Quantitative Magnetic Separation of Particles and Cells Using Gradient Magnetic Ratcheting

Extraction of rare target cells from biosamples is enabling for life science research. Traditional rare cell separation techniques, such as magnetic activated cell sorting, are robust but perform coarse, qualitative separations based on surface antigen expression. A quantitative magnetic separation technology is reported using high‐force magnetic ratcheting over arrays of magnetically soft micropillars with gradient spacing, and the system is used to separate and concentrate magnetic beads based on iron oxide content (IOC) and cells based on surface expression. The system consists of a microchip of permalloy micropillar arrays with increasing lateral pitch and a mechatronic device to generate a cycling magnetic field. Particles with higher IOC separate and equilibrate along the miropillar array at larger pitches. A semi‐analytical model is developed that predicts behavior for particles and cells. Using the system, LNCaP cells are separated based on the bound quantity of 1 μm anti‐epithelial cell adhesion molecule (EpCAM) particles as a metric for expression. The ratcheting cytometry system is able to resolve a ±13 bound particle differential, successfully distinguishing LNCaP from PC3 populations based on EpCAM expression, correlating with flow cytometry analysis. As a proof‐of‐concept, EpCAM‐labeled cells from patient blood are isolated with 74% purity, demonstrating potential toward a quantitative magnetic separation instrument.     

Direct Synthesis of MOF‐Derived Nanoporous Carbon with Magnetic Co Nanoparticles toward Efficient Water Treatment

Nanoporous carbon particles with magnetic Co nanoparticles (Co/NPC particles) are synthesized by one‐step carbonization of zeolitic imidazolate framework‐67 (ZIF‐67) crystals. After the carbonization, the original ZIF‐67 shapes are preserved well. Fine magnetic Co nanoparticles are well dispersed in the nanoporous carbon matrix, with the result that the Co/NPC particles show a strong magnetic response. The obtained nanoporous carbons show a high surface area and well‐developed graphitized wall, thereby realizing fast molecular diffusion of methylene blue (MB) molecules with excellent adsorption performance. The Co/NPC possesses an impressive saturation capacity for MB dye compared with the commercial activated carbon. Also, the dispersed magnetic Co nanoparticles facilitate easy magnetic separation.     

Magnetic barrier--A new concept in magnetic separation

Particles can be separated according to their mass magnetic susceptibilities by using a magnetic energy gradient barrier. When a stream of particles with different magnetic susceptibilities is fed to the barrier at an angle, a continuous separation can be obtained. The particles having susceptibilities higher than a predetermined value are deflected and guided by the magnetic barrier to a releasing region, where they pass through the barrier. Particles with lower susceptibilities which penetrate the barrier follow a different path from the more magnetic fraction and are separately collected.     

Tweezing of Magnetic and Non‐Magnetic Objects with Magnetic Fields

Although strong magnetic fields cannot be conveniently “focused” like light, modern microfabrication techniques enable preparation of microstructures with which the field gradients – and resulting magnetic forces – can be localized to very small dimensions. This ability provides the foundation for magnetic tweezers which in their classical variant can address magnetic targets. More recently, the so‐called negative magnetophoretic tweezers have also been developed which enable trapping and manipulations of completely nonmagnetic particles provided that they are suspended in a high‐magnetic‐susceptibility liquid. These two modes of magnetic tweezing are complimentary techniques tailorable for different types of applications. This Progress Report provides the theoretical basis for both modalities and illustrates their specific uses ranging from the manipulation of colloids in 2D and 3D, to trapping of living cells, control of cell function, experiments with single molecules, and more.     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

载有荧光量子点的纳米磁性微粒的合成方法及其应用前景

载有荧光量子点的纳米磁性微粒在生物医学中可以一步完成标记和分离的工作,近年来引起人们的广泛关注.综述了有关纳米磁性粒子与荧光量子点复合的最新研究成果及其应用.     

Effect of the Magnetic Dipole–Dipole Interaction on the Capture Efficiency in Open Gradient Magnetic Separation

In magnetic separation, the magnetic dipole-dipole (DD) interaction between particles has an important effect on the capture efficiency. By producing transient particle agglomerations, this interaction can considerably speed up the separation process. To take into account adequately this effect in ferromagnetic particle random dispersion, we have developed a modeling approach. The approach is based on the coupling of the magnetic force equation and a local homogenizing model for the material magnetic permeability. To verify the efficiency of the proposed approach on one hand and to estimate the effect of the DD interaction on the particle capture on the other hand, we consider a problem of open gradient magnetic separation (OGMS). We also conducted a limited experimental verification of the transient agglomeration for fine ferromagnetic particles.     

