RESUMEN

We introduce magnetophoresis-based microfluidics for sorting biological targets using positive Magnetophoresis (pM) for magnetically labeled particles and negative Magnetophoresis (nM) for label-free particles. A single, externally magnetized ferromagnetic wire induces repulsive forces and is positioned across the focused sample flow near the main channel's closed end. We analyze magnetic attributes and separation performance under two transverse dual-mode magnetic configurations, examining magnetic fields, hydrodynamics, and forces on microparticles of varying sizes and properties. In pM, the dual-magnet arrangement (DMA) for sorting three distinct particles shows higher magnetic gradient generation and throughput than the single-magnet arrangement (SMA). In nM, the numerical results for SMA sorting of red blood cells (RBCs), white blood cells (WBCs), and prostate cancer cells (PC3-9) demonstrate superior magnetic properties and throughput compared to DMA. Magnetized wire linear movement is a key design parameter, allowing device customization. An automated device for handling more targets can be created by manipulating magnetophoretic repulsion forces. The transverse wire and magnet arrangement accommodate increased channel depth without sacrificing efficiency, yielding higher throughput than other devices. Experimental validation using soft lithography and 3D printing confirms successful sorting and separation, aligning well with numerical results. This demonstrates the successful sorting and separating of injected particles within a hydrodynamically focused sample in all systems. Both numerical and experimental findings indicate a separation accuracy of 100% across various Reynolds numbers. The primary channel dimensions measure 100 µm in height and 200 µm in width. N52 permanent magnets were employed in both numerical simulations and experiments. For numerical simulations, a remanent flux density of 1.48 T was utilized. In the experimental setup, magnets measuring 0.5 × 0.5 × 0.125 inches and 0.5 × 0.5 × 1 inch were employed. The experimental data confirm the device's capability to achieve 100% separation accuracy at a Reynolds number of 3. However, this study did not explore the potential impact of increased flow rates on separation accuracy.

Asunto(s)

RESUMEN

For metal-based phosphate adsorbents, the dispersity and utilization of surface metal active sites are crucial factors in their adsorption performance and synthesis cost. In this study, a biochar material modified with amorphous Zr-Ce (carbonate) oxides (BZCCO-13) was synthesized for the phosphate uptake, and the adsorption process was enhanced by magnetic field. The beside-magnetic field was shown to have a better influence than under-magnetic field on adsorption, with maximum adsorption capacities (123.67 mg P/g) 1.14-fold greater than that without magnetic field. The beside-magnetic field could also accelerate the adsorption rate, and the time to reach 90% maximum adsorption capacity decreased by 83%. BZCCO-13 has a wide range of application pHs from 5.0 to 10.0, with great selectivity and reusability. The results of XPS and ELNES showed that the "magnetophoresis" of Ce3+ under the magnetic field was the main reason for the enhanced adsorption performance. In addition, increased surface roughness, pore size and oxygen vacancies, enhanced mass transfer by Lorentz force under a magnetic field, all beneficially influenced the adsorption process. The mechanism of phosphate adsorption by BZCCO-13 could be attributed to electrostatic attraction and CO32-dominated ligand exchange. This study not only provided an effective strategy for designing highly effective phosphate adsorbents, but also provides a new light on the application of rare earth metal-based adsorbent in magnetic field.

Asunto(s)

RESUMEN

Living organisms inspire the design of microrobots, but their functionality is unmatched. Next-generation microrobots aim to leverage the sensing and communication abilities of organisms through magnetic hybridization, attaching magnetic particles to them for external control. However, the protocols used for magnetic hybridization are morphology specific and are not generalizable. We propose an alternative approach that leverages the principles of negative magnetostatics and magnetophoresis to control nonmagnetic organisms with external magnetic fields. To do this, we disperse model organisms in dispersions of Fe3O4 nanoparticles and expose them to either uniform or gradient magnetic fields. In uniform magnetic fields, living organisms align with the field due to external torque, while gradient magnetic fields generate a negative magnetophoretic force, pushing objects away from external magnets. The magnetic fields enable controlling the position and orientation of Caenorhabditis elegans larvae and flagellated bacteria through directional interactions and magnitude. This control is diminished in live spermatozoa and adult C. elegans due to stronger internal biological activity, i.e., force/torque. Our study presents a method for spatiotemporal organization of living organisms without requiring magnetic hybridization, opening the way for the development of controllable living microbiorobots.

