Investigating Heterogeneous Cell Populations with Dielectrophoresis

Cell heterogeneity is essential in organism development and is a key feature in many diseases. Identifying the defining features of distinct cell types within a heterogeneous population can improve our understanding of development and disease progression and lead to the discovery of better therapeutics. Conventional label-based cell separation methods are often used to isolate distinct cell types from a heterogeneous population. However, this approach has a number of disadvantages, including a lack of unique biomarkers to identify cells of interest. This hampers mechanistic studies aimed at deciphering the unique properties of specific cell types in heterogeneous cell populations. Label-free cell separation techniques generate enriched cell populations necessary for investigating distinct cell functions without the need for unique cell type-specific labels. This body of work focuses on the utilization of dielectrophoresis (DEP), a label-free electrokinetic method, to study heterogeneous cell populations. It details the development of the Hydrophoretic Oblique Angle Parallel Electrode Sorting (HOAPES) device, a high-throughput DEP-based cell sorter that can separate cells based on intrinsic electrical properties. This novel cell sorter combined multiple microfluidic modules to enable continuous separation of distinct cell types and was used to analyze heterogeneous populations of neural stem and progenitor cells (NSPCs) and glioblastoma (GBM) cells. The HOAPES device utilizes continuous fluid flow to enable high throughput separation, providing sufficient cells for downstream assays to assess both sorting performance and identify distinct cell properties associated with sorted cell phenotype. Furthermore, this method helped uncover correlations between cell fate, cell surface N-glycosylation and electrophysiological properties of NSPCs. Similarly, links were identified between chemotherapeutic resistance, glycosylation, and membrane electrophysiological properties of GBM cells