Extrusion type uniform mixing device for magnetic cell sorting and magnetic cell sorting device

Abstract

The utility model discloses an extrusion type uniform mixing device for magnetic cell sorting and a magnetic cell sorting device, and relates to the field of magnetic cell sorting. The utility model provides an extrusion type uniform mixing device for magnetic separation of cells. The extrusion type uniform mixing device comprises an extrusion mechanism and a uniform mixing mechanism arranged on one side of the extrusion mechanism, the extrusion mechanism comprises a mixing bag tray and a mixing bag placed on the mixing bag tray; the mixing mechanism comprises a first driving motor arranged on one side of the mixing bag tray and a driving rod connected with the driving end of the first driving motor, the driving rod is provided with an adapter block connected with the driving rod in a sliding mode, and the adapter block is provided with a rolling shaft which extends from one side of the mixing bag tray to the other side of the mixing bag tray and makes contact with the mixing bag. During use, the first driving motor drives the rolling shaft to slide back and forth on the surface of the mixing bag, so that the magnetic bead mixed liquid is automatically and uniformly mixed.

Description

Technical Field

[0001] The utility model relates to the field of cell magnetic separation, in particular to an extrusion type mixing device and a cell magnetic separation device used for cell magnetic separation. Background Art

[0002] Magnetic cell sorting (MACS) originated in the 1970s. Because it is convenient, fast, simple to operate, and can obtain cells with high purity and high recovery rate without damaging the cells, this technology is widely used in the industry. The principle is: based on the ability of cell surface antigens to combine with specific monoclonal antibodies connected to magnetic beads, in an external magnetic field, cells connected to magnetic beads through antibodies are adsorbed and retained in the magnetic field, and cells without such surface antigens have no magnetism because they cannot bind to specific monoclonal antibodies connected to magnetic beads, and do not stay in the magnetic field, thereby allowing the cells to be separated. By adding a liquid containing specific antibodies and magnetic particles and incubating for a certain period of time, the specific antibody magnetic particles (magnetic beads for short) are combined with the target cells, and then an external magnetic field is applied to capture and adsorb the target cells in the magnetic field, and non-target cells are washed away. Finally, the magnet is removed to wash off the target cells and obtain the cells we ultimately want.

[0003] The current magnetic cell sorting instruments using MACS technology on the market primarily consist of the following components: a bag hanger, liquid sensor, squeeze valve, magnetic sorting unit, peristaltic pump, bag storage compartment, and display screen. Users manually add magnetic beads to the cell preparation bag for incubation, then hang the device on the instrument before proceeding. Gravity and the peristaltic pump work together to separate the sample, ultimately collecting the desired cells and removing them for the next step on another instrument.

[0004] In summary, there is an urgent need for a device that can automatically mix the magnetic bead mixture during the process of cell magnetic sorting. Utility Model Content

[0005] In order to solve the above problems, the first aspect of the present invention provides an extrusion-type mixing device for magnetic cell sorting, which can automatically mix the magnetic bead mixture during the process of magnetic cell sorting.

[0006] The extrusion-type mixing device for magnetic cell sorting provided by the present invention includes an extrusion mechanism and a mixing mechanism arranged on one side of the extrusion mechanism; the extrusion mechanism includes a mixing bag tray and a mixing bag placed on the mixing bag tray; the mixing mechanism includes a first drive motor arranged on one side of the mixing bag tray and a drive rod connected to the drive end of the first drive motor, the drive rod is provided with a conversion block slidably connected to the drive rod, and the conversion block is provided with a roller extending from one side of the mixing bag tray to the other side and in contact with the mixing bag.

[0007] In a feasible embodiment, a mixing mechanism is provided on both sides of the mixing bag tray; and both ends of the roller are respectively connected to the adapter blocks in the mixing mechanisms located on both sides of the mixing bag tray.

