Magnetic bead sorting equipment and magnetic bead sorting method

Abstract

The invention relates to the technical field of magnetic separation, in particular to magnetic bead separation equipment and a magnetic bead separation method. The magnetic bead separation equipment comprises a lifting device, a mixing and swinging device, a liquid path module and a shell, wherein the lifting device, the mixing and swinging device and the liquid path module are all arranged on the shell. The lifting device comprises a consumable mounting plate used for loading magnetic separation consumables, a magnet arranged below the consumable mounting plate, and a lifting module connected with the consumable mounting plate and used for driving the consumable mounting plate to move up and down relative to the magnet. The mixing and swinging device comprises a mixing and swinging bracket for mounting the lifting device and a mixing and swinging module which is connected with the lifting device through the mixing and swinging bracket and is used for driving the lifting device to swing; the liquid path module comprises a pipeline assembly used for conveying liquid in the liquid bag to the magnetic separation consumable and a liquid path panel used for controlling flowing of the liquid in a pipeline. By means of the magnetic bead sorting equipment and method, magnetic bead sorting of large-flux cell sap is achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of magnetic separation, and particularly relates to a magnetic bead sorting device and a magnetic bead sorting method. Background Art

[0002] Currently, in order to achieve the purification of antigen cells in cell therapy, it is often necessary to separate immunomagnetic bead cells by magnetic separation. Some cell surface antigens have specific antibodies that can bind to magnetic beads, and such cells can be connected to magnetic beads through antigens, thereby forming immunomagnetic bead cells. Magnetic separation technology is that in an externally applied magnetic field, the immunomagnetic bead cells that have already bound to magnetic beads are adsorbed and retained in the magnetic field, while other cells that have not bound to magnetic beads are not magnetic and cannot stay in the magnetic field, thereby achieving the purpose of separating immunomagnetic bead cells.

[0003] In the prior art, magnetic separation is usually carried out by combining a microfluidic chip with a magnetic field. When processing a large volume of cell fluid, due to the too large area of the liquid bag, the flow rates of different regions of the liquid are inconsistent when the liquid flows in the liquid bag, which in turn leads to inconsistent magnetization conditions in different regions of the liquid bag. For example, when the flow rate in some regions of the liquid bag is too large, the immunomagnetic bead cells will not be sufficiently adsorbed by the magnet because they do not contact the magnetic field enough, resulting in the escape of unadsorbed immunomagnetic bead cells. If the flow rate of the cell fluid is slowed down overall to reduce the escape of immunomagnetic bead cells, there will be defects such as a long magnetization time. Summary of the Invention

[0004] In order to solve the problem in the prior art that when performing magnetic separation on a large volume of cell fluid, the magnetization effects in different regions of the cell fluid are inconsistent due to inconsistent liquid flow rates, an embodiment of the present invention provides a magnetic bead sorting device and a magnetic bead sorting method.

[0005] In a first aspect, an embodiment of the present invention provides a magnetic bead sorting device, including:

[0006] A lifting device, including a consumable mounting plate for loading magnetic separation consumables, a magnet arranged below the consumable mounting plate, and a lifting module connected to the consumable mounting plate and used to drive the consumable mounting plate to move up and down relative to the magnet;

[0007] A mixing and swinging device, including a mixing and swinging bracket for installing the lifting device, and a mixing and swinging module connected to the lifting device through the mixing and swinging bracket and used to drive the lifting device to swing;

[0008] A liquid path module, including a pipeline assembly for transporting the liquid in the liquid bag to the magnetic separation consumables for magnetic separation, and a liquid path panel for controlling the flow of the liquid in the pipeline;

[0009] A housing, on which the lifting device, the mixing and swinging device, and the liquid path module are all installed.

[0010] In some embodiments, the lifting module includes a lateral movement unit and a guiding unit connected to the lateral movement unit. The guiding unit is movably connected to the consumable mounting plate and is configured to convert the lateral movement of the guiding unit into the longitudinal movement of the consumable mounting plate.

[0011] In some embodiments, the lateral movement unit includes a movement motor, a lead screw connected to the movement motor, a movement nut sleeved on the lead screw, and a guiding block connected to the movement nut. The guiding block is connected to the guiding unit and is configured to drive the guiding unit to move laterally following the movement nut when the movement motor drives the lead screw to rotate and drive the movement nut to move laterally.

[0012] In some embodiments, the guiding unit includes a connecting plate connected to the guiding block and at least one guiding plate connected to the connecting plate. The guiding plate is provided with an inclined strip-shaped guiding hole.

[0013] In some embodiments, a cam follower is provided on the consumable mounting plate. The cam follower is disposed in the inclined strip-shaped guiding hole and is configured to change the longitudinal position of the consumable mounting plate by changing the position of the cam follower in the inclined strip-shaped guiding hole when the guiding unit moves laterally.

[0014] In some embodiments, the mixing and swinging module includes a mixing and swinging motor, a speed reducer, a driving wheel, and a synchronous belt. The lifting device further includes a magnet mounting seat for mounting the magnet and movably connected to the consumable mounting plate, and a driven wheel mounted on one side of the magnet mounting seat. One end of the speed reducer is connected to the mixing and swinging motor, and the other end of the speed reducer is connected to the driving wheel. The synchronous belt is sleeved on the driving wheel and the driven wheel.

