MICROFLUIDIC ELECTRICAL IMPEDANCE TECHNOLOGY FOR POINT-OFCARE ASSESSMENT OF SICKLE CELL DISEASE

Sickle Cell Disease (SCD) is a genetic disease that affects approximately 100,000 people in the USA and millions worldwide. The disease is defined by a mutation in hemoglobin, the red blood cell’s oxygen carrying component. Under hypoxic (low oxygen) conditions, the mutated hemoglobin (known as HbS) polymerizes into rigid fibers that stretch the cell into a sickle shape. These rigid cells can occlude blood vessels and cause an individual immense pain. Currently, no point-of-care devices exist in the market for assisting those with SCD. Using microfluidics with custom designed portable impedance measuring hardware we can achieve label-free in vitro analyses of SCD rheology.
This dissertation presents two impedance-based devices for finger-prick volume blood testing, including a microflow cytometer for SCD diagnostics and a vaso-occlusion tester for monitoring blood flow activities. First, the microflow cytometer is validated by measuring the electrical impedance of individual cells flowing through a narrow microfluidic channel. Cellular impedance is interpreted by changes in subcellular components due to oxygen association-dissociation of hemoglobin, using an equivalent circuit model and Multiphysics simulation. Impedance values of sickle cells exhibit remarkable deviations from normal blood cells. Such deviation is quantified by a conformity score, which allows for measurement of SCD heterogeneity, and potentially disease severity. Findings from this study demonstrate the potential for SCD screening via electrical impedance. Second, a vaso-occlusion tester is validated by measuring the impedance response of blood flow within a microfluidic mimic of capillary bed.