Magnetic separation device and method

Abstract

The present invention belongs to the field of magnetic separation technology, and in particular, relates to a magnetic separation device and method. The first tooth tip and the tip of the second tooth tip of the magnetic separation device are arranged parallel to each other and form a tip installation gap; a separation channel with an outlet and an inlet is provided on the microfluidic chip; the extension direction of the first tooth tip is arranged parallel to the length direction of the replaceable microfluidic chip and the separation channel; the microfluidic chip is detachably installed in the tip installation gap, and the two opposite outer walls of the microfluidic chip are fitted with the tip of the first tooth tip and the tip of the second tooth tip; when the sample liquid flows into the inlet of the separation channel located in the tip installation gap, the high gradient magnetic field generated between the first tooth tip and the second tooth tip causes the immunomagnetic beads in the sample liquid to be adsorbed on the two opposite inner walls corresponding to the first tooth tip and the second tooth tip in the separation channel. The present invention has a simple structure and production, low cost, and improves the accuracy, separation purity and separation efficiency of magnetic separation.

Description

Technical Field

[0001] The present invention belongs to the technical field of magnetic separation, and in particular relates to a magnetic separation device and method. Background Art

[0002] Magnetic separation is a separation method that uses a magnetic field to separate magnetic substances from other components in a sample. This method has the advantages of simple equipment, easy operation, and low cell damage, and therefore has considerable application prospects in areas such as cell sorting. In existing magnetic separation methods, multiple magnetic beads are usually arranged in a magnetic field chamber, and fluid channels are created between the matrix of magnetic beads for magnetic separation. The shortcomings of this solution are: first, the preparation technology of the magnetic beads is complex, the channels created by stacking the magnetic beads are rugged and difficult to clean, and the separated samples need to directly contact the magnetic beads and be adsorbed on the surface of the magnetic beads. After separating the unwanted components, the desired sample retained between the magnetic beads needs to be eluted. This method is time-consuming and has complex operation steps. It often takes a lot of time and effort to collect the target cells retained on the magnetic beads. During the elution process, some residual cells cannot be completely collected, reducing the separation purity. Furthermore, if the sample on the magnetic beads is not fully eluted, the magnetic beads cannot be effectively reused for magnetic separation, which makes the overall separation process inefficient. Summary of the Invention

[0003] The present invention aims to solve the technical problems of low separation purity and efficiency of magnetic separation devices in the prior art during magnetic separation, and provides a magnetic separation device and method.

[0004] In view of the above technical problems, an embodiment of the present invention provides a magnetic separation device, comprising at least one replaceable microfluidic chip, a first magnetic component having a first tooth tip, and a second magnetic component having a second tooth tip;

[0005] The tip of the first tooth tip and the tip of the second tooth tip are arranged parallel to each other and opposite to each other, forming a tip installation gap; the microfluidic chip is provided with a sorting channel having an outlet and an inlet; the extension direction of the first tooth tip is arranged parallel to the length direction of the microfluidic chip and the sorting channel; the microfluidic chip is detachably mounted in the tip installation gap, and the two opposite outer side walls of the microfluidic chip are in contact with the tips of the first tooth tip and the second tooth tip;

[0006] When the sample liquid flows into the inlet of the sorting channel located in the tip mounting gap, the immunomagnetic beads in the sample liquid are adsorbed on the two opposite inner walls corresponding to the first tooth tip and the second tooth tip in the sorting channel through the high gradient magnetic field generated between the first tooth tip and the second tooth tip.

[0007] An embodiment of the present invention further provides a magnetic separation method, which is performed by the above-mentioned magnetic separation device and includes:

[0008] After receiving a magnetic separation instruction including sample liquid parameters, determining a microfluidic chip according to the sample liquid parameters and the size parameters of the separation channel, and determining a preset magnetic field strength corresponding to the sample liquid parameters, the first tooth tip, and the second tooth tip;

[0009] installing the determined microfluidic chip in a tip installation gap formed between the first tooth tip and the second tooth tip;

[0010] When it is detected that the sample liquid flows into the inlet of the sorting channel located in the tip mounting gap, the immunomagnetic beads in the sample liquid are adsorbed on the two opposite inner walls of the sorting channel corresponding to the first tooth tip and the second tooth tip through the high gradient magnetic field of the preset magnetic field strength generated between the first tooth tip and the second tooth tip, and the remaining liquid in the sample liquid except the immunomagnetic beads continues to flow out from the outlet along the sorting channel to the first collection container.