[0015] In some embodiments, the pipeline assembly includes a pinch valve for controlling the on / off of the pipeline in the pipeline assembly, a bubble sensor for judging whether the liquid in the liquid bag has run out by real-time monitoring whether there are bubbles mixed in the liquid flowing in the pipeline, a pressure sensor for real-time monitoring the liquid pressure in the pipeline, a peristaltic pump for driving the liquid to flow in the pipeline during operation, and a drive controller with an output end connected to the peristaltic pump and configured to drive the peristaltic pump to operate;

[0016] The pinch valve, the bubble sensor, the pressure sensor, and the peristaltic pump are all mounted on the front surface of the liquid path panel. The drive controller is mounted on the back surface of the liquid path panel at a position opposite to the peristaltic pump, and the drive controller is located inside the housing.

[0017] In some embodiments, the pipeline assembly further includes a weighing sensor for real-time monitoring of the change in the liquid weight in the liquid bag to determine whether the liquid in the liquid bag is emptied, and the weighing sensor is installed on the front of the liquid path panel.

[0018] In some embodiments, the magnetic bead sorting device further includes a liquid hanging rod installed on the housing, and a hook for hanging the liquid bag is provided on the liquid hanging rod.

[0019] In some embodiments, the magnetic bead sorting device further includes a controller installed in the housing, a code scanning device for scanning and identifying the liquid bag, and a display device for touch operation or parameter display. The lifting device, the mixing device, the liquid path module, the code scanning device, and the display device are all connected to the controller.

[0020] Second, embodiments of the present invention provide a magnetic bead sorting method, which is applied to the magnetic bead sorting device described in any of the above embodiments, and includes:

[0021] Fill the pipeline with cleaning liquid through the liquid path module, and detect the gas evacuation situation of the pipeline;

[0022] According to the gas evacuation situation, fill the pipeline with the magnetic cell liquid to be sorted by magnetic beads through the liquid path module and flow it into the magnetic separation consumables;

[0023] Place the magnetic cell liquid in the magnetic separation consumables in a magnetic bead sorting state through the lifting module;

[0024] Shake the magnetic cell liquid in the magnetic separation consumables through the mixing module;

[0025] After the magnetic bead sorting of the magnetic cell liquid is completed, empty the liquid in the magnetic separation consumables through the liquid path module;

[0026] Place the magnetic cell liquid in the magnetic separation consumables in a non-magnetic bead sorting state through the lifting module and collect the sorted immunomagnetic bead cells.

[0027] In some embodiments, before filling the pipeline with the cleaning liquid, perform an airtightness check on the magnetic separation consumables.

[0028] In some embodiments, the collection of the sorted immunomagnetic bead cells includes:

[0029] Connect the collection bag to the output end of the magnetic separation consumables;

[0030] Flow the magnetic separation buffer solution into the magnetic separation consumables through the liquid path module within a preset time, and bring the immunomagnetic bead cells into the collection bag;

[0031] Empty the liquid in the magnetic separation consumables through the liquid path module to obtain the immunomagnetic bead cells.

[0032] One or more technical solutions provided in the embodiments of the present invention have at least the following technical effects or advantages:

[0033] A magnetic bead sorting device proposed in an embodiment of the present invention lifts the consumable mounting plate through a lifting device, so that the consumable mounting plate moves away from or close to the magnet below, so as to remove the magnetic field or apply a magnetic field to the magnetic cell liquid on the consumable mounting plate; by setting a mixing and swinging device to swing the lifting device, the magnetic cell liquid on the lifting device is shaken evenly, avoiding the accumulation of immunomagnetic bead cells in the magnetic cell liquid and causing the loss of some immunomagnetic bead cells.

[0034] In addition, a magnetic bead sorting device proposed in an embodiment of the present invention is also provided with a liquid path module, which controls the flow and flow rate of the magnetic cell liquid through the liquid path module to achieve a better magnetic bead sorting effect, avoiding problems such as the escape of immunomagnetic bead cells due to too fast flow rate and long magnetization time due to too slow flow rate; by monitoring whether the liquid in the liquid bag is emptied through the liquid path module, it is convenient to replace the liquid bag in time and improve work efficiency.

[0035] An embodiment of the present invention also proposes a magnetic bead sorting method, which is applied to the magnetic bead sorting device proposed in the embodiment of the present invention. This magnetic bead sorting method uses the magnetic bead sorting device to achieve magnetic sorting of a large-throughput or large-capacity magnetic cell liquid, greatly improving the work efficiency of magnetic bead sorting while maintaining a good sorting rate. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The present invention will be further described below in conjunction with the drawings and embodiments.

[0037] Figure 1 is a schematic structural diagram of a magnetic bead sorting device proposed in an embodiment of the present invention;

[0038] Figure 2 is an exploded view of a magnetic bead sorting device proposed in an embodiment of the present invention;

[0039] Figure 3 is an exploded view of a lifting device in a magnetic bead sorting device proposed in an embodiment of the present invention;

[0040] Figure 4 is an exploded view of a mixing and swinging device in a magnetic bead sorting device proposed in an embodiment of the present invention;

[0041] Figure 5 is a schematic structural diagram of a liquid path module in a magnetic bead sorting device proposed in an embodiment of the present invention;

[0042] Figure 6 It is a schematic flow chart of a magnetic bead sorting method proposed in an embodiment of the present invention;

