Magnetic separation container, apparatus, method and medium

Abstract

The invention discloses a magnetic separation container, device and method and a medium. 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 defined by the upper plate, the lower plate and the outer frame; the magnetic separation container further comprises a plurality of flow guide strips connected between the upper plate and the lower plate. The flow guide strips are arranged in the magnetic separation space at intervals; the outer frame is provided with at least two inlet and outlet sets. Each entrance and exit group comprises two entrance and exits which are oppositely arranged on two opposite sides of the outer frame. According to the invention, the stability of a flow field is ensured, the magnetic separation efficiency and effect are improved, and the magnetic separation speed is integrally improved.

Description

Technical Field

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

[0002] 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 the magnetic sorting column (that is, magnetic sorting is performed through the magnetic sorting column), which has the effect of purifying or removing the target cells. However, 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 the magnetic markers be collected at high purity when the cells and magnetic beads are not dissociated. 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 sorting effect and efficiency; in other processes, because the volume of the cell fluid to be processed is very large, reaching more than 10L, the processing speed of magnetic sorting of the cell fluid through the magnetic sorting column is too slow and the processing efficiency is too low. Summary of the invention

[0003] The embodiments of the present invention provide a magnetic separation container, device, method and medium to solve the problems of low efficiency of magnetic separation processing in the prior art.

[0004] 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 in the magnetic separation space;

[0005] 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.

[0006] 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.

[0007] A magnetic separation method, wherein the magnetic separation device performs magnetic separation by the magnetic separation method, and the magnetic separation method comprises:

[0008] 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;

[0009] 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 from 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.

[0010] A computer-readable storage medium stores a computer program, and the computer program implements the magnetic separation method when executed by a processor.

[0011] 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 relatively arranged on opposite sides of the outer frame, and each of the inlet and outlet groups is connected to the magnetic separation space.

[0012] The present invention ensures that the magnetic separation space will not be deformed by bulging, collapsing, etc. that are easily caused by soft liquid bags through the hard support of the upper and lower plates by the outer frame of the magnetic separation container and the guide strips, 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 invention is hard supported by the outer frame and the guide strips, the magnetic separation space has a correspondingly larger fluid cross-section, so that when a larger flow rate passes through the above-mentioned larger fluid cross-section, a very low flow rate can be maintained, and the fluid force applied to the magnetic marker by the very low flow rate is also low. 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 having the same magnetic force, the present invention 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. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for use in the description of the embodiments of the present invention will be briefly introduced below. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying creative labor.

[0014] Figure 1 is a schematic structural diagram of a magnetic separation container in one embodiment of the present invention;

[0015] Figure 2 is a flow chart of a magnetic separation container in one embodiment of the present invention;

[0016] Figure 3 is a schematic diagram of fluid simulation in a magnetic separation container in one embodiment of the present invention;

[0017] Figure 4 is a schematic diagram of a computer device in one embodiment of the present invention.

[0018] The reference numerals in the specification are as follows:

[0019] 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 strip; 401. Through hole; 2. Magnetic plate. DETAILED DESCRIPTION

[0020] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0021] It should be understood that the directions or positional relationships indicated by terms such as "upper", "lower", "left", "right", "front", "back", and "middle" are based on the directions or positional relationships shown in the accompanying drawings and are only used to facilitate the description of the present invention and simplify the description. They do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as a limitation of the present invention.

