Real-time, label-free monitoring of the cell cycle with a cellular impedance sensing chip.

The cell cycle plays a crucial role in many cellular physiological processes and has drawn an increasing interest in past decades. In the current study, we have developed a bioelectronic chip-based system capable of performing real-time dynamic analysis of the cell cycle in live cells via non-invasive cellular impedance sensing. The cells were cultured on the cellular impedance sensing chip comprising microfabricated interdigitated electrode structures. HeLa cells were synchronized with double thymidine block and the cellular impedances were monitored in a time resolution of minutes during the whole 5 days' experiment. Our results show that real-time impedance sensing can clearly mirror the progression of the cell cycle-in G(1) phase and S phase, the cellular impedance increased with time, while in G(2) phase and M phase, the cellular impedance decreased. Correspondingly, the time-course impedance curves for the synchronized cells have marked "M-valleys" corresponding to the periods of mitosis of the cells. The cell cycle information revealed by the cellular impedance data was confirmed using flow cytometry and microscopy. This paper presents the first step towards in situ and label-free monitoring of the cell cycle of mammalian cells on chip in a real-time, non-invasive manner.