Microscale magnetic field modulation using rapidly patterned soft magnetic microstructures.

The ability to locally modulate the magnetic field distribution is a prerequisite for efficient manipulation in magnetic force-based microfluidic devices. Here, we report a simple, robust, and fast fabrication method of magnetic microstructures for locally modulating magnetic fields. In the proposed method, a photosensitive magnetic composite consisting of carbonyl-iron microparticles in a poly(ethylene glycol) diacrylate (PEGDA) matrix was utilized to photolithographically fabricate magnetic microstructures. The magnetic behavior of the composite was first evaluated, and then various complicated patterns were fabricated on a glass slide within a few minutes. To demonstrate the capability of magnetic microstructures as a magnetic field concentrator, magnetic microstructures with different orientations to the external magnetic field were designed and fabricated, such as square arrays and grid-like magnetic microstructures. The modulated magnetic fields from such magnetic microstructures were numerically analyzed and then experimentally validated by trapping magnetic hydrogel beads. Further, the magnetically labeled cells were applied to the magnetic microstructures to prove the possibility of cell confinement via magnetic guidance in regions that exhibit enhanced magnetic field gradients. Overall, the proposed approach facilitates simple and fast fabrication of soft magnetic microstructures for microscale modulation of magnetic fields, which exhibits an immense application potential in magnetic force-based microfluidic techniques.

Toxicity Assessment of Iron Oxide Nanoparticles Based on Cellular Magnetic Loading Using Magnetophoretic Sorting in a Trapezoidal Microchannel.

To accurately assess potential nanotoxicity on the basis of cellular iron content, the precise separation of cells into subpopulations according to their magnetic nanoparticle loading is of crucial importance. In this study, we developed a microfluidic magnetophoresis device consisting of a trapezoidal channel containing five side outlet branches and a narrow rectangular channel with three outlet branches. This unique structure enabled the sequential separation of cells loaded with tiny amounts of iron oxide and cells heavily labeled with iron oxide, in a single device. As a proof of concept, we attempted the sequential separation of Raw 264.7 cells with a large heterogeneity in uptake capabilities (1-50 pg of iron per cell). Consequently, we were able to differentiate the bulk cell population into seven subpopulations according to their mean iron oxide loading. We also evaluated potential nanotoxicity effects using the production of excess reactive oxygen species (ROS) and the inhibition of proliferation on the separated subpopulations, and we found that 46.6% of cells loaded with iron above the threshold value (16.4 pg) had higher ROS levels than the control group. Cells loaded with more than 3.7 pg of iron exhibited transiently inhibited cell-cycle progression. In particular, cells loaded with more than 35.4 pg of iron exerted a significant effect on cell proliferation. The proposed system could be useful in the investigation of nanotoxicity effects of iron oxide nanoparticle-induced cells, based on their iron oxide nanoparticle loading.

Magnetophoretic Sorting of Single Cell-Containing Microdroplets.

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.

Label-free cell separation using a tunable magnetophoretic repulsion force.

This paper describes a new label-free cell separation method using a magnetic repulsion force resulting from the magnetic susceptibility difference between cells and a paramagnetic buffer solution in a microchannel. The difference in the magnetic forces acting on different-sized cells is enhanced by adjusting the magnetic susceptibility of the surrounding medium, which depends on the concentration of paramagnetic salts, such as biocompatible gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), dissolved therein. As a proof-of-concept demonstration, Gd-DTPA solutions at concentrations of 0-80 mM were applied to separate U937 cells from red blood cells (RBCs) and to distinguish two different-sized polystyrene (PS) beads (8 and 10 µm in diameter). By increasing the Gd-DTPA concentration from 0 to 40 mM, the separation resolution of PS beads was increased from 0.08 to 0.91. Additionally, we successfully achieved label-free separation of U937 cells from RBCs with >90% purity and 1 × 10(5) cells/h throughput using a 40 mM Gd-DTPA solution.