Development of a noise elimination electrical impedance spectroscopy (neEIS) system for single cell identification

We propose a noise elimination electrical impedance spectroscopy (neEIS) system for single cell identification whose characteristics are cell-free clamp structure and cell-position independent calibration. The function of the cell-free clamp structure is to enable a single cell to be freely located into neEIS system. The cell-position independent calibration consists of three steps; impedance measurement, electrode cell constant calculation, and single cell dielectric properties estimation. The cell-position independent calibration enables elimination the influence of noise associated with ions as well as electrical double layer during the measurement process. We demonstrate an application of neEIS system to discriminate three types of MRC-5 human lung fibroblasts; wild type (WT), GFP-fused histone (HT) modification, and GFP transfected (GFPT) MRC-5 cells suspended in a sucrose medium. To further evaluate the neEIS system, we simulated the electrical potential distribution and root means square error of single cell dielectric properties numerically. As a result, we obtained electric potential distribution which clearly characterized the internal change of single cell components. Moreover, we determined that the neEIS system is capable of accurate single cell identification after noises elimination with less than 1.05% average root means square error. Taken together, these results demonstrate that the proposed neEIS system has the potential to improve the performance of biosensors. Thus, this study will bring a new insight into the development of a biosensor system for high accuracy single cell identification as well as inspire the development of a diagnostic device for early fetal lung diseases based on the neEIS system.