Understanding the coffee-ring effect of red blood cells for engineering paper-based blood analysis devices

Abstract

Red blood cells (RBCs), the most abundant cellular component in whole blood, are an important health indicator, and the morphology and behavior of RBCs on porous paper substrates plays a key role in the interpretation of the diagnostic results of paper-based blood analysis. The wetting of paper by a blood sample containing dispersed RBCs drives the allocation of RBCs through the fibre network. A blood stain left on paper, therefore, provides a wealth of information about the distribution and transport behaviors of RBCs. In this work, we studied the morphology and formation of and factors influencing the typical shape of blood stains, an RBC-based “coffee ring”, on paper substrates at both macroscopic and cellular levels. The results show that the ring-shaped RBC stain formed on paper is mainly the result of the combined effect of capillary wicking, filtration and evaporation flux, and is influenced by the fibre structure, RBC incubation time, relative humidity and paper additives. Most importantly, control of RBC stains was achieved by paper structure engineering and the dynamic transportation of RBCs on paper was quantified. These findings provide valuable insight into the control of the spatial distribution of RBCs on porous materials, which will be beneficial for the design of desirable paper-based diagnostics. A paper-based microfluidic device with advanced features was then fabricated to detect the hematocrit level, demonstrating the significance of this study for blood-based analysis and diagnostics on paper.