[0011] The magnetic sorting device of the present invention includes at least one replaceable microfluidic chip, a first magnetic component having a first tooth tip, and a second magnetic component having a second tooth tip; the tip of the first tooth tip and the tip of the second tooth tip are arranged parallel to each other and form a tip mounting gap; a sorting channel having an outlet and an inlet is provided on the microfluidic chip; the extension direction of the first tooth tip is arranged parallel to the length direction of the microfluidic chip and the sorting channel; the microfluidic chip is detachably mounted in the tip mounting gap, and the two opposite outer side walls of the microfluidic chip are in contact with the tip of the first tooth tip and the tip of the second tooth tip; when the sample liquid flows into the inlet of the sorting channel located in the tip mounting gap, the immunomagnetic bead cells in the sample liquid are adsorbed on the two opposite inner walls corresponding to the first tooth tip and the second tooth tip in the sorting channel through the high gradient magnetic field generated between the first tooth tip and the second tooth tip.

[0012] In the magnetic sorting device and method of the present invention, a tip mounting gap is formed between the first tooth tip and the second tooth tip, and a replaceable microfluidic chip can be selected as needed and inserted and installed in the tip mounting gap. In this way, when the sample liquid flows into the inlet of the sorting channel located in the tip mounting gap, a high gradient magnetic field is generated in the tip mounting gap between the first tooth tip and the second tooth tip, and the high gradient magnetic field acts in the sorting channel of the microfluidic chip, thereby causing the immunomagnetic bead cells in the sample liquid flowing through the sorting channel to be efficiently and stably adsorbed on the two opposite inner walls of the sorting channel corresponding to the first tooth tip and the second tooth tip; and, in the present invention, the provision of the tip mounting gap between the first tooth tip and the second tooth tip increases the magnetic field gradient generated by the material matrix itself, thereby improving the accuracy of immunomagnetic bead cell sorting through the high gradient magnetic field in the sorting channel.

[0013] In addition, in the present invention, in the process of adsorbing the immunomagnetic bead cells in the sample liquid on the inner wall of the sorting channel, the immunomagnetic bead cells do not need to be in direct contact with the magnetic induction material matrix (i.e., the first tooth tip and the second tooth tip, etc.), nor do they need to collect target particles such as magnetic beads separately, and there is only one sorting channel, and there will be no problems such as the channel being rugged and difficult to clean caused by the stacking of magnetic beads. Therefore, the immunomagnetic bead cells in the sample liquid will eventually be collected to the maximum extent without waste, thereby improving the separation purity; and after the immunomagnetic bead cells are adsorbed on the inner wall of the sorting channel, the microfluidic chip can be directly disassembled and the next magnetic sorting can be performed through the first tooth tip, the second tooth tip, and the replaced new microfluidic chip. There is no need to wait for the immunomagnetic bead cells to be flushed from the sorting channel before a new round of magnetic sorting operation can be performed again, and effective and rapid reuse improves the separation efficiency. At the same time, the magnetic sorting device of the present invention has a simple structure and manufacture, low cost, easy operation and use, and is particularly suitable for multiple continuous sample separation scenarios, and its advantage of reuse further reduces the cost of use. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The present invention will be further described below with reference to the accompanying drawings and examples.

[0015] Figure 1 It is a perspective structural diagram of a magnetic separation device provided by one embodiment of the present invention.

[0016] Figure 2 It is a structural schematic diagram of a magnetic separation device provided by one embodiment of the present invention.

[0017] Figure 3 It is a right side view of the magnetic separation device provided by one embodiment of the present invention.

[0018] Figure 4 This is a flow chart of a magnetic separation method provided by one embodiment of the present invention.

[0019] The reference numerals in the specification are as follows:

[0020] 1. Microfluidic chip; 11. Sorting channel; 111. Inlet; 112. Outlet; 12. First card slot; 13. Second card slot; 2. First magnetic component; 21. First tooth tip; 3. Second magnetic component; 31. Second tooth tip; 4. Tip mounting gap. DETAILED DESCRIPTION

[0021] In order to make the technical problems, technical solutions and beneficial effects solved by the present invention more clearly understood, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0022] It should be understood that the terms "upper", "lower", "left", "right", "front", "back", "middle", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operate in a specific orientation, and therefore cannot be understood as a limitation of the present invention.

[0023] like Figures 1 to 3 As shown, an embodiment of the present invention provides a magnetic separation device, comprising at least one replaceable microfluidic chip 1, a first magnetic component 2 having a first tooth tip 21, and a second magnetic component 3 having a second tooth tip 31; the tip of the first tooth tip 21 and the tip of the second tooth tip 31 are arranged parallel to each other and form a tip installation gap 4; the microfluidic chip 1 is provided with a separation channel 11 having an outlet 112 and an inlet 111; the extension direction of the first tooth tip 21 is arranged parallel to the length direction of the microfluidic chip 1 and the separation channel 11; the microfluidic chip 1 The chip 1 can be detachably installed in the tip mounting gap 4, and the two opposite outer side walls of the microfluidic chip 1 are in contact with the tip of the first tooth tip 21 and the tip of the second tooth tip 31; it can be understood that in some embodiments, one or more first tooth tips 21 can be set on the first magnetic component 2, and one or more second tooth tips 31 can be set on the second magnetic component 3. In this way, when multiple first tooth tips 21 and multiple second tooth tips 31 are relatively arranged, the microfluidic chips 1 installed in multiple tip mounting gaps 4 can be magnetically sorted at the same time, thereby further improving the sorting efficiency.

