Doctor of Philosophy, Case Western Reserve University, 2020, EECS - Electrical Engineering
This project has developed a microfluidic sensor for comprehensive assessment of human whole blood hemostasis using miniaturized broadband dielectric spectroscopy. In particular, first, a Gen-1 microfluidic sensor for dielectric coagulometry, termed ClotChip, has been developed. The sensor employs a three-dimensional (3D), parallel-plate, capacitive sensing structure with a floating electrode integrated into a microfluidic channel. Using an impedance analyzer, the sensor is shown to measure the real part of complex relative dielectric permittivity of human whole blood in a frequency range of 10kHz to 100MHz using <10 μL of it. The temporal variation of dielectric permittivity at 1MHz is taken as the ClotChip readout featuring a time to reach a permittivity peak parameter, Tpeak, which corresponds to the onset of CaCl2-initiated coagulation of the blood sample.
Next, a biocompatible version of the sensor (Gen-2), fabricated entirely out of PMMA, has been developed. The readout of the Gen-2 sensor features a time to reach a permittivity peak, Tpeak, as well as a maximum change in permittivity after the peak, Δεr,max, as two distinct parameters of the sensor readout that are respectively sensitive towards detecting non-cellular (i.e., coagulation factor) and cellular (i.e., platelet) abnormalities in the hemostatic process. The sensor performance has been benchmarked against standard coagulation assays like rotational thromboelastometry (ROTEM) and Light Transmission Aggregometry (LTA) to evaluate the utility of its readout parameters in capturing the clotting dynamics using ex vivo modified blood samples. Tpeak exhibited very strong positive correlations with the ROTEM clotting time (CT) parameter, whereas Δεr,max exhibited strong positive correlation both with the ROTEM maximum clot firmness (MCF) parameter and the LTA.
Finally, clinical studies with blood samples from patients suffering from a variety of coagulation defects, on factor replacement therapy and on d (open full item for complete abstract)
Committee: Pedram Mohseni (Advisor); Anirban Sen Gupta (Committee Member); Umut Gurkan (Committee Member); Philip Feng (Committee Member); Michael Suster (Committee Member)
Subjects: Biomedical Engineering; Electrical Engineering; Engineering