Increasing the Complexity of Magnetic Core/Shell Structured Nanocomposites for Biological Applications

This Review article ponders core/shell structured nanoparticles that can be prepared with features that combine properties of different materials, including ligands that enhance their biocompatibility. These nanocomposites are not classified in terms of synthesis, but rather by how these features are distributed in the final morphology, attending to connected or isolated materials that end up in interacting or not‐interacting functionalities. In particular, we have focused on magnetic core/shell‐structured particles with a directly connected, coupled, or isolated second functionality. The current progress on methods in colloidal solution that have allowed the great development of these multifunctional magnetic and active spheres on biological and biomedical fields is reported.     

Autonomous Magnetic Microrobots by Navigating Gates for Multiple Biomolecules Delivery

The precise delivery of biofunctionalized matters is of great interest from the fundamental and applied viewpoints. In spite of significant progress achieved during the last decade, a parallel and automated isolation and manipulation of rare analyte, and their simultaneous on‐chip separation and trapping, still remain challenging. Here, a universal micromagnet junction for self‐navigating gates of microrobotic particles to deliver the biomolecules to specific sites using a remote magnetic field is described. In the proposed concept, the nonmagnetic gap between the lithographically defined donor and acceptor micromagnets creates a crucial energy barrier to restrict particle gating. It is shown that by carefully designing the geometry of the junctions, it becomes possible to deliver multiple protein‐functionalized carriers in high resolution, as well as MCF‐7 and THP‐1 cells from the mixture, with high fidelity and trap them in individual apartments. Integration of such junctions with magnetophoretic circuitry elements could lead to novel platforms without retrieving for the synchronous digital manipulation of particles/biomolecules in microfluidic multiplex arrays for next‐generation biochips.     

Magnetic Nanocomposites: Magnetic Nanocomposites with Mesoporous Structures: Synthesis and Applications (Small 4/2011)

Magnetic nanocomposites with well‐defined mesoporous structures, shapes, and tailored properties are of immense scientific and technological interest. This review article is devoted to the progress in the synthesis and applications of magnetic mesoporous materials. The first part briefly reviews various general methods developed for producing magnetic nanoparticles (NPs). The second presents and categorizes the synthesis of magnetic nanocomposites with mesoporous structures. These nanocomposites are broadly categorized into four types: monodisperse magnetic nanocrystals embedded in mesoporous nanospheres, microspheres encapsulating magnetic cores into perpendicularly aligned mesoporous shells, ordered mesoporous materials loaded with magnetic NPs inside the porous channels or cages, and rattle‐type magnetic nanocomposites. The third section reviews the potential applications of the magnetic nanocomposites with mesoporous structures in the areas of heath care, catalysis, and environmental separation. The final section offers a summary and future perspectives on the state‐of‐the art in this area.     

Rapid,High‐Resolution Magnetic Microscopy of Single Magnetic Microbeads

Magnetic microparticles or “beads” are used in a variety of research applications from cell sorting through to optical force traction microscopy. The magnetic properties of such particles can be tailored for specific applications with the uniformity of individual beads critical to their function. However, the majority of magnetic characterization techniques quantify the magnetic properties from large bead ensembles. Developing new magnetic imaging techniques to evaluate and visualize the magnetic fields from single beads will allow detailed insight into the magnetic uniformity, anisotropy, and alignment of magnetic domains. Here, diamond‐based magnetic microscopy is applied to image and characterize individual magnetic beads with varying magnetic and structural properties: ferromagnetic and superparamagnetic/paramagnetic, shell (coated with magnetic material), and solid (magnetic material dispersed in matrix). The single‐bead magnetic images identify irregularities in the magnetic profiles from individual bead populations. Magnetic simulations account for the varying magnetic profiles and allow to infer the magnetization of individual beads. Additionally, this work shows that the imaging technique can be adapted to achieve illumination‐free tracking of magnetic beads, opening the possibility of tracking cell movements and mechanics in photosensitive contexts.     

