High-Precision Microfluidic Impedance Cytometry Integrating Cellular Size and Stiffness Sensing for Enhanced Tumor Cell Detection

Circulating tumor cell detection is crucial for the early diagnosis and treatment evaluation of cancer. Traditional cell detection methods based on bulky instrumentation, while accurate, often come with high costs and complexity. Therefore, there is a growing need for more cost-effective, user friendly, and label-free cell detection techniques. This article presents a microfluidic cell impedance detection system that utilizes cell size and elasticity for enhanced cell recognition, particularly for cells with similar sizes. In principle, quantitative analysis reveals that the impedance amplitude mainly reflects the cell size using the effective complex dielectric constant of the cell and solution, and that stiffer or larger cells take longer times to pass through the constriction channel, based on the Hertzian contact theory. We developed a microfluidic impedance chip with an 8- $\mu $ m-wide constriction channel, along with a detection system with differential input and impedance data processing. The counting and deformation detection capabilities of the system are validated by measuring impedance amplitude and passage time, achieving 93.9% precision in counting A549 tumor cells and more than 2.9 times longer passage times for hardened A549 cells compared to untreated ones. Furthermore, the system was tested using A549 cells and blood cells, achieving 99.4% precision for A549 cells using a 2-D scatter plot of passage time versus impedance amplitude. Finally, mixed solutions with different ratios of A549 cells to white blood cells (WBCs) are examined, and the detected ratios closely matched the predetermined ratios. These results demonstrate the potential of microfluidic cell impedance detection technology for precise identification and analysis of various cell types, offering a promising tool for clinical diagnostics and research.