Enterprise AI Analysis

Electric cell-substrate impedance sensing (ECIS) is a label-free and non-invasive technique that characterizes cell behaviors by monitoring impedance variations at the cell–electrode interface, and has been widely used to study cell adhesion, spreading, and barrier properties in real time. Beyond the classical ECIS configuration with small planar electrodes, interdigitated microelectrodes (IDEs) with microscale finger-gap patterns have been extensively adopted to enhance impedance sensitivity for detecting cell attachment by enlarging the effective electrode–cell interaction area. In addition, ECIS platforms based on microelectrode arrays enable parallel or spatially resolved impedance measurements, allowing statistical analysis of cell populations rather than single sensing sites. Despite these advances, conventional ECIS approaches exhibit inherent limitations when applied to primary clinical samples, particularly in scenarios involving low cell numbers and heterogeneous cell populations. In such cases, impedance signals from individual or sparse cells are often comparable to the background noise level, and overlapping impedance distributions from different cell types can hinder reliable discrimination. A major contributing factor is that traditional ECIS systems typically rely on external impedance analyzers and long electrical interconnections between electrodes and peripheral readout circuits, which introduce parasitic capacitance, environmental interference, and thermal noise that degrade signal fidelity. In this study, we propose an advanced method for fast tumor diagnosis based on single-cell electric cell-substrate impedance sensing on an integrated circuit (IC) chip. The IC right under the surface electrodes for electric cell-substrate impedance sensing maximizes the signal-to-noise ratio to distinguish cancer cells from non-cancerous cells at the single-cell level. The micro-electrode array integrated on the chip is highly scalable and offers high throughput.

To evaluate the performance of the IC-ECIS system for distinguishing cancer cells from non-cancerous cells in a biopsy sample at the single-cell level, we chose a commercial human gastric cancer cell line (SGC-7901) as the model cancer cell line and a gastric epithelial cell line (GES-1) as the corresponding non-cancerous cell line for investigation. Non-cancerous cells, including immune cells (B lymphocytes and T lymphocytes), which may be present in tumor tissue, and mesenchymal stem cells (MSCs), which are sometimes used in cancer therapy, were also investigated for accuracy evaluation. The impedance magnitude between two adjacent electrodes loaded with a single cell was measured for comparison. Compared with all four types of non-cancerous cells, cancer cells demonstrated a significantly greater magnitude of impedance. The higher impedance of cancer cells (SGC-7901) than non-cancerous tissue cells (GES-1) may be due to the unique physical properties and metabolic activities of cancer cells. As cells transition into a cancerous state, they undergo significant changes in transmembrane potential, surface charge, ion concentration, etc. Cancer cells tend to release higher quantities of lactate ions, which can cross the cytoplasmic membrane, leading to a substantial buildup of negative charges on the cell membrane surface. When applied to an electric field, this accumulated negative charge can generate a current in the opposite direction, thereby enhancing the impedance. Moreover, cancer cells express more proteins related to adhesion, migration, and invasion. When cells adhere to the electrode surface via these proteins, charge transfer becomes more challenging, as they must pass through a layer of non-conductive extracellular adhesion protein, leading to an increase in charge transfer resistance. Both mechanisms could cause an increase in the impedance amplitude of cancer cells compared with that of non-cancerous or precancerous cells. The reluctance of immune cells to adhere to electrodes results in their low impedance. Among the non-cancer cells, T cells had the lowest impedance magnitude, which is also attributed to their smaller size. MSCs had a lower impedance than cancer cells, but slightly higher compared with the immune cells. This may be due to the complicated differentiation states of the MSCs, which cause the overexpression of certain proteins.