Cell sorting equipment, method and equipment
By combining magnetic sorting columns and fluid filters in cell sorting equipment, using external magnetic field and separation column for three-stage sorting, the problem of low cell sorting efficiency and accuracy in the prior art is solved, and high efficiency and accuracy are achieved cell sorting.
Patent Information
- Application Number
- CN202310852199.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-07-11
- Publication Date
- 2025-01-14
AI Technical Summary
Existing cell sorting equipment has low efficiency and accuracy during magnetic sorting, resulting in low purity of target cells.
A cell sorting device containing a magnetic sorting column and a fluid filter was designed to filter impurities in the sample liquid through a fluid filter, and use an external magnetic field generation mechanism to enhance the magnetic field in the magnetic sorting column to achieve magnetic labeling of cells. Effective adsorption, combined with the separation column for three-stage sorting to avoid impurities blockage.
The efficiency and accuracy of cell sorting were improved, and magnetically labeled cells were successfully sorted, which avoided the impact of impurities on the sorting process and improved the purity of the target cells.
Smart Images

Figure CN119307360A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of cell processing, and in particular relates to a cell sorting device, method and device. Background Art
[0002] Magnetic separation is a method of separating magnetically labeled substances from a mixture using a magnetic field. At present, in the field of cell processing technology, cells are usually magnetically separated by cell separation equipment to separate target cells from non-target cells, thereby obtaining target cells with higher purity. When magnetically separating cells, cell separation equipment in the prior art has low cell separation efficiency and accuracy. Summary of the invention
[0003] The present invention aims at the technical problems of reduced efficiency and precision of cell sorting in the prior art, and provides a cell sorting device, method and equipment.
[0004] In view of the above technical problems, an embodiment of the present invention provides a cell sorting device, comprising:
[0005] A cell sorting tube set, comprising a magnetic sorting column and a fluid filter for filtering impurities in a sample liquid; the magnetic sorting column is provided with a first sorting space for the sample liquid filtered by the fluid filter to flow through, and the fluid filter is connected to the first sorting space;
[0006] The magnetic field generating mechanism is used to enhance or eliminate the magnetic field in the first sorting space. The magnetic sorting column is used to adsorb the magnetically labeled cells in the sample liquid flowing through the first sorting space through the enhanced magnetic field after the magnetic field generating mechanism enhances the magnetic field in the first sorting space.
[0007] An embodiment of the present invention further provides a cell sorting method, wherein the cell sorting device performs cell sorting according to the cell sorting method, and the cell sorting method comprises:
[0008] Controlling the sample liquid to flow from the sample container into the fluid filter so as to filter impurities in the sample liquid through the fluid filter;
[0009] After confirming that the magnetic field generating mechanism has enhanced the magnetic field in the first sorting space, the sample liquid filtered by the fluid filter is controlled to flow into the first sorting space of the magnetic sorting column, and the magnetically labeled cells in the sample liquid flowing through are adsorbed in the first sorting space through the enhanced magnetic field in the first sorting space.
[0010] An embodiment of the present invention further provides a computer device, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the cell sorting method is implemented when the processor executes the computer program.
[0011] In the cell sorting device provided by the present invention, the cell sorting tube group includes a magnetic sorting column and a fluid filter for filtering impurities in the sample liquid; a first sorting space is provided in the magnetic sorting column for the sample liquid filtered by the fluid filter to flow through, and the fluid filter is connected to the first sorting space; a magnetic field generating mechanism is used to enhance or eliminate the magnetic field in the first sorting space, and the magnetic sorting column is used to adsorb the magnetically labeled cells in the sample liquid flowing through into the first sorting space through the enhanced magnetic field after the magnetic field generating mechanism enhances the magnetic field in the first sorting space.
[0012] The present invention filters impurities in the sample liquid (such as blood clots, micropolymers and particulate debris in blood, blood clots and particulate debris in rescued blood products, etc.) through the fluid filter in the cell sorting tube group to perform a first screening of the sample liquid; then, a magnetic field generating mechanism is arranged outside the magnetic sorting column of the cell sorting tube group to enhance the magnetic field in the first sorting space, so that the magnetically labeled cells of the sample liquid flowing through the first sorting space are magnetically sorted by the enhanced magnetic field. In this way, the present invention successfully sorts out the magnetically labeled cells through the secondary screening (including filtration and magnetic sorting) of the fluid filter and the magnetic sorting column, while avoiding the impurities in the sample liquid from clogging the first sorting space of the magnetic sorting column, thereby improving the efficiency and accuracy of cell sorting. BRIEF DESCRIPTION OF THE DRAWINGS
[0013] The present invention is further described below in conjunction with the accompanying drawings and embodiments.
[0014] Figure 1 It is a schematic diagram of the structure of a cell sorting device provided in one embodiment of the present invention.
[0015] Figure 2 It is a schematic diagram of the explosion structure of a cell sorting device provided in another embodiment of the present invention.
[0016] Figure 3 It is a schematic diagram of the structure of a cell sorting tube set provided in one embodiment of the present invention.
[0017] Figure 4 It is a structural schematic diagram of a magnetic field generating mechanism provided in one embodiment of the present invention.
[0018] Figure 5 It is a structural schematic diagram of a panel mechanism provided by an embodiment of the present invention.
[0019] Figure 6It is a partial structural schematic diagram of a panel mechanism provided in one embodiment of the present invention.
[0020] Figure 7 It is a structural schematic diagram of a weighing mechanism provided in one embodiment of the present invention.
[0021] Figure 8 It is a partial structural schematic diagram of a weighing mechanism provided in one embodiment of the present invention.
[0022] Fig. 9 4 is a flow chart of the cell sorting method provided in the first embodiment of the present invention.
