Precise programmable tumor cell subpopulation sorting <i>via</i> an electromagnetic microfluidic platform.

Abstract

High-throughput phenotypic cell sorting is essential for elucidating disease mechanisms and identifying therapeutic targets. Conventional magnetic sorting methods largely fail to isolate multiple cell subpopulations based on membrane protein expression levels, while suffering from fixed capture thresholds, limited resolution, and harsh cell release. To address these challenges, we developed a modular, programmable electromagnetic microfluidic platform. By synergistically integrating an electromagnetic array with a microfluidic chip, the platform utilizes multi-channel, independently driven currents to generate multilevel, high-gradient magnetic fields along the flow direction on a soft magnetic core array. This architecture successfully transforms conventional physical structural limitations into dynamically adjustable electrical parameters, enabling flexible reconfiguration of cell capture thresholds and release strategies solely through preset current-combination programs. Simulation studies elucidate the underlying physical mechanisms governing the stepped magnetic potential landscape and tunable capture thresholds. Experimentally, the platform can precisely classify target cells into four phenotypic subpopulations (high, medium, low, and negative), according to their varied protein expression levels. Furthermore, by adjusting the combinations of driving currents, the phenotypic expression profile distributions of these four cell subpopulations can be dynamically regulated. Concurrently, the platform achieves spatially localized enrichment of multiple target cell types in distinct capture regions based on differences in their overall expression levels. Benefiting from semiconductor temperature control and a gentle recovery mechanism, cellular physiological functions are maximally preserved. With its excellent modular scalability, this platform holds broad prospects for tumor heterogeneity analysis, rare cell isolation, downstream single-cell omics, and precise drug evaluation.