Abstract: To overcome the limitations of current ferroptosis monitoring methods for tumor cells-namely poor real-time performance and high invasiveness-a label-free, non-contact dynamic monitoring approach was developed by integrating high-vacuum conditions with piezoelectric resonance principle. A piezoelectric resonator with a high quality factor (Q>10⁴) was designed, and a resonant sensing system with an ultimate vacuum level of 10^-4 Pa and a leakage rate below 10^-8 Pa·m³/s was established. Ferroptosis was induced in tumor cell models, during which resonance frequency shifts, damping changes, and mass-loading responses were recorded in real time. Signal features were extracted via Fourier transform and principal component analysis. The experimental results demonstrate that high vacuum significantly suppresses gas damping and thermal noise, thereby enhancing resonance sensitivity. Within 60 minutes of induction, frequency shifts exceeded 18.1 Hz and damping variations reached 21.0%, both highly correlated with intracellular ROS levels and iron ion concentrations (R²=0.81). Regression analysis revealed a nonlinear increase in Q-value with decreasing pressure, identifying 10^-3 Pa as the optimal vacuum window for sensing performance. By enhancing Q-factor and reducing background interference, the high-vacuum chamber enables the sensor to capture changes in cellular vibration modes, achieving high-precision, non-invasive, and label-free dynamic detection of ferroptosis at the cellular level. This work expands the applicability of vacuum-enabled biosensing technologies and provides a novel platform for tumor diagnosis and therapeutic monitoring.

Key words: high vacuum resonant sensor, ferroptosis, tumor cells, vacuum leakage suppression, Q-value enhancement