Impedance Spectroscopy
Electrical external page impedance spectroscopy (EIS) is a non-invasive technique for measuring the dielectric properties of a material of interest. The method is used in the biological domain to characterize cells and tissues.As opposed to typical cell colony average data, the differences between individual single cells can be evaluated. The tool dimensions for single-cell analysis needs to be on the length scale of individual cells. The dielectric properties of biological cells reveal information about cell size, membrane resistance, membrane capacitance and cytoplasmic conductivity. The presence of subcellular components, such as vacuoles, can also potentially be detected.
Cells or particles are dispersed in a liquid, typically an electrolyte, such as phosphate-buffered saline (PBS), and forced through a microfluidic channel with two pairs of planar electrodes patterned at the top and bottom. An AC voltage is applied to the electrodes, and the current change upon passage of a particle is measured differentially.
In collaboration with external page Zurich Instruments AG, we have developed an impedance cytometer capable of measuring the dielectric properties of single cells at frequencies of up to 600 MHz. We apply the increased frequency range to characterizing subcellular features, such as vacuoles and cell nuclei, in addition to the properties detectable at lower frequencies.
Impedance spectroscopy can be combined with other electrical functionalities in microfluidic chips, such aspplication of strong electric fields to induce pore formation in the cell membrane. These can be used to extract cellular contents for imaging or spectrometry or to introduce external material into the cell for labeling or external page transfection.
Collaborations
Swiss Tropical Health Institute, Basel, Switzerland, Groups at ETH Zurich, Switzerland; Zurich Instruments AG, Zurich, Switzerland.
Recent publications
P. S. Ravaynia, F. C. Lombardo, S. Biendl, M. A. Dupuch, J. Keiser, A. Hierlemann, M. M. Modena, "Parallelized impedance‐based platform for continuous dose‐response characterization of antischistosomal drugs", Advanced Biosystems 2020, Article 1900304 (DOI: 10.1002/adbi.201900304). external page Online
K. Chawla, M. Modena, P. Ravaynia, F. Lombardo, M. Leonhardt, G. Panic, S. Bürgel, J. Keiser, and A. Hierlemann, "Impedance-based microfluidic assay for automated antischistosomal drug screening", ACS Sensors 2018, 3 (12), pp. 2613–2620 (DOI: 10.1021/acssensors.8b01027). external page Online
V. Viswam, R. Bounik, A. Shadmani, J. Dragas, C. Urwyler, J. Boos, M. Obien, J. Müller, Y. Chen, A. Hierlemann, "Impedance spectroscopy and electrophysiological imaging of cells with a high-density CMOS microelectrode array system", IEEE Trans. Biomed. Circuits Syst. 2018, 12 (6), pp. 1356-1368 (DOI: 10.1109/TBCAS.2018.2881044). external page Online
K. Chawla, S Bürgel, G. Schmidt, H-M. Kaltenbach, F. Rudolf, O. Frey, Andreas Hierlemann, "Integrating impedance-based growth-rate monitoring into a microfluidic cell culture platform for live-cell microscopy", Microsystems & Nanoengineering 2018, 4:8 (DOI 10.1038/s41378-018-0006-5). external page Online
S. Bürgel, L. Diener, O. Frey, J.Y. Kim, A. Hierlemann, "Automated, multiplexed electrical impedance spectroscopy platform for continuous monitoring of microtissue spheroids", Analytical Chemistry 2016, 88 (22), pp. 10876–10883 (DOI: 10.1021/acs.analchem.6b01410). external page Online