Magnetic Devices and Techniques for the Study of Viscoelasticity of Biomaterials and Myocardial Forces

Thesis (Ph.D.)--University of Washington, 2016-06

Magnetic microdevices comprise a set of popular tools to study a number of properties of biological systems. In particular, magnetic microdevices are useful as methods to apply force to systems, and to measure the force being produced. One of the great benefits of using magnetic devices is the ability to produce force from a distance, and to develop devices that work in situ. Many systems, especially biological systems, have changes that occur between samples, even when split from the same sample, so the ability to measure trends on the same sample is ideal. Additionally, some materials may be valuable, and the ability to run multiple tests using large volumes is not possible. One particular application of this is the measurement of platelet viscoelasticity under shear flows. Traditionally, multiple blood samples are run through several different analysis systems to generate the desired data on the functionality of platelets. One of the intentions of my thesis is to develop new devices to measure elasticity of the shear-developed platelet clots in situ. In addition to applying forces to biomaterials, magnetic microdevices can also be useful for measuring forces without the need for a microscope and intensive imaging systems. The final aim of my thesis is to develop a force sensing device for the measurement of cardiomyocyte forces without the need for a microscope. I have split my thesis into three specific aims that I plan to accomplish to meet the goals described above: AIM 1: Fabricate and characterize a microfluidic device to measure viscoelasticity, AIM 2: Miniaturize the magnetic device for use in a shear flow device to measure platelet elasticity, AIM 3: Create a magnetic sensor for measuring cardiomyocyte twitch forces. Each of these three aims involves creating new magnetic devices and showcasing them in experiments to demonstrate their utilities. In aim 1, experiments are run with collagen gels to demonstrate the ability of the new tool to measure viscoelasticity. In aim 2, the device is miniaturized and placed into microfluidic flow channels. Whole blood is run through the channels to form platelet plugs, then in situ testing is used to measure the modulus of the platelet plugs. In aim 3, engineered heart tissues derived from induced pluripotent stem cells are formed between two posts, and the force generated by the tissues can be monitored in real time and in parallel by monitoring the change in field of a magnet embedded in a flexible post. Through these three aims, new information about the nature of mechano-biological systems can be understood by either gathering information that was unknown before, or by enabling an easier method for monitoring the condition of cells. This work demonstrates the use of these three devices and has impact on future directions for understanding of the role of platelets in clot elasticity, and for measuring cardiotoxicity in drug screening platforms.