A magnetic bead continuous separation device

Abstract

The application relates to the technical field of nanometer magnetic bead preparation, and discloses a magnetic bead continuous separation device. The magnetic bead continuous separation device comprises a magnetic bead separator, a magnetic field generating device and a driving device, the driving device is used for driving the magnetic field generating device to be close to or far away from the side wall of the magnetic bead separator, the magnetic bead separator is hollow, a first liquid inlet and a second liquid inlet are arranged at one end of the magnetic bead separator, and a first liquid outlet and a second liquid outlet are arranged at the other end of the magnetic bead separator. The application can integrate multiple separation processes in the same structure, simplifies the system configuration, and effectively meets the automation and large-batch continuous processing requirements of the magnetic bead purification process.

Description

Technical Field

[0001] This application relates to the technical field of nanomagnetic bead preparation, and in particular to a continuous magnetic bead separation device. Background Technology

[0002] Magnetic beads are micron- or nano-sized particles with excellent magnetic response characteristics. Their core is typically composed of a magnetic inorganic material (such as magnetite), coated with a polymer or silica material, and specific functional groups, such as carboxyl or amino groups, are introduced on the surface, enabling them to specifically bind to target molecules. Due to their magnetic controllability and high flexibility in functionalization, magnetic beads are widely used in various biological and industrial fields, including nucleic acid extraction, protein purification, cell sorting, immunoassay, and magnetically controlled drug delivery. However, after synthesis, magnetic beads often suffer from problems such as uneven magnetic properties, residual impurities, and inconsistent particle size distribution. Without purification and screening, these issues directly affect their magnetic responsiveness and binding specificity, thus reducing their separation efficiency and reusability in subsequent applications. Therefore, after magnetic bead preparation, separation and purification are usually necessary to remove weakly magnetic beads and waste liquid generated during the preparation process.

[0003] Currently, the separation and purification of magnetic beads mainly rely on manual operation or simple magnetic rack devices. Common methods include aliquoting the magnetic bead suspension into centrifuge tubes, manually manipulating the beads onto a fixed magnetic rack for magnetic adsorption and disposal, followed by multiple rounds of washing for coarse screening. In some scenarios, magnetic rod devices are used, with manual or robotic arm assistance for capture and transfer. However, these methods suffer from fragmented procedures, reliance on manual intervention, high bead loss rates, and a lack of standardization. Especially in large-scale sample processing scenarios, the limited capacity of the magnetic rack or magnetic rod capture unit significantly restricts processing efficiency. Summary of the Invention

[0004] In order to integrate multiple separation processes into the same structure and simultaneously meet the needs of automated and large-scale continuous processing of magnetic bead purification, this application provides a continuous magnetic bead separation device.

[0005] This application provides a continuous magnetic bead separation device, which adopts the following technical solution:

[0006] A continuous magnetic bead separation device includes a magnetic bead separator, a magnetic field generating device, and a driving device. The driving device is used to drive the magnetic field generating device to approach or move away from the side wall of the magnetic bead separator. The magnetic bead separator is hollow and has a first liquid inlet and a second liquid inlet at one end, and a first liquid outlet and a second liquid outlet at the other end.

[0007] Optionally, the magnetic bead separator is used for vertical placement, with the first liquid inlet and the second liquid inlet located at the top of the magnetic bead separator, and the first liquid outlet and the second liquid outlet located at the bottom of the magnetic bead separator.

[0008] Optionally, the second liquid inlet of the magnetic bead separator is located on the side of the magnetic bead separator closer to the magnetic field generating device, relative to the first liquid inlet; the second liquid outlet of the magnetic bead separator is located on the side of the end of the magnetic bead separator closer to the magnetic field generating device, relative to the first liquid outlet.

[0009] Optionally, the second liquid inlet of the magnetic bead separator is located on the side of the end of the magnetic bead separator closer to the magnetic field generating device, relative to the first liquid inlet; the second liquid outlet of the magnetic bead separator is located on the side of the magnetic bead separator closer to the magnetic field generating device, relative to the first liquid outlet.

[0010] Optionally, the second liquid inlet is tangent to the tube wall of the magnetic bead separator.

[0011] Optionally, the second drain outlet is tangent to the tube wall of the magnetic bead separator.

[0012] Optionally, the magnetic field generating device generates a magnetic field in the magnetic bead separator that gradually weakens from the tube wall to the middle of the tube.

[0013] Optionally, the magnetic bead separator has a magnetic bead separation zone and a magnetic bead capture zone, both of which are distributed along the axial direction of the magnetic bead separator. The two ends of the magnetic bead separation zone are respectively connected to the first liquid inlet and the first liquid outlet, and the two ends of the magnetic bead capture zone are respectively connected to the second liquid inlet and the second liquid outlet. A magnetic field gradient is formed between the magnetic bead separation zone and the magnetic bead capture zone.

[0014] Optionally, the driving device includes a motor module, a threaded transmission rod, and a support rod. The two ends of the support rod are respectively connected to the threaded transmission rod and the magnetic field generating device. The motor module is used to drive the threaded transmission rod to push the support rod and the magnetic field generating device toward or away from the magnetic bead separator.

[0015] Optionally, the magnetic field generating device includes an anti-detachment layer, a magnetizing layer, and a shielding layer arranged sequentially from the inside to the outside. A magnet is embedded in the magnetizing layer, and the anti-detachment layer and the shielding layer cooperate with the magnetizing layer to form a cavity for accommodating and limiting the magnet.