[0024] In one embodiment, the first tooth tip 21 and the second tooth tip 31 are made of magnets. In this case, as long as the microfluidic chip 1 is placed in the tip mounting gap 4, it will be affected by the magnetic field formed between the first tooth tip 21 and the second tooth tip 31. Sample liquid can be injected into the sorting channel 11 at any time for magnetic sorting. In another embodiment, the first tooth tip 21 and the second tooth tip 31 are made of metal; the first magnetic component 2 also includes a first magnetic field generating mechanism (not shown) for controlling the first tooth tip 21 to generate a magnetic field; and the second magnetic component 3 also includes a second magnetic field generating mechanism (not shown) for controlling the second tooth tip 31 to generate a magnetic field. The first magnetic field generating mechanism and the second magnetic field generating mechanism are mechanisms that can cause the first tooth tip 21 and the second tooth tip 31 to generate or eliminate a magnetic field, such as electromagnetic mechanisms such as energized coils. The specific principles of generating or eliminating magnetic fields are not further described here. The first tooth tip 21 and the second tooth tip 31 are made of metal materials that can generate (or eliminate) a magnetic field under the action of the magnetic field generating mechanism. Furthermore, the material of the microfluidic chip 1 is non-metallic, so that the microfluidic chip 1 itself can be prevented from being interfered with by the magnetic field between the first tooth tip 21 and the second tooth tip 31, and thus, the magnetic sorting process of the sample liquid in the sorting channel 11 of the microfluidic chip 1 can be not interfered with.

[0025] Furthermore, if Figure 1 and Figure 3 As shown, the first tooth tip 21 and the second tooth tip 31 are both triangular prism-shaped; and the first tooth tip 21 and the second tooth tip 31 are equal in size. That is, in this embodiment, the first tooth tip 21 and the second tooth tip 31 are equal in size, side length, height and other dimensions, and the two sides of the first tooth tip 21 (the second tooth tip 31) connected to the tip of the microfluidic chip 1 are equal in length; in this way, the first tooth tip 21 and the second tooth tip 31 can be Figure 3The magnetic field strength generated on the upper and lower sides of the microfluidic chip 1 shown in the figure is consistent and balanced, which is conducive to improving the magnetic sorting effect. Furthermore, the first tooth tip 21 and the second tooth tip 31 are both in the shape of a regular triangular prism; at this time, the first tooth tip 21 and the second tooth tip 31 are symmetrically arranged with the center line of the microfluidic chip 1 parallel to the horizontal plane as the symmetry axis; it can be understood that the contact position of the tip of the first tooth tip 21 and the tip of the second tooth tip 31 with the microfluidic chip 1 are both located at a position opposite to the central axis of the sorting channel 11, so that the magnetic lines of force can be distributed more evenly in the sorting channel 11, further improving the magnetic sorting effect. In addition, the side length of the first tooth tip 21 in the shape of a regular triangular prism is 50mm-500mm. At this time, since the side length of the second tooth tip 31 in the shape of a regular triangular prism is equal to that of the first tooth tip 21, it is also within the range of 50mm-500mm. After testing, it was found that within the above side length range, the sorting effect of the sorting channel 11 installed in the tip installation gap 4 formed between the first tooth tip 21 and the second tooth tip 31 will be better.

[0026] When the sample liquid flows into the inlet 111 of the sorting channel 11 located in the tip mounting gap 4, the immunomagnetic beads in the sample liquid are adsorbed onto the two opposing inner walls of the sorting channel 11 corresponding to the first and second tooth tips 21 and 31 through the high gradient magnetic field generated between the first and second tooth tips 21 and 31. That is, a high magnetic field gradient is generated between the tip mounting gaps between the two opposing tips of the first and second tooth tips 21 and 31. At this time, when the sample liquid to be separated is introduced into the sorting channel 11 of the microfluidic chip 1 through the inlet 111, the magnetic immunomagnetic beads in the sample liquid are attracted and fixed onto the two opposing inner walls of the sorting channel 11 (the two inner walls corresponding to the two tips).