[0023] The reference numerals in the specification are as follows:
[0024] 100, cell sorting tube set; 111, sample inlet; 112, cleaning inlet; 113, second waste liquid inlet and outlet; 120, fluid filter; 131, separation column; 132, magnetic sorting column; 140, output end; 141, first waste liquid inlet and outlet; 142, negative selection outlet; 143, positive selection outlet; 151, first pipeline; 152, second pipeline; 1521, first connecting pipe; 1522, second connecting pipe; 153, third pipeline; 154, fourth pipeline; 155, fifth pipeline; 156, sixth pipeline; 161, first connecting pipeline; 162, second connecting pipeline; 163, sixth pipeline; 164, first connecting pipeline; 165, second connecting pipeline; 166, sixth pipeline; 167, first connecting pipeline; 168, second connecting pipeline; 169, third pipeline; 170, first connecting pipeline; 171, second connecting pipeline; 172, second connecting pipeline; 173, third pipeline; 174, fourth pipeline; 175, fifth pipeline; 176, sixth pipeline; 177, first connecting pipeline; 178, second connecting pipeline; 179, first connecting pipeline; 180, first connecting pipeline; 181, first connecting pipeline; 182, second connecting pipeline; 183, first connecting pipeline; 184, first connecting pipeline; 185, first connecting pipeline; 186, first connecting pipeline; 187, first connecting pipeline; 188, second connecting pipeline; 189, first connecting pipeline; 190, first connecting pipeline; 191, first connecting pipeline; 192, second connecting pipeline; 193, first connecting pipeline; 194, first connecting pipeline; 195, first connecting pipeline; 196, first connecting pipeline; 197, first connecting pipeline; 198, second connecting pipeline; 3. The third connecting pipeline; 164. The fourth connecting pipeline; 165. The fifth connecting pipeline; 180. The sterile filter; 190. The filter drop bucket; 200. The driving pump; 300. The magnetic field generating mechanism; 310. The motion module; 311. The base; 312. The driving member; 313. The transmission assembly; 314. The moving assembly; 315. The sensor; 316. The screw rod; 317. The slide rail; 318. The slider; 319. The mounting bracket; 320. The magnet; 410. The first pressure sensor; 420. The second pressure sensor; 510. The first bubble sensor; 520. The second bubble sensor; 530. The third bubble sensor; 540, the fourth bubble sensor; 550, the fifth bubble sensor; 610, the first waste liquid container; 620, the second waste liquid container; 630, the negative selection container; 640, the positive selection container; 700, the rack; 710, the storage space; 720, the access container; 801, the first pinch valve; 802, the second pinch valve; 803, the third pinch valve; 804, the fourth pinch valve; 805, the fifth pinch valve; 806, the sixth pinch valve; 807, the seventh pinch valve; 808, the eighth pinch valve; 809, the ninth pinch valve; 810, the tenth pinch valve; 811, the eleventh pinch valve ; 812, the twelfth pinch valve; 813, the thirteenth pinch valve; 814, the fourteenth pinch valve; 815, the fifteenth pinch valve; 900, the panel mechanism; 910, the liquid circuit panel; 911, the first mounting block; 912, the first mounting groove; 914, the second mounting block; 915, the second mounting groove; 916, the mounting bracket; 917, the insertion hole; 918, the protective cover; 919, the take-and-put port; 1000, the weighing mechanism; 1100, the support assembly; 1200, the weighing assembly; 1210, the mounting support; 1220, the weighing sensor; 1230, the hook; 1300, the human-computer interaction assembly. DETAILED DESCRIPTION
[0025] In order to make the technical problems, technical solutions and beneficial effects solved by the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.
[0026] 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 for the convenience of describing the present invention and simplifying 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.
[0027] like Figures 1 to 3 As shown, one embodiment of the present invention provides a cell sorting device, including a cell sorting tube group 100, wherein the cell sorting tube group 100 includes a magnetic sorting column 132 and a fluid filter 120 for filtering impurities in a sample liquid; a first sorting space is provided in the magnetic sorting column 132 for the sample liquid filtered by the fluid filter 120 to flow through, and the fluid filter 120 is connected to the first sorting space.
[0028] The magnetic field generating mechanism 300 is used to enhance or eliminate the magnetic field in the first sorting space. The magnetic separation column 132 is used to adsorb the magnetically labeled cells (including immunomagnetic bead cells and bacteria labeled with magnetic beads, etc.) in the sample liquid flowing through the first sorting space after the magnetic field generating mechanism 300 enhances the magnetic field in the first sorting space. It can be understood that the target cells in the sample liquid are combined with the magnetic substance through magnetic labeling, and then have magnetism; that is, the target cells are magnetized to generate immunomagnetic bead cells, that is, magnetically labeled cells. The fluid filter 120 is used to filter impurities in the sample liquid (such as blood clots, micropolymers and microparticle debris in blood, blood clots and microparticle debris in rescued blood products, etc.). The magnetic field generating mechanism 300 can be set at a preset position outside the magnetic separation column 132 as needed. As long as the magnetic field generating mechanism 300 is in the preset position, the magnetic field in the first sorting space used to adsorb the magnetically labeled cells in the sample liquid flowing through the first sorting space can be enhanced.
[0029] Among them, the magnetic field generating mechanism 300 can be an electromagnetic mechanism or a movable magnet mechanism. In this way, the magnetic field in the first sorting space can be enhanced or eliminated by controlling the electromagnetic coil of the electromagnetic mechanism to be energized (to enhance the magnetic field) or de-energized (to eliminate the magnetic field), or controlling the movable magnet mechanism to approach (to enhance the magnetic field) or move away from (to eliminate the magnetic field) the magnetic sorting column 132, etc.
[0030] It can be understood that when the sample liquid passes through the fluid filter 120, impurities in the sample liquid (such as blood clots, micropolymers and particulate debris in blood, blood clots and particulate debris in rescued blood products, etc.) are filtered out by the fluid filter 120; thereafter, the sample liquid passes through the first sorting space in the magnetic sorting column 132, and the magnetic field in the first sorting space is enhanced by the magnetic field generating mechanism 300, so that the magnetically labeled cells passing through the first sorting space are adsorbed in the first sorting space through the enhanced magnetic field. After the magnetically labeled cells in the sample liquid are adsorbed in the first sorting space, the magnetic field generating mechanism 300 can also be made to eliminate the magnetic field in the first sorting space, so that the magnetically labeled cells adsorbed in the first sorting space can be transported to the target container (such as the positive selection container 640) through the cleaning fluid, thereby completing the sorting of the magnetically labeled cells in the sample liquid.
[0031] The cell sorting device provided by the present invention filters impurities in the sample liquid (such as blood clots, micropolymers and particulate fragments in blood, blood clots and particulate fragments in rescued blood products, etc.) through the fluid filter 120 in the cell sorting tube group 100 to perform a first screening of the sample liquid; then, a magnetic field generating mechanism 300 is arranged outside the magnetic sorting column 132 of the cell sorting tube group 100 to enhance the magnetic field in the first sorting space, thereby magnetically sorting the magnetically labeled cells of the sample liquid flowing through the first sorting space through the enhanced magnetic field. In this way, the present invention successfully sorts out the magnetically labeled cells through the secondary screening (including filtration and magnetic sorting) of the fluid filter 120 and the magnetic sorting column 132, while avoiding the impurities in the sample liquid clogging the first sorting space of the magnetic sorting column, thereby improving the efficiency and accuracy of cell sorting.