[0016] Optionally, the inner wall of the anti-detachment layer is fitted to the outer wall of the magnetic bead separator and its shape is adapted to the outer wall of the magnetic bead separator.

[0017] Optionally, the magnetized layer includes a support plate and a plurality of magnetic tiles. The support plate is provided with a plurality of limiting grooves for restricting the movement of the magnetic tiles, and the magnetic tiles are installed in the limiting grooves.

[0018] Optionally, the magnetic tile is a block with a cross-section of a regular hexagon, rhombus, or parallelogram.

[0019] Optionally, the magnetic tile can be embedded in the support plate in a manner including lateral embedding, longitudinal embedding, or Halbach array embedding.

[0020] Optionally, the magnetic field generating device and the driving device are two or more sets, and are arranged around the magnetic bead separator.

[0021] Optionally, different groups of magnetic field generating devices may be equipped with the same or different magnetic tile embedding methods; different groups of magnetic field generating devices may be equipped with magnetic tiles that can generate the same or different magnetic field strengths.

[0022] Optionally, the diameter of the magnetic bead separator is 10–300 mm.

[0023] Optionally, the magnetic bead separator is a transparent tube.

[0024] Optionally, when the liquid to be separated passes through the magnetic bead separator, the magnetic beads are exposed to a magnetic field generated by the magnetic field generator, which can capture the target magnetic beads on the tube wall of the magnetic bead separator.

[0025] In summary, this application includes at least one of the following beneficial technical effects:

[0026] 1. The continuous magnetic bead separation device has a high processing capacity and can be adapted to hollow separation tube structures with diameters of 10–300 mm. One or more magnetic field generating devices are installed on the outer periphery of the tube. By adopting multiple sets of modular, circumferentially arranged magnetic field generating devices, and combining them with a drive device to control the magnetic field to move closer to or away from the sidewall of the separation tube, a stable magnetic field strength that decreases from the outside to the inside can be formed inside the separation tube, effectively capturing the target magnetic beads to the tube wall.

[0027] 2. The magnetic field generating device employs various magnetic tile arrangement methods, including transverse embedding, longitudinal embedding, and Halbach array arrangement. The cross-section of the magnetic tiles can be regular hexagonal, rhomboid, or parallelogram, etc. By adjusting the number of magnetic tiles, their arrangement, and the direction of the magnetic poles, the magnetic field strength and distribution can be flexibly controlled, facilitating the separation of magnetic beads of different magnetic grades in different batches of processing.

[0028] 3. The continuous magnetic bead separation device allows the raw solution and washing solution to enter or exit from different paths, and complete the capture, separation and washing steps of the target magnetic beads in different processing stages, thereby realizing functional reuse. Attached Figure Description

[0029] Figure 1a This is a front view of a continuous magnetic bead separation device according to one embodiment of this application.

[0030] Figure 1b This is an overall schematic diagram of a continuous magnetic bead separation device in one embodiment of this application.

[0031] Figure 2 This is used to illustrate the fully enclosed structure of a magnetic field generating device.

[0032] Figure 3 This is a schematic diagram of the overall magnetic field generating device in one embodiment of this application.

[0033] Figure 4 This is an overall schematic diagram of a magnetic field generating device in one embodiment of this application. Figure 2 .

[0034] Figures 5a-5b This is a schematic diagram of the structure of a modular unit of the magnetic layer in one embodiment of this application.

[0035] Figure 6 This is a schematic diagram of the structure of a fully enclosed magnetically embedded layer in one embodiment of this application.

[0036] Figures 7a-7d This is a schematic diagram used to illustrate different magnetizing structures of magnetic tiles.

[0037] Figures 8a-8b This is used to illustrate the effect of the magnetization accuracy of the rhomboid magnetic tile on the magnetic field trapping area.

[0038] Figure 9 This is a schematic diagram illustrating that the magnetic tiles use a Halbach array as the embedded magnetic structure.

[0039] Figure 10 This is a front view of a continuous magnetic bead separation device in one embodiment. Figure 2 .

[0040] Figure label:

[0041] 1. Magnetic bead separator; 11. First liquid inlet; 12. Second liquid inlet; 13. First liquid outlet; 14. Second liquid outlet;

[0042] 2. Magnetic field generating device; 21. Anti-detachment layer; 22. Magnetized layer; 221. Support plate; 222. Magnet tile; 223. Limiting groove; 23. Shielding layer;

[0043] 3. Drive unit; 31. Motor module; 32. Support rod; 33. Transmission rod;

[0044] 4. Bracket; 5. Support column; 6. Sliding structure. Detailed Implementation

[0045] The embodiments of this application are described in detail below, and examples of the embodiments are shown in the accompanying drawings.

[0046] In the description of this specification, the references to "certain embodiments," "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," or "some examples" refer to specific features, structures, materials, or characteristics described in connection with the described embodiment or example, which are included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0047] Magnetic beads are magnetic microspheres whose core is typically composed of a magnetic inorganic material (such as magnetite), while the outer shell is encapsulated in a polymer or silica material. By introducing functional groups such as carboxyl, amino, and streptavidin onto their surface, magnetic beads can acquire the ability to specifically bind biomolecules, making them widely used in biomedical and industrial fields such as nucleic acid extraction, protein purification, cell sorting, immunoassay, and magnetically controlled drug delivery. Magnetic beads are generally between nanometer and micrometer in size and possess excellent magnetic responsiveness, enabling them to rapidly aggregate under the influence of an external magnetic field, achieving efficient capture and transfer of target analytes.

