Conductive polymer as a controlled microenvironment for the potentiometric high-throughput evaluation of ionic liquid cell toxicity

This paper presents both biological and potentiometric evaluations of the cell toxicity of a widely used ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate (bmim]BF(4)), to Chinese hamster lung fibroblast cells (V79 cell line). The innovative potentiometric study takes advantage of the unique properties of conductive polymer polypyrrole (PPY) for the potentiometric evaluation of cell toxicity of bmim]BF(4) to the V79 cells in a real-time, noninvasive and high-throughput manner. The conductive polymer PPY provides a controlled microenvironment that allows the quantitative release of the anions of the ionic liquids into the cells being monitored in real time and noninvasively. Parallel biological assay results showed that V79 cells exposed to bmim]BF(4) usually grew in clusters, and that many small vacuoles could be seen in the cytoplasm. At the 24th hour after the V79 cells had been exposed to the ionic liquid (IL), the half inhibition concentration (EC(50)) of bmim]BF(4) was around 5 mM. From a cell cycle study performed using a FACScan flow cytometer, it was found that the V79 cells could be partially locked to the G(1) phase by bmim]BF(4), which extended the doubling time for cell growth. Comparing with the EC(50) values of cadmium chloride and mercury chloride, bmim]BF(4) is not very toxic, but it may have a long-term toxic effect on mammalian cells. Compared to traditional biological in vitro assays, the use of a conductive polymer substrate in combination with a potentiometric sensor array is much more sensitive, faster, and enables a simpler evaluation of chemical cell toxicity. Additionally, it simplifies the study of the reversibility of cell toxicity, i.e., cell recovery, because there is no need to refresh the culture medium since a finite amount of chemicals can be doped and released. We found that the cytotoxicity of bmim]BF(4) at a concentration of less than 6 mM was reversible for the V79 cell line, because cell morphology and proliferation rate returned to normal after the removal of the IL from the culture medium. This finding suggests that the IL bmim]BF(4) could be used as a tool to control mammalian cell proliferation rate.