Blood typing using bioactive paper devices and liquid micro reactors

Blood typing is an important medical immunodiagnostic test for human blood transfusion and organ transplantation. Today, the global demand for accurate and rapid blood typing diagnosis is extremely large. However, highly sophisticated blood typing techniques are not appropriate for resource-limited regions, as they are either too expensive or require professional technicians to operate them. There is also an extensive demand for low-cost blood typing techniques with the capabilities of automation and high-throughput operation in blood bank laboratories and hospitals. To solve these problems, the research reported in this thesis focuses on the investigation and development of blood typing devices based on bioactive paper, and liquid micro reactors fabricated using superhydrophobic materials. This thesis includes two parts, which present research work on blood typing techniques based on bioactive paper devices and liquid micro reactors. In the first part, research into the fundamental mechanisms of paper-based blood typing devices combines scientific information with microscopic techniques and expertise in papermaking. The agglutination and immobilization mechanisms of red blood cells (RBCs) in antibody-treated paper are explored using confocal microscopy. The transport pathways of RBCs within the fibre network of paper are studied using a combined dual beam system with scanning electron microscopy (SEM) and focused ion beam (FIB) technology. Both these microscopic methods developed are powerful techniques for providing the details of RBCs at cellular level inside paper. This part also demonstrates a potential application for controlling the performance of paper-based blood analysis devices through paper structure design, which can be achieved during the papermaking process. Clear understanding of the fundamental mechanisms is essential for the design and production of paper-based blood typing devices which meet the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid, equipment-free and deliverable to those who need them). It is also important for the development of other paper-based blood analysis devices, and will contribute to the improvement of public health situations in rural areas and developing countries. The second part of this thesis presents innovations in the application of liquid micro reactors fabricated from superhydrophobic materials for blood typing devices. Two design concepts for the production of liquid micro reactors are demonstrated in this part: one is a superhydrophobic surface-supported liquid drop; the other is a liquid marble – a liquid drop wrapped in superhydrophobic powder. In both cases, the near-spherical shape of the liquid micro reactors enables the devices to provide clear and magnified side views to facilitate the observation of the detailed processes of RBC haemagglutination. Most importantly, by integrating these devices with advanced image capture and processing techniques, the automation of high-throughput blood typing, including rapid assay result interpretation, data storage, and transmission, can be achieved. The author sincerely hopes that the findings presented in this thesis on the applications of bioactive paper and liquid micro reactors in blood typing will serve the community by providing high-performance, simple blood typing devices. The author also hopes that the findings will be extended to the development of other blood-based diagnostic devices