(341e) Dielectrophoresis-Based Detection of Breast Cancer Using Peripheral Blood Mononuclear Cells in a Ductal Adenocarcinoma Pymt+/- Mouse Model on a Microfluidic Device

Breast cancer is a systemic disease that affects multiple body systems and can be detected in circulating immune cells before tumor cell circulation, due to their abundance in the body. In 2021, the US expects 284,200 new cases of breast cancer, making it the top cancer in women, with an estimated 43,600 deaths. However, early detection and adequate treatment can improve breast cancer outcomes. Isolated peripheral blood mononuclear immune cells (PBMCs) that we hypothesize are altered in a body that is growing cancer compared to those PBMCs in a body that is not. Although the mechanism of these PBMC changes are not being investigated here, we hypothesize that we can detect these alterations using dielectrophoresis, a dielectric characterization techniques. The change in the electrophysiological property of the plasma membrane of a cancer cell is one of the features that encourage the use of the dielectrophoresis technique to manipulate and carry out electrokinetic separations of normal or healthy cells from cancer cells and vice versa, as they tend to behave differently under a non-uniform electric field.

Animal models are powerful tools to analyze the mechanism of induction of human breast cancer. 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. To realize our long-term goal, we are probing the dielectric properties of the 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 the 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 (conductivity, σ, and permittivity, ε), thus affecting the bioelectric signals that aids in the detection of breast cancer. This hypothesis is developed based on our preliminary published data demonstrating: 1) unique dielectric properties of PBMCs under healthy and early stages of infiltrating ductal adenocarcinoma (ADCs), and 2) label-free sorting¹. The results obtained at our preliminary analysis identify the bioelectric signals that regulate human adenocarcinoma cells. Our results present the dielectric properties of murine PyMT +/- PBMCs, which exhibited unique cellular behavior. We conclude that these unique characteristics can be used to discriminate between cancer and noncancer cells. This novel tool is label-free, rapid (~2 min.), and low-cost cell sorting technology that detects early and late stages of breast cancer. This work will lead to preclinical development and future clinical trials of the developed detection platform.