Dielectrophoretic separation of cancer cells from blood

Abstract

Recent measurements have demonstrated that the dielectric properties of cells depend on their type and physiological status. For example, MDA-231 human breast cancer cells were found to have a mean plasma membrane specific capacitance of 26 mF/m(2), more than double the value (11 mF/m(2)) observed for resting T-lymphocytes. When an inhomogeneous ac electric field is applied to a particle, a dielectrophoretic (DEP) force arises that depends on the particle dielectric properties. Therefore, cells having different dielectric characteristics will experience differential DEP forces when subjected to such a field. In this article, we demonstrate the use of differential DEP forces for the separation of several different cancerous cell types from blood in a dielectric affinity column. 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 forces within a parabolic fluid flow profile. Electrorotation measurements were first made on the various cell types found within cell mixtures to be separated, and theoretical modeling 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 parameters. Cell separations were then undertaken for various ratios of cancerous to normal cells at different concentrations. Eluted cells were characterized in terms of separation efficiency, cell viability, and separation speed. For example, 100% efficiency was achieved for purging MDA-231 cells from blood at the tumor to normal cell ratio 1:1 x 10(5) or 1:3 x 10(5), cell viability was not compromised, and separation rates were at least 10(3) cells/s. Theoretical and experimental criteria for the design and operation of such separators are presented.

Continuous particle separation based on electrical properties using alternating current dielectrophoresis

“…Substituting Eqs (24) and (30) into Eq. (27), the set of equations that governs the motion of the particles can be written as…”

“…The dependence of the DEP force on the size and the electrical properties makes it possible for cell/ particle separation based on the size and electrical properties differences. Utilizing these, DEP has also been implemented for cell/particle separation [9,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. These separation applications include the separation of the cancer cells from the blood stream [23,24], the separation of the platelets from diluted whole blood [31], the separation of red blood cells and the white blood cells [34], the separation of viable and non-viable yeast cells [33], the separation of human leukocytes [25] and the separation of healthy and unhealthy oocyte cells [36].…”

Role of peroxide in AC electrical field exposure effects on Friend murine erythroleukemia cells during dielectrophoretic manipulations

“…As a cell sorting method, these techniques have the advantage of being simple, easy to use and non-invasive [22,23]. Furthermore, because it employs only cell dielectric properties, the approach of DEP separation could be applied as an adjunct to conventional cell separation methods to yield overall improved discrimination, speed and efficiency for diagnostic and clinical applications [18,22,23,25]. For these reasons, the dielectric characterization and manipulation of biological cells is currently attracting increasing interest.…”

“…Alternatively, if the field is rotating, the interaction between the field and the induced dipole will make the particle rotate (ROT: electrorotation) [9][10][11]. The techniques of DEP and ROT can be used noninvasively to characterize the dielectric properties of individual biological cells and have led to new methods for cell characterization, manipulation and, particularly, cell sorting [12][13][14][15][16][17][18][19][20][21][22][23][24]. As a cell sorting method, these techniques have the advantage of being simple, easy to use and non-invasive [22,23].…”

“…The techniques of DEP and ROT can be used noninvasively to characterize the dielectric properties of individual biological cells and have led to new methods for cell characterization, manipulation and, particularly, cell sorting [12][13][14][15][16][17][18][19][20][21][22][23][24]. As a cell sorting method, these techniques have the advantage of being simple, easy to use and non-invasive [22,23]. Furthermore, because it employs only cell dielectric properties, the approach of DEP separation could be applied as an adjunct to conventional cell separation methods to yield overall improved discrimination, speed and efficiency for diagnostic and clinical applications [18,22,23,25].…”