[0043] 100. Magnetic bead sorting device; 1. Lifting device; 11. Consumable installation plate; 111. Cam follower; 12. Magnet; 13. Lifting module; 131. Lateral movement unit; 1311. Movement motor; 1312. Lead screw; 1313. Movement nut; 1314. Guide block; 132. Guide unit; 1321. Connecting plate; 1322. Guide plate; 13221. Oblique strip-shaped guide hole; 133. Driven wheel; 2. Mixing and swinging device; 21. Mixing and swinging bracket; 22. Mixing and swinging module; 221. Mixing and swinging motor; 222. Reducer; 223. Driving wheel; 224. Synchronous belt; 3. Liquid path module; 31. Pipeline assembly; 311. Pipe clamp valve; 312. Bubble sensor; 313. Pressure sensor; 314. Peristaltic pump; 315. Drive controller; 32. Liquid path panel; 4. Housing; 5. Liquid hanging rod; 7. Scanning device; 8. Display device. Detailed implementation manners

[0044] The concept, specific structure and technical effects of the present invention will be clearly and completely described below in conjunction with the embodiments and the drawings, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative efforts shall fall within the scope of protection of the present invention. In addition, all the connection / connection relationships involved in the patent do not refer to the direct connection of components alone, but refer to the more optimal connection structure that can be formed by adding or reducing connection accessories according to the specific implementation situation. Each technical feature in the present invention can be combined interactively without conflicting with each other.

[0045] In addition, although the functional modules are divided in the device schematic diagram and the logical order is shown in the flow chart, in some cases, the steps shown or described can be executed in a different order from the module division in the device or the flow chart. In addition, the words "first", "second", "third", etc. used in this article do not limit the data and execution order, but only distinguish the same items or similar items with basically the same functions and effects.

[0046] Currently, in order to achieve the purification of antigen cells in cell therapy, it is often necessary to separate immunomagnetic bead cells through magnetic sorting. Some cell surface antigens have specific antibodies that can bind to magnetic beads. Such cells can be connected to magnetic beads through antigens, thereby forming immunomagnetic bead cells. Magnetic sorting technology is that in an externally applied magnetic field, the immunomagnetic bead cells that have already bound to magnetic beads are adsorbed and retained in the magnetic field, while other cells that have not bound to magnetic beads are non-magnetic and cannot stay in the magnetic field, thus achieving the purpose of separating immunomagnetic bead cells.

[0047] In the prior art, magnetic sorting is usually carried out by combining a microfluidic chip with a magnetic field. When processing a large volume of cell fluid, due to the too large area of the liquid bag, the flow rates of different regions of the liquid in the liquid bag are not consistent, which in turn leads to inconsistent magnetization conditions in different regions of the liquid bag. For example, when the flow rate in some regions of the liquid bag is too large, the insufficient contact between immunomagnetic bead cells and the magnetic field will result in insufficient adsorption by the magnet, and thus the unadsorbed immunomagnetic bead cells will escape. If the flow rate of the cell fluid is slowed down overall to reduce the escape of immunomagnetic bead cells, there will be defects such as a long magnetization time.

[0048] To solve the problem in the above prior art that the magnetization effects in different regions of the cell fluid are inconsistent due to inconsistent liquid flow rates during magnetic sorting of a large volume of cell fluid, an embodiment of the present invention provides a magnetic bead sorting device.

[0049] Please refer to Figure 1 to Figure 2 , Figure 1 which is a schematic structural diagram of a magnetic bead sorting device proposed by an embodiment of the present invention, Figure 2 and

[0050] As Figure 1 and Figure 2 shown, a magnetic bead sorting device 100 proposed by an embodiment of the present invention includes a lifting device 1, a mixing and swinging device 2, a liquid path module 3, and a housing 4. Among them, the lifting device 1, the mixing and swinging device 2, and the liquid path module 3 are all arranged on the housing 4.

[0051] Please refer to Figure 3 , Figure 3 which is an exploded view of the lifting device in a magnetic bead sorting device proposed by an embodiment of the present invention.

[0052] As Figure 3As shown in the figure, the lifting device 1 includes a consumable mounting plate 11, a magnet 12, and a lifting module 13. The consumable mounting plate 11 is used to load magnetic separation consumables, and the magnetic cell liquid flows from the liquid bag to the magnetic separation consumables for magnetic bead sorting. The magnet 12 is arranged below the consumable mounting plate 11 and is used to provide a magnetic field to enable magnetic bead sorting of the magnetic cell liquid. The lifting module 13 is connected to the consumable mounting plate 11 and can drive the consumable mounting plate 11 to move up and down relative to the magnet 12. When the lifting module 13 drives the consumable mounting plate 11 to move upward relative to the magnet 12, the consumable mounting plate 11 moves away from the magnet 12, and the magnetic cell liquid on the consumable mounting plate 11 is away from the magnetic field and no magnetic bead sorting is performed; when the lifting module 13 drives the consumable mounting plate 11 to move downward relative to the magnet 12, the consumable mounting plate 11 approaches the magnet 12, the magnetic cell liquid on the consumable mounting plate 11 is applied with a magnetic field, the immunomagnetic bead cells in the magnetic cell liquid are adsorbed by the magnetic field and placed at the bottom of the magnetic separation consumables, and the non-immunomagnetic bead cells flow into the waste liquid bag following the liquid, realizing the sorting of immunomagnetic bead cells.

[0053] Specifically, the lifting module 13 includes a lateral movement unit 131 and a guiding unit 132. The lateral movement unit 131 is connected to the guiding unit 132 and can drive the guiding unit 132 to move laterally. The guiding unit 132 is movably connected to the consumable mounting plate 11 and is used to convert the lateral movement of the guiding unit 132 into the longitudinal movement of the consumable mounting plate 11.