[0027] Furthermore, the magnetic field intensity range of the high gradient magnetic field generated between the first tooth tip 21 and the second tooth tip 31 is 0.01T-1T. Furthermore, the microfluidic chip 1 is rectangular; the height of the rectangular microfluidic chip 1 is 10mm-100mm. The width and length of the microfluidic chip 1 can be set according to the width and length of the first tooth tip 21. Thus, within the above-mentioned magnetic field intensity range and the height range of the microfluidic chip 1, the first position to adsorb the immunomagnetic bead cells will be the inner wall near the entrance 111. After the immunomagnetic bead cells are adsorbed at this position, its magnetism will weaken as the number of adsorbed immunomagnetic bead cells increases. At this time, the position will no longer attract immunomagnetic bead cells, and the unadsorbed immunomagnetic bead cells will continue to flow in the sorting channel 11 with the sample liquid and be attracted to the next position where no immunomagnetic bead cells are adsorbed or where less immunomagnetic bead cells are adsorbed. Thus, the entrance 111 of the sorting channel 11 will not be blocked. In an embodiment of the present invention, after all the sample liquid flows into the sorting channel 11 and the sorting is completed, the immunomagnetic bead cells are adsorbed on the inner wall of the sorting channel 11, and the remaining liquid in the sample liquid except the immunomagnetic bead cells continues to flow out from the outlet 112 along the sorting channel 11 and is collected. At this time, the microfluidic chip 1 can be directly removed for replacement, and the immunomagnetic bead cell liquid left in the sorting channel 11 can be directly collected (for example, by extracting and collecting through a syringe or injection pump, etc.) without the need for other complicated steps. In addition, after replacing the microfluidic chip 1, the magnetic sorting device can quickly enter the next round of work, and effective reuse greatly improves the separation yield and efficiency.

[0028] Understandably, compared to the method of magnetically sorting immunomagnetic bead cells by magnetic beads, the design of the tip mounting gap 4 and the microfluidic chip 1 in this embodiment can generate a high magnetic field gradient, and the immunomagnetic bead cells do not need to be in direct contact with the magnetic induction material matrix (that is, the first tooth tip 21 and the second tooth tip 31, etc.), nor do they need to collect target particles such as magnetic beads separately. There is only one sorting channel 11, and there will be no problems such as rugged channels and difficulty in cleaning caused by the stacking of magnetic beads. Therefore, the immunomagnetic bead cells in the sample liquid will be collected to the maximum extent without waste, thereby improving the separation purity. Moreover, the magnetic sorting device of the present invention is not only simple to manufacture, but also can be effectively reused to continuously perform a new round of sample separation operations, thereby greatly improving the separation yield and efficiency. Therefore, the present invention can achieve the effect of better separating immunomagnetic bead cells from non-magnetic substances, improving separation accuracy and purification rate.

[0029] In the magnetic separation device of the above embodiment of the present invention, a tip mounting gap 4 is formed between the first tooth tip 21 and the second tooth tip 31, and a replaceable microfluidic chip 1 can be selected as needed and inserted and installed in the tip mounting gap 4. In this way, when the sample liquid flows into the inlet 111 of the sorting channel 11 located in the tip mounting gap 4, a high gradient magnetic field is generated in the tip mounting gap 4 between the first tooth tip 21 and the second tooth tip 31, and the high gradient magnetic field acts on the sorting channel 11 of the microfluidic chip 1, thereby causing the immunomagnetic beads in the sample liquid flowing through the sorting channel 11 to be efficiently and stably adsorbed on the two opposite inner walls of the sorting channel 11 corresponding to the first tooth tip 21 and the second tooth tip 31; and, in the present invention, the provision of the tip mounting gap 4 between the first tooth tip 21 and the second tooth tip 31 enhances the magnetic field gradient generated by the material matrix itself, thereby improving the accuracy of immunomagnetic bead cell sorting through the high gradient magnetic field in the sorting channel 11.

[0030] In addition, in the present invention, in the process of adsorbing the immunomagnetic bead cells in the sample liquid on the inner wall of the sorting channel 11, the immunomagnetic bead cells do not need to directly contact the magnetic induction material matrix (that is, the first tooth tip 21 and the second tooth tip 31, etc.), nor do they need to collect target particles such as magnetic beads separately. There is only one sorting channel 11, and there will be no problems such as rugged channels caused by magnetic bead stacking and difficulty in cleaning. Therefore, the immunomagnetic bead cells in the sample liquid will be collected to the maximum extent without waste, thereby improving the separation purity. After the immunomagnetic bead cells are adsorbed on the inner wall of the sorting channel 11, the microfluidic chip 1 can be directly disassembled and the next magnetic sorting can be performed through the first tooth tip 21, the second tooth tip 31 and the replaced new microfluidic chip 1. There is no need to wait for the immunomagnetic bead cells to be flushed from the sorting channel 11 before a new round of magnetic sorting operation can be performed again. Effective and rapid reuse improves the separation efficiency. At the same time, the magnetic separation device of the present invention has a simple structure and manufacturing, low cost, and is easy to operate and use. It is particularly suitable for multiple continuous sample separation scenarios, and its advantage of reuse further reduces the cost of use.

