Magnetic sorting container, apparatus and method, and medium

Abstract

A magnetic sorting container (1), apparatus and method, and a medium. The magnetic sorting container (1) comprises an upper plate (10), a lower plate, and an outer frame (20) connected between the upper plate (10) and the lower plate; a magnetic sorting space (30) is defined among the upper plate (10), the lower plate, and the outer frame (20); the magnetic sorting container (1) further comprises a plurality of flow guide strips (40) connected between the upper plate (10) and the lower plate; the flow guide strips (40) are arranged at intervals in the magnetic sorting space (30); the outer frame (20) is provided with at least two outlet / inlet groups (201); each outlet / inlet group (201) comprises two outlets / inlets (2011) oppositely arranged on two opposite sides of the outer frame (20). The container ensures the stability of a flow field, improves the magnetic sorting efficiency and effect, and thus achieves an overall increase in the magnetic sorting speed.

Description

Magnetic separation container, device, method and medium

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on July 17, 2023, with application number 202310876898.8, and invention name “Magnetic separation container, device, method and medium”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present application relates to the field of cell separation technology, and in particular to a magnetic separation container, device, method and medium. Background Art

[0003] At present, in the field of cell therapy, micron magnetic beads are often used to specifically bind to target cells so that the target cells have magnetic markers. After the target cells have magnetic markers, they can be screened out using the magnetic force of a magnetic separation column (i.e., magnetic separation is performed by a magnetic separation column), which has the effect of purifying or removing the target cells. However, the inventors have found that with the development of the cell therapy industry, the operation of the process has become more diverse, which has put forward higher requirements for the adsorption effect. For example, some processes require that when the cells and magnetic beads are not dissociated, it is necessary to realize high-purity collection of magnetic markers. However, in this process, the undissociated cells increase the projected area of ​​the magnetic markers, thereby increasing the fluid force, making the original magnetic force traction effect insufficient, greatly affecting the magnetic separation effect and efficiency; and in other processes, since the volume of the cell fluid to be processed is very large, reaching more than 10L, the processing speed of magnetic separation of the cell fluid by a magnetic separation column is too slow, and the processing efficiency is too low.

[0004] Application Contents

[0005] The embodiments of the present application provide a magnetic separation container, device, method and medium to solve the problems of low efficiency of magnetic separation processing in the prior art.

[0006] A magnetic separation container, comprising an upper plate, a lower plate, and an outer frame connected between the upper plate and the lower plate; a magnetic separation space is enclosed between the upper plate, the lower plate, and the outer frame; the magnetic separation container further comprises a plurality of guide bars connected between the upper plate and the lower plate; the guide bars are arranged at intervals within the magnetic separation space;

[0007] At least two groups of entrances and exits are provided on the outer frame; each group of the entrances and exits includes two entrances and exits arranged on opposite sides of the outer frame, and each of the entrances and exits is connected to the magnetic separation space.

[0008] A magnetic separation device comprises a magnetic plate and the above-mentioned magnetic separation container; the magnetic plate is used to adsorb magnetic markers in a sample liquid flowing through a magnetic separation space onto the top surface of a lower plate placed in contact with the magnetic plate during magnetic separation.

[0009] A magnetic separation method, wherein the magnetic separation device performs magnetic separation by the magnetic separation method, and the magnetic separation method comprises:

[0010] Filling the magnetic separation space with non-magnetic liquid from the inlet of the outer frame, wherein the inlet refers to the inlet of all inlet and outlet groups located on the first side of the outer frame;

[0011] The sample liquid carrying magnetic markers in the sample container is injected into the magnetic separation space from the inlet, and the magnetic markers in the flowing sample liquid are adsorbed on the top surface of the lower plate by the magnetic plate to remove the magnetic markers in the sample liquid flowing out of the outlet; the outlet refers to the inlet and outlet of each inlet and outlet group located on the second side of the outer frame.

[0012] One or more readable storage media storing computer-readable instructions, wherein when the computer-readable instructions are executed by one or more processors, the one or more processors are caused to implement the following steps:

[0013] Filling the magnetic separation space with non-magnetic liquid from the inlet of the outer frame, wherein the inlet refers to the inlet of all inlet and outlet groups located on the first side of the outer frame;

[0014] The sample liquid carrying magnetic markers in the sample container is injected into the magnetic separation space from the inlet, and the sample liquid is guided to flow toward the outlet by the guide bar. At the same time, during the flow process, the magnetic markers in the sample liquid are adsorbed on the top surface of the lower plate by the magnetic plate to remove the magnetic markers in the sample liquid flowing out of the outlet; the outlet refers to the inlet and outlet of each inlet and outlet group located on the second side of the outer frame.

[0015] The above-mentioned magnetic separation container, device, method and medium, the magnetic separation container includes an upper plate, a lower plate and an outer frame connected between the upper plate and the lower plate; the upper plate, the lower plate and the outer frame form a magnetic separation space; the magnetic separation container also includes a plurality of guide bars connected between the upper plate and the lower plate; each of the guide bars is arranged at intervals in the magnetic separation space; at least two groups of inlet and outlet groups are provided on the outer frame; each group of the inlet and outlet groups includes two inlet and outlet groups arranged on opposite sides of the outer frame, and each of the inlet and outlet groups is connected to the magnetic separation space.

