Dieujuste, Darryl

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.

Sickle cell disease is an inherited blood cell disorder that affects about 100,000 people
in the US and results in high cost of medical care exceeding $1.1 billion annually. Sickle
cell patients suffer from unpredictable, painful vaso-occlusive crises. Portable, costeffective
approaches for diagnosis and monitoring sickle blood activities are important for
a better management of the disease and reducing the medical cost.
In this research, a mobile application controlled, impedance-based flow cytometer is
developed for the diagnosis of sickle cell disease. Calibration of the portable device is
performed using a component of known impedance value. The preliminary test results are
then compared to those obtained by a commercial benchtop impedance analyzer for further
validation. With the developed portable flow cytometer, experiments are performed on two
sickle cell samples and a healthy cell sample. The acquired results are subsequently
analyzed with MATLAB scripts to extract single-cell level impedance information as well as statistics of different cell conditions. Significant differences in cell impedance signals
are observed between sickle cells and normal cells, as well as between sickle cells under
hypoxia and normoxia conditions.