[0022] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "provided with", "mounted / connected", "connected", etc. should be understood in a broad sense. For example, "connected" can be 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 it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0023] In one embodiment, if Figure 1As shown, the present invention 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 also includes 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 has an upper plate 10 located above the outer frame 20 and a lower plate located below the outer frame 20, the spacing between the upper plate 10 and the lower plate is 2-5 mm, and the magnetic separation container 1 has ... the magnetic separation container 1 has a plurality of guide bars 40 connected between the upper plate 10 and the lower plate; the magnetic separation container 1 has a plurality of guide bars 40 connected between the upper plate 10 and the lower plate; the magnetic separation container 1 has a plurality of guide bars 40 connected between the upper plate 10 and the lower plate; the magnetic separation container 1 has a plurality of guide bars 40 connected between the upper plate 10 and the lower plate; the magnetic separation container 1 has a plurality of guide bars 40 connected between the upper plate 10 and the lower plate; the magnetic separation container 1 has a plurality of guide bars 40 connected between the upper plate 10 and the lower plate; the magnetic separation container 1 has a plurality of guide bars 40 connected between the upper plate 10 and the lower plate In the embodiment, 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 to use the magnetic force generated by the magnetic plate 2 to adsorb the magnetic markers on the top surface of the lower plate. Therefore, in order to make the same magnetic force produce a better adsorption effect (the lower plate is isolated between the magnetic markers of the sample liquid and the magnetic plate 2, which has a certain barrier 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 magnetic separation container 1 has a better adsorption effect when performing magnetic separation at the lower plate position. Since the upper plate 10 does not isolate the magnetic force, the thickness of the upper plate 10 can be designed according to the needs without limitation. The thickness of the upper plate 10 can be less than 5mm or greater than 5mm.

[0024] It can be understood that the guide strip 40 includes but is not limited to Figure 1 The waist shape shown in the figure can also be an elliptical, rectangular, etc. as long as the diversion effect can be achieved.

[0025] 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 invention, the shape and size of each inlet and outlet 2011 can be set according to requirements, for example, it can be set as a regular symmetrical cylindrical through hole or a trumpet shape, etc.; it can also be set to an irregular shape, as long as it can facilitate the entry and exit of fluids such as sample liquid as required. And 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, and the two can be symmetrically set with the outer frame 20 as a reference, or they can be asymmetrically set.

[0026] Specifically, Figure 1As shown, the opposite two ends of the outer frame 20 have an entrance and exit 2011. In the present invention, the entrance and exit 2011 at any end of the outer frame 20 can be used as an exit or an entrance at the same time, and the entrance and exit 2011 at the other end is correspondingly set to an entrance or an exit corresponding thereto, that is, if the entrance and exit 2011 at one end of the outer frame 20 is an exit, the entrance and exit 2011 at the other end is an entrance. The number of the entrance and exit 2011 on each side of the outer frame 20 can be set to 2-6, and the number of the entrance and exit 2011 at both ends is equal, and the entrance and exit 2011 at both ends is preferably a symmetrical design structure. That is, in one embodiment, each entrance and exit 2011 has a central axis and each entrance and exit 2011 is symmetrically arranged with its own central axis as a symmetric axis. However, the central axes of the two entrances and exits 2011 in the same group of the entrance and exit group 201 can overlap or not overlap.

[0027] In a further embodiment, the central axes of the two inlets 2011 in any group of the inlet and outlet groups 201 are coincident, and the central axis of each inlet and outlet 2011 is arranged parallel to all the guide bars 40. The guide bars 40 and the inlets and outlets 2011 are designed with reference to this embodiment, and the guiding effect of the sample liquid in the magnetic separation space 30 will be better.

[0028] In this embodiment, the upper plate 10 and the lower plate clamp the outer frame 20 to form a magnetic separation space 30, and a plurality of parallel arranged guide strips 40 are provided in the center of the magnetic separation space 30. Furthermore, the guide strips 40 can limit the speed and direction of the fluid in the magnetic separation space 30. At the same time, the guide strips 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 strips 40, ensuring that the magnetic separation space 30 will not have deformations such as bulging and collapse that are easy 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.