[0031] In one embodiment, if Figure 3As shown, the microfluidic chip 1 has a first slot 12 and a second slot 13 respectively provided on two opposing outer walls; the first tooth tip 21 is retained in the first slot 12, with the tip of the first tooth tip 21 abutting against the bottom of the first slot 12; the second tooth tip 31 is retained in the second slot 13, with the tip of the second tooth tip 31 abutting against the bottom of the second slot 13. Specifically, a detachable microfluidic chip 1 can be retained in the tip mounting gap 4 (between the tip of the first tooth tip 21 and the tip of the second tooth tip 31) corresponding to the edges of the two regular triangular prisms. In this case, the first slot 12 and the second slot 13 can be provided on two opposing outer walls of the microfluidic chip 1 to secure the microfluidic chip 1. Furthermore, the first magnetic component 2 can also include a first driving member for controlling the first tooth tip 21 to approach or move away from the second tooth tip 31; the second magnetic component 3 also includes a second driving member for controlling the second tooth tip 31 to approach or move away from the first tooth tip 21; in this way, the size of the tip installation gap 4 between the first tooth tip 21 and the second tooth tip 31 can be driven by the first driving member and the second driving member to change, thereby facilitating the installation or disassembly of the microfluidic chip 1, thereby realizing the replaceability of the microfluidic chip 1.

[0032] In one embodiment, the first tooth tip 21 is provided with a first non-metallic buckle (not shown), which is used to retain the first tooth tip 21 in the first retaining groove 12. The second tooth tip 31 is provided with a second non-metallic buckle (not shown), which is used to retain the second tooth tip 31 in the second retaining groove 13. That is, in this embodiment, the first non-metallic buckle can be removably connected to the first retaining groove 12, and the second non-metallic buckle can be removably connected to the second retaining groove 13. In this way, the microfluidic chip 1 can be securely fixed between the tip mounting gap 4, thereby improving the magnetic separation effect in the separation channel 11.

[0033] In one embodiment, the tip of the first tooth tip 21 is provided with a first arc chamfer (not shown), and the tip of the first tooth tip 21 is in contact with the outer wall of the microfluidic chip 1 through the first arc chamfer; the tip of the second tooth tip 31 is provided with a second arc chamfer (not shown); the tip of the second tooth tip 31 is in contact with the outer wall of the microfluidic chip 1 through the second arc chamfer. It can be understood that in some embodiments of the present invention, the tips of the first tooth tip 21 and the second tooth tip 31 are sharp corners, which can complete the magnetic separation process of the present invention. However, the edges of the two regular triangular prisms corresponding to the tips of the first tooth tip 21 and the second tooth tip 31 can also be chamfered to form an arc shape (that is, the first arc chamfer and the second arc chamfer), and after the chamfering treatment, the magnetic field gradient generated by the tips of the arc-shaped first tooth tip 21 and the second tooth tip 31 is stronger (a higher magnetic field gradient is more conducive to the retention of magnetic substances, and thus is conducive to the adsorption and screening of immunomagnetic beads from the sample liquid), which can further improve the magnetic separation effect.

[0034] An embodiment of the present invention further provides a magnetic separation method, which is performed by the magnetic separation device described above. Figure 4 As shown, the method includes the following steps:

[0035] S10, after receiving a magnetic separation instruction including sample liquid parameters, the microfluidic chip 1 is determined based on the sample liquid parameters and the dimensional parameters of the separation channel 11, and a preset magnetic field strength corresponding to the sample liquid parameters, the first tooth tip 21, and the second tooth tip 31 is determined. The sample liquid parameters refer to the biological components contained in the sample liquid and their related parameters, such as the size of the immunomagnetic beads and other components contained therein, and the maximum magnetic field strength they can withstand. The dimensional parameters of the separation channel 11 refer to the length, width, and height of the separation channel 11. Based on the dimensional parameters of the separation channel 11 and the size of the immunomagnetic beads and other components in the sample liquid parameters, the type of microfluidic chip 1 to be used can be determined, so that the sample liquid flows smoothly and without obstruction through the separation channel 11 of the microfluidic chip 1. Furthermore, based on the dimensional parameters of the separation channel 11 and the size of the immunomagnetic beads and other components in the sample liquid parameters, a flow rate control strategy adapted to the magnetic separation process of the sample liquid can be determined to better control the flow rate of the sample liquid and improve separation efficiency.

