Oladokun Raphael, Smith Christopher, Eubank Timothy, Srivastava Soumya
Department of Chemical & Biomedical Engineering, West Virginia University, Morgantown, West Virginia 26506-6201, United States.
Department of Microbiology, Immunology & Cell Biology, West Virginia University, Morgantown, West Virginia 26506-6201, United States.
ACS Omega. 2024 Sep 26;9(40):41378-41388. doi: 10.1021/acsomega.4c04210. eCollection 2024 Oct 8.
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.
外周血单个核细胞（PBMCs）是由造血干细胞（HSC）产生的特殊免疫细胞。它们积极监测感染迹象、外来入侵者以及与疾病相关的异常或畸变细胞。PBMCs与增殖的癌细胞之间存在许多内在相互作用，促进细胞间通讯，导致PBMCs组成发生改变。这些细微变化可通过介电电泳（DEP）检测到。最终目标是将这一知识应用于临床，实现乳腺癌的无创早期检测，同时尽量减少与乳房X线摄影等标准筛查方法常见的假阳性和假阴性情况。为实现我们的长期目标，我们正在使用微流控平台上的介电电泳技术，探测14周龄以上的FVB/N MMTV-PyMT+（晚期癌，PyMT+ PBMC）和FVB/N（野生型，WT-PBMC）年龄匹配小鼠的PBMCs的介电特性。本研究的核心假设是，癌发生时亚细胞成分（如细胞骨架、脂质双分子层膜、细胞质、粘着斑蛋白和细胞外基质（ECM））中引发的变化会调节介电特性（电导率，σ；和介电常数，ε），从而影响有助于检测乳腺癌的生物电信号。方差分析结果表明，在0.01和0.05 S/m的介质电导率水平下，PyMT+ PBMCs的交叉频率存在显著差异。对WT-PBMCs的事后两两分析表明，在0.01至0.05 S/m的介质电导率范围内，交叉频率各不相同。这项研究表明，与年龄匹配的野生型PBMCs相比，PyMT+ PBMCs平均具有更高的交叉频率、极化率、更高的膜电容和折叠因子。
