Dried Spot Paradigm: Problems and Prospects in Proteomics

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.