[0054] The lateral movement unit 131 includes a movement motor 1311, a lead screw 1312, a movement nut 1313, and a guiding block 1314. The input end of the movement motor 1311 is connected to the lead screw 1312 and can drive the lead screw 1312 to rotate. Both the movement nut 1313 and the guiding block 1314 are sleeved on the lead screw 1312, and the guiding block 1314 is connected to the movement nut 1313, and the guiding block 1314 is connected to the guiding unit 132. The lead screw 1312 is provided with helical threads, and the surface of the movement nut 1313 sleeved on the lead screw 1312 is provided with threads matching the helical threads of the lead screw 1312. When the lead screw 1312 rotates under the drive of the movement motor 1311, the movement nut 1313 will move laterally along the helical threads on the lead screw 1312. Since the guiding block 1314 is connected to the movement nut 1313, the movement nut 1313 drives the guiding block 1314 to move laterally, and further drives the guiding unit 132 to move laterally.

[0055] The guiding unit 132 includes a connecting plate 1321 and at least one guiding plate 1322. The connecting plate 1321 is connected to the guiding block 1314, the guiding plate 1322 is connected to the connecting plate 1321, and an obliquely strip-shaped guiding hole 13221 is provided on the guiding plate 1322. A cam follower 111 is provided on the consumable installation plate 11, and the cam follower 111 is arranged in the obliquely strip-shaped guiding hole 13221. The obliquely strip-shaped guiding hole 13221 is a strip-shaped hole extending obliquely, and there is a height difference at both ends thereof. Therefore, when the guiding unit 132 moves laterally, the obliquely strip-shaped guiding hole 13221 follows the guiding unit 132 to move laterally, and the position of the cam follower 111 located in the obliquely strip-shaped guiding hole 13221 changes. There is a height difference between different positions of the obliquely strip-shaped guiding hole 13221, so the position of the cam follower 111 changes longitudinally, and the position of the consumable installation plate 11 changes longitudinally accordingly. Through the obliquely strip-shaped guiding hole 13221, the lateral movement of the guiding unit 132 is converted into the longitudinal movement of the consumable installation plate 11.

[0056] Please refer to Figure 4 , Figure 4 which is an exploded view of a mixing and swinging device in a magnetic bead sorting device according to an embodiment of the present invention.

[0057] As Figure 4 shown, the mixing and swinging device 2 includes a mixing and swinging bracket 21 and a mixing and swinging module 22. The mixing and swinging bracket 21 is used to install the lifting device 1. The mixing and swinging module 22 is connected to the lifting device 1 through the mixing and swinging bracket 21 and can drive the lifting device 1 to swing. By swinging the lifting device 1 through the mixing and swinging device 2, the magnetic cell liquid placed on the lifting device 1 is shaken evenly to avoid the accumulation of immunomagnetic cells in the magnetic cell liquid, resulting in a weakening of the magnetic adsorption force in this area and causing the loss of some immunomagnetic bead cells.

[0058] The mixing and swinging module 22 includes a mixing and swinging motor 221, a speed reducer 222, a driving wheel 223, and a synchronous belt 224. The lifting device 1 further includes a magnet mounting seat and a driven wheel 133. The magnet 12 is installed in the magnet mounting seat, and the magnet mounting seat is movably connected to the consumable installation plate 11. The consumable installation plate 11 can move up and down relative to the magnet mounting seat above the magnet mounting seat under the action of the lifting module 13. The driven wheel 133 is arranged on one side of the magnet mounting seat and is fixedly connected to the magnet mounting seat.

[0059] One end of the speed reducer 222 is connected to the mixing and swinging motor 221, and the other end is connected to the driving wheel 233 through the mixing and swinging bracket 21; the synchronous belt 224 is sleeved on the driving wheel 233 and the driven wheel 133. The mixing and swinging motor 221 drives the driving wheel 233 to rotate through the speed reducer 222, and the driving wheel 233 drives the driven wheel 133 through the synchronous belt 224. Since the driven wheel 133 is fixedly connected to the magnet mounting seat, when the driven wheel 133 is driven by the driving wheel 233 to rotate, the magnet mounting seat swings. Through the consumable mounting plate 11 connected to the magnet mounting seat, the magnetic separation consumables in the consumable mounting plate 11 swing with the magnet mounting seat, and the magnetic cell liquid in the magnetic separation consumables is shaken evenly. Among them, the speed reducer 222 is used to increase the output torque while reducing the rotation speed of the mixing and swinging motor 221.

[0060] Please refer to Figure 5 , Figure 5 which is an exploded view of the liquid path module in a magnetic bead sorting device proposed in an embodiment of the present invention.

[0061] As Figure 5 shown, the liquid path module 3 includes a pipeline assembly 31 and a liquid path panel 32. The pipeline assembly 31 is used to transport the liquid in the liquid bag to the magnetic separation consumables for magnetic separation, and the liquid path panel 32 is used to control the flow of the liquid in the pipeline.