[0008] In a feasible embodiment, the squeezing mechanism further includes a second rotating motor, and the mixed bag tray is further provided with a tray rotating shaft connected to the driving end of the second rotating motor.

[0009] In a feasible implementation manner, the tray rotation axis can rotate at an angle of -90° to 90°.

[0010] The second aspect of the present invention provides a cell magnetic sorting device, comprising a bag hanging mechanism, a magnetic bead liquid adding mechanism, a shaking device for cell magnetic sorting as described in the first aspect of the present invention, a magnetic sorting mechanism and a collecting mechanism, which are arranged in sequence from top to bottom.

[0011] In a feasible embodiment, the bag hanging mechanism includes a plurality of bag hangers with adjustable lengths and cell bags suspended on the bag hangers; the bag hangers are also provided with gravity sensors, and the cell bags are connected to an external liquid inlet device through a pipeline.

[0012] In one feasible embodiment, the magnetic bead liquid adding mechanism includes a magnetic bead liquid adding bag; the magnetic bead liquid adding bag is connected to an external magnetic bead liquid inlet device through a pipeline, the magnetic bead liquid adding bag is connected and communicated with the cell bag through a first pipeline, and the magnetic bead liquid adding bag is connected and communicated with the mixing bag through a second pipeline.

[0013] In a feasible embodiment, the magnetic separation mechanism includes a magnetic module for magnetic separation and a magnetic separation column provided in the magnetic module, and the mixed bag is connected and communicated with the magnetic separation column through a third pipeline.

[0014] In a feasible embodiment, the collection mechanism includes a collection platform and a plurality of collection bags placed on the collection platform; the collection bags are connected and communicated with the magnetic separation column via a fourth pipeline.

[0015] In a feasible implementation manner, valves are provided on the first pipeline, the second pipeline, the third pipeline and the fourth pipeline.

[0016] The utility model provides an extrusion type mixing device and a cell magnetic sorting device for cell magnetic sorting, which have the following beneficial effects:

[0017] 1) The extrusion-type mixing device for magnetic cell sorting provided by the present invention includes an extrusion mechanism and a mixing mechanism located on one side of the extrusion mechanism. The extrusion mechanism includes a mixing bag tray and a mixing bag placed on the mixing bag tray. The mixing mechanism includes a first drive motor located on one side of the mixing bag tray and a drive rod connected to the drive end of the first drive motor. The drive rod is provided with an adapter block slidably connected to the drive rod. The adapter block is provided with a roller extending from one side of the mixing bag tray to the other side and contacting the cell bag. During use, the first drive motor drives the roller to slide back and forth on the surface of the mixing bag, thereby achieving automatic mixing of the magnetic bead mixture.

[0018] 2) The extrusion mechanism provided by the present invention further includes a second drive motor and a tray rotating shaft. When in use, the second drive motor drives the tray rotating shaft to rotate back and forth, thereby causing the mixing bag tray to swing back and forth to further mix the liquid in the mixing bag.

[0019] 3) The cell magnetic separation device provided by the present invention comprises, arranged sequentially from top to bottom, a bag hanging mechanism, a magnetic bead liquid adding mechanism, a shaking device for magnetic cell separation, a magnetic separation mechanism, and a collection mechanism. The bag hanging mechanism is used to hang the cell bag, the magnetic bead liquid adding mechanism is used to hang the magnetic bead liquid adding bag, the magnetic separation mechanism is used to generate a magnetic field and attract the target cells, and the collection mechanism is used to collect waste liquid and target cells. With the above arrangement, the cell magnetic separation device provided by the present invention can automatically complete the separation of target cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a schematic diagram of the overall structure of the extrusion-type mixing device for magnetic cell separation of the present invention.

[0021] Figure 2 This is a partial structural diagram of the extrusion-type mixing device for magnetic cell separation of the present invention.

[0022] Figure 3 This is a schematic diagram of the process of the cell magnetic separation device of the present invention.

