Sensitivity Analysis of Localized Electrochemical Impedance Spectroscopy Towards Tomography-on-a-Chip.

Electrical impedance measurements are traditionally macroscopic screening techniques designed to obtain information about the macroscopic internal structure of biological systems. In order to overcome the limitations that the technology detects, mainly with the bulk properties, a miniaturization is employed by developing a complex microfluidic system to achieve cell-scale information. In this work, a microelectrode array was incorporated into a microfluidic chip, allowing localized Electrochemical Impedance Spectroscopy (EIS) measurements, providing impedance data obtained in the spatial and frequency domains simultaneously. The height of the capillary in the microfluidic system was also systematically modified; hence, three types of channels with heights of 10 μm, 30 μm, and 50 μm were developed and studied. The EIS data collection was implemented using two different strategies (two- and four-electrode techniques). Sensitivity analysis was conducted using a microbead solution, where the linear mapping of the number of microbeads along the channel was achieved by EIS. Based on the findings, a complete overview of each measurement implementation was obtained, which is well explained by the physical background presented in the paper. In the case where the capillary height (10 μm) is comparable to the diameter of the microbeads (6 μm), the four-electrode technique detected the beads in a wider frequency range (approximately between 500 Hz and 50 kHz), while the two-electrode technique detected the beads in a narrower frequency range (approximately between 30 kHz and 300 kHz) with correlation greater than 0.9. In all other cases, a medium (or weak) correlation was found between the impedance data and the longitudinal bead distribution. Based on the results, the technology is ready for further development and adaptation for cell culture purposes.