Asunto(s)

RESUMEN

The spatiotemporal accuracy of microscale magnetophoresis has improved significantly over the course of several decades of development. However, most of the studies so far were using magnetic microbead composed of nanosphere particle for magnetophoretic actuation purpose. Here, we developed an in-house method for magnetic sample analysis called quadrupole magnetic steering control (QMSC). QMSC was used to study the magnetophoretic behavior of polystyrene microbeads decorated with iron oxide nanospheres-coated polystyrene microbeads (IONSs-PS) and iron oxide nanorods-coated polystyrene microbeads (IONRs-PS) under the influence of a quadrupole low field gradient. During a 4-s QMSC experiment, the IONSs-PS and IONRs-PS were navigated to perform 180° flip and 90° turn formations, and their kinematic results (2 s before and 2 s after the flip/turn) were measured and compared. The results showed that the IONRs-PS suffered from significant kinematic disproportion, translating a highly uneven amount of kinetic energy from the same magnitude of magnetic control. Combining the kinematic analysis, transmission electron microscopy micrographs, and vibrating sample magnetometry measurements, it was found that the IONRs-PS experienced higher fluid drag force and had lower consistency than the IONSs-PS due to its extensive open fractal nanorod structure on the bead surface and uneven magnetization, which was attributed to its ferrimagnetic nature.

Asunto(s)

RESUMEN

Precisely and accurately determining the magnetic force and its spatial distribution in microfluidic devices is challenging. Typically, magnetic microfluidic devices are designed in a way to both maximize the force within the separation region and to minimize the necessity for knowing such details-such as designing magnetic geometries that create regions of nearly constant magnetic force or that dictate the behavior of the magnetic force to be highly predictable in a specified region. In this work, we present a method to determine the spatial distribution of the magnetic force field in a magnetic microfluidic device by particle tracking magnetophoresis. Polystyrene microparticles were suspended in a paramagnetic fluid, gadolinium, and this suspension was exposed to various magnetic field geometries. Polystyrene particle motion was tracked using a microscope and images processed using Fiji (ImageJ). From a sample with a large spatial distribution of particle tracks, the magnetic force field distribution was calculated. The force field distribution was fitted to nonlinear spatial distribution models. These experimental models are compared to and supported by 3D simulations of the magnetic force field in COMSOL.

RESUMEN

Superparamagnetic iron oxide nanoparticles (SPIONs) have gathered tremendous scientific interest, especially in the biomedical field, for multiple applications, including bioseparation, drug delivery, etc. Nevertheless, their manipulation and separation with magnetic fields are challenging due to their small size. We recently reported the coupling of cooperative magnetophoresis and sedimentation using quadrupole magnets as a promising strategy to successfully promote SPION recovery from media. However, previous studies involved SPIONs dispersed in organic solvents (non-biocompatible) at high concentrations, which is detrimental to the process economy. In this work, we investigate, for the first time, the magnetic separation of 20 nm and 30 nm SPIONs dispersed in an aqueous medium at relatively low concentrations (as low as 0.5 g·L-1) using our custom, permanent magnet-based quadrupole magnetic sorter (QMS). By monitoring the SPION concentrations along the vessel within the QMS, we estimated the influence of several variables in the separation and analyzed the kinetics of the process. The results obtained can be used to shed light on the dynamics and interplay of variables that govern the fast separation of SPIONs using inexpensive permanent magnets.

