A planar halbach array based magnetophoresis device and method

Abstract

The application discloses a kind of based on flat Halbach array's magnetophoresis device and method, two push rod type linear stepping motors in device are set in guide rail two ends by L type push rod, L type push rod top is equipped with stage, the telescopic rotary motor is respectively arranged on the stage, telescopic rotary motor vertically connects magnet plate, third telescopic rotary motor is arranged in rear end of one of magnet plate, vertical guide rail groove and horizontal guide rail groove are equipped on one of magnet plate, control module is connected with each motor.The application utilizes the high gradient magnetic field advantage of flat Halbach array, combines the accurate control ability of motor, utilizes the automatic uniform field and gradient field conversion function of device, cooperates with the microscope with image acquisition function, realizes the observation of degree of automatic cell phagocytosis magnetic particle, does not need to additionally equip multiple sets of magnetic field device, it is convenient to operate and can effectively protect cell activity, adapts biomedical detection, analysis detection and other multi-field magnetic field application needs.

Description

Technical Field

[0001] This invention belongs to the field of magnetophoresis technology and magnetic field generation, specifically relating to a magnetophoresis device and method based on a flat Helbeck array. Background Technology

[0002] Magnetophoresis, a highly efficient separation and manipulation technology that utilizes magnetic field gradients to drive the directional motion of magnetic particles, is widely used in biomedicine, environmental monitoring, materials science, and other fields. Its core performance directly depends on the generation method, intensity, gradient, and adjustability of the magnetic field. Currently, the magnets used to generate the magnetic field in magnetophoresis are mainly divided into three categories: electromagnetic coils, permanent magnets, and Halebeck arrays. In practical applications, all of these have insurmountable technical defects, failing to meet the requirement for flexible switching between uniform and gradient fields during magnetophoresis, thus limiting the integration and multifunctional development of magnetophoresis technology.

[0003] Electromagnetic coils can achieve real-time adjustment of magnetic field strength, direction, and gradient through current regulation, and can generate alternating or dynamic magnetic fields. However, they require continuous power supply during use and are prone to generating significant heat during operation, which not only increases energy consumption but may also affect heat-sensitive samples such as cells and biological particles. Furthermore, electromagnetic coils have complex structures, are difficult to integrate, and are challenging to miniaturize. When used alone, their gradient field focusing effect is limited, requiring combination with other structures to meet high-resolution separation requirements.

[0004] Permanent magnets are widely used in conventional magnetophoretic separation devices due to their advantages such as simple structure, no need for external power supply, stable magnetic field, and low cost, making them suitable for building miniaturized and simplified magnetophoretic control systems. However, once a permanent magnet is formed, its magnetic field strength and gradient are basically fixed and cannot be adjusted according to the needs of different processes such as separation and observation; the uniformity of the generated magnetic field distribution is poor, and it relies on its own magnetic properties, making it impossible to control the magnetic field and achieve flexible switching between uniform and gradient fields, thus limiting the multifunctional development of magnetophoretic devices.

[0005] Helbeck array magnets can enhance the magnetic field on the demand side, homogenize or gradient the internal magnetic field through special magnetization orientation. They have high magnetic field utilization and can form a relatively stable uniform field or high gradient field, which has significant advantages in high-precision magnetophoresis manipulation. However, traditional Helbeck arrays are mostly fixed structures with non-adjustable magnetic field modes, and still require multiple sets of structures or additional devices to complete the complete magnetophoresis process.

[0006] In the existing technology, in order to achieve the switching between uniform field and gradient field during magnetophoresis, multiple independent magnetic field generating devices are usually required. This not only leads to a significant increase in equipment cost and cumbersome operation procedures, but also has problems such as poor stability and insufficient accuracy during magnetic field switching, making it difficult to meet the needs of integrated and efficient magnetophoresis applications. Summary of the Invention

[0007] To address the aforementioned issues, this invention discloses a magnetophoresis device and method based on a planar Hellbeck array. Utilizing the high gradient magnetic field advantage of the planar Hellbeck array and combining it with the precise control capabilities of a motor, the spacing between magnets is linearly adjusted with high precision, ensuring the controllability and stability of the magnetic field parameters. Using the same device, rapid and automatic conversion between uniform and gradient fields can be achieved, reducing manual intervention during the magnetophoresis process. This enables a single device to automatically complete the entire magnetophoresis operation, significantly improving the device's integration and ease of operation.

