Magnetophoresis device and method based on panel Halbach array

Abstract

Two push rod type linear stepping motors in the device are arranged at the two ends of a guide rail through L-shaped push rods, carrying tables are arranged above the L-shaped push rods, telescopic rotating motors are arranged on the carrying tables respectively, the telescopic rotating motors are vertically connected with magnet plates, and the magnet plates are arranged on the carrying tables. A third telescopic rotating motor is arranged at the rear end of one magnet plate, a vertical guide rail groove and a transverse guide rail groove are formed in one magnet plate, and the control module is connected with all the motors. According to the invention, the high gradient magnetic field advantage of the panel Halbach array is utilized, the precise control capability of the motor is combined, the automatic uniform field and gradient field conversion function of the device is utilized, and a microscope with an image acquisition function is matched, so that the degree of phagocytosis of magnetic particles by cells is automatically observed, and multiple sets of magnetic field devices do not need to be additionally arranged; the cell activity can be effectively protected, and the magnetic field application requirements in the fields of biomedical detection, analysis detection and the like are met.

Description

A magnetophoresis device and method based on a flat Helbeck array 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: A magnetophoresis device based on a flat Hellbeck array includes a guide rail, a first push rod type linear stepper motor and a second push rod type 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 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 the vertical guide rail groove below the first magnet plate, the second rotary motor is vertically connected to the lower part 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 a control module is connected to each motor.

[0009] 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.

[0010] 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.

[0011] 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.

[0012] Based on the above-mentioned magnetophoresis device based on a flat Hellbeck array, this invention also provides a controllable magnetophoresis method based on a flat Hellbeck array, comprising the following steps: S1: Construction and parameter control of gradient magnetic field. The flat Hellbeck controllable magnetic field generator is started and set to gradient field mode through the control module: the default state of the device is gradient field mode, so the first telescopic rotary motor, the second rotary motor, and the third telescopic rotary motor do not operate; the device provides two gradient value adjustment schemes: when the required gradient value is a definite value, it is directly input into the control module, and the first push rod linear stepper motor and the second push rod linear stepper motor are started, respectively driving the stage to the limited position; at this time, the first magnet plate and the second magnet plate are in a relative posture, the strong magnetic field side of the first magnet plate and the second magnet plate are located inside, and a gradient magnetic field with a zero magnetic field point is generated in the central region; when the required gradient value is uncertain, it is manually operated when the first push rod linear stepper motor and the second push rod linear stepper motor are not powered on. S1: The push rod is in a free state. The stage is manually moved while observing in the microscope (because the required magnetic field strength is unknown, it is manually adjusted while observing in the microscope to ensure that the slide or other carrier under the microscope is centered between the two magnet plates); S2: Construction and parameter control of a uniform magnetic field. The flat-plate Heilbeck controllable magnetic field generator is started and set to uniform field mode through the control module: At this time, the first telescopic rotary motor and the second rotary motor, which are perpendicular to the direction of the magnet plates, work to flip the first and second magnet plates 180° respectively; after completion, the third telescopic rotary motor rotates the first magnet plate 180° (at this time, the weak side of the first and second magnet plates is located inside, but the magnetic fields generated by the two magnet plates are in opposite directions and cancel each other out; then one set of magnet plates is rotated 180° in the horizontal direction, at which time the magnetic fields generated by the two magnet plates are in the same direction, completing the construction of a uniform field); at this time, the central area of ​​the magnet plates is a uniform field. The device provides two uniform field intensity adjustment schemes: when the required uniform field intensity value is a fixed value, it is directly input into the control module, and the first push rod linear stepper motor and the second push rod linear stepper motor are started, respectively driving the stage to the specified position; when the required uniform field intensity 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 is manually moved while being observed in the microscope.

[0013] S3: The device then automatically switches from uniform field mode to gradient field mode, and repeats this cycle. The distribution of magnetic particles in the cells and the number of cells that have undergone endocytosis are observed by taking pictures through the microscope's image acquisition system, thus observing the phagocytic process of the cell population.