[0036] At the same time, according to the corresponding extreme magnetic field strength that the immunomagnetic bead cells must withstand, and the magnetic field strength range of the magnetic field that can be generated in the tip installation gap 4 corresponding to the first tooth tip 21 and the second tooth tip 31 when they pass through the sorting channel 11, a larger preset magnetic field strength that does not exceed the extreme magnetic field strength can be determined (that is, the preset magnetic field strength corresponding to the sample liquid parameters, the first tooth tip 21 and the second tooth tip 31). While avoiding damage to the cells, the sorting accuracy can also be improved (a higher magnetic field gradient is more conducive to the retention of magnetic substances, and thus is conducive to the adsorption and screening of immunomagnetic bead cells from the sample liquid, and not exceeding the extreme magnetic field strength will not damage the immunomagnetic bead cells that need to be collected).

[0037] S20, the determined microfluidic chip 1 is installed in the tip installation gap 4 formed between the first tooth tip 21 and the second tooth tip 31; that is, the first magnetic component 2 can also include a first driving member for controlling the first tooth tip 21 to approach or move away from the second tooth tip 31; the second magnetic component 3 also includes a second driving member for controlling the second tooth tip 31 to approach or move away from the first tooth tip 21; in this way, the tip installation gap 4 between the first tooth tip 21 and the second tooth tip 31 can be driven to become larger by the first driving member and the second driving member, and then after the microfluidic chip 1 is placed therein, the tip installation gap 4 can be controlled to become smaller to achieve the installation of the microfluidic chip 1.

[0038] S30: Upon detecting the sample liquid flowing into the inlet 111 of the sorting channel 11 located in the tip mounting gap 4, a high-gradient magnetic field of a predetermined magnetic field strength is generated between the first tooth tip 21 and the second tooth tip 31, thereby adsorbing the immunomagnetic beads in the sample liquid onto the opposing inner walls of the sorting channel 11 corresponding to the first tooth tip 21 and the second tooth tip 31. The remaining liquid in the sample liquid, excluding the immunomagnetic beads, continues to flow out of the outlet 112 along the sorting channel 11 to the first collection container. In other words, the first collection container is used to collect the remaining liquid in the sample liquid, excluding the immunomagnetic beads; the immunomagnetic beads in the sample liquid will be separated and adsorbed in the sorting channel 11.

[0039] In one embodiment, the material of the first tooth tip 21 and the second tooth tip 31 is a magnet. At this time, after the microfluidic chip 1 is installed in the tip installation gap 4, a high gradient magnetic field of a preset magnetic field strength will be generated between the first tooth tip 21 and the second tooth tip 31. At this time, in step S10, it is necessary to select the tip installation gap 4 corresponding to the preset magnetic field strength for installation based on the parameters of the sample liquid to be separated (because the preset magnetic field strength cannot be changed after installation). In another embodiment, the material of the first tooth tip 21 and the second tooth tip 31 is metal; the first magnetic component 2 also includes a first magnetic field generating mechanism for controlling the first tooth tip 21 to generate a magnetic field; the second magnetic component 3 also includes a second magnetic field generating mechanism for controlling the second tooth tip 31 to generate a magnetic field. Among them, the first magnetic field generating mechanism and the second magnetic field generating mechanism refer to mechanisms that can cause the first tooth tip 21 and the second tooth tip 31 to generate or eliminate a magnetic field, such as an electromagnetic mechanism such as an energized coil. The specific principles of their generation or elimination of magnetic fields are not repeated here. At this time, in step S30, after the first magnetic field generating mechanism and the second magnetic field generating mechanism are started, they can directly control the generation of a magnetic field of a preset magnetic field strength in the sorting channel 11 located between the first tooth tip 21 and the second tooth tip 31, so that the inner wall of the sorting channel 11 adsorbs and sorts the immunomagnetic bead cells in the sample liquid.

[0040] In the magnetic sorting method of the present invention, a tip mounting gap 4 is formed between the first tooth tip 21 and the second tooth tip 31, and a replaceable microfluidic chip 1 can be selected as needed and inserted and installed in the tip mounting gap 4. In this way, when the sample liquid flows into the inlet 111 of the sorting channel 11 located in the tip mounting gap 4, a high gradient magnetic field is generated in the tip mounting gap 4 between the first tooth tip 21 and the second tooth tip 31, and the high gradient magnetic field acts on the sorting channel 11 of the microfluidic chip 1, thereby causing the immunomagnetic bead cells in the sample liquid flowing through the sorting channel 11 to be efficiently and stably adsorbed on the two opposite inner walls of the sorting channel 11 corresponding to the first tooth tip 21 and the second tooth tip 31; and, in the present invention, the provision of the tip mounting gap 4 between the first tooth tip 21 and the second tooth tip 31 enhances the magnetic field gradient generated by the material matrix itself, thereby improving the accuracy of immunomagnetic bead cell sorting through the high gradient magnetic field in the sorting channel 11.

