Simulated Microgravity Induces Rapid Dielectric Shifts in Erythrocytes of Pancreatic Cancer Patients

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, often diagnosed at advanced stages due to the absence of early symptoms and reliable screening tools. Recent studies suggest that systemic changes in cancer, including inflammation, metabolic alterations, and circulating biomarkers, can affect red blood cells (RBCs) or erythrocytes. Although RBCs lack nuclei, those from cancer patients exhibit measurable biophysical and biochemical alterations, offering potential for novel diagnostic approaches. However, it is not known how simulated microgravity might further modulate these cancer-associated RBC dielectric properties, and the effects of microgravity on RBCs from PDAC patients remain largely unexplored. In this study, we investigate the impact of simulated microgravity (SMG) on the dielectric properties of human red blood cells from pancreatic ductal adenocarcinoma (PDAC) patients and healthy donors as controls. Cells were exposed to SMG using a clinostat for 3 and 6 h in a suspending medium with a fixed conductivity of 0.01 S/m. Dielectrophoresis (DEP), a label-free electrokinetic technique, was used to analyze cellular responses to nonuniform electric fields ranging from 0.5 kHz to 45 MHz at a constant peak-to-peak voltage of 10 V _pp. Significant biophysical changes were observed as early as 3 h of SMG exposure. Specifically, a statistically significant increase in specific membrane conductance (G _spmem) was obtained (p < 0.0001), and both the force of maximum positive DEP (F _pDEP) and the second crossover frequency (f _{x o2}) exhibited consistent downshifts, suggesting reduced cytoplasmic conductivity and altered membrane capacitance. Receiver operating characteristic (ROC) analysis indicated that specific membrane capacitance (C _spmem) provides moderate discriminative performance as a candidate SMG-responsive biomarker. These findings demonstrate that RBCs from PDAC patients undergo rapid dielectric changes under simulated microgravity, and underscore the utility of DEP for noninvasive, real-time monitoring of cancer-related biophysical alterations, with applications in both cancer research and space medicine.