[0016] The present application uses the outer frame of the magnetic separation container and the guide strips to provide hard support for the upper and lower plates, thereby ensuring that the magnetic separation space will not experience deformations such as bulging and collapse that are easily caused by soft liquid bags, thereby ensuring that the flow field shape in the magnetic separation space will not be deformed, ensuring the stability of the flow field, and ensuring the magnetic separation effect; at the same time, since the magnetic separation container in the present application is hard supported by the outer frame and the guide strips, the magnetic separation space has a correspondingly larger fluid cross-section, thereby allowing a very low flow rate to be maintained when a large flow rate passes through the above-mentioned larger fluid cross-section, and the very low flow rate also applies a low fluid force to the magnetic marker. At this time, the magnetic force will be the dominant force causing the magnetic marker to move. In this way, under the condition of equal magnetic force, the present application reduces the fluid force of the fluid movement, thereby improving the magnetic separation efficiency and effect, and thereby improving the overall magnetic separation speed.

[0017] The details of one or more embodiments of the disclosure are set forth in the accompanying drawings and the description below, and other features and advantages of the disclosure will be apparent from the description, the drawings, and the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments of the present application. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0019] FIG1 is a schematic structural diagram of a magnetic separation container according to an embodiment of the present application;

[0020] FIG2 is a flow chart of a magnetic separation container according to an embodiment of the present application;

[0021] FIG3 is a schematic diagram of a fluid simulation in a magnetic separation container according to an embodiment of the present application;

[0022] FIG4 is a schematic diagram of a computer device in an embodiment of the present application.

[0023] The figures in the specification are as follows: 1. Magnetic separation container; 10. Upper plate; 20. Outer frame; 201. Inlet and outlet group; 2011. Inlet and outlet; 2012. Guide bell mouth; 30. Magnetic separation space; 40. Guide bar; 401. Through hole; 2. Magnetic plate. DETAILED DESCRIPTION

[0024] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are part of the embodiments of this application, not all of them. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0025] 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 this application 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 operated in a specific orientation, and therefore should not be understood as a limitation of this application.

[0026] In the description of this application, it should be noted that, unless otherwise expressly specified or limited, the terms "installed," "provided with," "mounted / connected," and "connected" should be understood in a broad sense. For example, "connected" can mean a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, or it can be internal communication between two components. Those skilled in the art will understand the specific meanings of the above terms in this application based on the specific circumstances.

[0027] In one embodiment, as shown in FIG1 , the present application provides a magnetic separation container 1, comprising an upper plate 10, a lower plate, and an outer frame 20 connected between the upper plate 10 and the lower plate; a magnetic separation space 30 is enclosed between the upper plate 10, the lower plate, and the outer frame 20; the magnetic separation container 1 further comprises a plurality of guide bars 40 connected between the upper plate 10 and the lower plate; each of the guide bars 40 is arranged at intervals in the magnetic separation space 30; wherein the magnetic separation container 1 comprises an upper plate 10 located above the outer frame 20 and a lower plate located below the outer frame 20, and the spacing between the upper plate 10 and the lower plate is 2- 5mm, wherein, since when magnetic separation is required by magnetic force, the bottom surface of the lower plate of the magnetic separation container 1 will be placed on the magnetic plate 2, so that the magnetic markers are adsorbed on the top surface of the lower plate by the magnetic force generated by the magnetic plate 2. Therefore, in order to make the same magnetic force produce a better adsorption effect (the lower plate is isolated between the magnetic markers in the sample liquid and the magnetic plate 2, and has a certain blocking effect on the magnetic force), the lower plate can be set to be thinner. In one embodiment, the thickness of the lower plate ranges from 0.1mm to 5mm. Within this thickness range, the adsorption effect of the magnetic separation container 1 when performing magnetic separation at the lower plate position is better. Since the upper plate 10 does not isolate the magnetic force, the thickness of the upper plate 10 can be designed according to needs and is not limited. The thickness of the upper plate 10 can be less than 5mm or greater than 5mm.

[0028] It is understandable that the guide strip 40 includes but is not limited to the waist shape shown in FIG. 1 , and may also be an elliptical shape, a rectangular shape, etc., as long as the guide effect can be achieved.

[0029] At least two groups of inlet and outlet groups 201 are provided on the outer frame 20; each group of the inlet and outlet groups 201 includes two inlet and outlet groups 2011 arranged on opposite sides of the outer frame 20, and each of the inlet and outlet groups 201 is connected to the magnetic separation space 30. It is understandable that in the present application, the shape and size of each inlet and outlet 2011 can be set according to requirements. For example, it can be set as a regularly symmetrical cylindrical through hole or a trumpet shape, etc.; it can also be set as an irregular shape, as long as it can facilitate the entry and exit of fluids such as sample liquid as required. The position setting of each inlet and outlet group 2011 can also be set according to requirements. For example, it can be relatively set on opposite sides of the outer frame 20. The two can be symmetrically arranged with the outer frame 20 as a reference, or they can be asymmetrically arranged.