[0029] In one embodiment, if Figure 1As shown, the plurality of guide strips 40 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 40 arranged at intervals, and the extension direction of the discontinuous guide strip is parallel to the central axis of the inlet and outlet. That is, the discontinuous guide strip refers to a guide strip whose extension direction is parallel to the central axis of the inlet and outlet, and includes at least two guide strips 40 arranged at intervals, and is used to guide the fluid flow direction of the sample liquid in the magnetic separation space. It can be understood that since the central axis of each of the inlets and outlets 2011 is arranged in parallel with all the guide strips 40, and the discontinuous guide strip refers to at least two guide strips 40 arranged at intervals, and the extension direction of the discontinuous guide strip is parallel to the central axis of the inlet and outlet, therefore, the extension direction of the discontinuous guide strip is arranged in parallel with the guide strip, that is, the discontinuous guide strip extends along the length direction of the guide strip 40.

[0030] In this embodiment, a plurality of guide strips 40 are arranged as a plurality of discontinuous guide belts, and all the guide strips 40 in each discontinuous guide belt are arranged on the same straight line (extending along the length direction of the guide belt) 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 belts, and the discontinuous guide belts 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.

[0031] In one embodiment, at least one discontinuous guide strip is provided between two inlets 2011 in any group of inlet and outlet groups 201, and the center line of one of the discontinuous guide strips coincides with the center axis of the two inlets 2011 in the inlet and outlet group 201. That is, in this embodiment, Figure 1 and Figure 3 As shown, at least one discontinuous guide belt is arranged between the two entrances and exits 2011, and the center line of a discontinuous guide belt between the two entrances and exits 2011 in any group of the entrance and exit groups 201 coincides with the center axis of the two entrances and exits 2011 in the group of the entrance and exit groups 201. In this way, no vortex will be generated in the flow channel in the magnetic separation space 30 corresponding to each group of the entrance and exit 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.

[0032] In one embodiment, the upper plate 10, the lower plate, the guide strip 40 and the outer frame 20 are split connection structures. In this embodiment, the upper plate 10 and the outer frame 20 and the guide strip 40, as well as the lower plate and the outer frame 20 and the guide strip 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, the thickness is 0.2 mm-0.5 mm, preferably 0.4 mm or 0.5 mm), it can be considered that it is in a softer film shape, at this time, it may be damaged by thermoforming and no longer have sealing properties, so it is better to use bonding at this time; and when the thickness is greater than or equal to 0.6 mm, it is in a plate shape with a certain hardness, at this time, it can be better to perform thermoforming, but bonding is also acceptable.

[0033] 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.

[0034] 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.

[0035] 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 and the outer frame 20 and the guide strip 40 are preferably connected by hot pressing; the lower plate and the outer frame 20 and the guide strip 40 are preferably connected by bonding.

[0036] 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.

[0037] 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. At this time, 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. At this time, the lower plate and the integral structure can be connected by bonding or thermoforming. 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 thermoforming. 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.

[0038] The present invention 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 hard support of the upper plate 10 and the lower plate by the outer frame 20 and the guide strip 40 of the magnetic separation container 1, thereby ensuring that the flow field shape in the magnetic separation space 30 will not deform, 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 invention is hard supported by the outer frame 20 and the guide strip 40, the magnetic separation space 30 has a larger fluid cross-section, so that when a larger flow rate passes through the above-mentioned larger fluid cross-section, a very low flow rate can be maintained, and the fluid force applied to the magnetic marker by the very low flow rate is also low. 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 invention reduces the fluid force of fluid movement, thereby improving the magnetic separation efficiency and effect, and thus improving the magnetic separation speed as a whole.

[0039] In one embodiment, the diversion distance of each of the diversion strips 40 is greater than a preset distance threshold; the diversion distance refers to the minimum distance between the diversion strip 40 and each of the inlets and outlets 2011. Further, the preset distance threshold is 5mm-50mm. For example, Figure 1 The diversion distances corresponding to the diversion strips 40 shown in the figure need to be less than a preset distance threshold, and the preset distance threshold needs to be selected from a range of 5mm-50mm as required. In a further embodiment, if the center line of the discontinuous diversion 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 diversion strip 40 close to the inlet and outlet 2011 and the inlet and outlet 2011; the diversion distance is set so that when the sample liquid flows in from the inlet or out from the outlet, there is enough flow space to avoid unsmooth flow of the sample liquid.

