Characterization of sequentially-staged cancer cells using electrorotation

Abstract

The identification and separation of cells from heterogeneous populations is critical to the diagnosis of diseases. Label-free methodologies in particular have been developed to manipulate individual cells using properties such as density and morphology. The electrical properties of malignant cells, including the membrane capacitance and cytoplasmic conductivity, have been demonstrated to be altered compared to non-malignant cells of similar origin. Here, we exploit these changes to characterize individual cells in a sequentially-staged in vitro cancer model using electrorotation (EROT)—the rotation of a cell induced by a rotating electric field. Using a microfabricated device, a dielectrophoretic force to suspend cells while measuring their angular velocity resulting from an EROT force applied at frequencies between 3 kHz to 10 MHz. We experimentally determine the EROT response for cells at three stages of malignancy and analyze the resultant spectra by considering models that include the effect of the cell membrane alone (single-shell model) and the combined effect of the cell membrane and nucleus (double-shell model). We find that the cell membrane is largely responsible for a given cell’s EROT response between 3 kHz and 10 MHz. Our results also indicate that membrane capacitance, membrane conductance, and cytoplasmic conductivity increase with an increasingly malignant phenotype. Our results demonstrate the potential of using electrorotation as a means making of non-invasive measurements to characterize the dielectric properties of cancer cells.

Determination of Dielectric Properties of Cells using AC Electrokinetic-based Microfluidic Platform: A Review of Recent Advances

“…In general, an array of metal-based electrodes powered by an externally applied AC bias potential with no phase difference would produce a non-uniform electric field resulting in cell polarization, as shown in Figure 2 [76]. The interaction between the cell and the non-uniform electric field would generate a DEP force exerted onto the cell, which is expressed as [77]: In addition, a more complex double-shell model is proposed to elucidate the polarization of cells using Equation (2) for each shell [70]. In the double-shell model, the inner layer is the nucleus with the associated radii r n -d n .…”

“…This finding demonstrated the feasibility of using ROT as a label-free and non-invasive means to determine the dielectric parameters and thus characterize the cancer malignancy and progression. A method that employs ROT spectra to extract dielectric parameters for the characterization of sequentially-staged cancer cells was demonstrated [70]. The mouse ovarian surface epithelial cell line (MOSE) at three stages of malignancy-from an early stage (MOSE-E), to a malignant stage (MOSE-L, slow-developing disease), to a late and highly aggressive/invasive stage (MOSE-LTICν, fast developing disease)-was selected to analyze the corresponding ROT spectra.…”

“…Focus should also be put on the application of the extracted dielectric parameters of cells. Currently, the dielectric parameters are mainly intended to characterize cells at different stages in order to support drug research activities [59,60,70,90,97,125] and facilitate the separation of cancer cells from cell lines or CTCs from clinical samples by DEP [126][127][128] and ODEP [129][130][131]. These functions are still at the lab research level, and they have a long way to go to realize real-world applications and bring tangible benefits to the end user.…”

A survey of electrokinetically‐driven microfluidics for cancer cells manipulation

“…( C) Schematic diagram of a microchip using DEP for trapping, guiding, and focusing nanoprobes‐bladder cancer cells (Adapted from [65] by permission of Lab on a Chip ). ( D) Schematic illustration of a microchip featuring the electrorotation technique for the analysis of ovarian cancer cells (Adapted from [66] by permission of PLoS ONE ). ( E) Device overview for an electrothermal study (Adapted from [67] by permission of Scientific Reports ).…”

Electrorotation Rates of K562 Cells Accompanied by Erythroid Differentiation Induced by Sodium Butyrate

“…The ROT rate also depends on the intrinsic dielectric properties (membrane capacitance, and cytoplasm conductivity and permittivity) of cells 4 . Therefore, the frequency dependence of the ROT rate (ROT spectrum) has been utilized to determine the dielectric properties of the wide variety of the cells [5][6][7][8][9][10][11] and identify the cell types 12 . Recently, we identified four types of white blood cells by determining their dielectric properties with the simultaneous ROT systems 13 .…”