A continuous microfluidic magneto-affinity cell sorter

Abstract

Continuous microfluidic magneto-affinity cell separator, which combines unique microscale flow phenomenon with advantageous nanobead properties, can isolate cells with high specificity. This dissertation is a theoretical and experimental study of a continuous flow cell separator microsystem. I have studied and validated the operational principle of such a microseparator system with two fluidic inlets merging into one main channel and subsequently splitting into two outlet channels. This results in two phase flow of identical aqueous solvents in the main channel. The first part of this dissertation is a study of magnetic nanoparticles only. A steady state convection diffusion model describes the transport of nanoparticles in the microchannel. It is shown how particle separation is affected by Peclet number, channel length to width ratio and magnetic field strength and field gradient. Experiments were conducted with three particle sizes. Results revealed a significant discrepancy between theoretical and experimental particle separation in the presence of an external magnetic field. A correction term was introduced into the magnetic force equation. Experiment and theory could be reconciled with the insight that the correction term scales linearly with the volume of the nanoparticle core. The second part of this dissertation is a theoretical and experimental study of the microfluidic magneto-affinity separation of cells. Owing to the comparable size of the cell-bead complexes and the microchannels, the walls of the microchannel exert a strong influence on the separation of cells by this method. A quantitative description of hydrodynamic wall interactions and wall rolling velocity of cells is presented. A transient convection model describes the transport of cells in two-phase microfluidic flow under the influence of an external magnetic field. Transport of cells along the microchannel walls is also considered via an additional equation. Experimentally measured cell rolling velocities on the wall indicate the presence of other near-wall forces in addition to fluid shear forces. Separation of a human colon carcinoma cell line from a mixture of red blood cells, with folic acid conjugated 1 um and 200 nm beads, is reported.