RESUMEN

Cancer diagnosis has recently been at the forefront of recent medical research, with ongoing efforts to develop devices and technologies for detecting cancer in patients. One promising approach for cancer diagnosis is the detection of Circulating Tumor Cells (CTCs) in blood samples. Separating these rare cells from the diverse background of blood cells and analyzing them can provide valuable insights into the disease's stage and lethality. Here we present the design and fabrication of a centrifugal microfluidic platform on a polymeric disk that utilizes centrifugal forces for cell isolation. The separation units exploit both active and passive methods. In other words, in addition to introducing novel geometry for channels, an external magnetic field is also employed to separate the target cells from the background cells. In order for the external field to function, the CTCs must first be labeled with antibody-conjugated nanoparticles; the separation process should be then performed. Before the experimental tests, a numerical study was done to determine the optimum parameters; the angular velocity and magnetization investigations showed that 2000 rpm and 868,000 (kA/m) are the optimum conditions for the designed device to reach the efficiency of 100% for both White Blood Cells (WBCs) and CTCs. These results indicate that the passive region of the channels primarily contributes to the focusing of the target cells, and showed that the focusing effect is more pronounced in the expansion-contraction geometry compared to the zigzag geometry. Additionally, the results proved that curved channel geometries performed better than straight ones in terms of separation efficiency. However, if the separation relies solely on channel geometry, the majority of cells would be directed towards the non-target chamber, leading to suboptimal results. This is due to the direction of the forces acting on the cells. However, including an external magnetic field improves the direction of the net force and enhances the separation efficiency. Finally, the numerical and experimental results of the study were compared, and the curved expansion-contraction channel is introduced as the best geometry having 100% and ∼92% CTC separation efficiency, respectively.

Asunto(s)

RESUMEN

Iron in blood cells has several physiological functions like transporting oxygen to cells and maintaining iron homeostasis. Iron is primarily contained in red blood cells (RBCs), but monocytes also store iron as these cells are responsible for the recycling of senescent RBCs. Iron also serves an important role related to the function of different leukocytes. In inflammation, iron homeostasis is dependent on cytokines derived from T cells and macrophages. Fluctuations of iron content in the body lead to different diseases. Iron deficiency, which is also known as anemia, hampers different physiological processes in the human body. On the other hand, genetic or acquired hemochromatosis ultimately results in iron overload and leads to the failure of different vital organs. Different diagnoses and treatments are developed for these kinds of disorders, but the majority are costly and suffer from side effects. To address this issue, magnetophoresis could be an attractive technology for the diagnosis (and in some cases treatment) of these pathologies due to the paramagnetic character of the cells containing iron. In this review, we discuss the main functions of iron in blood cells and iron-related diseases in humans and highlight the potential of magnetophoresis for diagnosing and treating some of these disorders.

Asunto(s)

RESUMEN

Centrifugal microfluidics enables fully automated molecular diagnostics at the point-of-need. However, the integration of solid-phase nucleic acid extraction remains a challenge. Under this scope, we developed the magnetophoresis under continuous rotation for magnetic bead-based nucleic acid extraction. Four stationary permanent magnets are arranged above a cartridge, creating a magnetic field that enables the beads to be transported between the chambers of the extraction module under continuous rotation. The centrifugal force is maintained to avoid uncontrolled spreading of liquids. We concluded that below a frequency of 5 Hz, magnetic beads move radially inwards. In support of magnetophoresis, bead inertia and passive geometrical design features allow to control the azimuthal bead movement between chambers. We then demonstrated ferrimagnetic bead transfer in liquids with broad range of surface tension and density values. Furthermore, we extracted nucleic acids from lysed Anopheles gambiae mosquitoes reaching comparable results of eluate purity (LabDisk: A260/A280 = 1.6 ± 0.04; Reference: 1.8 ± 0.17), and RT-PCR of extracted RNA (LabDisk: Ct = 17.9 ± 1.6; Reference: Ct = 19.3 ± 1.7). Conclusively, magnetophoresis at continuous rotation enables easy cartridge integration and nucleic acid extraction at the point-of-need with high yield and purity.

