Microfluidic cell sorting

Microfluidic cell sorting is the separation of cells using microfluidic systems. Microfluidic systems process or manipulate small amounts of fluidics (10⁻⁹ to 10⁻¹⁸L), using channels measuring from tens to hundreds of micrometers. Microfluidic cells sorting is used to enrich or purify cell samples into well-defined populations. The technique is used in research, diagnostics and therapeutic practices.

Microchip devices use microfluidics on a miniaturized platform. For lab-on-a-chip applications, microfluidics can be used to detect, focus, mix, count, lyse and analyze individual cells on an integrated platform.

Microchip cell sorting may recognize specific cell types based on fluorescent labels. Fluorescent label-based cell sorting using microfluidics is similar to traditional fluorescence-activated cell sorting (FACS), in that they use serial interrogation by laser light, real-time classification and rapid, command-driven sorting. In FACS, each cell is encapsulated into an aerosol droplet that is charged and electrostatically sorted. Microfluidic cell sorting uses electrokinetic mechanisms such as electrophoresis, dieletrophoresis and electroosmotic flow. Acoustophoresis, optical and mechanical manipulations are also used.

Bead-based cell sorting systems involve the attachment of beads to allow bound complexes to experience a force different from unbound cells. Unlike fluorescence-based sorting, bead-based sorting does not require serial interrogation of cells and can manipulate groups of cells simultaneously. Bead-based cell sorting systems use magnetophoresis (MAP), acoustophoresis and electrokinetic mechanisms.

Label-free sorting in microfluidic devices uses active systems (i.e. external fields) and also passive systems such as inertial flow, on-chip filtration and immobilization. Label-free sorting relies on the physical differences in the properties of cells such as size, shape, density, elasticity, polarizability and magnetic susceptibility.

Label-free cell sorting uses active systems such as acoustophoresis, electrokinetics, magnetophoresis and optics. Magnetophoresis is normally used to sort cells labeled with nanoparticles but erythrocytes can be sorted from blood dur to their natural iron content in methemoglobin.

Passive cell sorting strategies includes inertial focusing in curved channels. This type or system has been used to separate circulating cell tumors from blood. Pinched flow fractionation is another strategy where a flow stream of cells is pinched by a narrow channel cross section such that the cells are constrained and aligned against a side wall. They separate by size once the channel broadens due to the laminar flow profile. Deterministic lateral displacement is another method of cell separation where micropatterns are created within microfluidic channels such as posts, ridges, groves and ratchets to spatially manipulate cells. Hydrophoretic filtration is a method that uses ridge-induced hydrophoretic filtration due to the formation of a lateral pressure gradient within a microfluidic channel resulting from flow-altering micropatterns. Other techniques for separation include size exclusion filtration, cross-flow filtration, hydrodynamic filtration, transient cellular adhesion an cellular immobilization.