[0048] However, after the magnetic beads are synthesized, the system often exhibits magnetic inhomogeneity, meaning that the magnetic response intensity varies between different particles. Simultaneously, some magnetic beads may have incompletely removed reaction byproducts, free monomers, or inorganic impurities adhering to their surfaces. These factors all affect the separation efficiency and binding specificity of the magnetic beads in practical applications. Therefore, rigorous separation and screening operations are necessary to remove particles with weak magnetic properties, high impurity content, or sizes outside the specified range.

[0049] In this process, an external magnetic field can be used to effectively separate magnetic beads of varying magnetic strengths. Taking a common laboratory procedure as an example, researchers typically dispense the magnetic bead suspension into centrifuge tubes, dilute it manually, and place it on a fixed magnetic rack. The magnetic field then traps some sufficiently magnetically responsive particles against the tube wall, while the remaining non-magnetic or low-magnetic impurities are discarded with the supernatant. The retained magnetic beads are then resuspended in liquid, and this process of "capture-discard-liquid addition-mixing" is repeated to achieve coarse enrichment and purification. If a magnetic rod device is used, manual or robotic arm intervention is required to immerse the magnetic rod in the magnetic bead suspension, and after capture, the beads are transferred to a washing or purification solution for further washing.

[0050] However, the aforementioned traditional magnetic bead purification process has significant limitations. Firstly, the process is highly fragmented, with each step often requiring manual intervention, leading to increased bead loss, decreased processing efficiency, and a heavy workload for operators. Furthermore, the batch throughput is relatively small. In addition, most existing magnetic bead purification systems employ an open design, separating the magnetic field capture area from the liquid processing module. In such devices, the magnetic bead separation process cannot be completed within a single enclosed space, encompassing sample introduction, enrichment, and liquid drainage.

[0051] Therefore, this application discloses a continuous magnetic bead separation device, which has a compact structure, high functional integration, and can adapt to different processing volume requirements and support continuous process flow. (Refer to...) Figure 1a and Figure 1b The continuous magnetic bead separation device includes a magnetic bead separator 1, a magnetic field generator 2, and a drive device 3. The three work together to form a closed separation channel in a controllable magnetic field environment, which can realize the automatic capture, separation and washing of magnetic beads.

[0052] Specifically, the magnetic bead separator 1 has a hollow structure for passing the raw liquid to be treated, carrying the target magnetic beads. A magnetic field generating device 2 is disposed on the outer periphery of the magnetic bead separator 1, and is used to form a stable, strong magnetic field inside the magnetic bead separator 1 to capture the target magnetic beads to the tube wall. A driving device 3 is linked to the magnetic field generating device 2 and is used to adjust the distance between the magnetic field generating device 2 and the side wall of the magnetic bead separator 1, thereby changing the magnetic field strength inside the magnetic bead separator 1. In different embodiments, the magnetic bead separator 1 can be fixed by different types of supports 4. The form of the supports 4 depends on the arrangement of the magnetic bead separator 1. When the magnetic bead separator 1 is horizontal or vertical, the supports 4 should be adjusted accordingly; no specific limitation is made in this application.

[0053] Referring to Figure 1, the magnetic bead separator 1 has a first inlet 11 and a second inlet 12 at one end, and a first outlet 13 and a second outlet 14 at the other end. The first inlet 11 and the second inlet 12 are used to introduce the raw liquid containing the target magnetic beads and the washing liquid, achieving a step-by-step alternating liquid input. The first outlet 13 is used to discharge impurities and suspended waste liquid contained in the raw liquid, while the second outlet 14 is used to discharge the magnetic bead liquid containing the target magnetic beads. With the above interface configuration, the entire process of raw liquid treatment, magnetic bead capture, and impurity rinsing can be completed within a single cavity structure. The washing liquid can be selected differently depending on the raw material of the magnetic beads, such as deionized water, ethanol, salt solution, or polymer.

[0054] In various embodiments of this application, the magnetic bead separator 1 can be configured with a variety of structures to meet different application requirements and processing conditions. These include, but are not limited to, circular tubes, square tubes, rectangular tubes, elliptical tubes, hexagonal tubes, U-shaped groove tubes, D-shaped groove tubes, trapezoidal groove tubes, horseshoe-shaped tubes, etc. As long as the selected structure ensures uniform fluid flow while maintaining sufficient flatness of the tube wall and eliminating significant dead zones at the open ends, it is suitable for the magnetic bead separation operation described in this application. This diversity of forms can be flexibly configured according to specific equipment space and throughput requirements.

[0055] The inner wall of the magnetic bead separator 1 should have good smoothness to reduce the adhesion of magnetic beads after they leave the magnetic bead generator 2. In addition, its outer wall is preferably designed to fit tightly against the inner surface of the magnetic field generator 2 so that the magnetic field can effectively penetrate the tube wall and act on the inside of the tube cavity.