RESUMEN

Both passive and active microfluidic chips are used in many biomedical and chemical applications to support fluid mixing, particle manipulations, and signal detection. Passive microfluidic devices are geometry-dependent, and their uses are rather limited. Active microfluidic devices include sensors or detectors that transduce chemical, biological, and physical changes into electrical or optical signals. Also, they are transduction devices that detect biological and chemical changes in biomedical applications, and they are highly versatile microfluidic tools for disease diagnosis and organ modeling. This review provides a comprehensive overview of the significant advances that have been made in the development of microfluidics devices. We will discuss the function of microfluidic devices as micromixers or as sorters of cells and substances (e.g., microfiltration, flow or displacement, and trapping). Microfluidic devices are fabricated using a range of techniques, including molding, etching, three-dimensional printing, and nanofabrication. Their broad utility lies in the detection of diagnostic biomarkers and organ-on-chip approaches that permit disease modeling in cancer, as well as uses in neurological, cardiovascular, hepatic, and pulmonary diseases. Biosensor applications allow for point-of-care testing, using assays based on enzymes, nanozymes, antibodies, or nucleic acids (DNA or RNA). An anticipated development in the field includes the optimization of techniques for the fabrication of microfluidic devices using biocompatible materials. These developments will increase biomedical versatility, reduce diagnostic costs, and accelerate diagnosis time of microfluidics technology.

Asunto(s)

RESUMEN

Nanofabrication has been utilized to manufacture one-, two-, and three-dimensional functional nanostructures for applications such as electronics, sensors, and photonic devices. Although conventional silicon-based nanofabrication (top-down approach) has developed into a technique with extremely high precision and integration density, nanofabrication based on directed assembly (bottom-up approach) is attracting more interest recently owing to its low cost and the advantages of additive manufacturing. Directed assembly is a process that utilizes external fields to directly interact with nanoelements (nanoparticles, 2D nanomaterials, nanotubes, nanowires, etc.) and drive the nanoelements to site-selectively assemble in patterned areas on substrates to form functional structures. Directed assembly processes can be divided into four different categories depending on the external fields: electric field-directed assembly, fluidic flow-directed assembly, magnetic field-directed assembly, and optical field-directed assembly. In this review, we summarize recent progress utilizing these four processes and address how these directed assembly processes harness the external fields, the underlying mechanism of how the external fields interact with the nanoelements, and the advantages and drawbacks of utilizing each method. Finally, we discuss applications made using directed assembly and provide a perspective on the future developments and challenges.

RESUMEN

Identification of circulating tumor cells (CTCs) from a majority of various cell pools has been an appealing topic for diagnostic purposes. This study numerically demonstrates the isolation of CTCs from blood cells by the combination of dielectrophoresis and magnetophoresis in a microfluidic chip. Taking advantage of the label-free property, the separation of red blood cells, platelets, T cells, HT-29, and MDA-231 was conducted in the microchannel. By using the ferromagnet structure with double segments and a relatively shorter distance in between, a strong gradient of the magnetic field, i.e., sufficiently large MAP forces acting on the cells, can be generated, leading to a high separation resolution. In order to generate strong DEP forces, the non-uniform electric field gradient is induced by applying the electric voltage through the microchannel across a pair of asymmetric orifices, i.e., a small orifice and a large orifice on the opposite wall of the channel sides. The distribution of the gradient of the magnetic field near the edge of ferromagnet segments, the gradient of the non-uniform electric field in the vicinity of the asymmetric orifices, and the flow field were investigated. In this numerical simulation, the effects of the ferromagnet structure on the magnetic field, the flow rate, as well as the strength of the electric field on their combined magnetophoretic and dielectrophoretic behaviors and trajectories are systemically studied. The simulation results demonstrate the potential of both property- and size-based cell isolation in the microfluidic device by implementing magnetophoresis and dielectrophoresis.

Asunto(s)

RESUMEN

In this work, we present dielectrophoresis (DEP) and in situ electrorotation (ROT) characterization of reversibly stimuli-responsive "dynamic" microcapsules that change the physicochemical properties of their shells under varying pH conditions and can encapsulate and release (macro)molecular cargo on demand. Specifically, these capsules are engineered to open (close) their shell under high (low) pH conditions and thus to release (retain) their encapsulated load or to capture and trap (macro)molecular samples from their environment. We show that the steady-state DEP and ROT spectra of these capsules can be modeled using a single-shell model and that the conductivity of their shells is influenced most by the pH. Furthermore, we measured the transient response of the angular velocity of the capsules under rotating electric field conditions, which allows us to directly determine the characteristic time scales of the underlying physical processes. In addition, we demonstrate the magnetic manipulation of microcapsules with embedded magnetic nanoparticles for lab-on-chip tasks such as encapsulation and release at designated locations and the in situ determination of their physicochemical state using on-chip ROT. The insight gained will enable the advanced design and operation of these dynamic drug delivery and smart lab-on-chip transport systems.