[0041] In addition, in the present invention, in the process of adsorbing the immunomagnetic bead cells in the sample liquid on the inner wall of the sorting channel 11, the immunomagnetic bead cells do not need to directly contact the magnetic induction material matrix (that is, the first tooth tip 21 and the second tooth tip 31, etc.), nor do they need to collect target particles such as magnetic beads separately. There is only one sorting channel 11, and there will be no problems such as rugged channels caused by magnetic bead stacking and difficulty in cleaning. Therefore, the immunomagnetic bead cells in the sample liquid will be collected to the maximum extent without waste, thereby improving the separation purity. After the immunomagnetic bead cells are adsorbed on the inner wall of the sorting channel 11, the microfluidic chip 1 can be directly disassembled and the next magnetic sorting can be performed through the first tooth tip 21, the second tooth tip 31 and the replaced new microfluidic chip 1. There is no need to wait for the immunomagnetic bead cells to be flushed from the sorting channel 11 before a new round of magnetic sorting operation can be performed again. Effective and rapid reuse improves the separation efficiency. At the same time, the magnetic separation device of the present invention has a simple structure and manufacturing, low cost, and is easy to operate and use. It is particularly suitable for multiple continuous sample separation scenarios, and its advantage of reuse further reduces the cost of use.

[0042] In one embodiment, the magnetic separation device further includes a first sensing device arranged at the inlet 111 of the sorting channel 11, and a second sensing device arranged at the outlet 112 of the sorting channel 11; before step S30, that is, before detecting that the sample liquid flows into the inlet 111 of the sorting channel 11 located in the tip mounting gap 4, it includes: detecting whether the sample liquid flows into the inlet 111 of the sorting channel 11 by the first sensing device; wherein the first sensing device may include but is not limited to a sensing device such as a flow sensor that can detect the flow state of the fluid, which is arranged at the inlet 111 of the sorting channel 11.

[0043] Furthermore, after step S30, that is, after the high gradient magnetic field of the preset magnetic field strength is generated between the first tooth tip 21 and the second tooth tip 31, the immunomagnetic beads in the sample liquid are adsorbed on two opposite inner walls of the sorting channel 11 corresponding to the first tooth tip 21 and the second tooth tip 31, and the remaining liquid in the sample liquid except the immunomagnetic beads continues to flow out of the outlet 112 along the sorting channel 11 to the first collection container, the method further includes:

[0044] After the second sensing device detects that no liquid has flowed out of the outlet 112 of the sorting channel 11, the microfluidic chip 1 is removed from the tip mounting gap 4, and the immunomagnetic beads in the microfluidic chip 1 that have been separated from the inner wall of the sorting channel 11 due to the elimination of the magnetic field are collected into a second collection container. The second collection container is used to collect the immunomagnetic beads in the sample liquid.

[0045] Understandably, the second sensing device may include, but is not limited to, a flow sensor or other sensing device capable of detecting fluid flow conditions, and is disposed at the outlet 112 of the sorting channel 11. Specifically, when the second sensing device detects that no liquid has flowed out of the outlet 112 of the sorting channel 11, it indicates that the remaining liquid in the sample liquid, except for the immunomagnetic beads, has flowed out, and the immunomagnetic beads in the sample liquid will be separated and adsorbed in the sorting channel 11. At this time, the microfluidic chip 1 can be directly removed from the tip installation gap 4 for replacement. Understandably, the microfluidic chip 1 is removed from the tip installation gap 4 (understandably, the tip installation gap 4 between the first tooth tip 21 and the second tooth tip 31 can be driven to become larger by the above-mentioned first driving member and the second driving member, thereby removing the microfluidic chip 1; and after the new microfluidic chip 1 is put in again, the tip installation gap 4 is controlled to become smaller to achieve the replacement of the microfluidic chip 1), so that the magnetic field in the sorting channel 11 disappears. At this time, the immune magnetic bead cells in the sorting channel 11 are no longer affected by the magnetic field and are adsorbed on the inner wall of the sorting channel 11, and can be collected. Moreover, after replacing the microfluidic chip 1, the magnetic sorting device can quickly enter the next round of work, and effective reuse greatly improves the separation yield and efficiency.

[0046] In one embodiment, the immunomagnetic bead-containing cell solution remaining in the sorting channel 11 is directly withdrawn via a syringe or syringe pump and collected into a second collection container, without requiring any other complex steps. In another embodiment, a cleaning fluid can be injected into the inlet 111 of the sorting channel 11 to flush the immunomagnetic bead-containing cells that have detached from the inner wall of the sorting channel 11 out of the outlet 112 of the sorting channel 11 and collect them into a second collection container, thereby completing magnetic sorting. The cleaning fluid can be a reagent such as a cell culture medium or a buffer.