[0023] Figure 4 This is a pipeline diagram of the cell magnetic separation device of the present invention.

[0024] Reference numerals

[0025] Extrusion mechanism 1

[0026] Mixed bag pallet 11

[0027] Mixed Bag 12

[0028] Second drive motor 13

[0029] Tray rotation axis 14

[0030] Mixing mechanism 2

[0031] First drive motor 21

[0032] Drive rod 22

[0033] Transfer block 23

[0034] Roller 24

[0035] Bag hanging mechanism 3

[0036] Bag hanger 31

[0037] Cell Bag 32

[0038] Magnetic bead adding mechanism 4

[0039] Magnetic bead liquid bag 41

[0040] Magnetic separation mechanism 5

[0041] Magnetic module 51

[0042] Magnetic separation column 52

[0043] Collection Agency 6

[0044] Collection Platform 61

[0045] Collection Bag 62 DETAILED DESCRIPTION

[0046] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. In the description of the present invention, it should be noted that the orientations or positional relationships indicated by the terms "left side", "right side", "upper side", "lower side", "above", "below", etc. are based on the orientations or positional relationships shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention. In addition, the terms "first" and "second" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance.

[0047] In the description of this utility model, it should be noted that, unless otherwise expressly specified or limited, the terms "installed," "connected," and "connected" should be understood in a broad sense. For example, they can refer to fixed connections, detachable connections, or integral connections; mechanical connections, electrical connections; direct connections, indirect connections through an intermediate medium, and internal communication between two components. Those skilled in the art will understand the specific meanings of the above terms in this utility model based on specific circumstances.

[0048] In addition, in the description of the present invention, unless otherwise specified, “a plurality of” means two or more.

[0049] Example 1

[0050] This embodiment provides an extrusion type mixing device for magnetic cell separation, see Figure 1 The invention relates to a mixing mechanism 2, comprising a squeezing mechanism 1 and a mixing mechanism 2 disposed on one side of the squeezing mechanism 1. The squeezing mechanism 1 comprises a mixing bag tray 11 and a mixing bag 12 placed on the mixing bag tray 11. The mixing mechanism 2 comprises a first drive motor 21 disposed on one side of the mixing bag tray 11 and a drive rod 22 connected to the drive end of the first drive motor 21. The drive rod 22 is provided with a transfer block 23 slidably connected to the drive rod 22. The transfer block 23 is provided with a roller 24 extending from one side of the mixing bag tray 11 to the other side and contacting the mixing bag 12. Before shaking, the mixing bag 12 is loaded with a magnetic bead mixture; during shaking, the mixing bag 12 is placed on the mixing bag tray 11, and then the first drive motor 21 drives the drive rod 22 to rotate. The drive rod 22 and the adapter block 23 adopt the principle of a ball screw. When the drive rod 22 rotates, the adapter block 23 slides along the drive rod 22. The sliding of the adapter block 23 will synchronously drive the roller 24 to slide back and forth on the surface of the mixing bag 12, thereby mixing the liquid in the mixing bag 12 like a rolling pin, thereby achieving automatic mixing of the magnetic bead mixture. In addition, the mixing bag tray 11 usually has a low-temperature refrigeration function, which can provide the mixing bag 12 with a low-temperature environment of 4°C-8°C or an adjustable suitable temperature environment.

[0051] In the extrusion type mixing device for magnetic cell separation provided in this embodiment, refer to Figure 1 The mixing mechanism 2 is provided on both sides of the mixing bag tray 11. The ends of the roller 24 are connected to the adapter blocks 23 in the mixing mechanism 2 located on both sides of the mixing bag tray 11. For illustration, the two first drive motors 21 located on both sides of the mixing bag tray 11 typically rotate synchronously, which allows the roller 24 to more stably mix the mixed bag 12.