[0030] Specifically, as shown in Figure 1, the opposite two ends of outer frame 20 have entrances and exits 2011. In the present application, the entrance and exit 2011 at any one end of outer frame 20 can all be used as an exit or entrance at the same time, and the entrance and exit 2011 at the other end is then correspondingly set to an entrance or exit corresponding thereto. That is, if the entrance and exit 2011 at one end of outer frame 20 is an exit, the entrance and exit 2011 at the other end is an entrance. The quantity of the entrance and exit 2011 on each side of outer frame 20 can all be set to 2-6, and the quantity of the entrance and exit 2011 at two ends is equal, and the entrance and exit 2011 at two ends is preferably a symmetrical design structure. That is, in one embodiment, each entrance and exit 2011 all has a central axis and each entrance and exit 2011 is all symmetrically arranged with its own central axis as an axis of symmetry. But the central axes of the two entrances and exits 2011 in the same group of entrance and exit group 201 can overlap or not overlap.

[0031] In a further embodiment, the central axes of the two inlets 2011 in any inlet and outlet group 201 coincide with each other, and the central axis of each inlet and outlet 2011 is arranged parallel to all the guide bars 40. The guide bars 40 and inlets 2011 are designed according to this embodiment, thereby achieving a better flow guidance effect for the sample liquid within the magnetic separation space 30.

[0032] In this embodiment, the upper plate 10 and the lower plate clamp the outer frame 20 and form a magnetic separation space 30, and a plurality of parallel arranged guide bars 40 are provided in the center of the magnetic separation space 30. Furthermore, the guide bars 40 can limit the speed and direction of the fluid in the magnetic separation space 30. At the same time, the guide bars 40 themselves are hard structures, and can also strengthen the overall rigidity of the magnetic separation container 1 together with the outer frame 20, thereby achieving the effect of hard support for the upper plate 10 and the lower plate through the outer frame 20 and the guide bars 40, ensuring that the magnetic separation space 30 will not undergo deformations such as bulging and collapse that are prone to occur in soft liquid bags, thereby ensuring that the flow field shape in the magnetic separation space 30 will not be deformed, ensuring the stability of the flow field, and ensuring the magnetic separation effect.

[0033] In one embodiment, as shown in FIG1 , the plurality of guide strips 40 are arranged as a plurality of discontinuous guide strips spaced parallel to each other. Each discontinuous guide strip includes at least two guide strips 40 spaced apart, and the discontinuous guide strips extend in a direction parallel to the central axis of the inlet and outlet. That is, the discontinuous guide strips extend in a direction parallel to the central axis of the inlet and outlet, include at least two guide strips 40 spaced apart, and are used to guide the flow direction of the sample liquid in the magnetic separation space. It is understandable that since the central axis of each inlet and outlet 2011 is parallel to all the guide strips 40, and the discontinuous guide strips include at least two guide strips 40 spaced apart, and extend in a direction parallel to the central axis of the inlet and outlet, the discontinuous guide strips extend in a direction parallel to the guide strips, that is, they extend along the length of the guide strips 40.

[0034] In this embodiment, a plurality of guide strips 40 are arranged into a plurality of discontinuous guide strips, and all the guide strips 40 in each discontinuous guide strip are arranged on the same straight line (extending along the length direction of the guide strip) and are discontinuous and have gaps. In this way, the sample liquid entering from the inlet and outlet 2011 can be guided in an orderly manner by the above-mentioned discontinuous guide strips, and the discontinuous guide strips will prevent vortices from being generated in the magnetic separation space 30 (the generation of vortices will cause the sample liquid to flow out of the inlet and outlet 2011 unsmoothly), thereby further improving the efficiency and effect of magnetic separation.

[0035] In one embodiment, at least one discontinuous flow guide strip is provided between each of the two inlets and outlets 2011 in any group of the inlet and outlet groups 201, and the centerline of one of the discontinuous flow guide strips coincides with the center axes of the two inlets and outlets 2011 in the group of the inlet and outlet groups 201. That is, in this embodiment, as shown in FIG1 and FIG3 , at least one discontinuous flow guide strip is provided between each of the two inlets and outlets 2011, and the centerline of one of the discontinuous flow guide strips coincides with the center axes of the two inlets and outlets 2011 in the group of the inlet and outlet groups 201. In this way, no vortex is generated in the flow channel within the magnetic separation space 30 corresponding to each group of the inlet and outlet groups 201, the sample liquid can flow stably, and the flow field is stable and controllable, thereby further improving the efficiency and effect of magnetic separation.

[0036] In one embodiment, the upper plate 10, the lower plate, the guide bar 40, and the outer frame 20 are a split connection structure. In this embodiment, the upper plate 10 and the outer frame 20 and the guide bar 40, as well as the lower plate and the outer frame 20 and the guide bar 40, can be connected by bonding or thermoforming. Specifically, when the thickness of the upper plate 10 and the lower plate is less than 0.6 mm (for example, a thickness of 0.2 mm-0.5 mm, preferably 0.4 mm or 0.5 mm), it can be considered that they are in a relatively soft film shape. In this case, thermoforming may cause them to break and no longer have sealing properties. Therefore, it is better to use bonding. When the thickness is greater than or equal to 0.6 mm, they are in a plate shape with a certain hardness. In this case, thermoforming is better, but bonding is also acceptable.

[0037] Specifically, when the thickness of the upper plate 10 and the lower plate are both less than 0.6 mm, the upper plate 10 and the outer frame 20 and the guide bar 40, as well as the lower plate and the outer frame 20 and the guide bar 40, are preferably connected by bonding.