[0008] To achieve the above objectives, the technical solution of the present invention is as follows:

[0009] A magnetophoresis device based on a flat Helbeck array includes a guide rail, a first pusher-type linear stepper motor and a second pusher-type linear stepper motor mounted at both ends of the guide rail via L-shaped pushers, a platform above the L-shaped pushers, a first telescopic rotary motor and a second rotary motor respectively mounted on the platform, and a third telescopic rotary motor mounted at the rear end of the platform where the first telescopic rotary motor is mounted. The first telescopic rotary motor is vertically connected to a vertical guide rail groove below a first magnet plate, the second rotary motor is vertically connected to the lower part of a second magnet plate, and the third telescopic rotary motor is horizontally connected to a horizontal guide rail groove at the rear end of the first magnet plate. A control module is connected to each motor.

[0010] As a supplement to the present invention, the first magnet plate and the second magnet plate are composed of two sets of identical flat Helbeck magnets, with the two sets of magnets facing each other and placed in parallel.

[0011] As a supplement to the present invention, the first magnet plate or the second magnet plate is formed by splicing together several bar magnets along the length direction according to a specific magnetization direction to form an integrated flat plate structure.

[0012] As a supplement to the present invention, the specific magnetization direction is defined sequentially in a counterclockwise direction, the angle between the magnetization directions of two adjacent magnets is between 1 and 90°, and the number of magnets is not less than 4.

[0013] Based on the above-described magnetophoresis device based on a planar Hellbeck array, the present invention also provides a controllable magnetophoresis method based on a planar Hellbeck array, comprising the following steps:

[0014] S1: Construction and parameter control of gradient magnetic field

[0015] The flat-panel Helbeck controllable magnetic field generator is started and set to gradient field mode via the control module. This is the default state of the device, so the first, second, and third telescopic rotary motors are inactive. The device offers two gradient value adjustment schemes: When the required gradient value is definite, it is directly input into the control module, activating the first and second push-rod linear stepper motors, which move the stage to the specified position. At this time, the first and second magnet plates are in a relative position, with their magnetic field strength sides located internally, generating a gradient magnetic field with a zero magnetic field point in the central region. When the required gradient value is uncertain, it is manually operated when the first and second push-rod linear stepper motors are not powered on. In this case, the push rods are in a free state, and the stage is manually moved while observing under a microscope (because the required magnetic field strength is unknown, it is manually adjusted while observing under the microscope to ensure that the slide or other carrier under the microscope is ultimately centered between the two magnet plates).

[0016] S2: Construction and parameter control of a uniform magnetic field

[0017] The flat-panel Helbeck controllable magnetic field generator is activated and set to uniform field mode via the control module. At this point, the first and second telescopic rotary motors, perpendicular to the direction of the magnet plates, operate, rotating the first and second magnet plates 180° each. After this, the third telescopic rotary motor rotates the first magnet plate 180° (at this point, the weaker sides of the first and second magnet plates are inside, but the magnetic fields generated by the two plates are in opposite directions, canceling each other out). Then, one set of magnet plates is rotated 180° horizontally, at which point the magnetic fields generated by the two plates are in the same direction, completing the uniform field construction. The central region of the magnet plates is now a uniform field. The device provides two uniform field intensity adjustment schemes: when the required uniform field intensity is a fixed value, it is directly input into the control module, activating the first and second push-rod linear stepper motors, which drive the stage to the specified position. When the required uniform field intensity is uncertain, it can be manually operated when the motors are not powered on. In this case, the push rods are in a free state, allowing manual movement of the stage while observing through a microscope.

[0018] S3: The device then automatically switches from uniform field mode to gradient field mode, and repeats this cycle.

[0019] The distribution of magnetic particles within cells and the number of cells that have undergone endocytosis are observed through photographs taken using a microscope's image acquisition system, thus monitoring the phagocytic process of the cell population.

[0020] As a supplement to the present invention, in step S1, in gradient field mode, increasing the spacing between magnet plates decreases the gradient field strength, and decreasing the spacing between magnet plates increases the gradient field strength.

