Magnetophoretic Sorting of Single Cell-Containing Microdroplets

Abstract

Droplet microfluidics is a promising tool for single-cell analysis since single cell can be comparted inside a tiny volume. However, droplet encapsulation of single cells still remains a challenging issue due to the low ratio of droplets containing single cells. Here, we introduce a simple and robust single cell sorting platform based on a magnetophoretic method using monodisperse magnetic nanoparticles (MNPs) and droplet microfluidics with >94% purity. There is an approximately equal amount of MNPs in the same-sized droplet, which has the same magnetic force under the magnetic field. However, the droplets containing single cells have a reduced number of MNPs, as much as the volume of the cell inside the droplet, resulting in a low magnetic force. Based on this simple principle, this platform enables the separation of single cell-encapsulated droplets from the droplets with no cells. Additionally, this device uses only a permanent magnet without any complex additional apparatus; hence, this new platform can be integrated into a single cell analysis system considering its effectiveness and convenience.

On-chip polyelectrolyte coating onto magnetic droplets – towards continuous flow assembly of drug delivery capsules

“…The ability to manipulate the magnetic fluid by an external magnetic field has seen its use for a number of applications in microfluidics, including pumping, valving, and the deflection of microparticles and cells. [44][45][46] Since ferrofluids can be oil-based or aqueous, they can be used to generate magnetic droplets as easily as any other oil/water combination [47][48][49][50] by using a continuous phase that is immiscible with the ferrofluid, [51][52][53][54][55][56][57][58][59][60][61][62] while non-magnetic droplets have also been formed in a ferrofluid continuous phase.…”

Magnetophoretic sorting of microdroplets with different microalgal cell densities for rapid isolation of fast growing strains

“…By encapsulating dextran-coated superparamagnetic magnetite (Fe 3 O 4 ) nanoparticles, droplets containing microalgal cells can be attracted toward the permanent NdFeB magnet, and the same net force exerted on the magnetic droplet results in different acceleration and lateral displacements in the y -axis due to differences in the mass of the droplet. This approach is distinguished from previous magnetophoretic sorting system 31 , 32 which depends on difference in the amount of the magnetic force caused by the different number of encapsulated magnetic nanoparticles. To maximize the gap between the droplets, we investigated the lateral displacement of the deflected droplets by regulating four different parameters, including the flow rate of the main stream, the magnet position ( x - and y -axis) and the droplet diameter.…”

“…To overcome this limitation, it is necessary to increase the magnetic force affected by the number ( N ), volume ( V p ) of the magnetic nanoparticles, magnetic flux density ( B ) and its gradient ( ∇B ). There was a previous report on the use of a nickel microstructure near the magnet or an electromagnet to increase the magnetic flux density gradient 32 . Although there is limitation to applying this system to large sized microalgal strains due to the changes in the magnetic force, our platform can be applied to other useful microalgal strains which have much smaller cell size than the droplet and a great potential to be utilized as biofuel and high-value products.…”

“…Jo et al . used magnetophoretic sorting system to distinguish the single cell encapsulated droplets which have a reduced number of magnetic nanoparticles that can be applied to single cell analysis 32 . To utilize the magnetophoretic sorting system as cell screening technology, we used microdroplets containing the same concentration of 20 nm iron oxide magnetic nanoparticles coated with a biocompatible polymer, dextran 33 , which are superparamagnetic and have no magnetic memory 31 .…”

Study of a Microfluidic Chip Integrating Single Cell Trap and 3D Stable Rotation Manipulation

“…Biological cells need to be manipulated in many scenarios, such as cell characterization, sorting, injection, and enucleation [ 1 , 2 , 3 , 4 , 5 ]. For example, in enucleation, the chromosome of a recipient cell in the animal cloning process needs to be taken out by aspiration, during which the cell has to be rotated around normally by hand, such that the chromosome is oriented upwards for subsequent identification and pipette aspiration.…”