On-chip electroporation and impedance spectroscopy of single-cells

We present an integrated microplatform for handling, electroporation and label free analysis of single mammalian cells in suspension. Accurate axial positioning of a cell flowing through a channel is accomplished through microfluidic control and flow direction reversal; electroporation is achieved by applying 2 kV cm−1 at 50 kHz through on-chip microelectrodes; label-free detection of changes in the cell undergoing electroporation is performed by means of electric impedance spectroscopy (EIS). Shuttling the cell back and forth allows either (a) assessment of a single cell at multiple points of time to evaluate dynamic processes or (b) increased quality of EIS results by averaging subsequent passages of the same cell through the measurement region. Electrical parameters are extracted from the measurement by fitting the impedance magnitude spectrum to an equivalent-circuit model of the microchannel and by using a three-shell model for the cell. The fitting procedure is shown to be robust and suggests cell swelling, exchange of intra- and extracellular liquids, and change of the cell membrane and nuclear envelope capacitance. Cell swelling was in agreement with bright-field micrographs, while the exchange of intra- and extracellular liquids has also been observed via established fluorescent markers. The quantification of cellular changes as well as of the changes in cellular dielectric properties induced by electroporation enables a better understanding and control of the cell electroporation process.