Dielectrophoresis-Based Breast Cancer Study: Characterization and Separation of Peripheral Blood Mononuclear Cells from Pymt and WT Mouse Model

In 2021, the US is expected to see 284,200 new cases of breast cancer, making it the top cancer in women, with an estimated 43,600 deaths. Breast cancer is a systemic disease that affects multiple body systems and can be detected in circulating immune cells before tumor cells enter circulation due to their abundance in the body. However, early detection and proper treatment can enhance breast cancer outcomes. To realize our long-term goal, we are probing the dielectric properties of peripheral blood mononuclear cells (PBMCs) from peripheral blood sources of MMTV-PyMT mice at 14+ weeks (stage IV) using a microfluidic platform.

The central hypothesis of this research is that changes triggered in the subcellular components, such as the cytoskeleton, lipid bilayer membrane, cytoplasm, focal adhesion proteins, and extracellular matrix (ECM) at the onset of carcinoma regulate dielectric properties (conductivity, σ, and permittivity, ε), thereby affecting the bioelectric signals that aid in the detection of breast cancer. This hypothesis is developed based on our preliminary data demonstrating unique dielectric properties of PBMCs obtained from WT and PyMT tumor-bearing mice. The results obtained from our preliminary analysis identify the bioelectric signals that regulate human adenocarcinoma cells.

We hypothesize that isolated peripheral blood mononuclear immune cells (PBMCs) are altered in a body that has cancer compared to those PBMCs in a healthy body. This alteration is evident in the mouse model we are using, which is a powerful tool for analyzing the mechanisms of human breast cancer induction. Although the specific mechanisms behind these PBMC changes are not being investigated here, we hypothesize that these alterations can be detected using dielectrophoresis, a dielectric characterization technique. Changes in the electrophysiological properties of the plasma membrane of cancer cells are among the key features that support the use of dielectrophoresis to manipulate and carry out electrokinetic separations of normal or healthy cells from cancer cells and vice versa. This is because they tend to behave differently under a non-uniform electric field.

Our results present the dielectric properties of murine PyMT and WT PBMCs, which exhibited unique cellular behavior, and numerical simulations to validate these results. We conclude that these unique characteristics can be used to discriminate between cancer and non-cancer cells. This novel tool is label-free, rapid (~2 min.), and low-cost cell sorting technology that detects and separates early and late stages of breast cancer. This work will lead to preclinical development and future clinical trials of the developed detection platform. The long-term goal is to bring this analysis into the clinic to be able to non-invasively determine breast cancer at the earliest stages without the false positive and false negative rates of standard screening methods like mammography.