Chloride channels play a pivotal role in cell volume regulation. When cells suffer hypotonic stimulation, cell swelling activated volume-sensitive chloride channels (VSCC) to drive Cl- and water outflow leading to the shrinkage of cells, namely regulatory volume decrease (RVD). Most cancerous cells can alter expression of ion channels so that affect RVD function. It is significant to reveal the relation of VSCC and RVD in different cell line. However, besides electrophysiological technique, there is few means that are usable for this research. Thus, a piezoelectric cytosensor based on cell RVD and cell mass fluctuation is first developed to real-time and in-situ analyze the functional activities of VSCC. Hypotonicity-induced RVD causing cell mass variations can be monitored by acquiring dynamic frequency shift of piezosensor. The sensor with nasopharyngeal cancer cells (CNE-2Z) exhibited sensitively RVD responses to osmolarity from 280 to 160 mOsmol·L-1. The results showed that removing Cl- of perfusates caused cell RVD function lost, and inhibitors of ATP and TAM blocking VSCC produced similar results. The sensor was further used to evaluate functional activities of VSCC between normal and cancerous nasopharyngeal cells by monitoring RVD level of which normal cells was 39.1 ± 3.0% (n=3), and cancer cells was 63.6 ± 2.6% (n=3) increased by 62.7%. The results revealed that cancer cells had higher VSCC expression than that of normal cells. The piezoelectric cytosensor exhibited excellent analytical performance to study RVD and functional activities of VSCC in living cells. This approach will be great potential applications in biomedical field.