[0056] Regarding material selection, to ensure that the magnetic field can penetrate the tube wall without being shielded, the magnetic bead separator 1 is preferably made of a non-magnetic material, specifically, but not limited to, transparent glass, borosilicate glass, quartz glass, plexiglass (such as polymethyl methacrylate PMMA), polycarbonate (PC), polyethylene terephthalate (PET), polystyrene (PS), polytetrafluoroethylene (PTFE), polyetheretherketone (PEEK), polyimide (PI), polypropylene (PP), or polyethylene (PE). These materials not only possess good non-magnetic and magnetic permeability but also easily achieve a smooth inner wall surface after processing and molding.

[0057] Preferably, the magnetic bead separator 1 is made of a transparent tube, and the operator can observe the state of the target magnetic beads, the position of the liquid interface, and the magnetic bead separation process in real time through the naked eye or a matching imaging device, thereby realizing the monitoring of the separation process.

[0058] In several embodiments of this application, the specific arrangement of the magnetic bead separator 1 can be adjusted according to the angle between its axis and the horizontal plane. The spatial configuration of the magnetic bead separator 1 can include, but is not limited to, vertical arrangement, horizontal arrangement, and oblique arrangement, wherein the vertical arrangement can also be called a vertical arrangement, and the horizontal arrangement can also be called a horizontal arrangement.

[0059] As an example, in one embodiment, the magnetic bead separator 1 is used for vertical placement, with the first liquid inlet 11 and the second liquid inlet 12 of the magnetic bead separator 1 located at the top of the magnetic bead separator 1, and the first liquid outlet 13 and the second liquid outlet 14 of the magnetic bead separator 1 located at the bottom of the magnetic bead separator 1.

[0060] Furthermore, the second liquid inlet 12 is disposed on the side of the magnetic bead separator 1 near the magnetic field generating device 2 relative to the first liquid inlet 11, and the second liquid outlet 14 is disposed on the side of the end of the magnetic bead separator 1 near the magnetic field generating device 2 relative to the first liquid outlet 13.

[0061] In another exemplary embodiment, the magnetic bead separator 1 is placed horizontally, while the magnetic field generating device 2 remains attached to the outer adaptation area of ​​the tube body. In this arrangement, the first inlet 11 and the second inlet 12 are both located at one end of the magnetic bead separator 1, while the first outlet 13 and the second outlet 14 are located at the other end. By controlling the horizontal flow of the liquid to be separated within the tube cavity, the capture of the target magnetic beads can be continuously achieved.

[0062] Furthermore, the second liquid inlet 12 is disposed on the side of the magnetic bead separator 1 near the magnetic field generating device 2 relative to the first liquid inlet 11, and the second liquid outlet 14 is disposed on the side of the end of the magnetic bead separator 1 near the magnetic field generating device 2 relative to the first liquid outlet 13.

[0063] In a preferred embodiment, the edge of the second inlet 12 is tangential to the wall of the magnetic bead separator 1, allowing the injected liquid to flow along the axial direction of the magnetic bead separator 1. The second outlet 14 is similarly configured to be tangential to the wall of the magnetic bead separator 1, facilitating the axial discharge of the target magnetic beads. The advantage of this arrangement is that during the washing liquid injection stage, a rapid axial impact is generated through the second inlet 12, enabling the deposited target magnetic beads to be efficiently flushed to the second outlet 14.

[0064] In a preferred embodiment, the inlet and outlet can also be designed with different shapes, such as elliptical holes, strip-shaped openings, rectangular windows, chamfered short tubes, or flared openings, to produce different liquid jet diffusion effects. Furthermore, the number of the second inlet 12 and the second outlet 14 is not limited to one each, and can be adjusted according to the configuration of the magnetic field generator 2 and the specific arrangement of the magnetic bead separator 1.

[0065] Optionally, the diameter of the magnetic bead separator 1 is set within the range of 10–300 mm. This diameter range achieves a balance between the magnetic field strength and the throughput requirements of the pipeline. Specifically, during the magnetic field operation, the magnetic field gradient ΔB decreases exponentially with the increase of the distance r from the magnetic source surface (ΔB∝1 / r²). When the diameter of the separation tube increases significantly, it becomes difficult to maintain an effective magnetic field strength in the central region of the tube, leading to a sharp decrease in the magnetic bead capture efficiency. For example, when the diameter of the magnetic bead separator 1 is expanded from 350 mm to 500 mm, the magnetic field gradient at its center may drop to less than 1% of the original value, significantly reducing the capture effect of the target magnetic beads. The capture efficiency drops sharply from over 99% to less than 20%, severely affecting the separation purity and recovery rate.

[0066] To compensate for the magnetic field loss caused by the increased diameter, existing technologies require high-strength magnet systems, with some even incorporating superconducting magnets to maintain the necessary magnetic field gradient. However, such configurations are not only prohibitively expensive (superconducting systems can cost over 3 million RMB), but also place extremely high demands on energy consumption and thermal management during operation. Equipment power can surge from 1 kW to 100 kW, and the costs of heat dissipation, space, and safety design for the supporting systems also increase exponentially. Furthermore, large-diameter separators also face structural challenges such as bulkiness, low magnetic tile utilization, and packaging difficulties, significantly reducing their practicality and scalability.

[0067] In a preferred embodiment of this application, the magnetic field generating device 2 is disposed outside the magnetic bead separator 1, and its structure and magnet arrangement are designed to generate a magnetic field that gradually weakens from the tube wall to the middle of the tube within the magnetic bead separator 1.