RESUMEN

The separation and purification of a sample of interest is essential for subsequent detection and analysis procedures, but there is a lack of effective separation methods with which to purify nano-sized particles from the sample media. In this paper, a microfluidic system based on negative magnetophoresis is presented for the high-resolution separation of nanoparticles. The system includes on-chip magnetic pole arrays and permalloys that symmetrically distribute on both sides of the separation channel and four permanent magnets that provide strong magnetic fields. The microfluidic system can separate 200 nm particles with a high purity from the mixture (1000 nm and 200 nm particles) due to a magnetic field gradient as high as 10,000 T/m being generated inside the separation channel, which can provide a negative magnetophoretic force of up to 10 pN to the 1000 nm particle. The overall recovery rate of the particles reaches 99%, the recovery rate of 200 nm particles is 84.2%, and the purity reaches 98.2%. Compared with the existing negative magnetophoretic separation methods, our system not only exhibits high resolution on particle sizes (800 nm), but also improves the sample processing throughput, which reaches 2.5 µL/min. The microfluidic system is expected to provide a new solution for the high-purity separation of nanoparticles, as well as nanobiological samples.

RESUMEN

Introduction: Circulating tumor cells (CTCs) are the transformed tumor cells that can penetrate into the bloodstream and are available at concentrations as low as 1-100 cells per milliliter. To trap CTCs in the blood, one valid and mature technique that has been developed is the magnetophoresis-based separation in a microfluidic channel. Recently, nanostructured platforms have also been developed to trap specific targeted and marker cells in the blood. We aimed to integrate both in one platform to improve trapping. Methods: Here, we developed a numerical scheme and an integrated device that considered the interaction between drag and magnetic forces on paramagnetic labeled cells in the fluid as well as interaction of these two forces with the adhesive force and the surface friction of the nanowires substrate. We aimed on developing a more advanced technique that integrated the magnetophoretic property of some Fe3O4 paramagnetic nanoparticles (PMNPs) with a silicon nanowires (SiNWs) substrate in a microfluidic device to trap MDA-MB231 cell lines as CTCs in the blood. Results: Simulation indicated assuming that the nanoparticles adhere perfectly to the white blood cells (WBCs) and the CTCs, the magnetic moment of the CTCs was almost one order of magnitude larger than that of the WBCs, so its attraction by the magnetic field was much higher. In general with significant statistics, the integrated device can trap almost all of the CTCs on the SiNWs substrate. In the experimental section, we took advantage of the integrated trapping techniques, including micropost barriers, magnetophoresis, and nanowires-based substrate to more effectively isolate the CTCs. Conclusion: The simulation indicated that the proposed device could almost trap all of the CTCs onto the SiNWs substrate, whereas trapping in flat substrates with magnetophoretic force was very low. As a result of the magnetic field gradient, magnetophoretic force was applied to the cells through the nanoparticles, which would efficiently drive down the nanoparticle-tagged cells. For the experimental validation, anti-EpCAM antibodies for specific binding to tumor cells were used. Using this specific targeting method and by statistically counting, it was shown that the proposed technique has excellent performance and results in the trapping efficiency of above 90%.

RESUMEN

Cell clustering techniques are important to produce artificial cell clusters for in vitro models of intercellular mechanisms at the single-cell level. The analyses considering physical variables such as the shape and size of cells have been very limited. In addition, the precise manipulation of cells and control of the physical variables are still challenging. In this paper, a magnetophoretic device consisting of a trampoline micromagnet and active elements that enable the control of individual selective jumping motion and positioning of a micro-object is proposed. Based on a numerical simulation under various conditions, automatic separation or selective clustering of micro-objects according to their sizes is performed by parallel control and programmable manipulation. This method provides efficient control of the physical variables of cells and grouping of cells with the desired size and number, which can be a milestone for a better understanding of the intercellular dynamics between clustered cells at the single-cell level for future cell-on-chip applications.

