Sickle cell anemia

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.

Ischemic stroke is defined as a blockage or reduced flow of blood to select areas of brain tissue due to either plaque formation or buildup of blood clots in the small blood vessels. A characteristic of sickle cell anemic patients is the potential for them to experience a similar type of blockage due to the sticky nature of the sickled red blood cells as well as defective oxygen delivery to the brain. Because of this similarity, sickle cell anemia may represent a good animal research model for therapeutic intervention based on stroke models. In recent studies, Granulocyte-Colony Stimulating Factor (GCSF), has been shown to exhibit a robust range of neuroprotective properties against neurological disorders including ischemic stroke through preservation of the endoplasmic reticulum (ER) by modulating various ER stress pathways. Through cognitive deficit analysis in the form of behavioral and locomotor experiments in addition to in situ biomarker analysis by way of western blotting and immunohistochemistry, we found that G-CSF gene therapy exhibited neurogenic and neuroprotective effects in ischemic mouse models and could possibly serve as a good therapy for other diseases that share similar pathology to stroke.