Red blood cell transport mechanisms in polyester thread-based blood typing devices

Abstract

A recently developed blood typing diagnostic based on a polyester thread substrate has shown great promise for use in medical emergencies and in impoverished regions. The device is easy to use and transport, while also being inexpensive, accurate, and rapid. This study used a fluorescent confocal microscope to delve deeper into how red blood cells were behaving within the polyester thread-based diagnostic at the cellular level, and how plasma separation could be made to visibly occur on the thread, making it possible to identify blood type in a single step. Red blood cells were stained and the plasma phase dyed with fluorescent compounds to enable them to be visualised under the confocal microscope at high magnification. The mechanisms uncovered were in surprising contrast with those found for a similar, paper-based method. Red blood cell aggregates did not flow over each other within the thread substrate as expected, but suffered from a restriction to their flow which resulted in the chromatographic separation of the RBCs from the liquid phase of the blood. It is hoped that these results will lead to the optimisation of the method to enable more accurate and sensitive detection, increasing the range of blood systems that can be detected.

Recent advances in thread-based microfluidics for diagnostic applications

“…It also facilitates the fabrication of 3D structures and can be easily incorporated into garment due to its higher tensile strength than paper (Nilghaz et al, 2013). Typical thread materials used in making microfluidic devices are cotton Liu et al, 2017), polyester (Adhikari et al, 2018;Jarujamrus et al, 2018;Nilghaz et al, 2016), nylon Qiu et al, 2018), acrylic (Cabot et al, 2018), wool (Jeon et al, 2015a(Jeon et al, , 2015b or silk (Konwarh et al, 2016;Yan et al, 2015). Usually, threads consist of fibers of natural origin such as cotton or cellulose, or of artificial origin such as polymers, aligned or twisted together.…”

Novel applications of nonwood cellulose for blood typing assays

“…Recently, novel technologies such as 3D-printing have allowed researchers to reproduce a regular well-known paper network and tune the artificial paper properties more accurately to study the effects on blood motion [11] . The porous structure of threads motivated their application in a similar approach to perform low cost blood typing test, initially using polyester threads [12] [13] . However, there is an undeniable growing interest in using natural renewable resources.…”

A novel method for blood‐typing using nitrocellulose

“…Micro-fluidic paper-based and thread-based tools and methods present a new type of diagnostic technology which, owing to its low cost and ease of application, is being employed increasingly, especially in developing countries. Paper-based diagnostic tools incorporate some micro-fluidic system features with simple strips of paper and also thread employed as a low-cost substrate for the fabrication of microfluidic diagnostics (Ballerini et al, 2011;Cheng et al, 2007;Fu, Ramsey, Kauffman, Lutz, & Yager, 2011;Li, Tian, & Shen, 2010;Li et al, 2012a,b Liana, Raguse, Justin, & Chow, 2012Lisowki & Zarzycki, 2013;Martinez, Philips, & Whitesides, 2010a;Martinez et al, 2010b;Nilghaz, Ballerini, Guan, Li, & Shen, 2016;Nilghaz, Zhang, Li, Ballerini, & Shen, 2014). Paper was selected as the first low-cost tool in the diagnostic process for the three following reasons (Cheng et al, 2007;Li et al, 2010;Mabey et al, 2004;Martinez et al, 2010a,b):…”

“…Based on presence and absence of a separation zone between red blood cells and plasma on thread, it can be concluded whether agglutination has occurred or not. For instance, when there is no interaction between red blood cells and antibody coated on thread, there will be no separation zone and the test is negative (Ballerini et al, 2011;Nilghaz et al, 2014Nilghaz et al, , 2016. Although this method is easy, inexpensive , rapid and needs lower sample volume, it may cause a wrong interpretation of final result just because of the probability of making a mistake in recognizing the separation zone by the naked eye.…”

“…Thread is also a substrate which is able to wick liquid through its capillary structure. Recently, thread has been used as a flexible and low‐cost substrate for rapid blood‐typing (Nilghaz et al, ; Nilghaz et al, ). Based on presence and absence of a separation zone between red blood cells and plasma on thread, it can be concluded whether agglutination has occurred or not.…”