Electrical Cell Separation: Cell Separation Based Upon Electrical Properties

We have developed a new cell separation technique called iso-dielectric separation that separates cells based upon electrical properties. Iso-dielectric separation is an equilibrium separation technique that has the potential to be both preparative and analytic, meaning that it is able to provide both separation as well as quantitative information about the population of cells. The IDS device we have implemented allows for continuous-flow separation, at high throughput, is label-free, can resolve multiple sub-populations of cells from heterogeneous backgrounds, and only exposes cells to the separation conditions for a few seconds.

A particle or cell in a spatially non-uniform electric field experiences a force proportional to its polarizability. Because the polarizability of a particle is a function of the electrical conductivity of that particle as well as that of the surrounding medium, a cell placed in a conductivity gradient spanning an appropriate range will be characterized by the point along this gradient where its polarizability vanishes. This corresponds to the matching of cell and medium electrical properties at a particular location, which we refer to as the iso-dielectric point (IDP). Using dielectrophoresis, it is possible to direct particles to their IDPs, enabling the separation of electrically distinguishable particles. Importantly, although the polarization of a cell generally depends on factors other than the electrical conductivity and permittivity (e.g. size and shape), by selecting cells based upon their IDPs, we are able to suppress sensitivity to these additional factors. Thus IDS offers the potential for conductivity-specific separations, even in the presence of large variability in size.

We have used IDS to separate and/or characterize beads, bacteria, yeast, and mammalian cells. The goal is to develop IDS into a robust screening platform capable of measuring and/or separating large libraries of cells based upon electrical propert.