Dried Spot Paradigm: Problems and Prospects in Proteomics

Abstract

The analysis of biological fluids plays a crucial role in biomarker discovery, disease diagnostics, and precision medicine. Dried sample carriers-such as dried blood spots, dried plasma, serum, saliva, tears, and urine-have emerged as powerful tools, offering advantages in sample collection, storage, and transport, particularly in remote and resource-limited settings. Recent advances in proteomic methodologies have expanded the potential of these dried matrices, yet challenges related to protein stability, sensitivity, and standardization persist. This review critically examines the current state of proteomic investigations using dried biological fluids. Furthermore, we compare proteomics' progress in this field with other omics approaches, such as metabolomics, to contextualize its development and integration potential. While dried fluid proteomics is promising for non-invasive diagnostics and large-scale epidemiological studies, addressing technical limitations will be essential for its broader adoption in clinical and translational research.

Keywords: biomarker; diagnostics; dried sample; proteomics.

Figure 1

A chronological journey through key innovations in paper-based diagnostics, from the early use of DBSs to cutting-edge smart sampling techniques. The figure highlights Ivar Bang’s pioneering work in glucose detection [1], Guthrie’s breakthrough in newborn screening for PKU [2], and the introduction of lateral-flow pregnancy tests [3]. Advancements in VAMS and functionalized substrates further refined biomarker detection [4,5,6,7]. Recent developments in paper-based systems continue to expand their role in personalized medicine and large-scale health monitoring [8,9,10].

Figure 2

Number of articles in PubMed for each type of biological liquid discussed: G—genomics (blue); T—transcriptomics (yellow); P—proteomics (green); M—metabolomics (red). ∑ indicates the summarized number of articles for each type of biological sample. The search in PubMed was effected using the following queries: for DBS: ((“dried blood spot”[Title/Abstract]) OR (“dried bloodspot”[Title/Abstract])) AND (OMICS[Title/Abstract]); DPS: (“Dried Plasma Spot”[Title/Abstract]) AND (OMICS[Title/Abstract]); DSeS: (“Dried Serum Spot”[Title/Abstract]) AND (OMICS[Title/Abstract]); DTS: ((Schirmer’s Strip)[Title/Abstract] OR (“Dried Tear Strip”)[Title/Abstract]) AND (OMICS[Title/Abstract]); DUS: ((“Urine Strip”)[Title/Abstract] OR (“Dried Urine Strip”)[Title/Abstract] OR (“Dried Urine Spot”)[Title/Abstract]) AND (OMICS[Title/Abstract]); DSaS: (“Dried Saliva Spot”[Title/Abstract]) AND (OMICS[Title/Abstract]).