[0068] Preferably, the magnetic bead separator 1 can be divided into a magnetic bead separation zone and a magnetic bead capture zone according to the characteristics of the magnetic field and the layout of the fluid channels. Both zones extend along the axial direction of the magnetic bead separator 1. The two ends of the magnetic bead separation zone are connected to the first inlet 11 and the first outlet 13, and mainly serve the functions of injecting raw liquid and discharging impurities and waste liquid; the two ends of the magnetic bead capture zone are connected to the second inlet 12 and the second outlet 14, respectively, and are used for injecting washing liquid and discharging magnetic bead liquid. Specifically, the magnetic bead separation zone constitutes the main fluid channel, in which the target magnetic beads will be attracted by magnetic force and move towards the magnetic bead capture zone; while the magnetic bead capture zone is close to the magnetic field area and has a higher magnetic field strength, which can capture and fix the migrating magnetic beads.

[0069] It should be noted that the sizes of the first inlet 11 and the first outlet 13 do not strictly correspond to the width of the magnetic bead separation zone, and the sizes of the second inlet 12 and the second outlet 14 do not strictly correspond to the width of the magnetic bead capture zone. The magnetic bead separation zone and the magnetic bead capture zone do not actually exist, but are functional divisions of the interior of the magnetic bead separator 1 based on the behavior of the magnetic beads in the magnetic bead separation liquid.

[0070] During operation, the target magnetic beads in the liquid to be separated maintain a certain spatial dispersion between particles in the magnetic bead separation zone, preventing aggregation or deposition. However, under the influence of the magnetic field, they gradually move towards the magnetic bead capture zone. As they enter the capture zone, the magnetic beads are rapidly captured and pressed against the tube wall near the magnetic field generator, forming a densely packed layer of magnetic beads. The magnetic beads are fixed together by the magnetic field force. During the removal of the magnetic field, the magnetic field strength rapidly weakens, and the capturing force between the particles abruptly decreases to near-disappearance. At this point, only a certain volume of washing liquid needs to be injected to utilize the impact force of the liquid to quickly detach the magnetic beads from the tube wall and carry them into the fluid.

[0071] In different embodiments, the magnetic field generating device 2 and the driving device 3 can be configured as a group to partially cover the magnetic bead separator 1; or they can be configured as multiple groups, arranged around the magnetic bead separator 1 to increase the effective area of ​​the magnetic field action region. In specific implementations, multiple groups of magnetic field generating devices 2 can be distributed sequentially around the circumference of the magnetic bead separator 1, or sequentially arranged along the axial direction of the magnetic bead separator 1, or arrayed on the surface of the magnetic bead separator 1 to form a composite magnetic field system with directional and gradient characteristics.

[0072] Specifically, in one typical form, refer to Figure 2 The magnetic field generating device 2 adopts a fully enclosed configuration, that is, by combining two or more sets of magnetic field generating devices 2 with the driving device 3, the magnetic field generating device 2 forms a closed ring structure along the outer side wall of the magnetic bead separator 1, completely covering the entire circumference of the magnetic bead separator 1. This fully enclosed arrangement can build a higher intensity and more uniform magnetic field within the magnetic bead separator 1, ensuring that the target magnetic bead at any position in the cavity is effectively attracted.

[0073] Correspondingly, in another easily assembled implementation, the magnetic field generating device 2 can be configured in a semi-enclosed manner, that is, one or more sets of magnetic field generating devices 2 are set only in part of the outer wall area of ​​the magnetic bead separator 1, so that while forming an effective magnetic field capture area, some space is reserved for device observation or other functional module expansion.

[0074] Furthermore, by setting up multiple sets of magnetic field generating devices 2, different types or intensities of magnetic tiles 222 or magnet components can be configured in each set of magnetic field generating devices 2, or different embedding methods of magnetic tiles 222 or magnets can be adopted, thereby forming a magnetic field intensity region with a spatially differentiated distribution. Specifically, the magnetic field generating device 2 can provide different magnetic field intensities (0.5T-80T), which can be selected according to different magnetic beads and separation requirements.

[0075] Reference Figure 3 and Figure 4 In the embodiments of this application, the magnetic field generating device 2 includes an anti-detachment layer 21, a magnetic embedding layer 22 and a shielding layer 23 arranged sequentially from the inside to the outside. The three-layer structure is used to establish a suitable magnetic field environment inside the magnetic bead separator 1 to achieve the capture and release of the target magnetic bead.

[0076] The first layer is an anti-detachment layer 21, which is an inner bonding structure used to prevent the magnetic tiles 222 in the embedded magnetic layer 22 from falling off and to ensure close contact between the magnetic field generating device 2 and the outer wall of the magnetic bead separator 1. This anti-detachment layer 21 is typically made of stainless steel, possessing good mechanical strength and magnetic flux penetration. On the one hand, it can resist external stress impacts to prevent the magnetic tiles 222 from shifting or falling off; on the other hand, it will not significantly obstruct or weaken the magnetic field lines, ensuring that the magnetic field can effectively penetrate into the separation tube. In other embodiments, the anti-detachment layer 21 can also be made of non-magnetic titanium alloy, engineering plastic, or aluminum alloy; any material with good mechanical strength, wear resistance, and magnetic field penetration performance is acceptable. The geometric contour of the anti-detachment layer 21 is adapted to the shape of the outer wall of the magnetic bead separator 1 to achieve a tight-fitting covering effect.