[0032] like Figures 1 to 4As shown, in one embodiment, the magnetic field generating mechanism 300 includes a motion module 310 and a magnet 320 connected to the motion module 310, and the motion module 310 drives the magnet 320 to approach to enhance the magnetic field in the first sorting space, or to move away from the magnetic sorting column 132 to eliminate the magnetic field in the first sorting space, and the magnetic sorting column 132 is used to adsorb the magnetically labeled cells in the sample liquid flowing through the first sorting space by the enhanced magnetic field after the magnet 320 enhances the magnetic field in the first sorting space. It can be understood that in this embodiment, the magnetic field generating mechanism 300 controls the magnet 320 to approach (enhance the magnetic field) or move away from (eliminate the magnetic field) the magnetic sorting column 132 through the motion module 310, so as to enhance or eliminate the magnetic field in the first sorting space. The motion module 310 can be set at a preset position outside the magnetic separation column 132 as needed, as long as the motion module 310 can drive the magnet 320 to approach the magnetic separation column 132, so that the magnetic field in the first separation space for adsorbing the magnetically labeled cells in the sample liquid flowing through the first separation space is enhanced, and after driving the magnet 320 away from the magnetic separation column 132, the magnetic field in the first separation space for adsorbing the magnetically labeled cells in the sample liquid flowing through the first separation space is eliminated.
[0033] like Figure 4As shown, in one embodiment, the motion module 310 includes a base 311, a driving member 312 mounted on the base 311, a transmission assembly 313 connected to the driving member 312, and a moving assembly 314 connected to the magnet 320; the moving assembly 314 is connected to the transmission assembly 313, and drives the magnet 320 to move under the drive of the transmission assembly 313. It can be understood that the base 311 can be set at the preset position outside the magnetic separation column 132 as needed. The driving member 312 can include a linear driving member 312 (such as a cylinder or a hydraulic cylinder, etc.) or a rotating driving member 312 (such as a motor, etc.). When the driving member 312 is a linear driving member 312, the driving member 312 can directly drive the moving component 314 through the transmission component 313 (such as a driving arm, etc.), thereby driving the magnet 320 to move along a preset straight line through the moving component 314; when the driving member 312 is a rotary driving member 312, the transmission component 313 can be a component such as a screw rod 316, a worm gear or a chain that can convert rotary motion into linear motion. After the moving component 314 is connected to the transmission component 313, the magnet 320 is driven by the transmission component 313 to move along a preset straight line; when the driving member 312 is a rotary driving member 312, the driving member 312 can also directly drive the moving component 314 to rotate with the driving member 312 as the center through the transmission component 313 (such as a swing arm, etc.), thereby driving the magnet 320 to move along a preset arc through the moving component 314.
[0034] like Figure 4 As shown, in one embodiment, the driving member 312 includes a motor, the transmission assembly 313 includes a screw rod 316 and a slide rail 317 mounted on the base 311, and the slide rail 317 is arranged in parallel with the screw rod 316; the moving assembly 314 includes a slider 318 and a mounting bracket 319 for mounting the magnet 320; the slider 318 is slidably connected with the slide rail 317, and the motor drives the screw rod 316 to drive the slider 318 and the magnet 320 to slide along the slide rail 317. It can be understood that the motor can select different types of motors as needed. Further, the motor includes a stepping motor, so that the displacement of the slider 318 can be accurately controlled. The transmission assembly 313 includes a screw rod 316 that converts the rotational motion of the motor into a linear motion, and the slide rail 317 that is arranged in parallel with the screw rod 316 and used to support the slider 318. The mounting frame 319 is used to mount the magnet 320 , and the slider 318 slides along the slide rail 317 driven by the screw rod 316 , so that the magnet 320 moves along the slide rail 317 .
[0035] In one embodiment, if Figure 4 As shown, the motion module 310 further includes a sensor 315 mounted on the base 311 and used to detect the motion state of the slider 318. It can be understood that the motion state of the slider 318 includes the specific position of the slider 318 relative to the base 311 or the moving distance of the slider 318 relative to the sensor 315. The sensor 315 can be a travel switch or a photoelectric sensor 315 used to detect whether an object is in a specific position. The sensor 315 is respectively mounted on the base 311 at the position where the magnet 320 (or the slider 318) is close to and / or away from the magnetic separation column 132, so as to determine the motion state of the slider 318 (that is, the magnet 320) by detecting the specific position of the slider 318 (that is, the magnet 320) relative to the base 311. The sensor 315 may also be a distance sensor for detecting distance. The sensor 315 is mounted on the base 311 , so that the movement state of the slider 318 can be determined by detecting the moving distance of the slider 318 relative to the sensor 315 .
[0036] In one embodiment, the first sorting space contains a first iron bead; the magnetic field generating mechanism 300 is used to enhance or eliminate the magnetic field of the first iron bead, and after the magnetic field of the first iron bead is enhanced, the magnetically labeled cells are adsorbed through the enhanced magnetic field. It can be understood that the first iron bead can be magnetized under the magnetic field of the magnetic field generating mechanism 300, so that the magnetic field of the first iron bead to generate a magnetic adsorption force on the magnetically labeled cells can be enhanced. And the magnetic field generating mechanism 300 can also eliminate the magnetic field of the first iron bead, so that the first iron bead cannot adsorb the magnetically labeled cells after eliminating the magnetic field. The first iron bead is in the first sorting space, thereby forming a plurality of smaller holes or channels in the magnetic sorting column 132 than the first sorting space, so that the magnetically labeled cells can be more effectively adsorbed with a larger adsorption area.
[0037] In one embodiment, if Figures 1 to 5As shown, the cell sorting device further includes a frame 700 and a panel mechanism 900, wherein the panel mechanism 900 includes a fluid path panel 910; the fluid filter 120 and the cell sorting tube group 100 are both mounted on the fluid path panel 910; the fluid path panel 910 is mounted on the frame 700, and a receiving space 710 is formed between the fluid path panel 910 and the frame 700; the motion module 310 and the magnet 320 are both mounted in the receiving space 710. It can be understood that the shape of the frame 700 can be set according to requirements and is not limited to that shown in the figure. The frame 700 includes a support frame, a bottom plate mounted at the bottom of the support frame, side plates mounted around the support frame, and a top plate mounted on the top of the support frame. The bottom plate, top plate and side plates can be assembled together by screw connection, snap connection or welding, etc., wherein the bottom plate, top plate and side plates can be detachably connected to the support frame, so as to facilitate installation and maintenance of components inside the rack 700 from the disassembled position (e.g., replacement of the cell sorting tube set 100, etc.). The connection between the liquid path panel 910 and the rack 700 can also be detachably connected, so as to facilitate removal of the liquid path panel 910 from the rack 700, so as to directly replace the cell sorting tube set 100 on the liquid path panel 910.
[0038] Understandably, if Figure 2 As shown, at least one access container 720 is provided in the accommodating space 710, and a take-in and take-out port 919 is provided on the liquid path panel 910. In one embodiment, the access container 720 includes an access body provided with an access space and a door panel for opening and closing the access space; the door panel is rotatably mounted on the access body and is arranged corresponding to the take-in and take-out port 919, so that the door panel switch can be operated at the position of the take-in and take-out port 919 to open or close the access space to access items. The access space can be used to store the negative selection container, positive selection container, waste liquid container, etc. used in the present invention. It can be understood that the access container 720 can also be set as a drawer-type structure, and items can be accessed as long as the take-in and take-out port 919 is pulled out or pushed back.