[0021] As a supplement to the present invention, in step S2, in uniform field mode, increasing the spacing between magnet plates decreases the uniform field strength, and decreasing the spacing between magnet plates increases the uniform field strength.

[0022] As a supplement to the present invention, in step S3, the method of switching from a uniform field to a gradient field is as follows: in the uniform field state, the weak side of the magnetic field of the two sets of magnet plates is located inside. One set of magnet plates is rotated 180° in the horizontal direction, and then the two sets of magnet plates are rotated 180° in the vertical direction. Then the stepper motor is started to drive the stage to the specified position to complete the gradient field construction.

[0023] As a supplement to the present invention, the output shafts of the first telescopic rotary motor and the third telescopic rotary motor are in a telescopic state, and their front ends slide in the horizontal guide rail groove or the vertical guide rail groove.

[0024] As a supplement to the present invention, the microscope is positioned in the central region between the first magnet plate and the second magnet plate.

[0025] The beneficial effects of this invention are as follows:

[0026] This invention generates a stable gradient magnetic field using a plate-mounted Hellbeck magnet during the magnetophoretic separation, enrichment, or capture stage. In the particle observation stage after separation, enrichment, or capture, a motor adjusts the relative state of a pair of plate-mounted Hellbeck magnets to switch to a uniform magnetic field, enabling clear and stable imaging, counting, and other characterization operations on the separated, enriched, or captured target particles. The core benefits of this method are as follows:

[0027] It can linearly adjust the magnetic field strength: It adopts a linear drive motor to achieve high-precision linear adjustment of the distance between magnet plates with excellent stepping accuracy. It can continuously adjust the distance between magnets within a set range, thereby accurately changing the magnetic field strength and gradient value in the central area to meet the magnetic field parameter requirements of different application scenarios.

[0028] It can generate gradient fields and uniform fields using a single device: the magnetic field type can be flexibly switched using a flat Helbeck magnet device, which simplifies the overall structure of the magnetophoresis device. The device can be adapted to microscope use scenarios without major modifications to existing observation equipment. It is highly practical and can be widely used in fields such as magnetic particle performance testing and microscopic magnetic field experiments.

[0029] The device does not generate excessive energy during operation: Compared to traditional electromagnetic coil magnetophoresis devices, it does not rely on high-current coil excitation during operation, thus avoiding the Joule heating problem caused by current flowing through the wires. The entire device generates almost no significant heat during operation, effectively preventing damage to heat-sensitive biological samples such as cells, liposomes, and micro / nano bubbles caused by high temperatures. Furthermore, the absence of significant heat generation eliminates the need for additional heat dissipation structures, simplifying the overall structure, reducing energy consumption, improving integration, and enhancing reliability for long-term continuous operation. This makes it more suitable for temperature-sensitive biomedical observation and manipulation scenarios.

[0030] It can automatically and dynamically adjust the state of the magnet plate: through the coordinated control of the linear drive mechanism and the flip drive mechanism by the control module, it can realize the automated operation of magnetic field switching and magnet spacing adjustment. When used with a microscope with image acquisition function, it can automatically complete experimental operations that require multiple uses of gradient field and uniform field and record images, reduce manual intervention, improve work efficiency, and at the same time ensure the repeatability and accuracy of operation. Attached Figure Description

[0031] Figure 1 This is a schematic diagram of the overall structure of the flat-plate Heilbeck magnet device of the present invention;

[0032] Figure 2 This is a schematic diagram showing the magnet orientation and splicing of a single flat Helbeck magnet according to the present invention;

[0033] Figure 3 This is a graph showing the variation of gradient field intensity with the distance between magnet plates;

[0034] Figure 4 This is a graph showing the variation of uniform field intensity with the distance between magnet plates;

[0035] Figure 5 A diagram showing the magnetic field distribution in the central region of the magnet plate when generating the gradient field;

[0036] Figure 6 A diagram showing the magnetic field distribution in the central region of the magnet plate when a uniform field is generated.

