Dried Blood Spots for Global Health Diagnostics and Surveillance: Opportunities and Challenges

Abstract

Abstract.There is increasing interest in using dried blood spot (DBS) cards to extend the reach of global health and disease surveillance programs to hard-to-reach populations. Conceptually, DBS offers a cost-effective solution for multiple use cases by simplifying logistics for collecting, preserving, and transporting blood specimens in settings with minimal infrastructure. This review describes methods to determine both the reliability of DBS-based bioanalysis for a defined use case and the optimal conditions that minimize pre-analytical sources of data variability. Examples by the newborn screening, drug development, and global health communities are provided in this review of published literature. Sources of variability are linked in most cases, emphasizing the importance of field-to-laboratory standard operating procedures that are evidence based and consider both stability and efficiency of recovery for a specified analyte in defining the type of DBS card, accessories, handling procedures, and storage conditions. Also included in this review are reports where DBS was determined to not be feasible because of technology limitations or physiological properties of a targeted analyte.

Concentration Determination of >200 Proteins in Dried Blood Spots for Biomarker Discovery and Validation

“…Blood is the most used biofluid for clinical tests and for research purposes, as it can often indicate the health status of an individual. Although the most common method of blood collection is venipuncture, microsampling methods, requiring Ͻ100 l of blood, such as capillary blood sampling, are gaining acceptance (1). The dried blood spot (DBS) 1 microsampling technique has already been found to be useful for both population-wide screening and in research studies, as indicated by the total number of analytes currently measurably (using a variety of analytical methods and numerous assays), including 1001 small molecules, 677 large molecules (proteins), 309 nucleic acids and 31 elements (2).…”

A kinetic assay of total lipase activity for detecting lysosomal acid lipase deficiency (LAL‐D) and the molecular characterization of 18 LAL‐D patients from Russia

“…However, obscure DBS failures, such as hematocrit or blood cell count variations, are difficult to assess. 15 Reduced LAL activity was documented in individuals with advanced liver disease, including cryptogenic cirrhosis and cirrhosis of known etiology, who had lower WBC and PLT counts than control subjects. 10 Moreover, a direct correlation between WBC and PLT counts and LAL activity in DBS from healthy individuals has been described.…”

“…In 4.3% of the examined DBS, we observed a low LAL activity without detectable LIPA alterations. A reduced enzymatic activity in DBS is usually ascribed to poor specimen quality . DBS with gross preparation errors, such as clotting, disturbed integrity, low volume, and microbiological contamination, can be detected by visual inspection and excluded from analysis.…”

“…DBS with gross preparation errors, such as clotting, disturbed integrity, low volume, and microbiological contamination, can be detected by visual inspection and excluded from analysis. However, obscure DBS failures, such as hematocrit or blood cell count variations, are difficult to assess . Reduced LAL activity was documented in individuals with advanced liver disease, including cryptogenic cirrhosis and cirrhosis of known etiology, who had lower WBC and PLT counts than control subjects .…”

“…A reduced enzymatic activity in DBS is usually ascribed to poor specimen quality. 14,15 DBS with gross preparation errors, such as clotting, disturbed integrity, low volume, and microbiological contamination, can be detected by visual inspection and excluded from analysis. However, obscure DBS failures, such as hematocrit or blood cell count variations, are difficult to assess.…”