[0052] In the extrusion type mixing device for magnetic cell separation provided in this embodiment, refer to Figure 2 , also includes a second drive motor 13, and the mixing bag tray 11 is also provided with a tray rotating shaft 14 connected to the driving end of the second drive motor 13. As an explanation, the function of the second drive motor 13 is to drive the mixing bag tray 11 to rotate around the tray rotating shaft 14. Generally speaking, the second drive motor 13 can be used alternately with the first drive motor 21. For example: first start the first drive motor 21 to make the roller 24 squeeze the mixing bag 12 back and forth on the surface of the mixing bag 12; then, stop the first drive motor 21 and start the second drive motor 13 to make the mixing bag tray 11 rotate around the tray rotating shaft 14, so that the mixing bag tray 11 swings back and forth to further mix the liquid in the mixing bag 12; the above process can be repeated to make the liquid in the mixing bag 12 more fully mixed and improve the mixing effect. As a supplementary explanation, the rotatable angle of the tray rotating shaft 14 is -90° to 90°, preferably -45° to 45°.

[0053] This embodiment also provides a method for using an extrusion-type mixing device for magnetic cell separation, which includes at least the following steps:

[0054] 1) After the mixed liquid enters the mixing bag 12, the first drive motor 21 is started to cause the roller 24 to squeeze the mixing bag 12 back and forth on the surface of the mixing bag 12;

[0055] 2) Subsequently, the first drive motor 21 is stopped and the second motor is started to rotate the mixing bag tray 11 around the tray rotation axis 14, thereby further mixing the liquid in the mixing bag 12;

[0056] 3) Repeat steps 1) and 2) intermittently.

[0057] Example 2

[0058] This embodiment provides a cell magnetic separation device, see Figure 3 and Figure 4 The apparatus comprises, arranged from top to bottom, a bag hanging mechanism 3, a magnetic bead liquid adding mechanism 4, a shaking device for magnetic cell separation as described in Example 1, a magnetic separation mechanism 5, and a collection mechanism 6. Specifically, the bag hanging mechanism 3 is used to hang a cell bag 32, the magnetic bead liquid adding mechanism 4 is used to hang a magnetic bead liquid adding bag 41, the magnetic separation mechanism 5 is used to generate a magnetic field and attract target cells, and the collection mechanism 6 is used to collect waste liquid and target cells. With the above arrangement, the cell magnetic separation device provided by the present invention can automatically separate target cells.

[0059] In the cell magnetic separation device provided in this embodiment, refer to Figure 3 and Figure 4The bag hanging mechanism 3 includes multiple length-adjustable bag hangers 31 and cell bags 32 suspended from the bag hangers 31. The bag hangers 31 are also equipped with gravity sensors for weighing the cell bags 32. The cell bags 32 are connected to external liquid inlet devices via pipelines. For illustration, the top of the cell bag 32 typically includes multiple ports for connecting to multiple liquid inlet devices. Typically, the cell bag 32 contains sodium hydroxide, buffer, and activation solution.

[0060] In the cell magnetic separation device provided in this embodiment, refer to Figure 3 and Figure 4 The magnetic bead liquid addition mechanism 4 includes a magnetic bead liquid addition bag 41; the magnetic bead liquid addition bag 41 is connected to an external magnetic bead liquid inlet device via a pipeline. The magnetic bead liquid addition bag 41 is connected and communicated with the cell bag 32 via a first pipeline, and is connected and communicated with the mixing bag 12 via a second pipeline. For illustration, the bottom of the cell bag 32 and the top of the magnetic bead liquid addition bag 41 both include an interface for the first pipeline, and the bottom of the magnetic bead liquid addition bag 41 and the top of the mixing bag 12 both include an interface for the second pipeline. When the liquid is added, the mixed liquid in the cell bag 32 enters the magnetic bead liquid adding bag 41 through the first pipeline. At the same time, the top of the magnetic bead liquid adding bag 41 also includes an interface for an external magnetic bead liquid adding device. When the mixed liquid in the cell bag 32 enters the magnetic bead liquid adding bag 41, the magnetic bead liquid adding device also injects the magnetic beads into the magnetic bead liquid adding bag 41, so that the cell surface antigens can combine with the specific monoclonal antibody connected to the magnetic beads. Subsequently, the magnetic bead mixed liquid in the magnetic bead liquid adding belt enters the mixing bag 12 through the second pipeline.

