Electrical impedance tomography (EIT)-based intracellular conductivity imaging for non-invasive cell detection.

Abstract

Electrical impedance tomography (EIT)-based intracellular conductivity imaging is newly proposed as a non-invasive technique for mapping the electrical properties of living cells at the single-cell scale. In order to achieve this, a micro-EIT system is developed, which integrates two main components: a custom-designed micro-EIT sensor and a frequency-differential EIT coupled with a single-cell equivalent circuit-based reconstruction algorithm. The micro-EIT sensor is designed to match single-cell scale and fabricated on a glass substrate by electron beam lithography, which enables high spatial resolution (7 μm electrode width, 40 μm spacing), stable frequency response, and signal-to-noise ratios typically ranging from 50 to 200. The frequency-difference EIT achieves the reconstruction of conductivity distributions of the cytoplasm <i>σ</i>_cyt and nucleoplasm <i>σ</i>_nuc through current response analysis based on the equivalent circuit model of a single cell. To evaluate the performance, impedance spectra were measured to reconstruct the intracellular conductivity images in three types of Medical Research Council 5 (MRC-5) human lung fibroblast cell lines with different protein expressions. As a result, <i>σ</i>_cyt and <i>σ</i>_nuc of three cell types were successfully reconstructed, which revealed clear differences corresponding to variations in protein expression. Brightfield and fluorescence observations were also performed to verify the EIT results, which demonstrated the reliability of the coordinates and the size of the cytoplasm and nucleoplasm. This work represents the first demonstration of non-invasive intracellular conductivity mapping that distinguishes subcellular structures based on electrical properties.