[0039] like Figure 3As shown, in one embodiment, the cell sorting tube group 100 also includes one or more of the following pipelines: a first pipeline 151, a second pipeline 152, a third pipeline 153, a fourth pipeline 154, a fifth pipeline 155, a sixth pipeline 156, a first connecting pipeline 161, a second connecting pipeline 162, a third connecting pipeline 163, a fourth connecting pipeline 164, a fifth connecting pipeline 165, a sterile filter 180, a sample inlet 111 for inputting sample liquid, a cleaning inlet 112 for inputting cleaning liquid, a first waste liquid inlet and outlet 141 connected to the third pipeline 153, a negative selection outlet 142 for outputting negative selection liquid and connected to the third pipeline 153, a positive selection outlet 143 for outputting positive selection liquid and connected to the third pipeline 153, a second waste liquid inlet and outlet 113 connected to the sixth pipeline 156, and a filtering droplet 190 arranged on the first connecting pipe 1521 and used to filter bubbles in the liquid. It is understandable that the above pipelines can be set according to needs, and it is not necessary to set all pipelines at the same time. As long as the function and connection requirements of the cell sorting equipment are met, the specific connection relationship between the pipelines can also be adjusted accordingly.
[0040] Specifically, the first pipeline 151 is connected between the sample inlet 111 and the fluid filter 120; the second pipeline 152 includes a first connecting tube 1521 and a second connecting tube 1522, the first connecting tube 1521 is connected between the fluid filter 120 and the separation column 131, one end of the second connecting tube 1522 is connected to an end of the separation column 131 away from the first connecting tube 1521, and the other end is connected to an end of the magnetic separation column 132 away from the third pipeline 153; the third pipeline 153 is connected between the magnetic separation column 132 and The output end 140; the fourth pipeline 154 is connected between the cleaning inlet 112 and the second connecting pipe 1522; one end of the fifth pipeline 155 is connected to the sterile filter 180, and the other end is connected to the second connecting pipe 1522 and is located between the fluid filter 120 and the first connection point; the end of the sixth pipeline 156 away from the second waste liquid inlet and outlet 113 is connected to the fifth pipeline 155; the first connection point refers to the connection point between the fourth connecting pipeline 164 and the second connecting pipe 1522; the first connecting pipeline 161 is connected at The fourth pipeline 154 is connected to the first pipeline 151; one end of the second connecting pipeline 162 is connected to the fourth pipeline 154 and is located between the second connection point and the third connection point, and the other end is connected to the first connecting pipe 1521; one end of the third connecting pipeline 163 is connected to the fourth pipeline 154 and is located between the second connection point and the third connection point, and the other end is connected to the third pipeline 153; one end of the fourth connecting pipeline 164 is connected to the third pipeline 153 and is located between the magnetic separation column 132 and the fourth connection point, and the other end is connected to the second connecting pipe 152 2 and is located between the fluid filter 120 and the fifth connection point; the fifth connecting line 165 is connected between the first line 151 and the fifth line 155; the second connection point refers to the connection point between the first connecting line 161 and the fourth line 154; the third connection point refers to the connection point between the fourth line 154 and the second connecting line 1522; the fourth connection point refers to the connection point between the third connecting line 163 and the third line 153; the fifth connection point refers to the connection point between the second connecting line 162 and the first connecting line 1521.
[0041] like Figure 3 and Figure 5As shown, in one embodiment, the panel mechanism 900 further includes one or more of the following pinch valves, all of which are installed on the fluid path panel 910: a first pinch valve 801, a second pinch valve 802, a third pinch valve 803, a fourth pinch valve 804, a fifth pinch valve 805, a sixth pinch valve 806, a seventh pinch valve 807, an eighth pinch valve 808, a ninth pinch valve 809, a tenth pinch valve 810, an eleventh pinch valve 811, a twelfth pinch valve 812, a thirteenth pinch valve 813, a fourteenth pinch valve 814, and a fifteenth pinch valve 815. It is understandable that the above-mentioned pinch valves can be set according to requirements, and it is not necessary to set all the pinch valves at the same time, as long as the flow function and switch requirements of the cell sorting device are met, and the specific connection relationship between the pinch valves can also be adjusted accordingly.
[0042] Specifically, the first pinch valve 801 is arranged on the first pipeline 151 and is located between the connection point of the first connecting pipeline 161 and the first pipeline 151 and the sample inlet 111; the second pinch valve 802 is arranged on the fourth pipeline 154 and is located between the second connection point and the cleaning inlet 112; the third pinch valve 803 is arranged on the fourth pipeline 154 and is located between the connection point of the fourth pipeline 154 and the second connecting pipeline 162 and the third connection point; the fourth pinch valve 804 is arranged on the second pipeline 152 and is located between the third connection point and the fluid filter 120; the fifth pinch valve 805 is arranged on the second connecting pipe 1522 and is located between the fifth connection point and the separation column 131; the sixth pinch valve 806 is arranged on the first waste liquid inlet and outlet 141; the seventh pinch valve 806 is arranged on the first waste liquid inlet and outlet 141; 807 is arranged on the first connecting pipeline 161; the eighth pinch valve 808 is arranged on the second connecting pipeline 162; the ninth pinch valve 809 is arranged on the third connecting pipeline 163; the tenth pinch valve 810 is arranged on the fourth connecting pipeline 164; the eleventh pinch valve 811 is arranged on the fifth pipeline 155 and is located between the connection point between the fifth connecting pipeline 165 and the fifth pipeline 155 and the sterile filter 180; the twelfth pinch valve 812 is arranged on the fifth pipeline 155 and is located between the connection point between the fifth connecting pipeline 165 and the fifth pipeline 155 and the fifth connection point; the thirteenth pinch valve 813 is arranged on the sixth pipeline 156; the fourteenth pinch valve 814 is arranged on the negative selection outlet 142; the fifteenth pinch valve 815 is arranged on the positive selection outlet 143.
[0043] like Figure 3 and Figure 5As shown, in one embodiment, the panel mechanism 900 further includes a driving pump 200 installed on the fluid path panel 910 and used to drive the sample liquid to flow. It can be understood that under the drive of the driving pump 200, the sample liquid can be continuously input into the cell sorting tube set 100 through the sample inlet 111, and the liquid processed by the cell sorting tube set 100 can be output through the output end 140.
[0044] like Figure 3 and Figure 5 As shown, in one embodiment, the panel mechanism 900 also includes at least one bubble sensor installed on the liquid circuit panel 910 and used to monitor the flow state of the sample liquid in real time. It can be understood that the flow state of the sample liquid includes whether there are bubbles in the sample liquid, the flow direction of the sample liquid, or whether the sample liquid has flowed out. The flow state of the sample liquid is monitored in real time by the bubble sensor, so that it can be determined whether the relevant operation steps of the sample liquid flow have been completed. Further, the panel mechanism 900 includes at least one of the following bubble sensors: a first bubble sensor 510 arranged on the first pipeline 151, a second bubble sensor 520 arranged on the second pipeline 152, a third bubble sensor 530 arranged on the third pipeline 153, a fourth bubble sensor 540 arranged on the second connecting pipe 1522, and a fifth bubble sensor 550 arranged on the fifth pipeline 155.