磁镜场约束中粒子运动的数值计算

由单粒子轨道理论,从分析磁镜场中荷电粒子的受力情况出发,应用计算机数值求解方法模拟了磁镜场中荷电粒子的运动情况.结果表明:与经典的理论分析结果不同,当荷电粒子的起始位置与磁轴的距离不等于其拉摩尔半径时,荷电粒子在平行磁轴方向和垂直磁轴平面中的速度分量存在着周期性变化,其周期为荷电粒子的拉摩尔周期;同时其损失锥的临界角随着荷电粒子起始位置与磁轴的距离的增大而略有减小.     

Advection Flows‐Enhanced Magnetic Separation for High‐Throughput Bacteria Separation from Undiluted Whole Blood

A major challenge to scale up a microfluidic magnetic separator for extracorporeal blood cleansing applications is to overcome low magnetic drag velocity caused by viscous blood components interfering with magnetophoresis. Therefore, there is an unmet need to develop an effective method to position magnetic particles to the area of augmented magnetic flux density gradients while retaining clinically applicable throughput. Here, a magnetophoretic cell separation device, integrated with slanted ridge‐arrays in a microfluidic channel, is reported. The slanted ridges patterned in the microfluidic channels generate spiral flows along the microfluidic channel. The cells bound with magnetic particles follow trajectories of the spiral streamlines and are repeatedly transferred in a transverse direction toward the area adjacent to a ferromagnetic nickel structure, where they are exposed to a highly augmented magnetic force of 7.68 µN that is much greater than the force (0.35 pN) at the side of the channel furthest from the nickel structure. With this approach, 91.68% ± 2.18% of Escherichia coli (E. coli) bound with magnetic nanoparticles are successfully separated from undiluted whole blood at a flow rate of 0.6 mL h^?1 in a single microfluidic channel, whereas only 23.98% ± 6.59% of E. coli are depleted in the conventional microfluidic device.     

Magnetic Luminescent Porous Silicon Microparticles for Localized Delivery of Molecular Drug Payloads

Magnetic manipulation, fluorescent tracking, and localized delivery of a drug payload to cancer cells in vitro is demonstrated, using nanostructured porous silicon microparticles as a carrier. The multifunctional microparticles are prepared by electrochemical porosification of a silicon wafer in a hydrofluoric acid‐containing electrolyte, followed by removal and fracture of the porous layer into particles using ultrasound. The intrinsically luminescent particles are loaded with superparamagnetic iron oxide nanoparticles and the anti‐cancer drug doxorubicin. The drug‐containing particles are delivered to human cervical cancer (HeLa) cells in vitro, under the guidance of a magnetic field. The high concentration of particles in the proximity of the magnetic field results in a high concentration of drug being released in that region of the Petri dish, and localized cell death is confirmed by cellular viability assay (Calcein AM).     

Magnetic separation of the second kind: Magnetogravimetric, magnetohydrostatic, and magnetohydrodynamic separations

Magnetogravimetric, magnetohydrostatic, and magnetohydrodynamic separation techniques can be classified as magnetic separations of the second kind. Magnetic separation of the first kind (ordinary magnetic separation) relies on the inherent magnetic susceptibility of the material to be separated. When the medium of separation rather than the separated particles is made magnetizable, a new system of gravity separations can result (magnetic separation of the second kind). In magnetogravimetry, a colloidal solution of a ferro- or ferrimagnetic substance (magnetic fluid) acts as the separation medium. Magnetohydrostatic separations are conducted in an aqueous solution (or melt) of a strongly paramagnetic salt. Magnetohydrodynamics applies the Faraday effect (mutual orthogonality of the force thrust, electric, and magnetic fields) on suspended conducting minerals in an electrolytic solution placed in crossed electric and magnetic fields. The first technique was pioneered mainly in the United States, while the last two techniques were pioneered by Bunin and Andres in the Soviet Union and introduced to the West by Andres. The principles underlying the three separation techniques will be discussed.     

Magnetic Core/Shell and Quantum‐Confined Semiconductor Nanoparticles via Chimie Douce Organometallic Synthesis

Ligand‐stabilized metal atoms provide a unique entry to the synthesis of magnetic nanosized metal/metal oxide particles. When this technique is used in connection with a mesoporous template, formation of superparamagnetic particles in the pores of the template via a “ship‐in‐the‐bottle” technique is possible. This chimie douce approach works also for pure metal oxides, such as TiO₂. The Figure shows a sculpture found at the Trinity College campus, Dublin, Ireland representing a typical core/shell arrangement often found for composite nanoparticles.     