[0037] List of identifiers in attached diagrams:

[0038] 1. First magnet plate; 2. Second magnet plate; 3. First push rod linear stepper motor; 4. Second push rod linear stepper motor; 5. First telescopic rotary motor; 6. Second rotary motor; 7. Third telescopic rotary motor; 8. Control module; 9. Guide rail; 10. Vertical guide rail groove; 11. Horizontal guide rail groove. Detailed Implementation

[0039] The present invention will be further illustrated below with reference to the accompanying drawings and specific embodiments. It should be understood that the following specific embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0040] like Figure 1 As shown, the magnetophoresis device based on a flat Hellbeck array according to the present invention includes a first magnet plate 1, a second magnet plate 2, a first push rod linear stepper motor 3, a second push rod linear stepper motor 4, a first telescopic rotary motor 5, a second rotary motor 6, a third telescopic rotary motor 7, a control module 8, and a guide rail 9.

[0041] The first magnet plate 1 and the second magnet plate 2 are identical flat Helbeck magnets, arranged in parallel opposite directions on both sides of the magnetic field generation area. The first push rod linear stepper motor 3 and the second push rod linear stepper motor 4 are placed at both ends of the guide rail 9. The motor push rods are fixed below the platform (the platform is not separately marked), and the push rods can push the platform to slide on the guide rail 9. A pair of telescopic rotary motors (the first telescopic rotary motor 5 and the second rotary motor 6) are placed on the platform. In addition to the first telescopic rotary motor 5 connected vertically to the first magnet plate 1, there is also a third telescopic rotary motor 7 connected horizontally to the first magnet plate 1. The surface of the first magnet plate 1 has a horizontal guide rail groove 11 and a vertical guide rail groove 10 (the surface of the second magnet plate 2 does not have a horizontal guide rail groove or a vertical guide rail groove). The output shafts of the first telescopic rotary motor 5 and the third telescopic rotary motor 7 are in a telescopic state, and their front ends are placed in the vertical guide rail groove 10 and the horizontal guide rail groove 11. When the first telescopic rotary motor 5 rotates, the push rod of the third telescopic rotary motor 7 is in a telescopic state, and its front end slides freely in the horizontal guide rail groove 11; when the third telescopic rotary motor 7 rotates, the push rod of the first telescopic rotary motor 5 is in a telescopic state, and its end slides freely in the vertical guide rail groove 10.

[0042] Single flat panel Haierbe gram The magnets (first magnet plate 1 / second magnet plate 2) are composed of eight strip magnets, each measuring 10mm × 10mm × 40mm, tightly joined together along their length. After joining, each individual flat plate is a Helbein magnet. gram The overall dimensions of the magnet are 80mm × 10mm × 40mm (length × width × height); during the assembly process, the magnetic field direction of adjacent bar magnets strictly follows the Helbey standard. gram Array arrangement rules (such as) Figure 2 As shown in the figure, this ensures the magnetic field strength and uniformity of the central magnetic field generation area.

[0043] The linear drive motor enables the magnet plates to reciprocate along a straight line. The spacing between the magnet plates can be adjusted from 45mm to 60mm, and the minimum step distance of the motor is 1mm, which allows for continuous and high-precision adjustment of the magnet spacing.

[0044] How to use:

[0045] A: Construction and parameter control of gradient magnetic field

[0046] The magnetophoresis device based on a flat Hellbeck array is started and set to gradient field mode via the control module. The default state of this device is gradient field mode, in which the first telescopic rotary motor 5, the second rotary motor 6, and the third telescopic rotary motor 7 are not activated. The device provides two gradient value adjustment schemes: when the desired gradient value is a fixed value (e.g., ... Figure 3 As shown), for example, if the gradient value is 14T / m, then directly input 14T / m into the control module 8. The first push rod linear stepper motor 3 and the second push rod linear stepper motor 4 will start and automatically move the stage to the guide rail scale of -22.5cm and 22.5cm respectively. When the required gradient value is uncertain, it can be operated manually when the motor is not powered on. At this time, the push rod is in a free state, and the stage can be moved manually while observing in the microscope.

[0047] Implementation results:

[0048] After the magnet plate spacing is adjusted, a gradient magnetic field is formed in the central magnetic field generation area (e.g., Figure 5 As shown in the figure, the zero magnetic field point is generated at the center of the gradient magnetic field, and the gradient value of the gradient field is 14T / m.

