Dielectrophoretic separation of cancer cells from blood

Abstract

Measurements have demonstrated that the dielectric properties of cells depend on their type and physiological status. For example, MDB-MB-231 human breast cancer cells were found to have a mean plasma membrane specific capacitance value of 26 nF/m/sup 2/, more than double the value observed for resting T-lymphocytes. When an inhomogeneous DC electric field is applied to a particle, a dielectrophoretic (DEP) force arises that depends on the particle dielectric properties. Therefore, cell having different dielectric characteristics will experience differential DEP forces when subjected to such a field. In this article we demonstrate the use of these differential DEP forces for the reparation of several different cancerous cell types from blood. These separations were accomplished using thin, flat chambers having microelectrode arrays on the bottom wall. DEP forces generated by the application of AC fields to the electrodes were used to influence the rate of elution of cells from the chamber by hydrodynamic forcer from a parabolic fluid flow profile. Electrorotation measurements were first made on the various cell types found within cell mixtures to be separated and theoretical modelling was used to derive the cell dielectric parameters. Optimum separation conditions were then predicted from the frequency and suspension conductivity dependencies of cell DEP responses defined by these dielectric parameters. Cell separations were then undertaken for various ratios of cancerous to normal cells at different concentrations. Fluted cells were characterized in terms of separation efficiency, cell viability, and separation speed. For example, after the separation of mixtures of MDA-MB-231 cells and normal whole human blood (ratio 1:3), the eluted normal blood cell fraction contained less than 0.01% of the starting concentration of cancerous cells, cell viability was not compromised, and separation speeds of at least 10/sup 3/ cells/sec were achieved. Theoretical and experimental criteria for the design and operation of such separators are presented.