[0014] 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.

[0015] 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.

[0016] 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.

[0017] 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.

[0018] 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.

[0019] The beneficial effects of this invention are as follows: In the magnetophoretic separation, enrichment, or capture stage, a magnetic field with a stable gradient is generated by a flat Hellbeck magnet; in the particle observation stage after separation, enrichment, or capture, the relative state of a pair of flat Hellbeck magnets is adjusted by a motor 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: Linear adjustment of magnetic field strength: A linear drive motor achieves high-precision linear adjustment of the magnet plate spacing with excellent step accuracy. The magnet spacing can be continuously adjusted within a set range, thereby precisely changing the magnetic field strength and gradient value in the central region to meet the magnetic field parameter requirements of different application scenarios; A single device can generate gradient and uniform fields: Flexible switching of magnetic field types can be achieved through the flat Hellbeck magnet device, simplifying the overall structure of the magnetophoresis device. The device is adaptable to microscope applications without requiring significant modifications to existing observation equipment, making it highly practical and widely applicable in fields such as magnetic particle performance testing and microscopic magnetic field experiments.

[0020] 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.

[0021] 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

[0022] Figure 1 is a schematic diagram of the overall structure of the flat Helbeck magnet device of the present invention; Figure 2 is a schematic diagram of the magnet orientation and splicing of a single flat Helbeck magnet of the present invention; Figure 3 is a graph showing the variation of gradient field intensity with the spacing between magnet plates; Figure 4 is a graph showing the variation of uniform field intensity with the spacing between magnet plates; Figure 5 is a graph showing the magnetic field distribution in the central region of the magnet plate when generating a gradient field; Figure 6 is a graph showing the magnetic field distribution in the central region of the magnet plate when generating a uniform field.

[0023] List of reference numerals in the attached diagram: 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

[0024] 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.

[0025] As shown in Figure 1, 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 pusher-type linear stepper motor 3, a second pusher-type 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. The first magnet plate 1 and the second magnet plate 2 are flat Hellbeck magnets with identical structures, arranged in a parallel and opposite manner on both sides of the magnetic field generation area. The first pusher-type linear stepper motor 3 and the second pusher-type linear stepper motor 4 are placed at both ends of the guide rail 9, and the motor pushers are fixed below the stage. (The platform is not separately labeled), and the push rod can push the platform to slide on the guide rail 9. A pair of telescopic rotary motors (first telescopic rotary motor 5 and second rotary motor 6) are placed on the platform. In addition to being vertically connected to the first telescopic rotary motor 5, the first magnet plate 1 is also horizontally connected to the third telescopic rotary motor 7. The surface of the first magnet plate 1 has a transverse guide rail groove 11 and a vertical guide rail groove 10 (the surface of the second magnet plate 2 does not have transverse or vertical guide rail grooves). The output shafts of the first telescopic rotary motor 5 and the third telescopic rotary motor 7 are in a telescopic state, with their front ends positioned in the vertical guide rail groove 10 and the transverse 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, with its front end sliding freely in the transverse 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, with its end sliding freely in the vertical guide rail groove 10.

[0026] 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 The array arrangement rules (as shown in Figure 2) ensure the magnetic field strength and uniformity of the central magnetic field generation area.

[0027] 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.

[0028] Usage Method: A: Construction and Parameter Adjustment of Gradient Magnetic Field Start the magnetophoresis device based on a flat-plate Hellbeck array 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 telescopic rotary motor 5, the second rotary motor 6, and the third telescopic rotary motor 7 are not activated. This device provides two gradient value adjustment schemes: When the required gradient value is definite (as shown in Figure 3), for example, 14T / m, 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, automatically moving the stage to the guide rail scales of -22.5cm and 22.5cm respectively; when the required gradient value 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, and the stage can be manually moved while observing in the microscope.