[0077] It should be noted that in some other embodiments, when the magnetizing layer 22 can stably fix the magnetic tile 222 on its own, the anti-detachment layer 21 can be removed. That is, the magnetic field generating device 2 includes a two-layer structure consisting of a magnetizing layer 22 and a shielding layer 23 arranged sequentially from the inside to the outside.

[0078] The second layer is the magnetic embedding layer 22, which is the core functional layer of the magnetic field generating device 2. It contains multiple sets of magnetic tiles 222, commonly made of neodymium iron boron, samarium cobalt, or other high-performance rare-earth magnetic materials. This magnetic embedding layer 22 is also made of stainless steel to balance structural support and traditional magnetic field characteristics. Accordingly, the structural form of the magnetic embedding layer 22 can be divided into two types according to the magnetic field distribution requirements: semi-enclosed and fully enclosed, as shown in the reference... Figure 6 The fully enclosed structure covers the magnetic bead separator 1 with a continuous surrounding magnetic module, which can significantly increase the capture area.

[0079] The third layer is the shielding layer 23, which is the outermost protective layer of the magnetic field generating device 2, used to shield the leaked magnetic field. This shielding layer 23 can limit the diffusion of magnetic field lines beyond the magnetized layer 22, preventing the magnetic field from interfering with surrounding electronic components, signal lines, or operating equipment. At the same time, the shielding layer 23 also has a certain protective strength and can withstand external mechanical impacts.

[0080] Reference Figure 5a and Figure 5b In a further embodiment of this application, the magnetic embedding layer 22 includes a support plate 221 and a plurality of magnetic tiles 222. The support plate 221 is used to support and fix the magnetic tiles 222. The support plate 221 is integrally connected or separately connected to the shielding layer 23, and a plurality of limiting grooves 223 are formed on the support plate 221 to restrict the movement of the magnetic tiles 222. Each magnetic tile 222 is fixed by embedding into the corresponding limiting groove 223, thereby ensuring that the magnetic tile 222 will not shift or loosen during equipment operation.

[0081] In the continuous magnetic bead separation device of this application, a permanent magnet is preferably used to construct the magnetic field generating device 2 to replace the traditional electromagnet. Although electromagnets have the ability to adjust the magnetic field, they have drawbacks such as high energy consumption, heavy structure, and difficulty in heat dissipation. In contrast, permanent magnets (such as neodymium iron boron) can output magnetic fields of up to 8000 Gauss or more at room temperature. The permanent magnet structure does not require an external power supply to maintain the magnetic field, and its magnetic field output is stable and without fluctuations, making it particularly suitable for solving magnetic screening problems. During the magnetic bead separation process, the purpose of the magnetic field generating device 2 is not to dynamically adjust the magnetic field, but to maintain a stable gradient magnetic field with a certain magnetic field strength to achieve efficient capture of the target magnetic bead. The magnetic field changes generated by the electromagnet during adjustment may cause the target magnetic bead to not be completely captured, or impurity magnetic beads to be captured. In addition, the small magnetic tiles 222 have a higher edge area ratio. By densely arranging a large number of small magnetic tiles 222 in the magnetic embedding layer 22, the magnetic field lines will be concentrated at the junction between the magnetic poles, which can expand the effective capture area.

[0082] The magnetic tile 222 is preferably a block with a cross-section of regular hexagon, rhombus, or parallelogram. The specific cross-sectional shape can be selected according to the magnetic field arrangement requirements and processing technology limitations. (Refer to...) Figures 7a-7d , Figure 7a The example uses a regular hexagonal magnetic tile 222 for top surface magnetization. Figure 7b The example uses a regular hexagonal magnetic tile 222 for top surface magnetization. Figure 7c Square magnetic tile 222 used as an example for vertically embedded magnets Figure 7d The example uses a square magnetic tile 222 with horizontally embedded magnets. The yellow area represents the magnetic attraction area, the blue area represents the N pole of the magnetic tile, and the red area represents the S pole of the magnetic tile.

[0083] It should be noted that, referring to Figure 8aand Figure 8b While the rhomboid magnetic tile 222 theoretically maximizes the magnetic attraction area, the permanent magnet material manufacturer struggles to ensure the magnetic poles accurately land at the apex of the rhombus during the magnetization process, leading to magnetic pole misalignment at the edges of the rhombus. Specifically, this can be seen from... Figure 8b It can be seen that the magnetic attraction area was lost due to the magnetization process error. However, the hexagonal magnetic tile 222 effectively avoids the above-mentioned offset problem by adding two symmetrical edges.

[0084] Regarding the embedding method of magnetic tile 222, refer to Figure 7c , Figure 7d and Figure 9 The magnets can be arranged horizontally, vertically, or in a Halbach array. The Halbach array, through a specific arrangement of magnets, enhances the magnetic field strength on one side of the magnetic field generator 2 while significantly weakening it on the other side, thus creating a strong magnetic field region on one side of the tube wall while preventing the magnetic field from leaking outward.