[0038] When the thickness of the upper plate 10 and the lower plate are both greater than or equal to 0.6 mm, the upper plate 10 and the outer frame 20 and the guide bar 40, as well as the lower plate and the outer frame 20 and the guide bar 40, are preferably connected by hot pressing.

[0039] When the thickness of the upper plate 10 is greater than or equal to 0.6 mm and the thickness of the lower plate is less than 0.6 mm, the upper plate 10 is preferably connected to the outer frame 20 and the guide bar 40 by hot pressing; the lower plate is preferably connected to the outer frame 20 and the guide bar 40 by bonding.

[0040] When the thickness of the lower plate is greater than or equal to 0.6 mm and the thickness of the upper plate 10 is less than 0.6 mm, the lower plate and the outer frame 20 and the guide strip 40 are preferably connected by hot pressing; the upper plate 10 and the outer frame 20 and the guide strip 40 are preferably connected by bonding.

[0041] In another embodiment, the upper plate 10, the guide bar 40 and the outer frame 20 are an integrally formed structure, and the lower plate is connected to the outer frame 20 and the end of the guide bar 40 away from the upper plate 10. In this case, the upper plate 10, the outer frame 20 and the guide bar 40 are an integral structure, and the lower plate needs to be connected to the integral structure in a direction away from the upper plate 10. In this case, the lower plate and the integral structure can be connected by bonding or hot pressing. Specifically, when the thickness of the lower plate is greater than or equal to 0.6 mm, the lower plate is preferably connected to the outer frame 20 and the guide bar 40 by hot pressing. When the thickness of the lower plate is less than 0.6 mm, the lower plate is preferably connected to the outer frame 20 and the guide bar 40 by bonding.

[0042] The present application ensures that the magnetic separation space 30 will not deform, such as bulging and collapse, which is easy to occur in soft liquid bags, by the hard support of the outer frame 20 and the guide bar 40 of the magnetic separation container 1, thereby ensuring that the flow field shape in the magnetic separation space 30 will not be deformed, ensuring the stability of the flow field, and ensuring the magnetic separation effect; at the same time, since the magnetic separation container 1 in the present application is hard supported by the outer frame 20 and the guide bar 40, the magnetic separation space 30 has a larger fluid cross-section, and thus when a larger flow rate passes through the above-mentioned larger fluid cross-section, a very low flow rate can be maintained. The very low flow rate also exerts a low fluid force on the magnetic marker. At this time, the magnetic force will be the dominant force causing the movement of the magnetic marker. In this way, under the condition of equal magnetic force, the present application reduces the fluid force of the fluid movement, thereby improving the magnetic separation efficiency and effect, and thus improving the magnetic separation speed as a whole.

[0043] In one embodiment, the diversion distance of each of the guide strips 40 is greater than a preset distance threshold; the diversion distance refers to the minimum distance between the guide strip 40 and each of the inlets and outlets 2011. Furthermore, the preset distance threshold is 5mm-50mm. For example, the diversion distances corresponding to the guide strips 40 shown in FIG1 need to be less than the preset distance threshold, and the preset distance threshold needs to be selected from a value range of 5mm-50mm as needed. In a further embodiment, if the center line of the discontinuous guide strip coincides with the center axis of the inlet and outlet 2011, then the diversion distance is the distance between the end point of the guide strip 40 close to the inlet and outlet 2011 and the inlet and outlet 2011; the above-mentioned diversion distance is set so that when the sample liquid flows into the inlet or flows out of the outlet, there is sufficient flow space to avoid the sample liquid from flowing unsmoothly.

[0044] In one embodiment, as shown in Figures 1 and 3, the two inlets 2011 in each inlet and outlet group 201 are symmetrically arranged relative to a target flow guide zone; the target flow guide zone is a discontinuous flow guide zone whose central axis coincides with the central axis of the two inlets 2011 in the inlet and outlet group 201; the inlets 2011 include a guide bell mouth 2012, through which the inlets 2011 communicate with the magnetic separation space 30; the diameter of the guide bell mouth 2012 of each inlet and outlet 2011 gradually increases from a direction away from the target flow guide zone toward a direction closer to the target flow guide zone. In this embodiment, the two inlets 2011 in the inlet and outlet group 201 include an inlet and an outlet, and after the sample liquid flows from the inlet, it will flow into the magnetic separation space 30 through the guidance of the guide bell mouth 2012, and finally flow out of the inlet under the guidance of the guide bell mouth 2012. In a further embodiment, if the center line of the discontinuous guide strip coincides with the center axis of the entrance and exit 2011, the guide bell mouth 2012 is preferably designed symmetrically with the center line of the discontinuous guide strip as the axis of symmetry, thereby achieving a better guiding effect.

[0045] In one embodiment, the lower plate and the guide bar 40 are bonded together, and the guide bar 40 is provided with a through hole 401 for injecting glue to bond the lower plate and the guide bar 40. It is understood that when the guide bar 40 is a solid structure, if the lower plate and the guide bar 40 are bonded together, bonding can be achieved by simply applying glue to the bonding surfaces of the lower plate and the guide bar 40 and then butting them together.

