Dielectrophoretic Characterization and Computational Analysis of Peripheral Blood Mononuclear Cells from MMTV-PyMT Mammary Carcinoma Models for Late Carcinoma Detection

Abstract

Breast cancer is the leading cancer in women, with 284,200 new cases and an estimated 43,600 deaths in 2021. Early detection and proper treatment can enhance outcomes. This study probes the dielectric properties of peripheral blood mononuclear cells (PBMCs) from MMTV-PyMT mice at 14+ weeks (stage IV) using a microfluidic platform for early breast cancer detection. The central hypothesis is that changes in subcellular components like the cytoskeleton, membrane, cytoplasm, and extracellular matrix at carcinoma onset regulate dielectric properties (conductivity, permittivity), affecting bioelectric signals that aid cancer detection. This is based on preliminary data showing unique PBMC dielectric properties from WT and PyMT tumor-bearing mice, identifying bioelectric signals regulating human adenocarcinoma cells. We hypothesize isolated PBMCs are altered in cancer compared to healthy bodies, evident in the MMTV-PyMT mouse model for analyzing human breast cancer mechanisms. Although specific PBMC change mechanisms are not investigated, we hypothesize these alterations can be detected using dielectrophoresis, a dielectric characterization technique utilizing non-uniform electric fields to manipulate and separate normal and cancer cells based on differing electrophysiological plasma membrane properties. Our results present dielectric properties of murine PyMT and WT PBMCs exhibiting unique cellular behavior, with numerical simulations validating these results. These unique characteristics can discriminate between cancer and non-cancer cells. This novel, label-free, rapid (~2 min), low-cost cell sorting technology detects and separates early and late breast cancer stages, leading to preclinical development and future clinical trials. The long-term goal is a non-invasive tool to determine breast cancer at earliest stages without false positives/negatives of standard mammography screening