[0049] B: Construction and parameter control of a uniform magnetic field

[0050] Implementation Plan: The magnetophoresis device based on a flat Hellbeck array is started and set to uniform field mode via the control module. At this time, the first telescopic rotary motor 5 and the second rotary motor 6, perpendicular to the direction of the magnet plates, operate, rotating the first magnet plate 1 and the second magnet plate 2 by 180° respectively. After completion, the third telescopic rotary motor 7 rotates the first magnet plate 1 by 180°. At this point, the central region of the magnet plate is a uniform field. This device provides two uniform field intensity adjustment schemes. When the required uniform field intensity value is a fixed value (e.g., ...), ... Figure 4 As shown), for example, if 27mT is input directly into the control module 8, the first push rod linear stepper motor 3 and the second push rod linear stepper motor 4 will start and automatically move the stage to the guide rail scale of -25cm and 25cm respectively. When the required uniform field strength value is uncertain, it can be manually operated when the motor is not powered on. At this time, the push rod is in a free state, and the stage can be manually moved while observing in the microscope.

[0051] Implementation results:

[0052] After the magnet plate spacing is adjusted, a uniform magnetic field is formed in the central magnetic field generation area (e.g., Figure 6 As shown in the figure, the intensity of the uniform field is 27 mT.

[0053] Working principle:

[0054] By utilizing the automatic uniform field to gradient field conversion function of the magnetophoresis device based on a flat Hellbeck array of this invention, and in conjunction with a microscope with image acquisition capabilities, the degree of phagocytosis of magnetic particles by cells can be automatically observed. This eliminates the need for multiple additional magnetic field devices, making the operation convenient and effectively protecting cell viability. The specific steps are as follows:

[0055] Sample pretreatment: Mix the magnetic particles with the cells to be observed to obtain a suspension containing magnetic particles and cells. Transfer the suspension to the microscope and place it in the center of the field of view.

[0056] Device initialization and parameter settings: Start the device, set the magnetic field conversion mode to automatic conversion mode via control module 8, and preset the gradient field value to 14T / m, with a working time of 30 seconds; the uniform field magnetic field strength to 27mT, with a working time of 30 seconds. Set the number of cycles to 10. Simultaneously debug the matching microscopic observation system with image acquisition function, setting it to take pictures of the sample at the end of each 30-second uniform field maintenance time, for a total of 10 pictures.

[0057] In gradient field mode, both magnetic particles and cells converge in the central region of the field of view, and cells undergo endocytosis of the magnetic particles. After 30 seconds, the device automatically switches to uniform field mode. At this point, the magnetic particles, influenced by the uniform field, move towards the magnetic direction of the uniform field, moving away from the center of the field of view. Cells that have already endocytosed the magnetic particles also slowly move towards the magnetic direction of the uniform field, while unendocytosed cells remain in the center of the field of view. After maintaining the uniform field for 30 seconds, the microscope's image acquisition system automatically takes a picture, recording the image at the end of the first cycle. The device then automatically switches back to gradient field mode, and the cycle repeats. The images captured by the microscope's image acquisition system allow observation of the distribution of magnetic particles within the cells, the number of cells that have undergone endocytosis, and the phagocytic process of the cell population.

[0058] This embodiment utilizes the automatic uniform field and gradient field conversion function of the flat-plate Helbeck magnet device to accurately observe the entire process of cell phagocytosis without the need for manual switching of the magnetic field device. During observation, magnetic particles that have not been phagocytosed will move to one side under the influence of the uniform field, leaving the central observation area. This ensures that all observed magnetic particles have been phagocytosed, while cells that have not undergone phagocytosis remain in the center, facilitating observation and resulting in more accurate results.

[0059] It should be noted that the above content merely illustrates the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. For those skilled in the art, various improvements and modifications can be made without departing from the principle of the present invention, and all such improvements and modifications fall within the scope of protection of the claims of the present invention.