[0062] In some embodiments, the pipeline assembly 31 includes a pinch valve 311, a bubble sensor 312, a pressure sensor 313, a peristaltic pump 314, and a driver 315. Among them, the pinch valve 311 is used to control the on-off of the pipeline in the pipeline assembly 31; the bubble sensor 312 is used to judge whether the liquid in the liquid bag has run out by monitoring in real time whether there are bubbles mixed in the liquid flowing in the pipeline; the pressure sensor 313 is used to monitor the pressure of the liquid in the pipeline in real time; the peristaltic pump 314 is used to drive the liquid in the pipeline to flow when it operates; the output end of the driver 315 is connected to the peristaltic pump 314 to drive the peristaltic pump 314 to operate. The pinch valve 311, the bubble sensor 312, the pressure sensor 313, and the peristaltic pump 314 are all installed on the front of the liquid path panel 32, and the driver 315 is installed at a position on the back of the liquid path panel 32 opposite to the peristaltic pump 314, and the driver 315 is located in the housing 4.

[0063] In addition to the above-mentioned devices, the pipeline assembly 31 also includes pipelines connected between the devices. When the magnetic bead sorting device is in the working state, the driver 315 drives the peristaltic pump 314 to rotate to drive the liquid in the liquid bag to flow.

[0064] The pinch valve 311 controls the on / off of the pipeline for transferring the liquid in the liquid bag to the magnetic separation consumables. Its quantity can be set according to actual needs. When the quantity of the pinch valve 311 is set to two or more, the pinch valve 311 also has the function of changing the flow path. By opening or closing different pinch valves 311, the liquid in different liquid bags can be made to flow to the magnetic separation consumables.

[0065] The bubble sensor 312 is a sensor that uses the photoelectric effect of optoelectronic devices to detect bubbles in the liquid. It is used to monitor in real time whether the pipeline is in an empty pipeline condition as the judgment standard for whether the liquid enters the pipeline in the empty pipeline condition, and / or whether there are bubbles mixed in the liquid in the pipeline in the non-empty pipeline condition as the auxiliary judgment standard for whether the liquid in the liquid bag is used up.

[0066] The pressure sensor 313 is a device that can sense pressure signals and convert the pressure signals into available output electrical signals according to certain rules. The pressure sensor 313 is used to monitor in real time the pressure magnitude of the liquid in the pipeline. If it is monitored that the pressure magnitude of the liquid in the pipeline exceeds the set pressure value range, a feedback signal is sent so as to facilitate the main control or the staff to make corresponding adjustments.

[0067] In some embodiments, the pipeline assembly 31 further includes a weighing sensor installed on the front of the liquid path panel 32. The weighing sensor is used to monitor in real time the change in the weight of the liquid in the liquid bag to determine whether the liquid in the liquid bag is emptied.

[0068] The pipeline assembly 31 in the embodiment of the present invention is arranged in an open layout on the liquid path panel 32. The liquid path panel 32 can be installed on the housing 4 at a certain angle of inclination to facilitate operation, installation and disassembly. At the same time, a pressure sensor 313 is installed on the liquid path panel 32 to monitor the liquid path pressure and prevent pipeline blockage. A bubble sensor 312 and a weighing sensor 316 are also installed on the liquid path panel 32. The bubble sensor 312 monitors the bubble condition of the pipeline, and the weighing sensor monitors the weight change of the liquid bag to determine whether the liquid in the liquid bag is used up, making the use process more convenient.

[0069] Please refer to Figure 2 , the magnetic bead sorting device further includes a liquid hanging rod 5. The liquid hanging rod 5 is installed on the housing 4, and a hook 51 for hanging the liquid bag is provided thereon. The liquid hanging rod 5 is used to hang the liquid bag on one side of the magnetic bead sorting device to facilitate the liquid in the liquid bag to flow into the magnetic separation consumables for magnetic bead sorting and facilitate the replacement of the liquid bag. Among them, the quantity of the hooks 51 is set according to actual needs.

[0070] Please refer to Figure 2, the magnetic bead sorting device further includes a controller installed in the housing 4, a code scanning device 7 for scanning and identifying the liquid bag, and a display device 8 for touch operation or parameter display. The lifting device 1, the mixing device 2, the liquid path module 3, the code scanning device 7, and the display device 8 are all connected to the controller. Among them, the display device 8 sets, modifies, and monitors some relevant parameters during the magnetic bead sorting process through a touch human-computer interaction display interface. The code scanning device 7 is used to scan and identify the identification code on the liquid bag, and then transmit the identified data information to the controller for use. The size, shape, etc. of the code scanning device 7 can also be set according to requirements.

[0071] In addition, an embodiment of the present invention also proposes a magnetic bead sorting method, which is applied to the magnetic bead sorting device described in any of the above embodiments.

[0072] Please refer to Figure 6 , Figure 6 which is a schematic flow chart of a magnetic bead sorting method proposed by an embodiment of the present invention.

[0073] As Figure 6 shown, the magnetic bead sorting method includes:

[0074] Step S101: Fill the cleaning liquid into the pipeline through the liquid path module, and detect the gas evacuation situation of the pipeline.

[0075] To ensure that no liquid leakage occurs in the magnetic separation consumables during the magnetic bead sorting process of the magnetic bead sorting device for magnetic cell liquid. Before performing step S101, it is necessary to first check the airtightness of the magnetic separation consumables.

[0076] In an embodiment of the present invention, the airtightness of the magnetic separation consumables is checked through a liquid path component. Specifically, close all pinch valves 311, drive the peristaltic pump 314 to rotate forward or backward, and start the pressure sensor 313 to detect the pressure in the pipeline. Since the pipeline is connected to the magnetic separation consumables, the airtightness of the magnetic separation consumables is judged based on the pressure data in the pipeline collected by the pressure sensor 313.