[0040] In one embodiment, if Figure 1 and Figure 3As shown, the two inlets 2011 in each inlet and outlet group 201 are symmetrically arranged relative to the target flow guide belt; the target flow guide belt refers to the discontinuous flow guide belt that coincides with the central axis of the two inlets 2011 in the inlet and outlet group 201; the inlet and outlet 2011 includes a guide bell mouth 2012, and the inlet and outlet 2011 is connected to the magnetic separation space 30 through the guide bell mouth 2012; from the direction away from the target flow guide belt to the direction close to the target flow guide belt, the diameter of the guide bell mouth 2012 of each inlet and outlet 2011 gradually increases. In this embodiment, the two inlets and outlets 2011 in the inlet and outlet group 201 include an inlet and an outlet, and after the sample liquid flows into the inlet, it will flow into the magnetic separation space 30 through the guiding effect of the guide bell mouth 2012, and finally flow out from the inlet under the guidance of the guide bell mouth 2012. In a further embodiment, if the center line of the discontinuous guide belt coincides with the center axis of the entrance 2011, then the guide bell mouth 2012 is preferably designed symmetrically with the center line of the discontinuous guide belt as the axis of symmetry, thereby providing a better guiding effect.

[0041] In one embodiment, the lower plate and the guide bar 40 are bonded, 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 can be understood that when the guide bar 40 is a solid structure, if the lower plate and the guide bar 40 are bonded, at this time, it is only necessary to apply glue on the bonding surface of the lower plate and the guide bar 40 and butt them to achieve bonding.

[0042] 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 separate structures, at this time, the lower plate and the guide bar 40 can be bonded first (and 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, thereby further reinforcing the guide plate and the lower plate.

[0043] 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 first branch tube equal in number to the inlet and outlet groups 201; the first ends of the first branch tubes converge at the same point to connect to the first main line, and the second ends of the first branch tubes correspond to each of 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 second branch tube equal in number to the inlet and outlet groups 201; the first ends of the second branch tubes converge at the same point to connect to the second main line, and the second ends of the second branch tubes correspond to each of 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 respectively connected to the outlet end and the inlet end of the inlet and outlet 2011 of the outer frame 20; that is, when the first tube group is connected to the outlet end, the second tube group is connected to the inlet end; when the first tube group is connected to the inlet end, the second tube group is connected to the outlet end. 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 one by one.

[0044] In one embodiment, the lengths of all the first branches are equal; the lengths of all the second branches are equal. That is, when the lengths of all the branches in the same tube set (the first tube set or the second tube set) are equal, it means that the lengths of the flow channels in each branch are equal, so that the flow resistance of the sample liquid entering and exiting each inlet and outlet 2011 is as even as possible, thereby improving the stability of the flow field. In a further embodiment, the lengths of the first branch and the second branch are equal, and the sizes of the two are consistent, which is convenient for preparation.

[0045] In one embodiment, the magnetic separation container 1 also includes a flow channel frame connected to the end surface 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 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 the inlets and outlets 2011 located on the second side of the outer frame 20.

[0046] That is, in this embodiment, the magnetic separation container 1 is set to two layers, and then the first flow channel and the second flow channel are integrated in the upper layer of the upper plate 10; in this way, the first flow channel and the second flow channel are integrated in the magnetic separation container 1, rather than being scattered and messy as pipelines, so that the entire magnetic separation container 1 is more concise, compact and small in size. At the same time, the first flow channel and the second flow channel are respectively connected to the outlet end and the inlet end of the inlet and outlet 2011 of the outer frame 20; when the first flow channel is connected to the outlet end, the second flow channel is connected to the inlet end; when the first flow channel is connected to the inlet end, the second flow channel is connected to the outlet end.