[0045] Specifically, the first bubble sensor 510 is used to detect the flow state of the liquid flowing through the first pipeline 151, that is, the flow state of the sample liquid; the second bubble sensor 520 is used to detect the flow state of the liquid flowing through the second pipeline 152; the third bubble sensor 530 is used to detect the flow state of the liquid flowing through the third pipeline 153; the fourth bubble sensor 540 is used to detect the flow state of the liquid flowing through the second connecting tube 1522, that is, the third bubble sensor 530 and the fourth bubble sensor 540 can be used to jointly detect whether there is still liquid flowing in the magnetic separation column 132 and the flow direction of the liquid; the fifth bubble sensor 550 is used to detect the flow state of the liquid flowing through the fifth pipeline 155.
[0046] like Figure 3 and Figure 5As shown, in one embodiment, the panel mechanism 900 further includes a pressure sensor installed on the liquid circuit panel 910 and used to monitor the sample liquid pressure in real time. It can be understood that by monitoring the sample liquid pressure through the pressure sensor, the driving power of the driving pump 200 can be adjusted according to the measured pressure value. Further, the panel mechanism 900 also includes at least one of the following pressure sensors: a first pressure sensor 410 arranged on the third pipeline 153 and a second pressure sensor 420 arranged on the second connecting pipeline 162. The first pressure sensor 410 is used to detect the pressure value of the liquid flowing through the driving pump 200 through the third pipeline 153, so as to adjust the driving power of the driving pump 200 according to the measured pressure value. The second pressure sensor 420 is used to detect the pressure value of the liquid passing through the second connecting pipeline 162, so as to adjust the driving power of the driving pump 200 according to the measured pressure value.
[0047] like Figure 7 and Figure 8As shown, in one embodiment, the cell sorting device further includes a weighing mechanism 1000 mounted on the rack 700; the weighing mechanism 1000 includes a support assembly 1100 and at least one group of weighing assemblies 1200, the support assembly 1100 includes a bracket mounted on the rack 700 and used to support the weighing assembly 1200; each group of the weighing assemblies 1200 includes a mounting support 1210 mounted on the bracket, a weighing sensor 1220 mounted on the mounting support 1210, and a hook 1230 detachably mounted on the weighing sensor 1220 to hang a sample. It can be understood that the weighing sensor 1220 can be a pressure sensor that determines weight through a pressure signal. The bracket and the mounting support 1210 can both be sheet metal parts, so that the bracket is more solid and can achieve better load-bearing. At the same time, the mounting support 1210 of the sheet metal part that is not easily deformed can better protect the weighing sensor 1220, etc. The shape and size of the bracket can be set according to the requirements, as long as the weighing assembly 1200 can be stably installed on the bracket and the volume of the entire weighing device can be reduced as much as possible. In the above embodiment of the present invention, one or more groups of weighing assemblies 1200 with the same structure are set in the weighing device (the number of weighing assemblies 1200 can be set according to the requirements), and each group of weighing assemblies 1200 is installed on the bracket through the mounting support 1210, so that the disassembly and installation of a single group of weighing assemblies 1200 can be realized, and when a single group of weighing assemblies 1200 is damaged, it will not affect the use of other groups of weighing assemblies 1200. At the same time, since the structure of each group of weighing assemblies 1200 is the same, it is convenient for inspection and maintenance. It can be understood that the hook 1230 also adopts a structural design that can be detachably connected to the weighing sensor 1220. Therefore, while facilitating the disassembly and installation of the hook 1230, the efficiency of troubleshooting can also be improved. In one embodiment, the weighing sensor 1220 is provided with a threaded hole (not shown), the hook 1230 is provided with a connecting thread, and the hook 1230 is threadedly connected to the threaded hole through the connecting thread. That is, in this embodiment, the detachable connection between the hook 1230 and the weighing sensor 1220 is achieved by threading the connecting thread and the threaded hole.
[0048] like Figure 1 to Figure 2As shown, in one embodiment, the cell sorting device further includes a human-machine interaction component 1300 mounted on the rack 700 and used for touch operation or displaying parameters. It can be understood that the human-machine interaction component 1300 sets, modifies and monitors relevant parameters in the cell sorting process by touching the human-machine interaction display interface; the human-machine interaction component 1300 can be rotatably connected (for example, rotatably connected by a hinge) on the rack 700 to facilitate storage and reduce the size of the device. At the same time, it can also be achieved according to the operator's visual angle requirements to adjust the rotation angle of the human-machine interaction component 1300 to improve the user experience; the shape and size of the human-machine interaction component 1300 can be set according to requirements.
[0049] In one embodiment, the cell sorting device further includes a controller; the controller is connected to the motion module 310 to control the motion module 310 to drive the magnet 320 to approach or move away from the magnetic sorting column 132 in the cell sorting tube group 100. Furthermore, the controller is also connected to the human-machine interaction component 1300, the weighing mechanism 1000, the driving pump 200, the pressure sensor and the bubble sensor, so as to realize interactive control between the above components.
[0050] like Figure 2 , Figures 5 and 6 As shown, in one embodiment, the liquid circuit panel 910 includes a first mounting block 911, and the end surface of the first mounting block 911 facing away from the accommodating space 710 is recessed to form a first mounting groove 912; the magnetic separation column 132 is installed in the first mounting groove 912; the first mounting block 911 is provided with a groove connected to the accommodating space 710, and the motion module 310 is used to drive the magnet 320 to insert into the groove to approach the magnetic separation column 132, or to escape from the groove to move away from the magnetic separation column 132. It can be understood that the groove can be set on the first mounting block 911 as needed, as long as the magnet 320 can be inserted into the groove so that the distance between the magnet 320 and the magnetic separation column 132 is further shortened, thereby further improving the strength of the magnetic field generated in the first separation space that can adsorb the magnetically labeled cells. The positions of the motion module 310 and the magnetic separation column 132 are relatively fixed, that is, the motion module 310 can be arranged on the liquid path panel 910 or the frame 700 as needed to drive the magnet 320 to be inserted into or removed from the groove to approach or move away from the magnetic separation column 132. In one embodiment, a buckle is provided in the first installation groove 912, and the magnetic separation column 132 is clamped in the first installation groove 912 by the buckle, so that the magnetic separation column 132 can be installed and removed more conveniently.
