Development of impedance/external field potential dual measurement system for evaluation of electrophysiological properties of cells on microelectrodes

A combination of extracellular field potential (FP) and impedance measurement technologies for multielectrode array (MEA) chip architecture is developed for the simultaneous evaluation of information on the ion current and resistance of cells and microelectrodes. The simultaneous measurement system can not only evaluate the time course changes of characteristics in the MEAs but also clarification of the origin of the difference in the waveform of the field potentials of each cell on an microelectrode whether it is caused by the changes in the electrophysiological properties of cells or by the changes in the performance of an microelectrode (and cell-to-electrode contacts). The automatic impedance measurement technology in the system exploited the swiping of the wide frequency range of impedances of microelectrodes and calculated the true impedance of each microelectrode without significant effects on the cells on the MEA chip. Hence, the system can give us invisible cell-toelectrode contact information and its change, and also information on the degradation of the performance of microelectrodes during long-term cultivation and after the application of compounds into the MEA chip. The impedance spectrum measurement showed that (1) the increase in the impedance of microelectrodes correlated with its area decrease from 10^-7 to 10^-10m², (2) even the area of microelectrodes decreased from 10^-8 to 10^-10m², the noise level of field potential signals was independent and did not change, and (3) the attachment of cells on the microelectrode surface can be determined by a significant increase in impedance at 1 kHz corresponding to the width of the depolarization peak on the field potential recordings. These results indicate the potential to evaluate the cell-to-electrode contact and degradation of microelectrodes, which was not evaluated in conventional FP measurements only. These results also indicate that this method should be used for the evaluation of the changes in cell network conditions caused by various compounds.