Measuring Electrical Properties of Cancer Cells Via Electrorotation

Measuring Electrical Properties of Cancer Cells via Electrorotation

Circulating tumor cells are cancer cells that can be extracted from patient blood, and their capture provides a window through which we can examine the progression of cancer in real time with minimal invasiveness. As these cells circulate, they are exposed to a variety of physical and chemical stimuli that we hypothesize change the structure and composition of the membrane, nucleus, and cytoplasm. For example, the morphology of the cell membrane is sensitive to the deprivation of growth factors or the acquired resistance to Gemcitabine chemotherapy. Because these cellular changes are dynamic, it is critical to characterize this process in order to effectively capture and analyze the cells.

We have conducted experiments to understand how stimuli that cancer cells experience in circulation affect their electrical phenotype in order to 1) gain insights into cancer cell membrane physiology, which will help reveal connections between primary tumors, circulating cells, and metastases, and 2) inform better cell capture with electrokinetic techniques, such as dielectrophoresis (DEP), which will enable new sets of genetic and other analyses that require higher purity than the current state of the art in cell capture provides.

Although DEP is suitable for applying forces to cells for separations, electrorotation, a technique related to DEP in which torques are applied to cells in response to rotating electric fields, is more suitable for experimental characterization of cells. An electrorotation spectrum gives complete information necessary to infer a DEP spectrum and extract electrical properties such as the cytoplasmic conductivity and membrane specific capacitance.

We present data on changes in pancreatic cancer cell lines' electrorotation spectra after serum starvation, a stress known to alter cell membrane morphology and cytoplasmic contents. (See attached figure for electrorotation spectra of serum-starved and serum-supplemented BxPC3 pancreatic cancer cells). We also present electrorotation spectra of a Gemcitabine-resistant pancreatic cancer cell subclone, which we compare to their Gemcitabine-naïve counterparts.