Clot-in-a-Chip and Innovative Programmable Materials

[eng] Stroke is a medical condition in which vessel or artery obstruction leads to tissue damage due to a lack of nutrients and oxygen in the affected area. In the past decade, stroke has become the most common circulatory disease in the European Union (EU) and one of the leading causes of death and disability globally, ranking second and third in 2019 and 2020, respectively. The research presented in this thesis was conducted as part of the European-funded ANGIE project (magnetically steerable wireless nanodevices for targeted delivery of therapeutic agents in any vascular region of the body, HORIZON 2020). This thesis contributes to ANGIE by developing novel technologies for producing submillimeter-sized blood clots and investigating innovative materials for programming micrometer-sized robotics to dissolve blood clots. We propose technical approaches for creating blood clots within microfluidic devices that will support future research on magnetically guided entities that promote lytic processes in complex environments. This thesis comprises multiple chapters that contain experimental results. Initially, we developed a microfluidic device with five inlets for controlled generation of blood clots containing tissue factor. The device flow conditions facilitated precise manipulation of the straight blood clot dimensions by adjusting the flow rates of the side streams. This experimental setup enabled the production of both heterogeneous and homogeneous blood clots, which were used to investigate the variation in thrombolytic agent efficacy based on the clot composition. Quake valve systems were employed as a secondary approach for the formation of free interface diffusion between whole blood and tissue factors. The reaction under diffusive mass transport facilitated the formation of homogeneous blood clots with volumes on the order of nanoliter. The latter acquired a semi-hemispherical shape as determined by the channel contour. Dissolution studies revealed a correlation between blood clot size and the injected volume of the thrombolytic agent. As a third approach, the mass transport phenomena through an in situ produced PDMS membrane was investigated. Blood clots were generated within the control chambers, separated by a thin membrane from the fluidic channel carrying thrombogenic agents. The blood clots assumed complex morphologies determined by chamber geometry, and structural alterations were contingent on the concentration of the thrombogenic agent. The generated blood clots were used to develop a high-throughput printing system for drug testing in future research. This study introduces a novel method for creating programmable robots using polymeric meshes for dissolution treatments. This process integrates Liquid Crystal Elastomers and hydrogels via sequential photopolymerization. A tailored photopolymerization setup was devised to control hydrogel alignment via Lyotropic Chromonic Liquid-Crystal templating regulated by a permanent magnetic field during polymerization. High-temperature water applications have demonstrated composite actuation. In addition, the setup allows the printing of complex designs.