[0029] Results: After the magnet plate spacing was adjusted, a gradient magnetic field was formed in the central magnetic field generation area (as shown in Figure 5), and a zero magnetic field point was generated at the center of the gradient magnetic field. The gradient value of the gradient field was 14T / m.

[0030] B: Construction and Parameter Control Implementation Scheme of Uniform Magnetic Field: The magnetophoresis device based on a flat Hellbeck array is started and set to uniform field mode through 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 plate, work to rotate 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 time, the central area of ​​the magnet plate is a uniform field. The device provides two uniform field intensity adjustment schemes. When the required uniform field intensity value is a fixed value (as shown in Figure 4), for example, 27mT, 27mT is directly input into the control module 8, and the first push rod linear stepper motor 3 and the second push rod linear stepper motor 4 are started, automatically moving the stage to the guide rail scale of -25cm and 25cm respectively; when the required uniform field intensity 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 is manually moved while observing in the microscope.

[0031] Results: After the spacing between the magnet plates was adjusted, a uniform magnetic field was formed in the central magnetic field generation area (as shown in Figure 6), with a uniform field strength of 27 mT.

[0032] Working principle: This invention utilizes the automatic uniform field and gradient field conversion function of the magnetophoresis device based on a flat Helbeck array, combined with a microscope with image acquisition function, to achieve automated observation of the degree of cell phagocytosis of magnetic particles. It does not require additional magnetic field devices, is easy to operate, and can effectively protect cell viability. The specific steps are as follows: 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 position it in the center of the field of view.

[0033] 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.

[0034] 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.

[0035] 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.

[0036] 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 device based on a flat Hellbeck array, characterized in that: The system includes a guide rail, a first push-rod type linear stepper motor, and a second push-rod type linear stepper motor, which are mounted at both ends of the guide rail via L-shaped push rods. A platform is provided above the L-shaped push rods, on which a first telescopic rotary motor and a second rotary motor are respectively mounted. A third telescopic rotary motor is 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 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, and the third telescopic rotary motor is horizontally connected to the horizontal guide rail groove at the rear end of the first magnet plate. The control module is connected to each motor.

2. The magnetophoresis device based on a flat Hellbeck array according to claim 1, characterized in that: 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.

3. The magnetophoresis device based on a flat Hellbeck array according to claim 1, characterized in that: 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.

4. The magnetophoresis device based on a flat Hellbeck array according to claim 1, characterized in that: 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.

5. A magnetophoresis method using a magnetophoresis apparatus based on a flat Hellbeck array according to any one of claims 1-4, characterized in that: S1: Construction and Parameter Adjustment of Gradient Magnetic Field The flat-plate 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, during which the first, second, and third telescopic rotary motors are inactive. The device provides 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 respectively move the stage to the specified position. At this time, the first and second magnet plates are in a relative posture, with their strong magnetic field 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. The push rods are in a free state, and the stage is manually moved while observation is performed under a microscope. S2: Construction and Parameter Adjustment of Uniform Magnetic Field The flat-plate Helbeck controllable magnetic field generator is started. The device is 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°; at this time, the central area of ​​the magnet plate is a uniform field. The device provides two uniform field intensity adjustment schemes: when the required uniform field intensity value is fixed, it is directly input into the control module, and the first and second push-rod linear stepper motors start, driving the stage to the specified position respectively; when the required uniform field intensity value is uncertain, it can be manually operated when the 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. S3: Afterwards, the device automatically switches from uniform field mode to gradient field mode, cycling sequentially; through the image acquisition system of the microscope, the distribution of magnetic particles in the cells, the number of cells that have undergone endocytosis, and the phagocytic process of the cell population are observed.

6. The magnetophoresis method according to claim 5, 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.

7. The magnetophoresis method according to claim 5, 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.

8. The magnetophoresis method according to claim 5, 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.

9. The magnetophoresis method according to claim 5, 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.

10. The magnetophoresis method according to claim 5, characterized in that: The microscope is positioned in the central area between the first and second magnet plates.

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