[0047] In one embodiment, 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 201, 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 correspond 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 flow channel and a plurality of second branches equal in number to the inlet and outlet groups 201, the first ends of the second branches converge at the same point to connect to the second main flow channel, and the second ends of the second branches correspond to each of the inlets and outlets 2011 located on the second side of the outer frame 20. That is, in this embodiment, the first flow channel and the second flow channel are divided into multiple ones through the above-mentioned one-to-many settings, so that they can correspond to each other and connect different outlets of the outlet end and different inlets of the inlet section.

[0048] In one embodiment, the lengths of all the first branches are equal; the lengths of all the second branches are equal. That is, when the lengths of all branches in the same flow channel (the first flow channel or the second flow channel) are equal, it means that the lengths of the flow channels in each branch are equal, so that the flow resistance of the sample liquid entering and exiting each inlet and outlet 2011 is as even as possible, thereby improving the stability of the flow field. In a further embodiment, the lengths of the first branch and the second branch are equal, and the sizes of the two are consistent, which is convenient for preparation.

[0049] In one embodiment, a magnetic separation device is provided, which includes a magnetic plate 2 and a magnetic separation container 1 in the above embodiment; the magnetic plate 2 is used to adsorb the magnetic marker in the sample liquid flowing through the magnetic separation space 30 on the top surface of the lower plate placed in contact with it during magnetic separation. It can be understood that the magnetic marker can be a magnetically labeled cell. For the specific definition of the magnetic separation device, please refer to the definition of the magnetic separation container 1 above, which will not be repeated here. The above magnetic separation device may also include a controller, which is used to execute the magnetic separation method mentioned later. For the specific definition of the controller, please refer to the definition of the magnetic separation container 1 and the magnetic separation method above, which will not be repeated here. Each module in the above controller can be implemented in whole or in part by software, hardware and a combination thereof. Each of the above modules can be embedded in or independent of the processor in the controller in hardware form, or can be stored in the memory in the controller in software form, so that the processor can call and execute the operations corresponding to each of the above modules.

[0050] In one embodiment, if Figure 2 As shown, 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 comprises the following steps:

[0051] S10: Fill the magnetic separation space 30 with non-magnetic liquid from the entrance of the outer frame 20, 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; understandably, when the magnetic marker is a magnetically labeled cell, 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 in the magnetic separation container 1. Understandably, the above non-magnetic liquid refers to a liquid that does not contain any substance that has an adsorption effect with the magnet and is allowed by the corresponding cells in the labeled magnetic substance (that is, after the liquid is mixed with the sample liquid, it will not damage the cells corresponding to the magnetic marker in the sample liquid). The non-magnetic liquid needs to be pre-filled before the sample liquid is injected to empty the air in the magnetic separation container 1. Understandably, the non-magnetic liquid includes but is not limited to physiological saline or culture medium.

[0052] S20: inject the sample liquid carrying magnetic markers in the sample container from the inlet into the magnetic separation space 30, guide the sample liquid to flow toward the outlet through the guide bar 40, and at the same time, adsorb the magnetic markers in the sample liquid on the top surface of the lower plate through the magnetic plate 2 during the flow process, so as to remove the magnetic markers in the sample liquid flowing out from 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, through the specific setting of the guide bar 40 structure, the sample liquid can be guided to flow toward the outlet without vortex through the guiding effect of the guide bar 40, that is, the vortex-free flow means that no vortex will be generated in the process of the sample liquid flowing from the inlet to the outlet, so that the stability of the flow field in the magnetic separation space 30 is further guaranteed, thereby ensuring the magnetic separation effect.

