Microfluidic Dielectrophoresis-based Systems for Cell Analysis and Sorting

Microfluidic analysis systems are revolutionizing our understanding of mammalian cells and revealing new insights into biological processes by providing unique ways of exploring cells. Many cell analysis and isolation techniques utilize cell-type specific markers or use label-free fluidics to separate cells based on size. However, these approaches are not effective for cells that lack specific markers or do not differ in size. Electrokinetic techniques using electric fields provide different approaches that are label free and depend on inherent cell components. My lab has focused on the electrokinetic technique dielectrophoresis (DEP), in which non-homogeneous electric fields are utilized to induce cell movement based on intrinsic cellular properties. Using DEP, we identified and separated cells with subtle phenotypic differences in neural stem cell and cancer cell populations. We found that the electrophysiological property whole cell membrane capacitance distinguishes neural stem cells linked to specific differentiated cell fates and also identifies glioma cancer cells that are resistant to chemotherapeutics. By developing DEP-based sorting devices, we were able to enrich fate-specific stem cells and drug-resistant cancer cells. The isolated cells did not differ in cell size despite their significant phenotypic differences, indicating that size-based separations would not be useful for these cells. We focused on defining unique cellular characteristics, and identified novel links between cell surface glycosylation and cell phenotype. Glycosylation regulates cell surface retention and ligand binding of multiple classes of cell surface receptors governing cell function. Thus, DEP-based cell analysis and sorting revealed novel characteristics of stem and glioma cells that directly relate to factors regulating cell function. Further development of novel microfluidic cell analysis and sorting platforms is needed to continue pushing the boundaries of biological studies.