[0061] In the cell magnetic separation device provided in this embodiment, refer to Figure 3 and Figure 4 The magnetic separation mechanism 5 includes a magnetic module 51 for magnetic separation and a magnetic separation column 52 disposed in the magnetic module 51. The mixing bag 12 is connected to and communicates with the magnetic separation column 52 via a third pipeline. As an illustration, the bottom of the mixing bag 12 includes an interface for the third pipeline. When the liquid is added, the magnetic bead mixture in the mixing bag 12 flows through the magnetic separation column 52 through the third pipeline. The magnetic separation column 52 will form a corresponding magnetic field to adsorb the target cells bound to the magnetic beads in the magnetic field.

[0062] In the cell magnetic separation device provided in this embodiment, refer to Figure 3 and Figure 4The collection mechanism 6 includes a collection platform 61 and a collection bag 62 placed on the collection platform 61. The collection bag 62 is connected to and communicates with the magnetic separation column 52 via a fourth pipeline. For illustration, the top of the collection bag 62 includes an interface for the fourth pipeline. Collection bags 62 typically include negative cell bags 32, waste liquid bags, and pre-collection bags 62. These three types of bags are connected in parallel to the fourth pipeline via a branch, and each branch is equipped with a valve to control the opening and closing of the branch. During the first collection, the target cells are adsorbed in the magnetic field by the magnetic force generated by the magnetic separation column 52 and cannot enter the collection bag 62 through the fourth pipeline, while non-target cells will enter the negative cell bag 32 through the fourth pipeline; during the second collection, the buffer solution in the cell bag 32 loaded with buffer solution flows through and flushes each pipeline and bag body in turn, and enters the waste liquid bag through the fourth pipeline; during the third collection, the magnetic field generated by the magnetic separation column 52 is removed, and the target cells will enter the pre-collection bag 62 through the fourth pipeline. At this time, the collection of the target cells is completed.

[0063] In the cell magnetic separation device provided in this embodiment, refer to Figure 3 and Figure 4 The first pipeline, the second pipeline, the third pipeline and the fourth pipeline are all provided with valves. As an illustration, the liquid produced in each of the above steps usually needs to stay in the corresponding bag for a period of time. Therefore, the valve can ensure that the liquid can stay in the bag, ensuring the safety of the experiment.

[0064] This embodiment also provides a method for using a cell magnetic separation device, which includes at least the following steps:

[0065] 1) Different liquids and cells are injected into the cell bag 32 through the liquid inlet device. At the same time, the gravity sensor is used to detect whether the weight in the cell bag 32 meets the standard.

[0066] 2) After the weight in the cell bag 32 reaches the specified value, the valve on the first pipeline is opened to allow the mixed solution in the cell bag 32 to flow into the magnetic bead liquid-adding bag 41 through the first pipeline. At the same time, the gravity sensor detects the real-time weight of the cell bag 32, and the host computer calculates the reduction amount to control the weight of the mixed solution in the magnetic bead liquid-adding bag 41. Subsequently, the magnetic beads are injected into the magnetic bead liquid-adding bag 41 through the magnetic bead liquid-injection device.

[0067] 3) Open the valve on the second pipeline to allow the magnetic bead mixture in the magnetic bead liquid adding bag 41 to flow into the mixing bag 12 through the second pipeline; at the same time, start the shaking device for cell magnetic sorting to shake the magnetic bead mixture in the mixing bag 12.

