Design and optimization of circulating tumor cells separation devices

Mohammad Aghaamoo

Circulating tumor cells (CTCs) separation technology has had positive impacts on the cancer science in many aspects. The ability of detecting and separating CTCs can play a key role in early cancer detection and treatment. Most of previous studies in this area are mainly based on experimental work. Although experimental research provides useful insights in designing CTC separation devices, there is still a lack of design guidelines based on fundamental understandings of cell separation process in such devices. While experimental efforts face challenges, especially microfabrication difficulties, we adopt numerical simulation here to study the fundamental concepts and provide design guidelines for two different CTC separation techniques. First, we investigate, in detail, the label-free deformability-based CTC separation technique using conicalshaped microfilters. To achieve this, we develop numerical models to predict the passing event of CTCs and normal blood cells through such microfilters. Using numerical simulations, we study fundamentally the concept of the deformability-based microfiltration technique and investigate comprehensively different parameters affecting system performance. Furthermore, the most important design criteria of the system such as system throughput and clogging issue are introduced and discussed in detail. Regarding the performance optimization, the effect of different geometrical and operational parameters, such as applied pressure profile and other possible microfilter geometries, on the system performance are studied. In the second part of the thesis, we propose a novel label-free CTC separation method by combining the concept of dielectrophoresis (DEP) and deterministic lateral displacement (DLD) CTC separation techniques. A numerical model is developed to study the concept and evaluate the performance of the proposed coupled DLD-DEP method. In addition, we provide design guidelines on choosing appropriate operation parameters such as flow rate and electric field characteristics. Finally, Joule heating and the corresponding electrothermal flows, as one of the important phenomena associated with the coupled DLD-DEP method, are modelled and discussed thoroughly.

Design and optimization of circulating tumor cells separation devices

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