[0077] Among them, if the driving peristaltic pump 314 rotates forward according to the set parameters within the set time, the peristaltic pump 314 conveys air to the pipeline and the magnetic separation consumables. When the airtightness of the magnetic separation consumables is qualified, the pressure value in the pipeline and the magnetic separation consumables will increase to the preset value; when the airtightness of the magnetic separation consumables is unqualified, the pressure value in the pipeline and the magnetic separation consumables will not increase to the preset value, and this is used as the judgment standard for whether the airtightness of the magnetic separation consumables is qualified. Similarly, if the driving peristaltic pump 314 rotates backward according to the set parameters within the set time, the peristaltic pump 314 extracts air from the pipeline and the magnetic separation consumables. When the airtightness of the magnetic separation consumables is qualified, the pressure value in the pipeline and the magnetic separation consumables will decrease to the preset value; when the airtightness of the magnetic separation consumables is unqualified, the pressure value in the pipeline and the magnetic separation consumables will not decrease to the preset value, and this is used as the judgment standard for whether the airtightness of the magnetic separation consumables is qualified.

[0078] When the airtightness of the magnetic separation consumables is qualified, step S101 is performed.

[0079] Hang a cleaning liquid bag loaded with cleaning liquid, a cell liquid bag loaded with magnetic bead sorted magnetic cell liquid, and a magnetic separation buffer bag loaded with magnetic separation buffer on the liquid hanging rod, connect the cleaning liquid bag, the cell liquid bag, and the magnetic separation buffer bag to the liquid path module, and connect the output end of the magnetic separation consumables to the waste liquid bag.

[0080] Fill the pipeline with cleaning liquid through the liquid path module. Specifically, open the pinch valve between the magnetic separation consumables and the cleaning liquid bag to connect the cleaning liquid bag and the magnetic separation consumables. Start the bubble sensor to monitor whether the cleaning liquid enters the pipeline and collect the moment when the cleaning liquid enters the pipeline. Drive the peristaltic pump to pump out the cleaning liquid in the cleaning liquid bag and fill it into the pipeline, and flush the gas in the pipeline into the waste liquid bag. Set the preset cleaning duration. Calculated from the moment when the cleaning liquid enters the pipeline, through the preset cleaning duration, it can be judged that the cleaning liquid fills the pipeline and empties the air in the pipeline. Detect the emptying situation of the air in the pipeline through the bubble sensor and the pressure sensor. When the bubble sensor cannot detect bubbles and the pressure data value collected by the pressure sensor conforms to the pressure data range of the air emptied in the pipeline, it proves that the air in the pipeline has been emptied.

[0081] Step S102: According to the gas emptying situation, fill the magnetic bead sorted magnetic cell liquid to be magnetically separated into the pipeline through the liquid path module and flow it into the magnetic separation consumables.

[0082] Specifically, after confirming that the gas in the pipeline has been emptied, close the pinch valve between the magnetic separation consumables and the cleaning liquid bag, open the pinch valve between the cell liquid bag and the magnetic separation consumables to connect the cell liquid bag and the magnetic separation consumables. Drive the peristaltic pump to pump out the magnetic bead sorted magnetic cell liquid to be magnetically separated in the cell liquid bag and fill it into the pipeline and flow it into the magnetic separation consumables.

[0083] Step S103: Place the magnetic cell liquid in the magnetic separation consumable into the magnetic bead sorting state through the lifting module.

[0084] Specifically, the lifting module drives the consumable mounting plate to move downward relative to the magnet and approach the magnet. In the embodiment of the present invention, the moving motor 1311 is started, the moving motor 1311 drives the lead screw 1312 to rotate, and the moving nut 1313 drives the guide block 1314 to move horizontally on the lead screw 1312. Under the action of the guide block 1314, the guide unit 132 follows the guide block 1314 to move horizontally. The consumable mounting plate 11 realizes downward movement in the longitudinal direction through the cooperation of the cam follower 111 and the inclined strip-shaped guide hole 13221 on the guide unit 132. The magnetic separation consumable is arranged on the consumable mounting plate. The magnitude of the magnetic field where the magnetic cell liquid on the magnetic separation consumable is located increases, and the magnetic cell liquid is placed in the magnetic bead sorting state. The immunomagnetic beads cells are adsorbed to the bottom of the magnetic separation consumable under the action of the magnetic field, and the non-immunomagnetic beads cells are suspended in the liquid.

[0085] Step S104: Shake the magnetic cell liquid in the magnetic separation consumable through the mixing and swinging module.

[0086] Specifically, start the mixing and swinging motor 221 to rotate forward and backward periodically, thereby driving the driving wheel 223. The driving wheel 223 drives the driven wheel 133 through the synchronous belt 224. The driven wheel 133 is fixedly arranged on the lifting device 1, and the driven wheel 133 will drive the lifting device 1 to swing forward and backward periodically, thereby realizing the shaking of the magnetic cell liquid, so as to avoid the accumulation of immunomagnetic cells resulting in insufficient magnetism in local areas of the magnetic separation consumable and losing the adsorption force for the unadsorbed immunomagnetic cells, resulting in the loss of immunomagnetic cells.

[0087] Under the action of the lifting module and the mixing and swinging module, the magnetic cell liquid performs magnetic bead sorting in the magnetic separation consumable. The immunomagnetic cells are adsorbed to the bottom of the magnetic separation consumable under the action of the magnetic field, and the non-immune cells flow into the waste liquid bag following the liquid. Continuously introduce the magnetic cell liquid to be magnetic bead sorted into the magnetic separation consumable for magnetic bead sorting. Monitor the weight change in the cell liquid bag through the weight sensor to judge the empty bag situation of the cell liquid bag, and monitor the situation during the transmission of the magnetic cell liquid through the bubble sensor and the pressure sensor.