[0085] In one optional embodiment of this application, referring to FIG1, the drive device 3 includes a motor module 31, a transmission rod 33, and a support rod 32. A bracket 4 is located on both sides of the motor module 31 and has the transmission rod 33 inside. The motor module 31 outputs power through the transmission rod 33 and transmits power to the transmission rod 33 inside the bracket 4 via a helical gear. The rotation of the transmission rod 33 drives the sliding structure 6, which is screwed to it, to move upward, thereby pushing the magnetic field generator 2 to move vertically. In different embodiments, the motor module can be a cylinder, an electric push rod, or other different forms. Furthermore, the transmission form of the transmission rod 33 can also be specifically manifested in different forms, such as equivalent replacement with a worm gear and worm shaft transmission, or equivalent replacement with a gear and rack transmission, or equivalent replacement with hydraulic transmission, lead screw transmission, etc. The motor module 31 is mounted on a support column located in the middle of the bracket 4. The support rod 32 is located at the top of the support column and is slidably connected to the top of the support column axially, providing orientation for the translation of the magnetic field generator 2.

[0086] In another alternative embodiment of this application, reference is made to... Figure 10The drive device 3 includes a motor module 31, a threaded transmission rod 33, and a support rod 32. Brackets 4 are located on both sides of the motor module 31, and their tops are connected to the magnetic field generator 2 via a sliding structure 6. The rotation of the threaded transmission rod 33 is controlled by the motor module 31, which can be a servo motor, stepper motor, or DC motor, etc., and its output shaft is connected to the threaded transmission rod 33. The support rod 32 is positioned between the brackets 4, with its top end fixedly connected to the magnetic field generator 2 and its bottom end threadedly connected to the top end of the threaded transmission rod 33. The rotation of the threaded transmission rod 33 drives the support rod 32, which is threadedly connected to it, to move axially, thereby allowing the magnetic field generator 2, connected to one end of the support rod 32, to move vertically.

[0087] In practical applications, the aforementioned drive mechanism can be adjusted according to different requirements of spatial arrangement, response speed, or load intensity. For example, mechanical transmission methods, such as worm gear, gear, and rack and pinion structures, can be used to achieve the transmission requirements of high torque and small speed ratio; or linear drive components such as electric push rods, ball screws, hydraulic cylinders, or pneumatic cylinders can be used to achieve rapid linear movement.

[0088] Working principle:

[0089] During the operation of the continuous magnetic bead separation device of this application, when the liquid to be separated, carrying magnetic beads, is injected into the magnetic bead separator 1 through the first inlet 11, it will flow along the axial direction of the magnetic bead separator 1. The magnetic field generating device 2 is attached to the outer wall of the magnetic bead separator 1, and the magnetic tiles 222 embedded inside it can form a stable magnetic field inside the magnetic bead separator 1. When the magnetic beads pass through the area of ​​magnetic field action, they will be subjected to the magnetic field force, thus undergoing a deflection motion, and will eventually be captured on the inner wall of the magnetic bead separator 1 near the magnetic field source. During this process, the waste liquid is discharged through the first outlet 13.

[0090] During the capture process, the target magnetic beads are tightly packed together, adhering to the pipe wall and forming a deposition zone under the influence of the magnetic field, preventing them from being washed away by the liquid flow. After the capture process is completed, the magnetic field generating device 2 leaves the magnetic bead separator 1, and the magnetic force on the magnetic beads is greatly reduced. The washing liquid is introduced from the second inlet 12 and impacts the deposition zone of the target magnetic beads, carrying the target magnetic beads out from the second outlet 14.

[0091] As an example, a continuous magnetic bead separation device can achieve the processes of magnetic bead separation, washing, and enrichment purification through the following steps S1-S6.

[0092] S1. Pre-fill the magnetic bead separator 1 through the first liquid inlet 11, and input washing liquid into it until it is full;

[0093] S2. The driving device 3 controls the magnetic field generating device 2 to approach and adhere to the magnetic bead separator 1, and at the same time introduces the raw liquid to be treated containing the target magnetic beads into the first inlet 11, so as to capture the magnetic particles in the magnetic bead capture area by magnetic field capture, and discharge the non-magnetic waste liquid through the first outlet 13 until the concentration of the target magnetic beads at the first outlet 13 reaches the first set value; wherein, the target magnetic beads are particles that can be effectively captured by the magnetic field generating device 2, and the non-magnetic components in the non-magnetic waste liquid are impurities that have not been captured by the magnetic field generating device 2.

[0094] S3. The drive device 3 controls the magnetic field generator 2 to move away from the magnetic bead separator 1 and injects washing liquid through the first liquid inlet 11 to flush the target magnetic beads enriched in the magnetic bead capture area out to the external container through the second liquid outlet 14.

[0095] S4. The drive device 3 controls the magnetic field generator 2 to approach and adhere to the magnetic bead separator 1, and reintroduces the enriched liquid stored in the external container into the first inlet 11, so as to capture the magnetic particles in the magnetic bead capture area by magnetic field capture, and discharge the non-magnetic waste liquid through the first outlet 13.

[0096] S5. The drive device 3 controls the magnetic field generator 2 to move away from the magnetic bead separator 1 field and injects washing liquid into the first inlet 11 to flush the target magnetic beads enriched in the magnetic bead capture area to the finished product tank through the second outlet 14 until the target magnetic bead concentration at the second outlet 14 is lower than the third set value.

[0097] S6. Check if all the original solutions to be processed have been processed; otherwise, return to S1.

[0098] Although embodiments of this application have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting this application. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of this application.