[0053] Understandably, 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 placed close to the magnetic plate 2, and the upper plate 10 of the magnetic separation container 1 can be pressed with a pressure cover when necessary, so that the magnetic separation container 1 is stably fixed on the magnetic plate 2, thereby achieving a better magnetic separation effect. Understandably, 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 invention, the first side and the second side are not fixed sides, but correspond to the opposite sides of the outer frame 20 where the entrance and exit 2011 are provided. That is, as Figure 1As shown, the outer frame 20 has an inlet and outlet 2011 on opposite sides. In the present invention, all the inlet and outlet 2011 on the second side of the outer frame 20 can also be used as an inlet at the same time. In this case, all the inlet and outlet 2011 on the first side of the outer frame 20 become outlets. In the present invention, the number of the inlet and outlet 2011 on each side of the outer frame 20 can be set to 2-6, and the number of the inlet and outlet 2011 at both ends is equal, and the inlet and outlet 2011 at both ends is preferably a symmetrical design structure. In the present invention, the magnetic markers in the sample liquid flowing out of the outlet will be adsorbed on the lower plate, and then, there is basically no magnetic marker 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 from the outlet with the non-magnetic liquid, thereby achieving the collection of the magnetic markers.

[0054] The present invention 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 hard support of the upper plate 10 and the lower plate by the outer frame 20 and the guide strip 40 of the magnetic separation container 1, thereby ensuring that the flow field shape in the magnetic separation space 30 will not deform, 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 invention is hard supported by the outer frame 20 and the guide strip 40, the magnetic separation space 30 has a larger fluid cross-section, so that when a larger flow rate passes through the above-mentioned larger fluid cross-section, a very low flow rate can be maintained, and the fluid force applied to the magnetic marker by the very low flow rate is also low. 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 invention reduces the fluid force of fluid movement, thereby improving the magnetic separation efficiency and effect, and thus improving the magnetic separation speed as a whole.

[0055] It should be understood that the order of execution of the steps in the above embodiment does not necessarily 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 embodiment of the present invention.

[0056] In one embodiment, a computer device is provided. The computer device may be a client or a server. The internal structure diagram may be as follows: Figure 4As shown. The computer device includes a processor, a memory, a network interface and a database connected through 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, a computer program and a database. The internal memory provides an environment for the operation of the operating system and the computer program in the readable storage medium. The network interface of the computer device is used to communicate with an external terminal through a network connection. When the computer program is executed by the processor, a magnetic separation method is implemented.

[0057] In one embodiment, a computer device is provided, including a memory, a processor, and a computer program stored in the memory and executable on the processor. When the processor executes the computer program, the magnetic separation method in the above embodiment is implemented.

[0058] In one embodiment, a computer-readable storage medium is provided, wherein the computer-readable storage medium stores a computer program, and when the computer program is executed by a processor, the above-mentioned magnetic separation method is implemented.

[0059] Those skilled in the art can understand that all or part of the processes in the above-mentioned embodiment methods can be completed by instructing the relevant hardware through a computer program, and the computer program can be stored in a non-volatile computer-readable storage medium. When the computer program is executed, it 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 can include non-volatile and / or volatile memory. Non-volatile memory can include read-only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM) or flash memory. Volatile memory can include random access memory (RAM) or external cache memory. As an 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 (Synchlink) DRAM (SLDRAM), memory bus (Rambus) direct RAM (RDRAM), direct memory bus dynamic RAM (DRDRAM), and memory bus dynamic RAM (RDRAM).

[0060] Those skilled in the art can clearly understand that for the convenience and simplicity 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.

[0061] The embodiments described above are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention, and should all be included in the protection scope of the present invention.

Claims

1. A magnetic separation container, characterized in that: 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, characterized in that: 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, characterized in that: The preset distance threshold is 5mm-50mm.

4. The magnetic separation container according to claim 1, characterized in that: 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, characterized in that: 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, characterized in that: 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, characterized in that: 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, characterized in that: 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, characterized in that: The thickness of the lower plate ranges from 0.1 mm to 5 mm.

10. The magnetic separation container according to claim 1, characterized in that: 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, characterized in that: 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, characterized in that: 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, characterized in that: 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, characterized in that: 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, characterized in that: The lengths of all the first branches are equal; the lengths of all the second branches are equal.

16. A magnetic separation device, characterized in that: 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, characterized in that: 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. A computer-readable storage medium storing a computer program, characterized in that: When the computer program is executed by a processor, the magnetic separation method according to claim 17 is implemented.

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