLQGVLPALPQVVCNY(R*), where R* denotes arginine-labelled 13 C and 15 N, was purchased from Innovagen AB (Lund, Sweden). The internal standard was reduced and alkylated in-house according to the protocol from Lund et al 26 Human serum from healthy blood donors was obtained from Oslo University Hospital Ullevål (Oslo, Norway) and stored at À30 C. Whatman Grade CF12 filter paper was purchased from Cytiva (Buckinghamshire, UK).…”

“…12 Advancements in instrumentation have made mass spectrometry (MS) one of the most versatile techniques for DBS analysis today, especially for protein determination. 13 Despite the many advantages of DBS, it also comes with its limitations and challenges regarding MSbased protein analysis. Due to the complexity of blood samples and the low abundant nature of many biologically interesting proteins, extensive and intensive sample preparation is usually needed.…”

Advancements in clinical approaches, analytical methods, and smart sampling for LC–MS‐based protein determination from dried matrix spots

“…At least six comprehensive reviews discussing the use of DBS in the determination of low‐ and high‐molecular substances have been published since 2017 [5–10], all with a different focus. Both Nys et al.…”

“…The tutorial on VAMS [8] as well as the reviews on multi‐omics from DBS [7] and applications of DBS within clinical chemistry [5] also cover a broad range of compounds but focus either on the use of VAMS [8] or the use of cellulose paper [5, 7] to collect the sample. In the latter reviews, the determination of proteins with respect to the general aspects of targeted and untargeted proteomics from DBS using LC–MS is discussed.…”

Targeted and untargeted metabolomics and lipidomics in dried blood microsampling: Recent applications and perspectives

“…Recent applications of DBS samples include the analysis of small metabolites, such as vitamin D and opioids, as well as larger molecules like peptides and proteins. 29 VAMS has also seen extensive implementation, particularly in studies related to COVID‐19 analytes, immunosuppressants and anticonvulsants. 30 For instance, VAMS has been used to study various endogenous metabolites, including creatinine, steroids, vitamins, phosphatidyl ethanols and amino acids, as recently reviewed.…”