Oscillatory Flow enables Size Separation at the Nanoscale

A novel microfluidic oscillatory viscoelastic focusing method allows isolation of nanosized particles

Mohammad Asghari and coworkers from the deMello group have developed a new microfluidic system for focusing and separating particles in the micrometer to nanometer size regime. The novelty lies in the combination of a viscoelastic fluid with oscillatory motions of flow, enabling sheathless (i.e. without a secondary outer flow) focusing of particles less than 100 nm in size.

Thorough investigation of the composition of biofluids, e.g. blood, is of great importance and growing interest in the medical and pharmaceutical community. These investigations necessitate the isolation of different particle types, e.g. by size and/or shape. Mohammad showed that the addition of the polymer poly(ethylene oxide) (PEO) into biofluids allows for the development of viscoelastic properties. In a colloidal and viscoelastic solution, lateral, size-dependent particle movement occurs as a response to shear stress. This lateral movement depends on the size of the particles thus allowing formation of focused streams of similarly-sized particles.

In the demonstrated methodology, separation and focusing of particles of different sizes from 3 μm to 20 nm are introduced. By using a flow with regular reversal of direction (oscillatory flow), it is possible to cover a long distance in a short channel. Typically, particles below 100 nm in size are difficult to focus due to Brownian motion. Here, the combination of oscillatory flow and the viscoelastic character of the PEO in solution overcomes this problem and thus allows for the separation of microparticles from 1 to 10 um, sub-micrometer particles of 100 to 500 nm, and nanosized particles of 20 and 40 nm. The pressurized microfluidic chip is controlled through a computer operated electronic board. The geometry is designed such that the single inlet channel after focusing is diverged into several outlet channels corresponding to the different streams of focused particles. With this platform, both polymeric particles and particles from biofluids, including p-bodies, lambda-DNA and extracellular vesicles (EVs), were successfully focused and isolated. This technique could for example enable the isolation of exomeres, a subgroup of EVs with dimensions less than 50 nm, whose biological functions remain a mystery.

The presented oscillatory viscoelastic method provides particle isolation from micro- to nano-dimensions and is compatible with biological fluids. This new technology for rapid particle separation over a wide size range sets new standards for the study of biological species in biofluids.

Written by Julia Nette.

Read the full paper here.

A square channel focusing 1, 5 and 20 um particles with an oscillation frequency of 2 Hz


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