Asunto(s)

RESUMEN

Microfluidic separation technologies are the focus of various biological applications, such as disease diagnostics, single-cell analysis, and therapeutics. Different methods and devices were proposed in the micro-separation field, focusing on minimizing the chemical deformation and physical damage to the particles throughout the separation process; however, it is still a challenge. This paper proposes a hydrodynamic focusing-based microfluidic separation device equipped with a dual-neodymium magnet for positive magnetophoretic microparticles and cell separation. Hydrodynamic focusing is used to help to sort the particles and minimize the damage to the microparticles through the proposed different inlet flow rates between the two focusing channels. The dual magnets help to separate the particles in two stages. The system's novelty is integrating the hydrodynamic focusing with the dual magnetics system, where the hydrodynamic focusing is with variable inlet flow rates. The performance of the proposed microfluidic particle separator is numerically assessed under various operating parameters, including the concentration of the particle in the injected solution and flow rate ratios of high to the low focusing flows on the efficiency of the separation. Following the proposed separation method, it was possible to separate the 16 and 10 [Formula: see text] microparticles with the first-round efficiency of 21% with a quality of 92%, respectively. The developed particle separation system can significantly broaden its applications in a variety of biomedical research studies.

Asunto(s)

RESUMEN

The equilibrium concentration distribution of magnetic nanoparticles in a nonuniform magnetic field is studied theoretically. A linear current-carrying wire is used as a source of a nonuniform field. An exact solution for the concentration profile of a dilute monodisperse suspension is obtained within the framework of the continuous mass transfer theory. The applicability of this solution in a broad range of amperage values is tested using Langevin dynamics simulations. Obtained solution is also generalized for polydisperse suspensions. It is demonstrated that the particle size distribution in a polydisperse system strongly depends on the distance from the wire and in general does not coincide with the original distribution of a uniform suspension.

RESUMEN

Microfluidic particle focusing has been a vital prerequisite step in sample preparation for downstream particle separation, counting, detection, or analysis, and has attracted broad applications in biomedical and chemical areas. Besides all the active and passive focusing methods in Newtonian fluids, particle focusing in viscoelastic fluids has been attracting increasing interest because of its advantages induced by intrinsic fluid property. However, to achieve a well-defined focusing position, there is a need to extend channel lengths when focusing micrometer-sized or sub-microsized particles, which would result in the size increase of the microfluidic devices. This work investigated the sheathless viscoelastic focusing of particles and cells in a zigzag microfluidic channel. Benefit from the zigzag structure of the channel, the channel length and the footprint of the device can be reduced without sacrificing the focusing performance. In this work, the viscoelastic focusing, including the focusing of 10 µm polystyrene particles, 5 µm polystyrene particles, 5 µm magnetic particles, white blood cells (WBCs), red blood cells (RBCs), and cancer cells, were all demonstrated. Moreover, magnetophoretic separation of magnetic and nonmagnetic particles after viscoelastic pre-focusing was shown. This focusing technique has the potential to be used in a range of biomedical applications.

Asunto(s)

RESUMEN

Multipotent adult stem cells (MASCs) derived from Pluripotent stem cells (PSCs) have found widespread use in various applications, including regenerative therapy and drug screening. For these applications, highly pluripotent PSCs need to be selectively separated from those that show low pluripotency for reusage of PSCs, and MASCs need to be collected for further application. Herein, we developed immunomagnetic microfluidic integrated system (IM-MIS) for separation of stem cells depending on potency level. In this system, each stem cell was multiple-separated in microfluidics chip by magnetophoretic mobility of magnetic-activated cells based on the combination of two sizes of magnetic nanoparticles and two different antibodies. Magnetic particles had a difference in the degree of magnetization, and antibodies recognized potency-related surface markers. IM-MIS showed superior cell separation performance than FACS with high throughput (49.5%) in a short time (<15 min) isolate 1 × 107 cells, and higher purity (92.1%) than MACS. IM-MIS had a cell viability of 89.1%, suggesting that IM-MIS had no effect on cell viability during isolation. Furthermore, IM-MIS did not affect the key characteristics of stem cells including its differentiation potency, phenotype, genotype, and karyotype. IM-MIS may offer a new platform for the development of multi-separation systems for diverse stem cell applications.

Asunto(s)