Dielectrophoresis has broad applicability to marker-free isolation of tumor cells from blood by microfluidic systems

Abstract

The number of circulating tumor cells (CTCs) found in blood is known to be a prognostic marker for recurrence of primary tumors, however, most current methods for isolating CTCs rely on cell surface markers that are not universally expressed by CTCs. Dielectrophoresis (DEP) can discriminate and manipulate cancer cells in microfluidic systems and has been proposed as a molecular markerindependent approach for isolating CTCs from blood. To investigate the potential applicability of DEP to different cancer types, the dielectric and density properties of the NCI-60 panel of tumor cell types have been measured by dielectrophoretic field-flow fractionation (DEP-FFF) and compared with like properties of the subpopulations of normal peripheral blood cells. We show that all of the NCI-60 cell types, regardless of tissue of origin, exhibit dielectric properties that facilitate their isolation from blood by DEP. Cell types derived from solid tumors that grew in adherent cultures exhibited dielectric properties that were strikingly different from those of peripheral blood cell subpopulations while leukemia-derived lines that grew in non-adherent cultures exhibited dielectric properties that were closer to those of peripheral blood cell types. Our results suggest that DEP methods have wide applicability for the surface-marker independent isolation of viable CTCs from blood as well as for the concentration of leukemia cells from blood.

The potential of a dielectrophoresis activated cell sorter (DACS) as a next generation cell sorter

“…In particular, the condition in which the frequency at the CM factor is zero is called cross-over frequency. This is expressed as [41,42].…”

Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells

“…Indeed, it is known that tumor cells of epithelial origin may undergo epithelial to mesenchymal transition 21,22 . In contrast, the non-affinity methods, including centrifuging deflection [23][24][25][26][27] , dielectrophoretic separation [28][29][30] and size-based filtration 12,[31][32][33][34][35][36][37][38][39][40][41][42][43][44] , are able to isolate both epithelial and mesenchymal phenotypes, which are more appropriate for analyses of tumor heterogeneity, tumor drug resistance, etc. However, these approaches are technologically biased and it is often difficult to reach a trade-off between capture efficiency, purity and cell viability which are all important criteria for both fundamental and clinical studies.…”

Dielectrophoretic sample preparation for environmental monitoring of microorganisms: Soil particle removal

“…are being designed and fabricated, mainly focused at present for biomedical/life science applications but with applicability to environmental monitoring automated lab on a chip systems. [24][25][26][27][28] Whilst the dielectric properties of soil/water composites have been measured in the past, 29-32 manipulation of soils using AC electric fields in microflows has not been reported to our knowledge and the work described in this paper will represent a novel approach to improve bacterial concentrations from contaminating soils using DEP in order to enhance, for example, downstream biosensor detection limits. In this paper, we present the separation of Bacillus atrophaeus (analogous to B. anthracis) from four soil types using electric fields in a microfluidic system.…”