Correlations between the dielectric properties and exterior morphology of cells revealed by dielectrophoretic field‐flow fractionation

Abstract

Although dielectrophoresis (DEP) has great potential for addressing clinical cell isolation problems based on cell dielectric differences, a biological basis for predicting the DEP behavior of cells has been lacking. Here, the dielectric properties of the NCI-60 panel of tumor cell types have been measured by dielectrophoretic (DEP) field-flow fractionation, correlated with the exterior morphologies of the cells during growth, and compared with the dielectric and morphological characteristics of the subpopulations of peripheral blood. In agreement with earlier findings, cell total capacitance varied with both cell size and plasma membrane folding and the dielectric properties of the NCI-60 cell types in suspension reflected the plasma membrane area and volume of the cells at their growth sites. Therefore, the behavior of cells in DEP-based manipulations is largely determined by their exterior morphological characteristics prior to release into suspension. As a consequence, DEP is able to discriminate between cells of similar size having different morphological origins, offering a significant advantage over size-based filtering for isolating circulating tumor cells, for example. The findings provide a framework for anticipating cell dielectric behavior on the basis of structure-function relationships and suggest that DEP should be widely applicable as a surface marker-independent method for sorting cells.

Estimation of the physical properties of neurons and glial cells using dielectrophoresis crossover frequency

“…From Table 3, most of the conductivity of the suspension mixture is magnitudes higher than that of DEP buffers previously used [11,14,21,24,26,27] because of the addition of cell culture media, which compromises the validity of the lowfrequency approximation, as mentioned earlier. In order to ensure the survival of cells in these suspension mixtures, we investigated the viability of hippocampal cells in the Fig.…”

“…For instance, the work reported by Pethig et al [12,17] and Gascoyne et al [20,24] determined the effective cell membrane capacitance from the slope of the plots of CF versus the medium conductivity based on a low-frequency (DC) approximation of Schwan [25], to represent the effective permittivity and conductivity of a cell. However, this DC approximation can only be applied when the CF measurement is performed in a medium with lower conductivity (e.g., <10 −3 Sm −1 ), where the measured CF is sufficiently lower than the dispersion frequency (∼1 MHz) [26,27], which is usually associated with the internal polarization between the cell membrane and cytoplasm.…”

Automated electrorotation shows electrokinetic separation of pancreatic cancer cells is robust to acquired chemotherapy resistance, serum starvation, and EMT

“…According to Wang et al, 41 Shim et al, 8 and Gascoyne et al, 42 this increase in surface area would putatively change the ruffles and folds in the cell membrane, increasing their effective surface area and specific membrane capacitance. Furthermore, Salmanzadeh et al 49 and Mulhall et al 50 observed that aggressiveness of cancer cell phenotype correlates with an increase in specific membrane capacitance for mouse ovarian surface epithelial and oral cancer cells, respectively.…”

“…Because the time constant associated with this relaxation is approximately proportional to the product of specific membrane capacitance and cell radius, the observed decrease in crossover frequency is explainable due to the observed increase in median cell radius and in median specific membrane capacitance of the gemcitabineresistant sub-clones (Table I). Wang et al, 41 Shim et al, 8 and Gascoyne et al 42 attribute higher specific membrane capacitances to larger effective membrane areas due to ruffles and folds in the membrane, changing the apparent effective specific capacitance. Alternatively, Gagnon et al 43 FIG.…”

Enhancing sensitivity and specificity in rare cell capture microdevices with dielectrophoresis

“…It is possible to select the frequency f so that target rare cells (e.g., CTCs) undergo pDEP while contaminating leukocytes (e.g., peripheral blood mononuclear cells, PBMCs) undergo nDEP. [16][17][18][19][20][21][22][23][24] DEP has been used with microfluidic obstacle arrays to concentrate micro-and nanoscale beads, 25,26 and to enrich cancer cell lines by DEP trapping. 18 Separately, these obstacle arrays have been used to generate size-dependent collision dynamics, bringing target cells into contact with the antibodies on the obstacle surface, while displacing contaminating cells onto trajectories with infrequent cell-obstacle collisions; this technique has been termed geometrically enhanced differential immunocapture (GEDI).…”