[0046] However, when a first through hole 401 is provided on the guide bar 40, if the guide bar 40, the outer frame 20 and the upper plate 10 are a separate structure, at this time, the lower plate and the guide bar 40 can be bonded first (the lower plate can be connected last), that is, glue is applied to the bonding surface of the lower plate and the guide bar 40 to bond the two. However, if after bonding, it is found that the bonding effect is not good (even when it is about to fall off), glue can be injected from the end of the through hole 401 away from the lower plate, so that the glue overflows from the connection position between the guide bar 40 and the lower plate (the position where the connection is not firm and there is a gap), so as to further reinforce the connection between the guide plate and the lower plate. It can be understood that if the guide bar 40, the outer frame 20 and the upper plate 10 are an integrally formed structure, at this time, the guide bar 40, the outer frame 20 and the upper plate 10 are an integral structure, and the through hole 401 will directly penetrate the guide bar 40 and the upper plate 10. Therefore, the glue can also be injected from the end of the through hole 401 away from the lower plate, thereby causing the glue to overflow from the connection position between the guide bar 40 and the lower plate, further reinforcing the guide plate and the lower plate.

[0047] In one embodiment, the magnetic separation container 1 further includes a first tube group and a second tube group; the first tube group includes a first main line and a number of first branch tubes equal to the number of the inlet and outlet groups 201; the first ends of the first branch tubes converge at a common point to connect to the first main line, and the second ends of the first branch tubes are connected one-to-one to the inlets and outlets 2011 located on the first side of the outer frame 20; the second tube group includes a second main line and a number of second branch tubes equal to the number of the inlet and outlet groups 201; the first ends of the second branch tubes converge at a common point to connect to the second main line, and the second ends of the second branch tubes are connected one-to-one to the inlets and outlets 2011 located on the second side of the outer frame 20. That is, the first tube group and the second tube group are connected to the outlet and inlet ends of the inlets and outlets 2011 of the outer frame 20, respectively; that is, when the first tube group is connected to the outlet, the second tube group is connected to the inlet; when the first tube group is connected to the inlet, the second tube group is connected to the outlet. By configuring the first tube group and the second tube group in multiple ways, they can correspond to different outlets of the outlet end and different inlets of the inlet section.

[0048] In one embodiment, all first branches are of equal length; all second branches are of equal length. That is, when all branches within the same tube set (either the first or second tube set) are of equal length, the flow paths within each branch are of equal length, thereby ensuring that the flow resistance of the sample liquid entering and exiting each inlet and outlet 2011 is as uniform as possible, thereby improving flow field stability. In a further embodiment, the first and second branches are of equal length and have the same dimensions, facilitating preparation.

[0049] In one embodiment, the magnetic separation container 1 also includes a flow channel frame connected to the end face of the upper plate 10 facing away from the outer frame 20, and a top plate connected to the side of the flow channel frame facing away from the upper plate 10, and a first flow channel connecting each of the inlets and outlets 2011 located on the first side of the outer frame 20 is formed between the flow channel frame, the upper plate 10 and the top plate, and a second flow channel connecting each of the inlets and outlets 2011 located on the second side of the outer frame 20.

[0050] That is, in this embodiment, the magnetic separation container 1 is configured as a two-layer structure, and the first and second flow channels are integrated into the upper layer of the upper plate 10. Thus, the first and second flow channels are integrated into the magnetic separation container 1, rather than being scattered and cluttered as pipelines, making the entire magnetic separation container 1 more compact and compact. Furthermore, the first and second flow channels respectively connect to the outlet and inlet ends of the inlet and outlet 2011 of the outer frame 20. When the first flow channel connects to the outlet, the second flow channel connects to the inlet; when the first flow channel connects to the inlet, the second flow channel connects to the outlet.

[0051] In one embodiment, the first flow channel includes a first main channel and a plurality of first branches equal in number to the inlet and outlet groups 201, the first ends of each of the first branches converge at a common point to connect to the first main channel, and the second ends of each of the first branches are connected one-to-one to each of the inlets and outlets 2011 located on the first side of the outer frame 20; the second flow channel includes a second main channel and a plurality of second branches equal in number to the inlet and outlet groups 201, the first ends of each of the second branches converge at a common point to connect to the second main channel, and the second ends of each of the second branches are connected one-to-one to each of the inlets and outlets 2011 located on the second side of the outer frame 20. That is, this embodiment divides the first flow channel and the second flow channel into multiple channels through the above-mentioned one-to-many arrangement, so that they can correspond one-to-one to different outlets of the outlet end and different inlets of the inlet section.

[0052] In one embodiment, all first branches are of equal length; all second branches are of equal length. That is, when all branches within the same flow channel (first or second) are of equal length, the lengths of the flow channels in each branch are equal, thereby maximizing the flow resistance of the sample liquid entering and exiting each inlet and outlet 2011, thereby improving flow field stability. In a further embodiment, the first and second branches are of equal length and have consistent dimensions, facilitating fabrication.

[0053] In one embodiment, a magnetic separation device is provided, comprising a magnetic plate 2 and the magnetic separation container 1 of the above-described embodiment. The magnetic plate 2 is configured to adsorb magnetic markers in a sample fluid flowing through a magnetic separation space 30 onto the top surface of a lower plate placed adjacent thereto during magnetic separation. It is understood that the magnetic markers may be magnetically labeled cells. For specific definitions of the magnetic separation device, reference may be made to the above-described definitions of the magnetic separation container 1 and are not further elaborated here. The magnetic separation device may further comprise a controller configured to execute the magnetic separation method described below. For specific definitions of the controller, reference may be made to the above-described definitions of the magnetic separation container 1 and the magnetic separation method and are not further elaborated here. The various modules in the controller may be implemented in whole or in part via software, hardware, or a combination thereof. The modules may be embedded in or independent of the processor in the controller in hardware form, or may be stored in the controller's memory in software form, so that the processor can call and execute the corresponding operations of the modules.