[0051] In one embodiment, if Figure 1 As shown, the liquid circuit panel 910 includes a mounting bracket 916 for mounting the magnetic separation column 132, a through hole 917 provided on at least one side of the mounting bracket 916 and connected to the accommodating space 710, and a protective cover 918 covering the mounting bracket 916 and the through hole 917; the motion module 310 is used to drive the magnet 320 to insert from the accommodating space 710 into the through hole 917 to approach the magnetic separation column 132, or to retract from the through hole 917 to the accommodating space 710 to move away from the magnetic separation column 132. In this embodiment, the magnetic separation column 132 is mounted on the liquid circuit panel 910 through the mounting bracket 916, and the magnetic separation column 132 can be installed and removed more conveniently. The mounting bracket 916 is provided with through holes 917 connected to the accommodating space 710 on opposite sides, and the protective cover 918 covers the mounting bracket 916 and the through holes 917, which can protect the magnetic separation column 132 and the magnet inserted in the through holes 917 to prevent water or dirt from contaminating them. The magnet 320 extends from the through holes 917 and approaches the magnetic separation column 132. At this time, there is no object blocking the magnet 320 and the magnetic separation column 132, which can enhance the magnetic field of the magnet 320 on the magnetic field of the magnetic separation column 132.
[0052] like Figures 1 to 3 As shown, in one embodiment, the cell sorting tube group 100 also includes a separation column 131; the separation column 131 is installed on the liquid path panel 910, and the fluid filter 120 is connected to the magnetic separation column 132 through the separation column 131; the separation column 131 is provided with a second sorting space for the sample liquid filtered by the fluid filter 120 to flow through; the second sorting space contains second iron beads; the separation column 131 is used to separate specific cells from the sample liquid flowing through by the second iron beads, and then output the remaining sample liquid to the first sorting space. It can be understood that the separation column 131 in this embodiment is used to separate specific cells from the sample liquid; wherein, specific cells refer to some components in the sample liquid that need to be captured and removed by the separation column 131 and do not need to appear in the final positive selection liquid, including but not limited to sticky cells such as monocytes, granulocytes and platelets present in the cell suspension during the blood cell separation process, and components that may be non-specifically bound to the magnetic separation column 132 and therefore need to be pre-filtered by the separation column 131.
[0053] In this embodiment, the cell sorting tube set 100 is provided with a fluid filter 120, a separation column 131 and a magnetic separation column 132 at the same time, so that the sample liquid is subjected to three-stage sorting by the fluid filter 120, the separation column 131 and the magnetic separation column 132 respectively. Specifically, firstly, impurities in the sample liquid (such as blood clots, micropolymers and microparticle debris in blood, blood clots and microparticle debris in rescued blood products, etc.) are filtered out in the fluid filter 120, and the remaining sample liquid is output to the separation column 131, and then the specific cells are separated from the remaining sample liquid by the first iron bead of the separation column 131 (the specific cells are separated by the second iron bead and remain in the separation column 132). The remaining sample liquid (including cells labeled with magnetic beads and negative cells, etc.) is output to the magnetic separation column 132, and then the cells labeled with magnetic beads are magnetically adsorbed by the magnetic separation column 132, that is, the cells labeled with magnetic beads are adsorbed on the first iron beads which are magnetic due to the external magnetic field, and the remaining negative selection liquid flows out from the output end 140. In this way, after the above three-stage sorting, it is avoided that impurities and sticky cells in the sample liquid block the gaps between the first iron beads in the magnetic separation column 132 (blockage will lead to a decrease in the sorting efficiency of the cells labeled with magnetic beads). In this way, the cells labeled with magnetic beads can be accurately sorted, thereby improving the sorting efficiency and accuracy.
[0054] It is understandable that the size of the separation column 131 and the magnetic separation column 132, as well as the diameters of the second iron bead / magnetic bead and the first iron bead, etc. can be set according to the requirements. For example, the size of the second separation space and the first separation space of the separation column 131 and the magnetic separation column 132 can be the same or different, and the diameters of the second iron bead / magnetic bead and the first iron bead can also be the same or different, so that the separation column 131 can provide holes or channels of different sizes and numbers from those in the magnetic separation column 132. In addition, the second iron bead in the separation column 131 and the first iron bead in the magnetic separation column 132 are made of the same material. In this way, the components that may be non-specifically bound to the first iron bead in the magnetic separation column 132 during the separation process will be captured by the separation column 131 first, and then the possibility of scaling of the magnetic separation column 132 during the separation process is reduced by the separation column 131. This setting also ultimately reduces the presence of unnecessary cells or fluid components in the final positive selection liquid, thereby improving the sorting accuracy of the sorting device.
[0055] In one embodiment, the second iron bead and the first iron bead are made of the same material, and the diameter of the first iron bead in the first sorting space is greater than or equal to the diameter of the second iron bead in the second sorting space. In this way, the pore size between the second iron beads in the separation column 131 will be smaller than the pore size between the first iron beads. In this way, the pore size of the permeable matrix formed by the second iron beads can be selected to remove large tumor cells from the sample before the fluid passes through the magnetic sorting column 132; in this way, after the remaining sample liquid after separating the specific cells flows out from the gaps between the second iron beads of the separation column, if the cells marked with magnetic beads are magnetically adsorbed by the first iron beads in the first sorting space, the remaining liquid (negative selection liquid) can flow out smoothly from the gaps between the first iron beads (if the diameter of the first iron bead is smaller than that of the second iron bead, part of the negative selection liquid may be blocked by the first iron bead and cannot flow out, and the negative cells in the negative selection liquid blocked between the first iron beads will eventually be flushed into the positive selection liquid, thereby affecting the sorting accuracy of the magnetic sorting column 132).
[0056] In this embodiment, the cells labeled with magnetic beads in the sample solution are magnetically labeled, thereby binding to the magnetic substance and thus becoming magnetic; that is, the cells labeled with magnetic beads are magnetized, thereby generating magnetically labeled cells (including immunomagnetic bead cells and bacteria labeled with magnetic beads, etc.). The sample solution also contains the above-mentioned specific cells (wherein, specific cells refer to some components in the sample solution that need to be captured and removed by the separation column 131 and do not need to appear in the final positive selection liquid, including but not limited to sticky cells such as monocytes, granulocytes and platelets present in the cell suspension during the blood cell separation process, and components that may be non-specifically bound to the magnetic separation column 132 and therefore need to be pre-filtered by the separation column 131, etc.), so that the second separation space in the separation column 131 contains the second iron beads, and when the sample solution passes through the separation column 131, the above-mentioned specific cells (such as sticky cells) in the sample solution will be separated and The cells labeled with magnetic beads remain in the second sorting space, while other sample liquids except the above-mentioned specific cells (including cells labeled with magnetic beads) will continue to flow to the magnetic sorting column 132 driven by the driving pump 200. At this time, since the cells labeled with magnetic beads in the sample liquid are not separated by the separation column 131, the magnetic sorting column 132 in this embodiment magnetically sorts the cells labeled with magnetic beads in the sample liquid through an external magnetic field (the magnetic field strength can be adjusted in real time according to actual conditions), so that the cells labeled with magnetic beads are adsorbed on the first iron beads in the first sorting space, and then the cells labeled with magnetic beads can be accurately sorted, thereby improving the efficiency and accuracy of sorting.
