Microfluidics, Arterial Thrombosis, Platelets, vWF
Atherothrombosis is a common event in myocardial infarction and stroke. In the critical care of patients, it is vital to properly diagnose and provide appropriate therapy. An ideal diagnostic tool would be able to determine patient-specific drug regimens; however, there currently does not exist a reliable tool to do so. Current platelet function tests do not have relevant fluid mechanics and, along with current microfluidic models, have variable diagnostic end-points. Therefore, there is still a need for a diagnostic device.
Antiplatelet therapies, such as aspirin and Plavix, have been developed to irreversibly inhibit platelet activation or binding. However, both do not work as intended for a large percentage of the population, as 5-60% of patients exhibit resistance to therapy. Resistance persists even with dual antiplatelet therapy (DAPT). The therapeutic resistance and bleeding risks indicate the need for both a diagnostic device and improved antithrombotic agents.
The overall goal of this proposal is to develop a low variability device for diagnostic and research use. I hypothesize that the main sources of variability observed in previous microfluidic assays are due to three fundamental design factors. Further, I hypothesize that the end-point of occlusion time will provide diagnostic utility for individual antiplatelet responsiveness. Finally, I hypothesize that such a device can be utilized to develop antithrombotic nanoparticle therapies.