Toxicology with ECIS
In 1992, we published an article suggesting the application of cell impedance measurement for this purpose [Giaever, I. and Keese, C.R., "Toxic? Cells Can Tell", Chemtech, 116-125 (Feb. 1992)]. Since that time, we have developed ECIS-based assays for this purpose and have acquired considerable data demonstrating the efficacy of this method to collect relevant toxicological data. The ECIS approach furnishes data that are by nature quantitative, and since the instrument is computer interfaced, very little technician labor is required to acquire large amounts of information. This sort of precision and cost effectiveness are important attributes of ECIS.
In 1998 dose response curves using ECIS were published [Keese, C., Karra, N., Dillon, B., Goldberg, A., Giaever, I., "Cell-Substratum Interactions as a Predictor of Cytotoxicity." In Vitro & Molecular Toxicology 11 (2), (1998)]. In this study cells in vitro were exposed to different levels of potential toxicants and their response monitored. Specifically, established confluent monolayers (WI-38/VA13 fibroblastic and MDCK epithelial cells) were exposed to varying concentrations of four detergents (Tween 20, benzalkonium chloride, Triton X100 and sodium lauryl sulfate). ECIS measurements were used to follow subsequent changes of the overall impedance of the cell monolayer and of cell micromotions detected as impedance fluctuations. Analysis of these measurements correctly ranked the detergents according to their established in vivo toxicity. Of interest in this work was a dramatic increase of impedance fluctuations sometimes recorded from cells upon exposure to the toxicants. This occurred when detergent concentrations were below those showing a decline in overall impedance; this hormesis effect was particularly evident in the MDCK cells. A portion of these published results is shown below.
Related ECIS Publications
Electric cell-substrate impedance sensing (ECIS) based real-time measurement of titer dependent cytotoxicity induced by adenoviral vectors in an IPI-2I cell culture model. J Muller, C Thirion, and MW Pfaffl. Biosens Bioelectron. 2010.
Development of an electrode cell impedance method to measure osteoblast cell activity in magnesium-conditioned media. Y Yun, Z Dong, Z Tan, and MJ Schulz. Anal Bioanal Chem. 2010. Volume: 396 Issue: 8 Pages: 3009-3015.
Theresa M. Curtis, Mark W. Widder, Linda M. Brennan, Steven J. Schwager, William H. van der Schalie, Julien Fey and Noe Salazar, “A portable cell-based impedance sensor for toxicity testing of drinking water.” Lab Chip, 2009, DOI: 10.1039/b901314h.
Theresa M. Curtis, Joel Tabb, Lori Romeo, Steven J. Schwager, Mark W. Widder and William H. van der Schaliec, “Improved cell sensitivity and longevity in a rapid impedance-based toxicity sensor.” Journal of Applied Toxicology (January 2009).
Campbell, C.E., Motzfeldt-Laane, M., Haugarvoll, E., and Giaever, I., "Monitoring Viral Induced Cell Death using Electric Cell-Substrate Impedance Sensing." Biosensors and Bioelectronics: 23(4): 536-542 (2007).
van der Schalie, W.H,. James, R.R., Gargan, T.P. 2nd, "Selection of a battery of rapid toxicity sensors for drinking water evaluation." Biosens Bioelectron, (2006).
Chanana, M., Gliozzi, A., Diaspro, A., Chodnevskaja, I., Huewel, S., Moskalenko, V., Ulrichs, K., Galla, H.J., Krol, S., "Interaction of polyelectrolytes and their composites with living cells." Nano Lett. 5(12):2605-12 (2005).
Xiao, C., Luong, J.HT., "The Assessment of Cytotoxicity by Emerging Impedance Spectroscopy." Toxicology and Applied Pharmacology, (2004).
Xiao, C., Luong, J., "On-Line Monitoring of Cell Growth and Cytotoxicity Using Electric cell-substrate Impedance Sensing (ECIS)." ,Biotechnal Prog, 19, 1000-2005 (2003)
Xiao,C., Lachance, B., Sunahara, G., Luong, J., "Assessment of Cytotoxicity Using Electric Cell-Substrate Impedance Sensing: Concentration and Time Response Function Approach.", Anal. Chem., 74(22), 5748-5753 (2002)
Noiri, E., Nakao, A., Uchida, K., Tsukahara, H., Ohno, M., Fujita, T., Brodsky, S., Goligorsky, M., "Oxidative and nitrosative stress in acute renal ischemia", Am J Physiol Renal Physiol 281: F948-F957 (2001)
Keese, C., Karra, N., Dillon, B., Goldberg, A., Giaever, I., "Cell-Substratum Interactions as a Predictor of Cytotoxixity." In Vitro & Molecular Toxicology 11 (2), (1998)
Giaever, I. and Keese, C.R., "Toxic? Cells Can Tell", Chemtech, 116-125 (Feb. 1992).