[0057] like Figure 5As shown, in one embodiment, the liquid circuit panel 910 includes a second mounting block 914, and the end surface of the second mounting block 914 facing away from the accommodating space 710 is recessed to form a second mounting groove 915; the separation column 131 is installed in the second mounting groove 915. It can be understood that the side wall of the second mounting groove 915 can be used to clamp the separation column 131, and the separation column 131 is clamped in the second mounting groove 915, so that the separation column 131 can be installed and removed more conveniently.
[0058] like Fig. 9 As shown, in one embodiment, the present invention further provides a cell sorting method, wherein the cell sorting device performs cell sorting according to the cell sorting method, and the cell sorting method comprises:
[0059] S10, controlling the sample liquid to flow from the sample container into the fluid filter 120, so as to filter impurities in the sample liquid through the fluid filter 120. The fluid filter 120 is used to filter impurities in the sample liquid (such as blood clots, micropolymers and particulate debris in blood, blood clots and particulate debris in rescued blood products, etc.).
[0060] S20, after confirming that the magnetic field generating mechanism 300 has enhanced the magnetic field in the first sorting space, the sample liquid filtered by the fluid filter 120 is controlled to flow into the first sorting space of the magnetic sorting column 132, and the magnetically labeled cells in the sample liquid flowing through are adsorbed in the first sorting space by the enhanced magnetic field in the first sorting space. It can be understood that the magnetic field generating mechanism 300 can be an electromagnetic mechanism or a movable magnet mechanism, so that the magnetic field in the first sorting space is enhanced or eliminated by controlling the electromagnetic coil of the electromagnetic mechanism to be energized (enhanced magnetic field) or de-energized (eliminated magnetic field), or controlling the movable magnet mechanism to approach (enhanced magnetic field) or move away from (eliminated magnetic field) the magnetic sorting column 132, etc. After the magnetic field generating mechanism 300 enhances the magnetic field in the first sorting space, the magnetically labeled cells in the sample liquid flowing through can be adsorbed in the first sorting space by the enhanced magnetic field in the first sorting space.
[0061] The cell sorting method provided by the present invention filters impurities in the sample liquid (such as blood clots, micropolymers and particulate fragments in blood, blood clots and particulate fragments in rescued blood products, etc.) through the fluid filter 120 in the cell sorting tube group 100 to perform a first screening of the sample liquid; then, a magnetic field generating mechanism 300 is provided outside the magnetic sorting column 132 of the cell sorting tube group 100 to enhance the magnetic field in the first sorting space, thereby magnetically sorting the magnetically labeled cells of the sample liquid flowing through the first sorting space through the enhanced magnetic field. In this way, the present invention successfully sorts out the magnetically labeled cells through the secondary screening (including filtration and magnetic sorting) of the fluid filter 120 and the magnetic sorting column 132, while avoiding the impurities in the sample liquid clogging the first sorting space of the magnetic sorting column, thereby improving the efficiency and accuracy of cell sorting.
[0062] In one embodiment, the cell sorting tube set 100 further includes a separation column 131; the fluid filter 120 is connected to the magnetic separation column 132 through the separation column 131; a second sorting space is provided in the separation column 131 for the sample liquid filtered by the fluid filter 120 to flow through; the step S10, after controlling the sample liquid to flow from the sample container into the fluid filter 120 to filter impurities in the sample liquid through the fluid filter 120, further includes:
[0063] S30, control the sample liquid filtered by the fluid filter 120 to flow into the second sorting space, so as to separate specific cells from the sample liquid flowing through the second sorting space through the second iron beads. It can be understood that the separation column 131 is used to separate specific cells from the sample liquid; wherein, the specific cells refer to the sample liquid that needs to be captured and removed by the separation column 131 and does not need to appear in the final positive selection liquid, including but not limited to the sticky cells such as mononuclear cells, granulocytes and platelets in the cell suspension during the blood cell separation process, and the components that may be non-specifically bound to the magnetic separation column 132 and therefore need to be pre-filtered by the separation column 131. Then, before the magnetically labeled cells in the sample liquid are magnetically sorted by the magnetic separation column 132, the above-mentioned specific cells are first removed from the sample liquid by the separation column 131 to prevent the specific cells from blocking the first sorting space (such as blocking the gap formed between the first iron beads), thereby affecting the magnetic sorting effect of the magnetic separation column 132.
[0064] In one embodiment, in step S20, controlling the sample liquid filtered by the fluid filter 120 to flow into the first separation space of the magnetic separation column 132 includes:
[0065] S21 , controlling the sample liquid after being filtered by the fluid filter 120 and after the specific cells are separated by the separation column 131 to flow from the second sorting space into the first sorting space. It can be understood that the sample liquid passes through the fluid filter 120, the separation column 131 and the magnetic separation column 132 in sequence, so that the sample liquid can be subjected to three-stage sorting. Specifically, first, impurities in the sample liquid (such as blood clots, micropolymers and particulate debris in blood, blood clots and particulate debris in rescued blood products, etc.) are filtered out in the fluid filter 120, and the remaining sample liquid is output to the separation column 131, and then the above-mentioned specific cells are separated from the sample liquid by the separation column 131 (the above-mentioned specific cells are separated by the second iron beads and remain in the second sorting space of the separation column 131), and the remaining sample liquid (including cells labeled with magnetic beads and negative cells, etc.) is output to the magnetic separation column 132, and then the cells labeled with magnetic beads are magnetically adsorbed by the magnetic separation column 132. In this way, the cells labeled with magnetic beads can be accurately sorted out through the above-mentioned three-stage sorting, thereby improving the sorting efficiency, purity and accuracy.
[0066] In one embodiment, in step S20, after the magnetically labeled cells in the sample liquid flowing through are adsorbed in the first sorting space by means of the enhanced magnetic field in the first sorting space, the method further comprises:
[0067] S40, outputting the sample liquid flowing out of the first sorting space to the negative sorting container 630. It can be understood that the negative sorting container 630 is arranged at the negative sorting outlet 142. The remaining sample liquid (including cells labeled with magnetic beads and negative cells, etc.) in step S21 is output to the magnetic sorting column 132, and then the cells labeled with magnetic beads are magnetically adsorbed by the magnetic sorting column 132, and finally the remaining sample liquid (i.e., the negative sorting liquid) flows out from the negative sorting outlet 142 and flows into the negative sorting container 630.
