Introduction
Materials and method
Device fabrication
Magnetic nanoparticles conjugated with opsonin molecules
Capture efficiency of MBL conjugated superparamagnetic nanoparticles
Magnetic separation efficiency of device
Results and discussion
Device design and fabrication
The device consists of one inlet where the sample is injected into the channel, two outlets where the sample flows out of the channel. Spiral flow can be formed by the asymmetric pressure gradients across the channel induced by the inclined microrib arrays[14] (Figure 1A). The magnetic particles that bind with target cells are transferred by the spiral flow and pass through the area of higher magnetic flux density gradients near the ferromagnetic structure (Figure 1B).
When the external magnetic field is applied using a permanent magnet, the nickel structure generates locally enhanced magnetic flux density gradients and isolates magnetizable objects moving close to the ferromagnetic structure (Figure 2). The particles magnetically separated by the nickel structures followed the streamlines and then exited through outlet 2, while the particle-depleted sample solution flowed out through outlet 1 (Figure 3 A). Inclined ridge arrays pattern induces the asymmetric pressure gradient and then generates the spiral flow in the channel.
The red arrows represent the swirling currents that can transfer magnetic particles to the formed area of high magnetic forces. A schematic view of the magnetic separation device we proposed to improve the efficiency performance of magnetic separation by inducing spiral flow. When the magnetic particles that are transferred by the rotating advective flow meet the high magnetic flux density gradient area, due to the crushing speed of the magnetic drug, the magnetic particles are isolated by the magnetic force.
We fabricated the microfluidic device, which contained the barrier array patterns in the channel using the photolithography process. The magnetic separation channel (channel height height of the ridge part in the channel channel width; 100 µm 50 µm 1000 µm) was modeled on the micro-barrier arrays (Figure 3 B). The steep obstacle structures were angled at 45° to generate sufficient swirling flows in the channel.
Therefore, the channel with inclined ridge arrays will generate spiral flows as the fluid passes through the microfluidic channel. The enhanced magnetic flux density gradients were formed in the region of the microfluidic channel adjacent to the nickel microstructure. This composition of magnetic force provides high efficiency for isolation of target sample bound with magnetic beads.
Simulation about the spiral flow of theoretical model
An angle of θ = 8.17 ° along the sidewall of the channel, while for other conventional channels, a parallel movement of particles along the sidewall of the channel was assumed.
Simulation of improved magnetic separation in designed model
To position the magnetic particles from the low magnetic flux density area to the high magnetic flux density area, we designed the device with a pattern of inclined obstacle arrays where the particles are transferred by the spiral flow. The lateral displacement of the magnetic particles was overwhelmingly determined by the rotating advection flow directed toward the nickel ferromagnetic structure. This simple line forces the magnetic particle away from the nickel structure to move adjacent to the nickel structure.
When we applied the external magnetic force, we defined the trajectory of magnetic particles as 𝑑 = 𝑑𝑚𝑎𝑔𝑛𝑒𝑡+ 𝑑𝑎𝑑𝑣𝑒𝑐𝑡𝑖𝑛𝑖𝑛𝑖𝑛. We assumed the speed of magnetic particles in spiral flow as the maximum speed, which was revealed by the computer simulation program. The magnetic particle's trajectory plotted on Figure 6 showed that the magnetic particles were transferred to the area next to a region of high magnetic flux gradient (~20 µm), even they started at a distance of 660 µm away from the nickel structure.
Plot of magnetic flux density gradients along the distance from a nickel microstructure magnetized by a NdFeB permanent magnet. The result of a computer simulation of the trajectories of magnetic particles passing through a magnetic separation device integrated with (A) arrays of inclined ridges.
Advective rotational flow induce by slanted ridge arrays in channel
Improved magnetic separation efficiency of magnetic particles
Isolation of Escherichia Coli captured by MBL-Magnetic Nanoparticles
Isolation efficiency of magnetic particles (diameter: 1um) using microfluidic devices with different ridge angles and patterns. Alternatively, two other magnetic separation devices, including 90° angle travel arrays and flat surfaces, yielded low isolation efficiencies of 77.6% and 71.7%, respectively, at a flow rate of 1.4 mL/h.
Isolation of Bacteria in diluted blood
Isolation of Bacteria in whole blood
We proposed a magnetic separation device using advective rotational currents induced by patterned obstacle array on the wall of channel for the separation of micrometer particles. Many of the current continuous magnetic separation devices are limited to the separation of cells and micrometer-sized biological molecules such as bacteria in blood samples remain a challenge due to the high viscosity. The use of rotational flows transfers the magnetic nanoparticles to the region of high magnetic force and then improves the magnetic separation efficiency by overcoming the limitation.
We theoretically predicted the superiority of the inclined ridge integrated device for the separation of magnetic nanoparticles and then experimentally validated that our intended device outperforms the spiral currents for the isolation of magnetic particles or magnetic nanoparticle bound bacteria. Our demonstration of the effectiveness of the spiral current-induced magnetic separation device provides an efficient approach to high-throughput magnetic separation that may be valuable for various applications such as contaminated water purification food diagnostics[18], [19]. Park, “Magnetophoretic Continuous Purification of Single-Walled Carbon Nanotubes from Catalytic Urities in a Microfluidic Device,” Small, vol.
Ingber, "A combined micromagnetic-microfluidic device for rapid capture and cultivation of rare circulating tumor cells," Lab on a Chip, vol. Lee et al., "Synthetic Ligand-Coated Magnetic Nanoptics for Microfluidic Bacterial Separation from Blood," Nano Letters, vol. Ingber, "Application of a Halbach magnetic array for long-range cell and particle separations in biological samples," Appl.
Kang et al., "Optimization of pathogen capture in liquid fluids with magnetic nanoparticles," Small, vol. Park, "Continuous hydrophoretic separation and sizing of microparticles using inclined obstacles in a microchannel," Lab on a Chip, vol. Park, "Isomagnetophoresis to Discriminate Subtle Differences in Magnetic Susceptibility," Journal of the American Chemical Society, vol.
Gijs, “Microfluidic applications of functionalized magnetic particles for environmental analysis: focus on waterborne pathogen detection,” Microfluidics and Nanofluidics, vol. I deeply thank all the members of our laboratory for their kind help and cooperation throughout my study period. I am also grateful to Professor Young Ki Hahn, Sein Oh, Doctor Seyong Kwon, Professor Eujin Um and Professor Sungyoung Choi for their guidance and constant supervision.
Conclusion
Acknowledgement