[0047] The above are merely embodiments of the magnetic separation device and method of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A magnetic separation device, characterized in that: The microfluidic chip comprises at least one replaceable microfluidic chip, a first magnetic component having a first tooth tip, and a second magnetic component having a second tooth tip; The tip of the first tooth tip and the tip of the second tooth tip are arranged parallel to each other and opposite to each other, forming a tip installation gap; the microfluidic chip is provided with a sorting channel having an outlet and an inlet; the extension direction of the first tooth tip is arranged parallel to the length direction of the microfluidic chip and the sorting channel; the microfluidic chip is detachably mounted in the tip installation gap, and the two opposite outer side walls of the microfluidic chip are in contact with the tips of the first tooth tip and the second tooth tip; When the sample liquid flows into the inlet of the sorting channel located in the tip installation gap, the immunomagnetic beads in the sample liquid are adsorbed on the two opposite inner walls of the sorting channel corresponding to the first tooth tip and the second tooth tip due to the high gradient magnetic field generated between the first tooth tip and the second tooth tip; A first slot and a second slot are respectively provided on two opposite outer side walls of the microfluidic chip; the first tooth tip is retained in the first slot, and the tip of the first tooth tip is in contact with the bottom of the first slot; the second tooth tip is retained in the second slot, and the tip of the second tooth tip is in contact with the bottom of the second slot; The first tooth tip is provided with a first non-metallic buckle, and the first tooth tip is clamped in the first clamping groove by the first non-metallic buckle; the second tooth tip is provided with a second non-metallic buckle, and the second tooth tip is clamped in the second clamping groove by the second non-metallic buckle; The tip of the first tooth tip is provided with a first arc chamfer, and the tip of the first tooth tip is in contact with the outer wall of the microfluidic chip through the first arc chamfer; The tips of the second tooth tips are each provided with a second arc chamfer; the tips of the second tooth tips are fitted with the outer side wall of the microfluidic chip through the second arc chamfer.

2. The magnetic separation device according to claim 1, characterized in that The first tooth tip and the second tooth tip are both triangular prism-shaped; and the first tooth tip and the second tooth tip are equal in size.

3. The magnetic separation device according to claim 2, characterized in that The first tooth tip and the second tooth tip are both in the shape of a regular triangular prism; the side length of the regular triangular prism-shaped first tooth tip is 50 mm-500 mm.

4. The magnetic separation device according to claim 1, characterized in that The magnetic field strength range of the high gradient magnetic field generated between the first tooth tip and the second tooth tip is 0.01T-1T.

5. The magnetic separation device according to claim 1, characterized in that The first tooth tip and the second tooth tip are made of magnets; or The first tooth tip and the second tooth tip are made of metal; the first magnetic component also includes a first magnetic field generating mechanism for controlling the first tooth tip to generate a magnetic field; the second magnetic component also includes a second magnetic field generating mechanism for controlling the second tooth tip to generate a magnetic field.

6. A magnetic separation method, characterized in that: The magnetic separation method is performed by the magnetic separation device according to any one of claims 1 to 5, and the method comprises: After receiving a magnetic separation instruction including sample liquid parameters, determining a microfluidic chip according to the sample liquid parameters and the size parameters of the separation channel, and determining a preset magnetic field strength corresponding to the sample liquid parameters, the first tooth tip, and the second tooth tip; installing the determined microfluidic chip in a tip installation gap formed between the first tooth tip and the second tooth tip; When it is detected that the sample liquid flows into the inlet of the sorting channel located in the tip mounting gap, the immunomagnetic beads in the sample liquid are adsorbed on the two opposite inner walls of the sorting channel corresponding to the first tooth tip and the second tooth tip through the high gradient magnetic field of the preset magnetic field strength generated between the first tooth tip and the second tooth tip, and the remaining liquid in the sample liquid except the immunomagnetic beads continues to flow out from the outlet along the sorting channel to the first collection container.

7. The magnetic separation method according to claim 6, characterized in that: The magnetic separation device further comprises a first induction device provided at the entrance of the separation channel, and a second induction device provided at the exit of the separation channel; Before detecting that the sample liquid flows into the inlet of the sorting channel located in the tip installation gap, the method includes: detecting, by the first sensing device, whether the sample liquid flows into the inlet of the sorting channel; After the immunomagnetic beads in the sample liquid are adsorbed on two opposing inner walls of the sorting channel corresponding to the first and second tooth tips by the high gradient magnetic field of a preset magnetic field strength generated between the first tooth tip and the second tooth tip, and the remaining liquid in the sample liquid except the immunomagnetic beads continues to flow out of the outlet along the sorting channel to the first collection container, the method further includes: After the second sensing device detects that no liquid has flowed out of the outlet of the sorting channel, the microfluidic chip is removed from the tip mounting gap, and the immunomagnetic bead cells in the microfluidic chip that have detached from the inner wall of the sorting channel due to the elimination of the magnetic field are collected into a second collection container.

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