Dielectric Signatures of Late Carcinoma Immune Cells Using MMTV-PyMT Mammary Carcinoma Models

Peripheral blood mononuclear cells (PBMCs) are specialized immune cells produced from hematopoietic stem cells (HSC). They actively surveil for any signs of infection, foreign invaders, and abnormal or aberrant cells associated with diseases. Numerous inherent interactions between PBMCs and proliferating cancer cells facilitate cellular communication, inducing alterations in the composition of the PBMCs. These subtle alterations can be detected by using dielectrophoresis (DEP). The ultimate objective is to apply this knowledge in a clinical setting to achieve noninvasive early detection of breast cancer while minimizing the occurrence of false positives and negatives commonly associated with standard screening methods like mammography. To realize our long-term goal, we are probing the dielectric properties of the PBMCs from FVB/N MMTV-PyMT+ (late carcinoma, PyMT+ PBMC) and FVB/N (wild-type, WT-PBMC) age-matched mice at 14+ weeks using dielectrophoresis on 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 properties (conductivity, σ; and permittivity, ε), thus affecting the bioelectric signals that aid in the detection of breast cancer. The ANOVA results suggest a significant difference in PyMT+ PBMCs crossover frequencies at 0.01 and 0.05 S/m medium conductivity levels. Post hoc pairwise analysis of WT-PBMCs showed that the crossover frequencies are distinct across the medium conductivity ranges from 0.01 to 0.05 S/m. This study revealed that on average, PyMT+ PBMCs have increased crossover frequency, polarizability, higher membrane capacitance, and a folding factor compared with the age-matched wild-type PBMCs.