Centrifugo-magnetophoretic particle separation

There has been a recent surge of research output on magnetophoretic lab-on-a-chip systems due to their prospective use in a range of applications in the life sciences and clinical diagnostics. Manifold applications for batch-mode or continuous-flow magnetophoretic separations of cells, proteins, and nucleic acids are found in bioanalytics, cell biology, and clinical diagnostics. To ensure stable hydrodynamic conditions and thus reproducible separation, state-of-the-art magnetophoretic lab-on-a-chip systems have been based on pressure-driven flow (Gijs in Microfluid Nanofluid 1:22–40, 2004; Pamme and Manz in Anal Chem 76:7250–7256, 2004; Pamme in Lab Chip 7:1644–1659, 2007; Karle et al. in Lab Chip 10:3284–3290, 2010), which involves rather bulky and costly instrumentation. In a flow-based system, suspended particles are following the liquid phase as a result of the Stokes drag, thus being fully exposed to divergent flow lines around obstacles and pump-induced pressure fluctuations. To eventually achieve more stable hydrodynamic conditions, improved control of magnetic particles, a more compact instrumentation footprint, and integration of high-performance upstream sample preparation, this work introduces a novel two-dimensional particle separation principle by combining magnetic deflection with centrifugal sedimentation in a stopped-flow mode (i.e., mere particle sedimentation). The experimental parameters governing our centrifugo-magnetophoretic system are the strength and orientation of the co-rotating magnetic field, the rotationally induced centrifugal field, and the size-dependent Stokes drag of the various particles with respect to the (residual) liquid phase. In this work, the following set of basic functional modes is demonstrated as proof-of-concept: separation of magnetic from non-magnetic particles, routing of magnetic particles based on control of the spin speed, and size separation of various magnetic particles. Finally, a biomimetic application involving the separation of particles representing healthy cells from a very small concentration of magnetic particles of a similar size, mass and magnetization as a immuno-magnetically tagged target cell, for instance mimicking a circulating tumor cell.