Deterministic Lateral Displacement for Cell Separation

Abstract: In the fields of medicine and biology, the separation of particles is a central step in many preparative and analytical processes. Deterministic Lateral Displacement (DLD) has been a promising technique in the field of microfluidic particle and cell sorting, specifically for label-free separation with several applications of sorting by size, morphology, and deformation reported in the literature over the last decade.Separation of cancer cells from a heterogeneous sample is known as a challenging task due to the similarity of the cells involved. Deformability is a potential bio-marker for cell isolation where specific molecular markers are lacking. In the thesis, we demonstrate an efficient measurement tool for cell deformation in the DLD device as well as a sorting tool for cell isolation based on deformability among breast cancer cells (MCF7), human breast cells (MCF10A) and metastasizing breast cancer cells (MDA-MB-231). (Paper 2).Many sorting problems require careful optimization for a successful result. We have approached this problem in two ways: a combination of electrokinetics and DLD for controlling the rotation of RBCs (Paper 3) or through the deformation of the DLD devices by control of the driving pressure (Paper 5).An important limitation of microfluidics is that conventional pumps are difficult to transport, need trained personnel and are associated with high running costs. They are often not fully compatible with point-of-care applications, especially in resource-poor settings. The second part of this thesis therefore focuses on alternative ways to operate microfluidic DLD devices, to ensure portability and user friendliness. A combination of an open DLD device and a paper-based pump is a key component of this approach (Paper 1). Several sorting applicationsinvolving blood fractionation, trypanosome enrichment, and breast cancer cell extraction are performed efficiently in terms of potential purity and capture rate. Moreover, our open-fluidics platform is shown to have advantages with regards to easy cleaning, reusability and electrokinetic integration. Finally, an approach for fast and easy fabrication for devices based on single or multilayer stacks is discussed in Paper 4.