Qualitative Blood Coagulation Test Using Paper-Based Microfluidic Lateral Flow Device

Research on paper-based microfluidic devices has grown into prosperity since 2007 when the Whitesides group in Harvard University first announced their work of qualitative bioassays on paper platform. These devices have a huge potential to be used in screening and point-of-care applications because they are easy to fabricate, simple to use, and low in cost. In this work, paper properties, wax printing, and micro-level fluid flow on paper-based materials are investigated first as preliminary study, and then a qualitative blood coagulation test device is developed utilizing traditional lateral flow platform.In order to utilize paper-based materials as test platform, various paper properties are studied to understand their behaviors with fluid present. When conducting different type of tests, different types of paper may be considered due to their unique properties. As a fabrication technique of paper device, wax printing is studied in detail to learn the printing accuracy and resolution of wax printer during device fabrication. By printing hydrophobic wax barriers on hydrophilic paper, wax printing is a very cheap, simple and fast way to fabricate microfluidic channels on paper device.Microfluidic flow behaviors of water and dextran aqueous solution with different viscosity are studied on cellulose papers and nitrocellulose membranes. Both fluids display the characteristics of Washburn flow on both types of materials. On cellulose material, fluid flows faster in narrower channels, which makes it possible to achieve flow control by manipulating channel geometry. On nitrocellulose material, fluid with smaller viscosity travels faster than that with larger viscosity, and the slope of (traveled distance)2 vs traveling time is linearly proportional to fluid viscosity on semi-log scale. This property makes it possible to anticipate fluid viscosity by measuring its traveling distance in a certain amount of time on nitrocellulose membrane.In the development of qualitative blood coagulation test device, traditional LFA structure consisting of sample pad, analytical membrane, and wick pad is utilized as diagnostic platform, and citrated rabbit blood and coagulant CaCl2 solution with different concentration are utilized to mimic human whole blood with various coagulation ability. Qualitative analysis of blood coagulation ability is performed by measuring the distance that different blood sample travels on analytical membrane. The further traveled distance indicates weaker coagulation ability, and the shorter traveled distance indicates stronger coagulation ability. A linear relationship between traveled distance and coagulation ability of blood sample is established, and whole blood coagulation ability can be anticipated by measuring its traveled distance on blood coagulation diagnostic LFA device in a certain amount of time.