[0068] 4) Open the valve on the third pipeline to allow the magnetic bead mixture in the mixing bag 12 to flow into the magnetic separation column 52 through the third pipeline; at the same time, start the magnetic separation column 52 to generate a corresponding magnetic field, which will adsorb the target cells bound to the magnetic beads into the magnetic field.

[0069] 5) Open the valve on the fourth pipeline to allow non-target cells to enter the collection bag 62 through the fourth pipeline; then, remove the collection bag 62 that has collected non-target cells, replace it with a new collection bag 62, and close the magnetic separation column 52. The target cells will then enter the collection bag 62 through the fourth pipeline.

[0070] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and replacements can be made without departing from the technical principles of the present invention. These improvements and replacements should also be regarded as the scope of protection of the present invention.

Claims

1. An extrusion mixing device for magnetic cell separation, characterized in that: It comprises an extrusion mechanism (1) and a mixing mechanism (2) arranged on one side of the extrusion mechanism (1); The squeezing mechanism (1) comprises a mixing bag tray (11) and a mixing bag (12) placed on the mixing bag tray (11); the mixing mechanism (2) comprises a first driving motor (21) arranged on one side of the mixing bag tray (11) and a driving rod (22) connected to the driving end of the first driving motor (21); the driving rod (22) is provided with a transfer block (23) slidably connected to the driving rod (22); the transfer block (23) is provided with a roller (24) extending from one side of the mixing bag tray (11) to the other side and contacting the mixing bag (12).

2. The extrusion mixing device according to claim 1, characterized in that: Both sides of the mixing bag tray (11) are provided with a mixing mechanism (2); both ends of the roller (24) are respectively connected to the adapter blocks (23) in the mixing mechanism (2) located on both sides of the mixing bag tray (11).

3. The extrusion mixing device according to claim 1 or 2, characterized in that: The squeezing mechanism (1) further comprises a second driving motor (13), and the mixing bag tray (11) is further provided with a tray rotating shaft (14) connected to the driving end of the second driving motor (13).

4. The extrusion mixing device according to claim 3, characterized in that: The tray rotation axis (14) can rotate at an angle of -90° to 90°.

5. A cell magnetic separation device, characterized in that: The invention comprises a bag hanging mechanism (3), a magnetic bead liquid adding mechanism (4), an extrusion mixing device for magnetic cell separation according to any one of claims 1 to 4, a magnetic separation mechanism (5) and a collection mechanism (6) which are arranged in sequence from top to bottom.

6. The cell magnetic separation device according to claim 5, characterized in that: The bag hanging mechanism (3) comprises a plurality of bag hangers (31) with adjustable lengths and cell bags (32) hung on the bag hangers (31); a gravity sensor is also provided on the bag hangers (31), and the cell bags (32) are externally connected to a liquid inlet device through a pipeline.

7. The cell magnetic separation device according to claim 6, characterized in that: The magnetic bead liquid adding mechanism (4) comprises a magnetic bead liquid adding bag (41); the magnetic bead liquid adding bag (41) is externally connected to a magnetic bead liquid inlet device via a pipeline; the magnetic bead liquid adding bag (41) is connected and communicated with a cell bag (32) via a first pipeline; and the magnetic bead liquid adding bag (41) is connected and communicated with a mixing bag (12) via a second pipeline.

8. The cell magnetic separation device according to claim 7, characterized in that: The magnetic separation mechanism (5) comprises a magnetic module (51) for magnetic separation and a magnetic separation column (52) arranged in the magnetic module (51); the mixing bag (12) is connected and communicated with the magnetic separation column (52) via a third pipeline.

9. The cell magnetic separation device according to claim 8, characterized in that: The collecting mechanism (6) comprises a collecting platform (61) and a plurality of collecting bags (62) placed on the collecting platform (61); the collecting bags (62) are connected and communicated with the magnetic separation column (52) via a fourth pipeline.

10. The cell magnetic separation device according to claim 9, characterized in that: Valves are provided on the first pipeline, the second pipeline, the third pipeline and the fourth pipeline.

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