[0088] Step S105: After the magnetic cell liquid completes magnetic bead sorting, empty the liquid in the magnetic separation consumable through the liquid path module.

[0089] When the cell fluid bag is empty and the magnetic cell fluid to be sorted by magnetic beads has all completed magnetic bead sorting, close the pinch valve between the cell fluid bag and the magnetic sorting consumables, and open the pinch valve between the sterile filter and the magnetic sorting consumables to connect the sterile filter and the magnetic sorting consumables. Start the sterile filter, and use sterile gas passing through the sterile filter to empty the liquid in the magnetic sorting consumables. The liquid in the magnetic sorting consumables takes away the non-immunomagnetic bead cells that are not adsorbed, leaving the immunomagnetic bead cells adsorbed to the bottom of the magnetic sorting consumables.

[0090] Step S106: Place the magnetic cell fluid in the magnetic sorting consumables in a non-magnetic bead sorting state through the lifting module and collect the sorted immunomagnetic bead cells.

[0091] Specifically, the lifting module drives the consumable mounting plate to move upward relative to the magnet and away from the magnet. In the embodiment of the present invention, start the moving motor 1311, the moving motor 1311 drives the lead screw 1312 to rotate, and the moving nut 1313 drives the guide block 1314 to move horizontally on the lead screw 1312. Under the action of the guide block 1314, the guide unit 132 follows the guide block 1314 to move horizontally. The consumable mounting plate 11 realizes upward movement in the longitudinal direction through the cooperation of the cam follower 111 and the inclined strip-shaped guide hole 13221 on the guide unit 132. The magnetic sorting consumables are arranged on the consumable mounting plate. The magnitude of the magnetic field where the magnetic cell fluid on the magnetic sorting consumables is located decreases, and the magnetic cell fluid is placed in a non-magnetic bead sorting state. The adsorption force of the magnetic field on the immunomagnetic bead cells decreases, and the suction force on the immunomagnetic bead cells adsorbed to the bottom of the magnetic sorting consumables decreases to a negligible level.

[0092] Collect the sorted immunomagnetic bead cells. Specifically, switch the output end of the magnetic sorting consumables to be connected to the collection bag. Open the pinch valve between the magnetic sorting buffer bag and the magnetic sorting consumables to connect the magnetic sorting buffer bag and the magnetic sorting consumables. Drive the peristaltic pump to pump out the magnetic sorting buffer in the magnetic sorting buffer bag and fill it into the pipeline and flow into the magnetic sorting consumables. Continuously introduce the magnetic sorting buffer into the magnetic sorting consumables within a preset time, and bring the immunomagnetic bead cells in the magnetic sorting consumables into the collection bag together through the magnetic sorting buffer. Within this preset time, the immunomagnetic bead cells on the magnetic sorting consumables are basically collected into the collection bag.

[0093] Close the pinch valve between the magnetic sorting buffer bag and the magnetic sorting consumables, open the pinch valve between the sterile filter and the magnetic sorting consumables to connect the sterile filter and the magnetic sorting consumables. Start the sterile filter, and use sterile gas passing through the sterile filter to empty the liquid in the magnetic sorting consumables, and drain all the liquid in the magnetic sorting consumables into the collection bag to obtain all the immunomagnetic bead cells sorted out by this magnetic bead sorting. This immunomagnetic bead cell is an immunopositive cell with magnetism, and immunocytes with the required antibodies can be obtained by incubating the immunopositive cells.

[0094] In summary, a magnetic bead sorting device proposed in an embodiment of the present invention lifts the consumable mounting plate through a lifting device, so that the consumable mounting plate moves away from or close to the magnet below, so as to achieve the purpose of removing or applying a magnetic field to the magnetic cell liquid on the consumable mounting plate; a swinging device is provided to swing the lifting device, so as to shake the magnetic cell liquid on the lifting device and avoid the accumulation of immunomagnetic bead cells in the magnetic cell liquid, resulting in the loss of some immunomagnetic bead cells.

[0095] In addition, a magnetic bead sorting device proposed in an embodiment of the present invention is also provided with a liquid path module, which controls the flow and flow rate of the magnetic cell liquid through the liquid path module to achieve a better magnetic bead sorting effect, and avoid problems such as the escape of immunomagnetic bead cells caused by too fast flow rate and long magnetization time caused by too slow flow rate; the liquid path module monitors whether the liquid in the liquid bag is emptied, which is convenient for timely replacement of the liquid bag and improves work efficiency.

[0096] An embodiment of the present invention also proposes a magnetic bead sorting method, which is applied to the magnetic bead sorting device proposed in the embodiment of the present invention. The magnetic bead sorting method uses the magnetic bead sorting device to achieve magnetic sorting of a large-throughput or large-capacity magnetic cell liquid, greatly improving the work efficiency of magnetic bead sorting while maintaining a good sorting rate.

[0097] The above is a specific description of the preferred embodiments of the present invention, but the present invention is not limited to the described embodiments. Those skilled in the art can make various equivalent deformations or substitutions without departing from the spirit of the present invention, and these equivalent deformations or substitutions are all included in the scope defined by the claims of this application.

