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.
Highlights
The processes of identification, selection, and separation of cells from complex, heterogeneous sample populations are of fundamental importance in the development of novel cancer diagnostic tests and treatments
A Markov Chain Monte-Carlo (MCMC) algorithm was used to fit the models to the EROT spectra for each cell type, enabling the goodness of fit to be explored by varying the parameter spaces for each model
In addition to confirming that cytoplasmic conductivity and membrane specific capacitance increase with phenotypic malignancy, our analysis reveals that the specific conductance of the cell membrane increases with malignancy, when each cell type was considered in aggregate (Table 2) and individually (Fig 5)
Summary
The processes of identification, selection, and separation of cells from complex, heterogeneous sample populations are of fundamental importance in the development of novel cancer diagnostic tests and treatments. Cancer presents in a number of different forms, which affect various tissues and have different characteristics depending on the origin tissue and degree of malignancy. Tumors typically appear with several common characteristics, including the capacity for self-proliferation and aggressiveness towards the host’s other cells and tissues.
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