Multifunctional Silver‐Embedded Magnetic Nanoparticles as SERS Nanoprobes and Their Applications

In this study, surface‐enhanced Raman spectroscopy (SERS)‐encoded magnetic nanoparticles (NPs) are prepared and utilized as a multifunctional tagging material for cancer‐cell targeting and separation. First, silver‐embedded magnetic NPs are prepared, composed of an 18‐nm magnetic core and a 16‐nm‐thick silica shell with silver NPs formed on the surface. After simple aromatic compounds are adsorbed on the silver‐embedded magnetic NPs, they are coated with silica to provide them with chemical and physical stability. The resulting silica‐encapsulated magnetic NPs (M‐SERS dots) produce strong SERS signals and have magnetic properties. In a model application as a tagging material, the M‐SERS dots are successfully utilized for targeting breast‐cancer cells (SKBR3) and floating leukemia cells (SP2/O). The targeted cancer cells can be easily separated from the untargeted cells using an external magnetic field. The separated targeted cancer cells exhibit a Raman signal originating from the M‐SERS dots. This system proves to be an efficient tool for separating targeted cells. Additionally, the magnetic‐field‐induced hot spots, which can provide a 1000‐times‐stronger SERS intensity due to aggregation of the NPs, are studied.     

磁性累托石的制备及其对含有机染料废水的吸附性能

采用共沉淀法制备了纳米Fe3O4磁性微粒,将其与累托石复合制得一系列不同Fe3O4载量的磁性累托石,用XRD、SEM、TEM和VSM对样品的性质进行了表征,研究了样品对含有机染料废水的吸附性能与磁分离回收率。结果表明,Fe3O4粒度为10~25nm,结晶良好,具有尖晶石结构;制得的磁性累托石均具有良好的超顺磁性,当Fe3O4载量为25%时,Ms、Mr、Hci分别为12.867emu/g、0.355emu/g、15.524G;当吸附剂添加量为0.4%时,Fe3O4载量为16%的磁性累托石对含甲基橙及亚甲基蓝染料废水的脱色率分别达76.9%、99.4%;Fe3O4载量分别为10%~25%的磁性累托石,其磁分离回收率为95.6%~98.4%。     

Setting up High Gradient Magnetic Separation for combating eutrophication of inland waters

To find new approaches to devise technologies for handling with eutrophication of inland waters is a global challenge. Separation of the P from water under conditions of continuous flow is proposed as an alternative and effective method. This work is based on using highly magnetic particles as the seeding adsorbent material and their later removal from solution by High Gradient Magnetic Separation (HGMS). Contrast to other methods based on batch conditions, large volumes of water can be easily handled by HGMS because of decreasing retention times. This study identifies the best working conditions for removing P from solution by investigating the effects of a set of four different experimental variables: sonication time, flow rate (as it determines the retention time of particles in the magnetic field), magnetic field strength and the iron (Fe) particles/P concentration ratio. Additionally, the change of P removal efficiency with time (build up effect) and the possibility of reusing magnetic particles were also studied. Our results evidenced that while flow rate does not significantly affect P removal efficiency in the range 0.08-0.36 mL s(-1), sonication time, magnetic field strength and the Fe particles/P concentration ratio are the main factors controlling magnetic separation process.     

Nanotentacle‐Structured Magnetic Particles for Efficient Capture of Circulating Tumor Cells

Circulating tumor cells (CTCs) have attracted considerable attention as promising markers for diagnosing and monitoring the cancer status. Despite many technological advances in isolating CTCs, the capture efficiency and purity still remain challenges that limit clinical practice. Here, the construction of “nanotentacle”‐structured magnetic particles using M13‐bacteriophage and their application for the efficient capturing of CTCs is demonstrated. The M13‐bacteriophage to magnetic particles followed by modification with PEG is conjugated, and further tethered monoclonal antibodies against the epidermal receptor 2 (HER2). The use of nanotentacle‐structured magnetic particles results in a high capture purity (>45%) and efficiency (>90%), even for a smaller number of cancer cells (≈25 cells) in whole blood. Furthermore, the cancer cells captured are shown to maintain a viability of greater than 84%. The approach can be effectively used for capturing CTCs with high efficiency and purity for the diagnosis and monitoring of cancer status.