Claims

1. A magnetophoresis method based on a flat Hellbeck array magnetophoresis device, characterized in that: S1: Construction and parameter control of gradient magnetic field Start the flat-panel Helbeck controllable magnetic field generator and set it to gradient field mode via the control module. The default state of this device is gradient field mode, in which the first, second, and third telescopic rotary motors are not activated. The device provides two gradient value adjustment schemes: When the required gradient value is definite, it is directly input into the control module, and the first and second push-rod linear stepper motors are activated, driving the stage to the specified position. At this time, the first and second magnet plates are in a relative posture, with the strong magnetic field side of the first and second magnet plates located inside, generating a gradient magnetic field with a zero magnetic field point in the central region. When the required gradient value is uncertain, it is manually operated when the first and second push-rod linear stepper motors are not powered on. At this time, the push rods are in a free state, and the stage is manually moved while observing in the microscope. S2: Construction and parameter control of a uniform magnetic field The flat-plate Helbeck controllable magnetic field generator is activated and set to uniform field mode via the control module. At this time, the first and second telescopic rotary motors, perpendicular to the direction of the magnet plate, operate, rotating the first and second magnet plates 180° each. After completion, the third telescopic rotary motor rotates the first magnet plate 180°. The center region of the magnet plate is now a uniform field. The device provides two methods for adjusting the uniform field intensity: when the desired uniform field intensity is fixed, it is directly input into the control module, activating the first and second push-rod linear stepper motors to move the stage to the specified position; when the desired uniform field intensity is uncertain, it can be manually operated without motor power. In this case, the push rods are in a free state, allowing manual movement of the stage while observing under a microscope. S3: The device then automatically switches from uniform field mode to gradient field mode, and repeats this cycle. The distribution of magnetic particles within cells and the number of cells that have undergone endocytosis are observed through photographs taken using a microscope's image acquisition system, thus monitoring the phagocytic process of the cell population. The flat-plate Helbeck controllable magnetic field generator described in step S1 includes a guide rail, a first push rod linear stepper motor and a second push rod linear stepper motor are mounted at both ends of the guide rail via L-shaped push rods, a platform is provided above the L-shaped push rods, a first telescopic rotary motor and a second rotary motor are respectively mounted on the platform, a third telescopic rotary motor is provided at the rear end of the platform where the first telescopic rotary motor is mounted, the first telescopic rotary motor is vertically connected to the vertical guide rail groove below the first magnet plate, the second rotary motor is vertically connected to the bottom of the second magnet plate, the third telescopic rotary motor is horizontally connected to the horizontal guide rail groove at the rear end of the first magnet plate, and the control module is connected to each motor. The first magnet plate or the second magnet plate is formed by splicing together several bar magnets magnetized in a specific magnetization direction along the length direction to form an integrated flat plate structure. The specific magnetization direction is defined sequentially in a counterclockwise direction, the angle between the magnetization directions of two adjacent magnets is between 1 and 90°, and the number of magnets is not less than 4.

2. The magnetophoresis method according to claim 1, characterized in that: In step S1, in gradient field mode, increasing the spacing between magnet plates decreases the gradient field strength, and decreasing the spacing between magnet plates increases the gradient field strength.

3. The magnetophoresis method according to claim 1, characterized in that: In step S2, in uniform field mode, increasing the spacing between magnet plates decreases the uniform field strength, and decreasing the spacing between magnet plates increases the uniform field strength.

4. The magnetophoresis method according to claim 1, characterized in that: In step S3, the method of switching from a uniform field to a gradient field is as follows: in the uniform field state, the weak side of the magnetic field of the two sets of magnet plates is located inside. One set of magnet plates is rotated 180° in the horizontal direction, and then the two sets of magnet plates are rotated 180° in the vertical direction. Then the stepper motor is started to drive the stage to the specified position to complete the gradient field construction.

5. The magnetophoresis method according to claim 1, characterized in that: The output shafts of the first and third telescopic rotary motors are in a telescopic state, and their front ends slide in the horizontal or vertical guide rail grooves.

6. The magnetophoresis method according to claim 1, characterized in that: The microscope is positioned in the central area between the first and second magnet plates.

7. The magnetophoresis method according to claim 1, characterized in that: In the flat-plate Helbeck controllable magnetic field generator, the first magnet plate and the second magnet plate are composed of two sets of identical flat-plate Helbeck magnets, with the two sets of magnets facing each other and placed in parallel.

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