Improved methods in the collection of biological samples for complex occupational and environmental settings

Problem Statement: In the collection of traditional biological samples, such as liquid venous whole blood, plasma, and serum, the need for phlebotomy and cold chain often constrains their use in complex occupational and environmental settings. Less invasive methods that do not require phlebotomy or cold chain, such as dried blood spots (DBS), provide a potential alternative to traditional samples. Despite the advantages of DBS, scientific questions remain as to the range of potential applications of the method, as do technical challenges associated with field collection. Among these challenges, the requirement of open-air drying, which is not currently standardized and exposes DBS samples to potential contaminants while creating logistical hurdles in collection and storage, continues to hinder wider adoption of DBS. Methods: In the first of three related manuscripts, we conducted a review of the current state of the science in DBS sampling using a scoping review of reviews methodology. In the second manuscript, we designed and demonstrated proof-of-concept for novel methods in field collection and storage of DBS samples. This study measured drying rates of DBS samples collected under novel methods through use of resistance sensors designed specifically for the study. In the third manuscript, we conducted a validation of assay protocol for comparing RNA measurements in DBS samples collected under our novel methods with those of the current methods recommended by the United States Centers for Disease Control and Prevention (CDC). Results: In our first study, we identified approximately 2,000 (n=1,947) analytes that have been measured by one of more than 150 (n=169) different analytic methods. In our second study, we found that DBS samples collected under our novel methods in conditions of moderate and high humidity dried, on average, 30% and 50% faster respectively than DBS samples allowed to open-air dry under similar conditions as reported in the scientific literature. In our third study, our findings suggest that our novel methods demonstrated an overall improvement in performance on detection and quantification of RNA from DBS samples as compared with current methods. Conclusions: DBS provide researchers and practitioners a wide-ranging tool with potential applications for biosampling in complex occupational and environmental settings. Our novel methods in DBS collection and storage provide several advantages over current methodologies, including removal of the requirement for open-air drying of samples, reduced risk of sample contamination, reduced variability in environmental conditions incurred by samples, and overall improvements in measurements derived from DBS. Our findings support adoption of our novel methods in the collection and storage of DBS samples