A long-term universal impedance flow cytometry platform empowered by adaptive channel height and real-time clogging-release strategy

Abstract

Impedance flow cytometry is a widely used label-free technique for single-cell analysis; however, its limited sensitivity and lack of universality have hindered its ability to replace conventional flow cytometry. In this study, we propose an adaptive microfluidic channel platform that dynamically adjusts the channel height to improve both measurement performance and system versatility. We found that reducing the channel height by one-third effectively decreases the distance between particles and the sensing electrodes, resulting in an average 3.2-fold amplification of the impedance signal. This approach also reduces signal variability by half, thereby enhancing measurement precision. Enhanced particle discrimination was demonstrated using a mixture of yeast cells and 6 μm beads, while robust cell phenotyping was achieved across multiple cell lines, including A549, C6, and NIH/3T3. By integrating this adaptive channel with an object detection algorithm, we successfully created a self-optimizing system that utilizes intentional, temporary clogging as a strategy to regulate channel height. These findings underscore the potential for a universal, high-performance impedance flow cytometry platform that simple, clog-resistant, and adaptable for a wide range of biomedical applications.