Enhancing the performance of a coagulometer through optimization of microfluidic cartridge and fiber optic-based optomechanical systems

More than 800 million clotting tests are performed each year in hospitals and clinical laboratories for emergencies, surgical operations, and periodic monitoring of patients. Monitoring of adequate anticoagulant dosage is essential to maintain the delicate balance between bleeding and thrombosis. The primary means of monitoring the response to warfarin (VKAs) is the Prothrombin Time (PT) test and the international normalized ratio (INR) while activated partial thrombosplastin time (aPTT) is used for heparin monitoring. Current clinical laboratory tests used to routinely measure blood coagulation still lack in rapidity and simplicity. Whole-blood Point-of-Care (PoC) coagulation devices that respond to the exact needs of both clinicians and patients are still emerging in the field. Portable PoC and self- care PT/INR monitoring devices are gaining in popularity as they provide crucial advantages over traditional laboratory methods such as ease of use, instant results, rapid turnaround for timely anticoagulant dose adjustment and improved patient convenience by removing the need for routine hospital/laboratory visits and venipunctures. Moreover, PoC devices are using whole capillary blood usually from a finger prick while conventional laboratory methods utilize centrifuged plasma obtained from citrated venous blood. This thesis presents several optimization activities that was performed on the disposable cartridge unit of an opto-mechanical-based Point-of-care and Self-care coagulometer. This study demonstrates several design optimization and validation activities undertaken during the product development stage in order to move the initial cartridge design into a commercializable product. Thus, this work focused of increasing the manufacturability and usability of the previous cartridge design developed by our group in terms of passive capillary flow/Microfluidics, biochemical functionalization, optical fiber assembly, and reagent optimization. Furthermore, the final cartridge design was used to conduct a proof-of-concept study in the topic of heparin monitoring and aPTT measurement on control plasma and blood samples, suggesting a reliable and rapid testing as a PoC device. A preclinical trial was conducted with an n=42 sample size to assess the correlation between our device and the standard hospital method, further validating its efficacy and potential for clinical use.