A Microfluidic Device Integrating Impedance Flow Cytometry and Electric Impedance Spectroscopy for High-Efficiency Single-Cell Electrical Property Measurement

Abstract

Single-cell impedance measurement is a label-free, noninvasive method for characterizing the electrical properties of single cells. At present, though widely used for impedance measurement, electric impedance flow cytometry (IFC) and electric impedance spectroscopy (EIS) are used alone for most microfluidic chips. In this paper, we present a microfluidic device combining the IFC and EIS techniques for single-cell electrical property measurement. The device uses hydrodynamic constriction to passively trap single cells and uses coplanar electrodes to obtain the impedance spectrum of the trapped cell via EIS and discrete impedance data points of the passing cells via IFC. Through experiment, we verified the individual functionality of IFC and EIS respectively, by revealing through IFC the impedance magnitude difference and quantifying through EIS the area-specific membrane capacitance and cytoplasm conductivity of the three types of cancer cells. We also demonstrated the complementarity of IFC and EIS, which holds for a wide range of the flow rate. We envision that the strategy of combining IFC and EIS provides a new thought in the efforts to enhancing the efficiency of electrical property measurement for single cells.

Impedance Spectroscopy as a Tool for Monitoring Performance in 3D Models of Epithelial Tissues

“…Therefore, combination of IS with other techniques significantly expands the capabilities of the method. Another important development is recently described combination of impedance flow cytometry and electric IS within the same microfluidic device suitable for single cell measurements allowing to evaluate properties of heterogeneous populations of cancer cells by dealing with them one at a time (Feng et al, 2019). It is expected that more of the hybrid cell analysis systems of this kind should be introduced in the future.…”

Recent Advances in Monitoring Cell Behavior Using Cell-Based Impedance Spectroscopy

“…The results obtained from the impedimetric data were also supported by microscopy imaging and transwell assays [72]. Nguyen et al [54] designed an electrical cell-substrate impedance sensing (ECIS) chip using the Boyden chamber design to study the kinetics of migration and invasion of single cancer cells. The designed chip consisted of three main parts: microelectrode arrays (MEAs), cell capture arrays (CCAs), and a microfluidic channel with an inlet and an outlet (Figure 11).…”

“…The CBI system can also be used as a tomography sensor for cell imaging [50][51][52][53]. Combining CBI with microfluidic systems and flow cytometry provided the development of miniaturized devices for automated bioanalysis [54][55][56][57][58][59][60]. Although these devices may be far from high throughput applications, they have the advantages of simplicity, low sample size that make them valuable tools for fundamental and applied research.…”

Review: Dielectrophoresis in cell characterization

“…Other on‐chip methods to assess cell electrophysiology, such as impedance cytometry, allow for single‐cell analysis [30–33], however, early methods’ resolution and accuracy were affected by the positional dependence of the signal and did not offer significant throughput. Current strategies to implement cell focusing and microfluidics to meet these challenges are often complex or optimized for a particular cell size [34–36]. Recent work has shown a marked increase in throughput from less than 100 cells/s to reports of over 300 cells/s [35–37].…”