Challenges and opportunities in blood flow through porous substrate: A design and interface perspective of dried blood spot

Blood microsampling is desired in clinical, pharmaceutical and biomedical fields to overcome the challenges of conventional whole blood sampling. One of the popular methods for blood microsampling is the dried blood spot (DBS) kit and the collected sample is subsequently used for bioanalysis. The current practice of DBS is simple to use, cheap and very well standardized from sample collection to analysis. However, DBS suffers from several well documented challenges related to blood spot formation such as varying hematocrit volume, thin layer chromatography effect and subsequent bio-analysis resulting in a variable and ocassionally high failure rate. A major source of these problems is our limited understanding of blood flow in porous media under different ambient and material conditions. Therefore, it is highly desirable to understand the parameters that affect blood flow in a porous medium to enable a more robust design of DBS and generally blood microsampling kits. In this review, we discuss some existing blood microsampling techniques while focusing on the challenges associated with blood flow dynamics. We also review existing studies on the potential factors that affect the permeation (imbibition or wicking) and spreading of blood in a thin, porous substrate as means to understand and overcome the challenges in designing new DBS kits and blood microsampling devices. Thereafter, we have discussed recent advances in the design of passive flow-based devices to overcome these challenges of current blood microsampling by DBS. Finally, we present a few applications of DBS in clinical and non-clinical studies. This review can benefit researchers working at the interface of complex fluid flow, surface chemistry, and material and device design for biomedical and biological applications