[0054] In one embodiment, as shown in FIG2 , a magnetic separation method is provided. The magnetic separation device in the above embodiment performs magnetic separation by the magnetic separation method. The magnetic separation method includes the following steps:

[0055] S10: Fill the magnetic separation space 30 with non-magnetic liquid from the entrance of the outer frame 20, where the entrance refers to the entrance 2011 of all the entrance and exit groups 201 located on the first side of the outer frame 20. It is understood that when the magnetic markers are magnetically labeled cells, the magnetic separation container 1 can be filled with non-magnetic liquid (the magnetic separation container 1 can be tilted if necessary) to empty the air, etc., in the magnetic separation container 1. It is understood that the above-mentioned non-magnetic liquid refers to a liquid that does not contain substances that have an adsorption effect on magnets and is allowed by the corresponding cells in the labeled magnetic objects (that is, after the liquid is mixed with the sample liquid, it will not damage the cells corresponding to the magnetic markers in the sample liquid). The non-magnetic liquid needs to be pre-filled before the sample liquid is injected to empty the air, etc. in the magnetic separation container 1. It is understood that the non-magnetic liquid includes but is not limited to physiological saline or culture medium.

[0056] S20: The sample liquid carrying the magnetic marker in the sample container is injected into the magnetic separation space 30 from the inlet, and the sample liquid is guided to flow toward the outlet by the guide bar 40. At the same time, during the flow process, the magnetic markers in the sample liquid are adsorbed on the top surface of the lower plate by the magnetic plate 2 to remove the magnetic markers in the sample liquid flowing out of the outlet; the outlet refers to the inlet and outlet 2011 of each inlet and outlet group 201 located on the second side of the outer frame 20. In a further embodiment, by specifically configuring the structure of the guide bar 40, the guide effect of the guide bar 40 can be used to guide the sample liquid toward the outlet without vortexes. That is, vortex-free flow means that no vortexes are generated during the sample liquid's flow from the inlet to the outlet. In this way, the stability of the flow field in the magnetic separation space 30 is further guaranteed, thereby ensuring the magnetic separation effect.

[0057] It is understandable that after the magnetic separation space 30 is filled with non-magnetic liquid, the bottom surface of the lower plate of the magnetic separation container 1 can be pressed against the magnetic plate 2, and if necessary, the upper plate 10 of the magnetic separation container 1 can be pressed with a pressure cover, so that the magnetic separation container 1 is stably fixed on the magnetic plate 2, thereby making the magnetic separation effect better. It is understandable that in the last magnetic separation process, the magnetic separation container 1 and the magnetic plate 2 can actually be placed parallel to the horizontal plane, or the magnetic separation container 1 and the magnetic plate 2 can be placed together at a certain angle. In the present application, the first side and the second side are not fixed sides, but correspond to the opposite sides of the outer frame 20 with the entrance and exit 2011. That is, as shown in Figure 1, the opposite sides of the outer frame 20 have entrances and exits 2011. In the present application, all the entrances and exits 2011 on the second side of the outer frame 20 can also be used as entrances at the same time. At this time, all the entrances and exits 2011 on the first side of the outer frame 20 become exits. In the present application, the number of the entrances and exits 2011 on each side of the outer frame 20 can be set to 2-6, and the number of the entrances and exits 2011 at both ends is equal, and the entrances and exits 2011 at both ends are preferably symmetrically designed structures. In the present application, the magnetic markers in the sample liquid flowing out of the outlet will be adsorbed on the lower plate, and then, there will be basically no magnetic markers in the sample liquid flowing out of the outlet, thereby achieving accurate separation of the magnetic markers. If you want to collect the above-mentioned magnetic markers later, you only need to inject non-magnetic liquid from the inlet again, separate the magnetic separation container 1 from the magnetic plate 2 or remove the magnetism of the magnetic plate 2, so that the magnetic markers are no longer adsorbed on the lower plate, but flow out of the outlet with the non-magnetic liquid, thereby achieving the collection of the magnetic markers.

[0058] The present application ensures that the magnetic separation space 30 will not deform, such as bulging and collapse, which is easy to occur in soft liquid bags, by the hard support of the outer frame 20 and the guide bar 40 of the magnetic separation container 1, thereby ensuring that the flow field shape in the magnetic separation space 30 will not be deformed, ensuring the stability of the flow field, and ensuring the magnetic separation effect; at the same time, since the magnetic separation container 1 in the present application is hard supported by the outer frame 20 and the guide bar 40, the magnetic separation space 30 has a larger fluid cross-section, and thus when a larger flow rate passes through the above-mentioned larger fluid cross-section, a very low flow rate can be maintained. The very low flow rate also exerts a low fluid force on the magnetic marker. At this time, the magnetic force will be the dominant force causing the movement of the magnetic marker. In this way, under the condition of equal magnetic force, the present application reduces the fluid force of the fluid movement, thereby improving the magnetic separation efficiency and effect, and thus improving the magnetic separation speed as a whole.

