High-throughput separation of circulating tumor cells by dielectrophoretic filtration

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The separation of particles according to properties other than size or density is a highly relevant task but one that cannot be solved universally. Such separation requires a deterministic force that acts much stronger on the target particle than on all other particles of a mixture; consequently, it becomes increasingly difficult to separate particles that show only slightly different properties. A due to its diagnostic value in liquid biopsy significant example is the separation of circulating tumor cells (CTC) from whole blood. Several different approaches are currently investigated for this separation while most of them rely on specific surface markers on the tumor cells. This however limits the universal applicability, as the presence of these surface markers on all cells is questionable. Dielectrophoresis (DEP), a highly adaptable and selective electrokinetic separation technique, has already shown to be successful for the detection of CTC in a blood sample. Because the DEP force scales linearly with the spatial inhomogeneity of the electric field square, most contemporary DEP applications are realized using microelectrode structures and micro channels. This is necessary to generate forces that are strong enough in order to achieve separation.Together with our working group, I have pioneered the concept of dielectrophoretic filtration, which is capable of bridging the inherent DEP throughput gap. In this, the required field inhomogeneities are induced in the pore structure of a porous medium (which could be, for example, a macroscopic monolithic ceramic foam). This allows for selective and electrically switchable retention (trapping) of target particles from a mixture in the separation matrix. Consequently, compared to conventional DEP separators, we can operate the process using larger channels and higher throughputs. So far, we have tested this concept on model particle systems. In this project, I want to investigate the feasibility of the DEP filtration process for the selective retention of cancer cells from peripheral blood mononuclear cells (PBMC). Microfluidic model filters are used to find suitable separation parameters (throughput, applied voltage, field frequency) to separate a leukaemia cell line (RPMI-8226) and a breast cancer cell line (MCF-7) from T-cells. Subsequently, the target cell concentration will be decreased towards clinically relevant values and the separation process will be transferred towards separation in porous alumina foams as DEP filtration matrix. This project brings us a step closer towards solving a very relevant and difficult separation problem but it also explores the possibilities for selective separation of biological cell systems using the DEP filtration concept.