Claims

1. A magnetic bead sorting device, characterized in that, Comprising: A lifting device, including a consumable installation plate for loading magnetic separation consumables, a magnet disposed below the consumable installation plate, and a lifting module connected to the consumable installation plate and used to drive the consumable installation plate to move up and down relative to the magnet; A mixing and swinging device, including a mixing and swinging bracket for installing the lifting device, and a mixing and swinging module connected to the lifting device through the mixing and swinging bracket and used to drive the lifting device to swing; A liquid path module, including a pipeline assembly for transporting the liquid in the liquid bag to the magnetic separation consumables for magnetic separation, and a liquid path panel for controlling the flow of the liquid in the pipeline; A housing, on which the lifting device, the mixing and swinging device, and the liquid path module are all installed.

2. The magnetic bead sorting device according to claim 1, wherein The lifting module includes a lateral movement unit and a guiding unit connected to the lateral movement unit. The guiding unit is movably connected to the consumable installation plate and used to convert the lateral movement of the guiding unit into the longitudinal movement of the consumable installation plate.

3. The magnetic bead sorting device according to claim 2, wherein The lateral movement unit includes a movement motor, a lead screw connected to the movement motor, a movement nut sleeved on the lead screw, and a guiding block connected to the movement nut. The guiding block is connected to the guiding unit, and the guiding block is used to drive the guiding unit to move laterally following the movement nut when the movement motor drives the lead screw to rotate to drive the movement nut to move laterally.

4. The magnetic bead sorting device according to claim 2, wherein, The guiding unit includes a connecting plate connected to the guiding block and at least one guiding plate connected to the connecting plate. The guiding plate is provided with an obliquely strip-shaped guiding hole.

5. The magnetic bead sorting device according to claim 4, wherein, A cam follower is provided on the consumable installation plate. The cam follower is disposed in the obliquely strip-shaped guiding hole, and the cam follower is used to change the longitudinal position of the consumable installation plate by changing the position of the cam follower in the obliquely strip-shaped guiding hole when the guiding unit moves laterally.

6. The magnetic bead sorting device according to claim 1, characterized in that The mixing and swinging module includes a mixing and swinging motor, a speed reducer, a driving wheel, and a synchronous belt. The lifting device further includes a magnet mounting seat for mounting the magnet and movably connected to the consumable installation plate, and a driven wheel mounted on one side of the magnet mounting seat. One end of the speed reducer is connected to the mixing and swinging motor, the other end of the speed reducer is connected to the driving wheel, and the synchronous belt is sleeved on the driving wheel and the driven wheel.

7. The magnetic bead sorting device according to claim 1, wherein, The pipeline assembly includes a pinch valve for controlling the on / off of the pipeline in the pipeline assembly, a bubble sensor for judging whether the liquid in the liquid bag has run out by real-time monitoring whether there are bubbles mixed in the liquid flowing in the pipeline, a pressure sensor for real-time monitoring the liquid pressure in the pipeline, a peristaltic pump for driving the liquid to flow in the pipeline during operation, and a drive controller with an output end connected to the peristaltic pump and used to drive the peristaltic pump to operate; The pinch valve, the bubble sensor, the pressure sensor, and the peristaltic pump are all installed on the front surface of the liquid path panel. The drive controller is installed on the back surface of the liquid path panel at a position opposite to the peristaltic pump, and the drive controller is located inside the housing.

8. The magnetic bead sorting device according to claim 1, wherein, The pipeline assembly further includes a weighing sensor for real-time monitoring of the change in the liquid weight in the liquid bag to determine whether the liquid in the liquid bag is emptied, and the weighing sensor is installed on the front of the liquid path panel.

9. The magnetic bead sorting device according to claim 1, characterized in that, The magnetic bead sorting device further includes a liquid hanging rod installed on the housing, and a hook for hanging the liquid bag is provided on the liquid hanging rod.

10. The magnetic bead sorting device according to claim 1, characterized in that, The magnetic bead sorting device further includes a controller installed in the housing, a code scanning device for scanning and identifying the liquid bag, and a display device for touch operation or parameter display. The lifting device, the mixing and swinging device, the liquid path module, the code scanning device, and the display device are all connected to the controller.

11. A magnetic bead sorting method, which is applied to the magnetic bead sorting device according to any one of claims 1 to 10, characterized in that, Including: Fill the pipeline with cleaning liquid through the liquid path module, and detect the gas evacuation condition of the pipeline; According to the gas evacuation condition, fill the magnetic cell liquid to be sorted by magnetic beads into the pipeline through the liquid path module and flow it into the magnetic separation consumable; Place the magnetic cell liquid in the magnetic separation consumable in a magnetic bead sorting state through the lifting module; Shake the magnetic cell liquid in the magnetic separation consumable through the mixing and swinging module; After the magnetic bead sorting of the magnetic cell liquid is completed, empty the liquid in the magnetic separation consumable through the liquid path module; Place the magnetic cell liquid in the magnetic separation consumable in a non-magnetic bead sorting state through the lifting module and collect the sorted immunomagnetic bead cells.

12. The magnetic bead sorting method according to claim 11, wherein Before filling the pipeline with the cleaning liquid, perform an airtightness check on the magnetic separation consumable.

13. The magnetic bead sorting method according to claim 11, wherein The collection of the sorted immunomagnetic bead cells includes: Connect the collection bag to the output end of the magnetic separation consumable; Flow the magnetic separation buffer solution into the magnetic separation consumable through the liquid path module within a preset time, and bring the immunomagnetic bead cells into the collection bag; Empty the liquid in the magnetic separation consumable through the liquid path module to obtain the immunomagnetic bead cells.

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