Challenges and opportunities in mass spectrometric analysis of proteins from dried blood spots

Abstract

Dried blood spots (DBS) have been used as a clinical sample format for over 50 years, and have been analyzed for small molecules and metabolites by mass spectrometry (MS) since the early 1990s. In the meantime, MS has become the tool of choice in proteomics. Despite this obvious avenue of scientific investigation, the marriage of MS and DBS protein analysis has been comparatively recent. DBS are a potentially rich source of protein biomarkers that remain to be exploited. This article focuses on the progress made in the mass spectrometric analysis of proteins from DBS and discusses the benefits and challenges facing this emerging field.

Keywords::

• biomarkers
• clinical diagnostics
• dried blood spots
• mass spectrometry
• proteins
• proteomics

Financial & competing interests disclosure

H Cooper is an EPSRC Established Career Fellow (EP/L023490/1). N Martin is in receipt of an EPSRC CASE studentship in collaboration with Advion Biosciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Dried blood spot (DBS) sampling by mass spectrometry has been commonplace for many decades but has largely focused on metabolite and small molecule analysis. DBS are potentially a rich source of protein biomarkers.

• Newborn DBS screening for hemoglobinopathies currently uses isoelectric focusing and/or cation exchange HPLC. The advantages of mass spectrometry-based screening have been demonstrated, yet it has only been adopted by two population-wide screening programs.

• A number of targeted multiple reaction monitoring assays for specific proteins have been developed, both for single proteins and multiplexed assays. Broad adoption of such assays is yet to be achieved.

• Untargeted shotgun proteomic analyses of DBS have identified many different proteins across a large concentration range in the human plasma proteome. DBS could replace plasma as the sample format of choice.