[0059] It should be understood that the size of the serial numbers of the steps in the above embodiments does not mean the order of execution. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of this application.

[0060] In one embodiment, a computer device is provided, which can be a client or a server, and its internal structure diagram can be shown in Figure 4. The computer device includes a processor, a memory, a network interface and a database connected via a system bus. Among them, the processor of the computer device is used to provide computing and control capabilities. The memory of the computer device includes a readable storage medium and an internal memory. The readable storage medium stores an operating system, computer-readable instructions and a database. The internal memory provides an environment for the operation of the operating system and computer-readable instructions in the readable storage medium. The network interface of the computer device is used to communicate with an external terminal via a network connection. When the computer-readable instructions are executed by the processor, the above-mentioned magnetic separation method is implemented. The readable storage medium provided in this embodiment includes a non-volatile readable storage medium and a volatile readable storage medium.

[0061] In one embodiment, a computer device is provided, including a memory, a processor, and computer-readable instructions stored in the memory and executable on the processor. When the processor executes the computer-readable instructions, the following steps are implemented:

[0062] Filling the magnetic separation space with non-magnetic liquid from the inlet of the outer frame, wherein the inlet refers to the inlet of all inlet and outlet groups located on the first side of the outer frame;

[0063] The sample liquid carrying magnetic markers in the sample container is injected into the magnetic separation space from the inlet, and the sample liquid is guided to flow toward the outlet by the guide bar. At the same time, during the flow process, the magnetic markers in the sample liquid are adsorbed on the top surface of the lower plate by the magnetic plate to remove the magnetic markers in the sample liquid flowing out of the outlet; the outlet refers to the inlet and outlet of each inlet and outlet group located on the second side of the outer frame.

[0064] In one embodiment, one or more readable storage media storing computer-readable instructions are provided, wherein when the computer-readable instructions are executed by one or more processors, the one or more processors implement the above-mentioned magnetic separation method. Specifically, in a specific embodiment, when the computer-readable instructions are executed by one or more processors, the one or more processors implement the following steps:

[0065] Filling the magnetic separation space with non-magnetic liquid from the inlet of the outer frame, wherein the inlet refers to the inlet of all inlet and outlet groups located on the first side of the outer frame;

[0066] The sample liquid carrying magnetic markers in the sample container is injected into the magnetic separation space from the inlet, and the sample liquid is guided to flow toward the outlet by the guide bar. At the same time, during the flow process, the magnetic markers in the sample liquid are adsorbed on the top surface of the lower plate by the magnetic plate to remove the magnetic markers in the sample liquid flowing out of the outlet; the outlet refers to the inlet and outlet of each inlet and outlet group located on the second side of the outer frame.

[0067] Those skilled in the art will understand that all or part of the processes in the above-mentioned embodiment methods can be implemented by instructing related hardware through computer-readable instructions. The computer-readable instructions can be stored in a non-volatile readable storage medium or a volatile readable storage medium. When the computer-readable instructions are executed, they can include the processes of the embodiments of the above-mentioned methods. Among them, any reference to memory, storage, database or other media used in the embodiments provided in this application may include non-volatile and / or volatile memory. Non-volatile memory may include read-only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM) or flash memory. Volatile memory may include random access memory (RAM) or external cache memory. By way of illustration and not limitation, RAM is available in many forms, such as static RAM (SRAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), double data rate SDRAM (DDRSDRAM), enhanced SDRAM (ESDRAM), Synchronous Link DRAM (SLDRAM), Rambus direct RAM (RDRAM), direct memory bus dynamic RAM (DRDRAM), and memory bus dynamic RAM (RDRAM), etc.

[0068] Those skilled in the art will clearly understand that for the sake of convenience and brevity of description, only the division of the above-mentioned functional units and modules is used as an example. In actual applications, the above-mentioned functions can be distributed and completed by different functional units and modules as needed, that is, the internal structure of the device can be divided into different functional units or modules to complete all or part of the functions described above.

[0069] The above-described embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. These modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present application, and should all be included in the scope of protection of the present application.

Claims

1. A magnetic separation container, wherein: The magnetic separation container comprises an upper plate, a lower plate and an outer frame connected between the upper plate and the lower plate; a magnetic separation space is enclosed between the upper plate, the lower plate and the outer frame; the magnetic separation container further comprises a plurality of guide bars connected between the upper plate and the lower plate; the guide bars are arranged at intervals in the magnetic separation space; At least two groups of inlet and outlet groups are arranged on the outer frame; each group of the inlet and outlet groups includes two inlet and outlet groups arranged on opposite sides of the outer frame, and each of the inlet and outlet groups is connected to the magnetic separation space.

2. The magnetic separation container according to claim 1, wherein: The diversion distance of each of the guide strips is greater than a preset distance threshold; the diversion distance refers to the minimum distance between the guide strip and each of the entrances and exits.

3. The magnetic separation container according to claim 2, wherein: The preset distance threshold is 5mm-50mm.

4. The magnetic separation container according to claim 1, wherein: The central axes of the two inlets and outlets in any group of the inlets and outlets coincide with each other; and the central axis of each of the inlets and outlets is arranged parallel to all of the guide strips.