Claims

1. A method for continuous separation of magnetic beads applied to a magnetic bead continuous separation device, characterized by, The magnetic bead continuous separation device comprises a magnetic bead separator (1), a magnetic field generating device (2) and a driving device (3) for driving the magnetic field generating device (2) to approach or move away from the side wall of the magnetic bead separator (1). The magnetic bead separator (1) is hollow and has a first liquid inlet (11) and a second liquid inlet (12) at one end, and a first liquid outlet (13) and a second liquid outlet (14) at the other end. The second liquid inlet (12) is tangent to the tube wall of the magnetic bead separator (1). The second liquid outlet (14) is tangent to the tube wall of the magnetic bead separator (1). The magnetic bead separator (1) is used for transverse placement. The second liquid inlet (12) of the magnetic bead separator (1) is arranged on the side of the end of the magnetic bead separator (1) close to the magnetic field generating device (2) relative to the first liquid inlet (11). The second liquid outlet (14) of the magnetic bead separator (1) is arranged on the side of the end of the magnetic bead separator (1) close to the magnetic field generating device (2) relative to the first liquid outlet (13). A magnetic bead separation zone and a magnetic bead capture zone are formed in the magnetic bead separator (1). The magnetic bead separation zone and the magnetic bead capture zone are both distributed along the axial direction of the magnetic bead separator (1). The two ends of the magnetic bead separation zone are respectively connected to the first liquid inlet (11) and the first liquid outlet (13). The two ends of the magnetic bead capture zone are respectively connected to the second liquid inlet (12) and the second liquid outlet (14). A magnetic field gradient is formed from the magnetic bead separation zone to the magnetic bead capture zone. The magnetic bead continuous separation method performs the following steps: S1. Pre-charging operation is performed on the magnetic bead separator (1) through the first liquid inlet (11). The inside of the magnetic bead separator (1) is input with washing liquid until it is full. S2. The driving device (3) controls the magnetic field generating device (2) to approach and adhere to the magnetic bead separator (1). At the same time, the first liquid inlet (11) is introduced with the target magnetic bead-containing raw liquid to be treated. The magnetic particles are captured in the magnetic bead capture zone by the magnetic field capture method, and the non-magnetic waste liquid is discharged through the first liquid outlet (13) until the target magnetic bead concentration at the first liquid outlet (13) reaches the first set value. The target magnetic bead is a particle that can be captured by the magnetic field generating device (2). The non-magnetic component in the non-magnetic waste liquid is an impurity component that is not captured by the magnetic field generating device (2). S3. The driving device (3) controls the magnetic field generating device (2) to move away from the magnetic bead separator (1), and injects washing liquid through the first liquid inlet (11) to flush out the target magnetic beads enriched in the magnetic bead capture zone to an external container through the second liquid outlet (14). S4. The driving device (3) controls the magnetic field generating device (2) to approach and adhere to the magnetic bead separator (1) again, and re-introduces the enriched liquid stored in the external container into the first liquid inlet (11) to capture the magnetic particles in the magnetic bead capture zone by the magnetic field capture method, and discharge the non-magnetic waste liquid through the first liquid outlet (13). S5. The drive device (3) controls the magnetic field generator (2) to move away from the magnetic bead separator (1) and injects washing liquid into the first inlet (11) to flush the target magnetic beads enriched in the magnetic bead capture area to the finished product tank through the second outlet (14) until the concentration of target magnetic beads at the second outlet (14) is lower than the third set value. S6. Check if all the original solutions to be processed have been processed; otherwise, return to S1.

2. The magnetic bead continuous separation method for the magnetic bead continuous separation apparatus according to claim 1, wherein The driving device (3) includes a motor module (31), a transmission rod (33) and a support rod (32). The two ends of the support rod (32) are respectively connected to the transmission rod (33) and the magnetic field generating device (2). The motor module (31) is used to drive the transmission rod (33) to push the support rod (32) and the magnetic field generating device (2) toward or away from the magnetic bead separator (1).

3. The magnetic bead continuous separation method for the magnetic bead continuous separation apparatus according to claim 1, wherein The magnetic field generating device (2) includes an anti-detachment layer (21), a magnetizing layer (22) and a shielding layer (23) arranged sequentially from the inside to the outside. A magnet is embedded in the magnetizing layer (22). The anti-detachment layer (21) and the shielding layer (23) cooperate with the magnetizing layer (22) to form a cavity for accommodating and limiting the magnet.

4. The magnetic bead continuous separation method for the magnetic bead continuous separation apparatus according to claim 3, wherein The inner wall of the anti-detachment layer (21) is fitted to the outer wall of the magnetic bead separator (1) and its shape is adapted to the outer wall of the magnetic bead separator (1).

5. The magnetic bead continuous separation method for the magnetic bead continuous separation apparatus according to claim 3, wherein The magnetic embedding layer (22) includes a support plate (221) and a plurality of magnetic tiles (222). The support plate (221) is provided with a plurality of limiting grooves (223) for restricting the movement of the magnetic tiles (222). The magnetic tiles (222) are installed in the limiting grooves (223).

6. The magnetic bead continuous separation method for the magnetic bead continuous separation apparatus according to claim 5, wherein The magnetic tile (222) is embedded in the support plate (221) in the following ways: horizontal embedding, vertical embedding, and Halbach array embedding.

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