| Summary: | There are many situations in medicine and biology where it is desirable to sort cells in a heterogeneous sample based on their mechanical deformability, which can potentially serve as a proxy for morphology or pathology. This biophysical characteristic is particularly relevant for cells in the circulatory system, such as red blood cells and white blood cells, because deformability determines the capacity for these cells to transit through the microvasculature. Since deformability is such a fundamental characteristics of blood cells, deviations in normal cell deformability can contribute to a range of pathological conditions, such as microvascular occlusion, tissue necrosis and organ failure, observed in diseases such as malaria caused by Plasmodium falciparum. A commonly employed approach for deformability-based cell sorting is microfiltration. However, this method suffers from cell clogging at the filter microstructures, leading to reduced selectivity and device malfunction.
This dissertation presents an improved microfiltration strategy performed using the microfluidic ratchet mechanism, which relies on the deformation of individual cells through micrometer-scale tapered constrictions. Deforming single cells through such constrictions requires directionally asymmetrical forces, which enables oscillatory flow to create a ratcheting transport that depends on cell size and deformability. Simultaneously, oscillatory flow continuously agitates the cells to limit the contact time with the filter microstructure to prevent clogging and adsorption.
This work demonstrates the utility of the ratchet mechanism for cell sorting by developing a microfluidic device to sort red blood cells based on deformability. The device is used to separate Plasmodium falciparum infected red blood cells from uninfected cells. The method was shown to dramatically improve the sensitivity of malaria diagnosis performed using both microscopy and rapid diagnostic tests by converting samples with difficult-to-detect parasitemia (<0.01%) into samples with easily detectable parasitemia (>0.1%). This work further demonstrates the utility of the microfluidic ratchet mechanism by developing a microfluidic device to isolate and sort leukocytes directly from whole blood. The method is capable of separating leukocytes from whole blood with 100% purity (i.e. no contaminant erythrocytes) and <2% leukocytes loss. Furthermore, the approach demonstrates the potential to phenotypically sort leukocytes to enrich for granulocytes and lymphocytes subpopulations. === Applied Science, Faculty of === Mechanical Engineering, Department of === Graduate
|
|---|
