Microfluidic magnetophoretic separations of immunomagnetically labeled rare mammalian cells

Abstract

Immunomagnetic isolation and magnetophoresis in microfluidics have emerged as viable techniques for the separation, fractionation, and enrichment of rare cells. Here we present the development and characterization of a microfluidic system that incorporates an angled permanent magnet for the lateral magnetophoresis of superparamagnetic beads and labeled cell–bead complexes. A numerical model, based on the relevant transport processes, is developed as a design tool for the demonstration and prediction of magnetophoretic displacement. We employ a dimensionless magnetophoresis parameter to efficiently investigate the design space, gain insight into the physics of the system, and compare results across the vast spectrum of magnetophoretic microfluidic systems. The numerical model and theoretical analysis are experimentally validated by the lateral magnetophoretic deflection of superparamagnetic beads and magnetically labeled breast adenocarcinoma MCF-7 cells in a microfluidic device that incorporates a permanent magnet angled relative to the flow. Through the dimensionless magnetophoresis parameter, the transition between regimes of magnetophoretic action, from hydrodynamically dominated (magnetic deflection) to magnetically dominated (magnetic capture), is experimentally identified. This powerful tool and theoretical framework enables efficient device and experiment design of biologically relevant systems, taking into account their inherent variability and labeling distributions. This analysis identifies the necessary beads, magnet configuration (orientation), magnet type (permanent, ferromagnetic, electromagnet), flow rate, channel geometry, and buffer to achieve the desired level of magnetophoretic deflection or capture.