Capture, Confine, Characterize: High-Throughput Dielectrophoresis-Based Single-Cell Microfluidics Platform to Analyze Mammalian and Yeast Cells Using Raman Spectroscopy

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Abstract

Single-cell analysis technologies are pivotal in unraveling complex biological mechanisms, yet existing platforms are often limited to sequencing-based end-point measurements, which fail to capture live cell dynamics. Here, we present a microfluidic– microelectronic device, the Microfluidic dielectrophoretic Arresting System (MiDAS) that employs dielectrophoresis (DEP) for high-throughput single-cell and droplet trapping in a compact array. We tested multiple trap geometries, including a 20 μm-diameter DEP trap for polymer microbeads, fungal and mammalian cells, and a 40 μm-diameter trap for water-in-oil droplets. The platform demonstrates broad sample compatibility, reliably immobilizing cells and beads of varying sizes. By integrating optical imaging and Raman spectroscopy, we enable rapid, non-destructive interrogation of individual cells with temporal resolution. We describe different modes of MiDAS operation to trap and manipulate single-cells or reverse emulsion droplets on demand, with applications in droplet microfluidics. Our MiDAS platform’s simple fabrication, robust performance, and broad compatibility with diverse sample types position it as a versatile tool with transformative potential for single-cell analysis, offering researchers an innovative approach to interrogate cellular dynamics with unprecedented precision and throughput.

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