5. The magnetic separation container according to claim 4, wherein: The plurality of guide strips are arranged as a plurality of discontinuous guide strips arranged in parallel and at intervals; each of the discontinuous guide strips includes at least two guide strips arranged at intervals, and the extension direction of each of the discontinuous guide strips is parallel to the central axis of the entrance and exit.

6. The magnetic separation container according to claim 5, wherein: At least one discontinuous guide belt is provided between two inlets and outlets in any group of the inlet and outlet groups, and the center line of one of the discontinuous guide belts coincides with the center axes of the two inlets and outlets in the group of the inlet and outlet groups.

7. The magnetic separation container according to claim 5, wherein: The two inlets and outlets in each group of the inlet and outlet groups are symmetrically arranged relative to the target guide belt; the target guide belt refers to the discontinuous guide belt that coincides with the central axes of the two inlets and outlets in the group of the inlet and outlet groups; The inlet and outlet include a guide bell mouth; from the direction away from the target guide belt toward the direction close to the target guide belt, the diameter of the guide bell mouth of each of the inlet and outlet gradually increases.

8. The magnetic separation container according to claim 1, wherein: The upper plate, the lower plate, the guide strip and the outer frame are a separate connection structure; or The upper plate, the guide bar and the outer frame are an integrally formed structure, and the lower plate is connected to the outer frame and an end of the guide bar away from the upper plate.

9. The magnetic separation container according to claim 1, wherein: The thickness of the lower plate ranges from 0.1 mm to 5 mm.

10. The magnetic separation container according to claim 1, wherein: The lower plate and the guide bar are bonded together, and the guide bar is provided with a through hole for injecting glue to bond the lower plate and the guide bar.

11. The magnetic separation container according to claim 1, wherein: The magnetic separation container further comprises a first tube group and a second tube group; the first tube group comprises a first main pipe and a first branch pipe having the same number as the inlet and outlet groups; the first ends of the first branch pipes converge at the same point to connect to the first main pipe, and the second ends of the first branch pipes are connected to the inlets and outlets located on the first side of the outer frame one by one; The second pipe group includes a second main pipe and second branch pipes whose number is equal to that of the inlet and outlet group; the first ends of the second branch pipes converge at the same point to connect to the second main pipe, and the second ends of the second branch pipes are connected to the inlets and outlets located on the second side of the outer frame in a one-to-one correspondence.

12. The magnetic separation container according to claim 11, wherein: The lengths of all the first branches are equal; the lengths of all the second branches are equal.

13. The magnetic separation container according to claim 1, wherein: The magnetic separation container also includes a flow channel frame connected to the end surface of the upper plate facing away from the outer frame, and a top plate connected to the side of the flow channel frame facing away from the upper plate, and a first flow channel connecting the inlets and outlets located on the first side of the outer frame is formed between the flow channel frame, the upper plate and the top plate, and a second flow channel connecting the inlets and outlets located on the second side of the outer frame.

14. The magnetic separation container according to claim 13, wherein: The first flow channel includes a first main flow channel and a plurality of first branches equal in number to the inlet and outlet groups, the first ends of the first branches converge at the same point to connect to the first main flow channel, and the second ends of the first branches are connected to the inlets and outlets located on the first side of the outer frame one by one; The second flow channel includes a second main channel and a plurality of second branches equal in number to the inlet and outlet groups, the first ends of the second branches converge at the same point to connect to the second main channel, and the second ends of the second branches are connected one-to-one to the inlets and outlets located on the second side of the outer frame.

15. The magnetic separation container according to claim 14, wherein: The lengths of all the first branches are equal; the lengths of all the second branches are equal.

16. A magnetic separation device, wherein: It comprises a magnetic plate and a magnetic separation container as described in any one of claims 1 to 15; the magnetic plate is used to adsorb magnetic markers in the sample liquid flowing through the magnetic separation space onto the top surface of the lower plate placed in contact with it during magnetic separation.

17. A magnetic separation method, wherein: The magnetic separation device according to claim 16 performs magnetic separation by the magnetic separation method; the magnetic separation method comprises: Filling the magnetic separation space with non-magnetic liquid from the inlet of the outer frame, wherein the inlet refers to the inlet of all inlet and outlet groups located on the first side of the outer frame; The sample liquid carrying magnetic markers in the sample container is injected into the magnetic separation space from the inlet, and the sample liquid is guided to flow toward the outlet by the guide strip. At the same time, during the flow process, the magnetic markers in the sample liquid are adsorbed on the top surface of the lower plate by the magnetic plate to remove the magnetic markers in the sample liquid flowing out of the outlet; the outlet refers to the inlet and outlet of each inlet and outlet group located on the second side of the outer frame.

18. One or more computer-readable storage media storing computer-readable instructions, wherein: When the computer readable instructions are executed by one or more processors, the one or more processors implement the following steps: Filling the magnetic separation space with non-magnetic liquid from the inlet of the outer frame, wherein the inlet refers to the inlet of all inlet and outlet groups located on the first side of the outer frame; The sample liquid carrying magnetic markers in the sample container is injected into the magnetic separation space from the inlet, and the sample liquid is guided to flow toward the outlet by the guide strip. At the same time, during the flow process, the magnetic markers in the sample liquid are adsorbed on the top surface of the lower plate by the magnetic plate to remove the magnetic markers in the sample liquid flowing out of the outlet; the outlet refers to the inlet and outlet of each inlet and outlet group located on the second side of the outer frame.

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