[0068] S50, after detecting that the sample liquid in the sample container has been drained, the cleaning liquid is sequentially injected from the cleaning container into the fluid filter 120, the second sorting space and the first sorting space, so as to output the remaining sample liquid in the fluid filter 120, the second sorting space and the first sorting space to the negative selection container 630. It can be understood that after detecting that the sample liquid in the sample container has been drained, the sample liquid may still exist in the cell sorting tube set 100. In this embodiment, by sequentially injecting the cleaning liquid from the cleaning container into the fluid filter 120, the second sorting space and the first sorting space, the remaining sample liquid in the fluid filter 120, the second sorting space and the first sorting space can be output to the negative selection container 630 after three-stage filtration.
[0069] S60, after the cleaning liquid is continuously injected for a preset time, the injection of the cleaning liquid is stopped, and the remaining cleaning liquid in the fluid filter 120, the second sorting space, and the first sorting space is output to the negative selection container 630. It can be understood that the preset time is determined according to the length of the cell sorting tube group 100 and the flow rate of the cleaning liquid in the cell sorting tube group 100, so as to ensure that the sample liquid in the cell sorting tube group 100 is completely drained. In some embodiments, the cell sorting tube group 100 can be connected to the atmosphere so that the remaining cleaning liquid in the fluid filter 120, the second sorting space, and the first sorting space can be output to the negative selection container 630 under the action of gravity or the driving pump 200.
[0070] In one embodiment, in the step S60, after the remaining cleaning liquid in the fluid filter 120, the second sorting space and the first sorting space is output to the negative separation container 630, the step further includes:
[0071] S70, controlling the magnetic field generating mechanism 300 to eliminate the magnetic field in the first sorting space. It can be understood that the magnetically labeled cells are adsorbed in the first sorting space by the magnetic field generating mechanism 300. In order to collect the magnetically labeled cells in the first sorting space, it is necessary to first control the magnetic field generating mechanism 300 to eliminate the magnetic field in the first sorting space.
[0072] S80, inject the cleaning liquid from the cleaning container into the first sorting space, so that the magnetically labeled cells that are no longer adsorbed by the magnetic field of the magnet 320 are suspended in the cleaning liquid in the first sorting space, and then the cleaning liquid containing the magnetically labeled cells is output to the positive selection container 640. It can be understood that the positive selection container 640 is arranged at the positive selection outlet 143 for collecting the magnetically labeled cells. After the magnetic field in the first sorting space is eliminated by the magnetic field generating mechanism 300, the magnetically labeled cells will not be adsorbed in the first sorting space, and the magnetically labeled cells can be output to the positive selection container 640 through the cleaning liquid.
[0073] In one embodiment, in the step S10, before controlling the sample liquid to flow from the sample container into the fluid filter 120, the step further includes:
[0074] S90, inject the cleaning liquid from the cleaning container into the fluid filter 120, the second sorting space and the first sorting space in sequence, so that the fluid filter 120, the second sorting space and the first sorting space are filled with cleaning liquid, and the cleaning liquid flowing out of the first sorting space is output to the waste liquid container. It can be understood that the waste liquid container includes a first waste liquid container 610 arranged at the first waste liquid inlet and outlet 141 and a second waste liquid container 620 arranged at the second waste liquid inlet and outlet 113. In this embodiment, by filling the fluid filter 120, the second sorting space and the first sorting space with cleaning liquid, air is prevented from entering the magnetic sorting column 132, thereby preventing the influence of air on the sorting effect of the magnetic sorting column 132.
[0075] In one embodiment, in the step S60, after the remaining cleaning liquid in the fluid filter 120, the second sorting space and the first sorting space is output to the negative separation container 630, the step further includes:
[0076] S100, controlling the magnetic field generating mechanism 300 to eliminate the magnetic field in the first sorting space. It can be understood that the magnetically labeled cells are adsorbed in the first sorting space by the magnetic field generating mechanism 300. In order to collect the magnetically labeled cells in the first sorting space, it is necessary to first control the magnetic field generating mechanism 300 to eliminate the magnetic field in the first sorting space.
[0077] S110, after the first sorting space is connected to the air, the waste liquid container and the cleaning container are controlled to be opened alternately, so that the cleaning liquid in the cleaning container and the cleaning liquid collected in the waste liquid container alternately enter the first sorting space, so that the magnetically labeled cells that are no longer adsorbed by the magnetic field of the magnet 320 are suspended in the cleaning liquid in the first sorting space, and then the cleaning liquid containing the magnetically labeled cells is output to the positive selection container 640. It can be understood that after the magnetic field in the first sorting space is eliminated by the magnetic field generating mechanism 300, the magnetically labeled cells will not be adsorbed in the first sorting space, and the magnetically labeled cells can be output to the positive selection container 640 through the cleaning liquid. In order to save the consumption of the cleaning liquid, the cleaning liquid containing the magnetically labeled cells can be output to the positive selection container 640 by alternating the cleaning liquid in the cleaning container and the cleaning liquid collected in the waste liquid container.
[0078] 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.
[0079] In one embodiment, a computer device is provided, which includes a processor, a memory, a network interface and a database connected through a system bus. 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 cell sorting method is implemented.
[0080] 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, and the cell sorting method in the above embodiment is implemented when the processor executes the computer program.
[0081] 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 cell sorting method is implemented.
[0082] 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).
[0083] 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.
[0084] 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 cell sorting device, characterized in that: include: A cell sorting tube set, comprising a magnetic sorting column and a fluid filter for filtering impurities in a sample liquid; the magnetic sorting column is provided with a first sorting space for the sample liquid filtered by the fluid filter to flow through, and the fluid filter is connected to the first sorting space; The magnetic field generating mechanism is used to enhance or eliminate the magnetic field in the first sorting space. The magnetic sorting column is used to adsorb the magnetically labeled cells in the sample liquid flowing through the first sorting space through the enhanced magnetic field after the magnetic field generating mechanism enhances the magnetic field in the first sorting space.
2. The cell sorting device according to claim 1, characterized in that: The magnetic field generating mechanism comprises a motion module and a magnet connected to the motion module; the motion module drives the magnet to approach to enhance the magnetic field in the first sorting space, or to move away from the magnetic sorting column to eliminate the magnetic field in the first sorting space; The magnetic separation column is used to absorb the magnetically labeled cells in the sample liquid flowing through the first separation space through the enhanced magnetic field after the magnet enhances the magnetic field in the first separation space.
3. The cell sorting device according to claim 2, characterized in that: The motion module includes a base, a driving member installed on the base, a transmission component connected to the driving member, and a moving component connected to the magnet; the moving component is connected to the transmission component and drives the magnet to move under the drive of the transmission component.
4. The cell sorting device according to claim 3, characterized in that: The driving member includes a motor, and the transmission assembly includes a screw rod and a slide rail mounted on the base, wherein the slide rail is arranged parallel to the screw rod; The moving assembly includes a slider and a mounting frame for mounting the magnet; the slider is slidably connected to the slide rail, and the motor drives the lead screw to drive the slider and the magnet to slide along the slide rail.
5. The cell sorting device according to claim 4, characterized in that: The motion module further includes a sensor installed on the base and used for detecting the motion state of the slider.
6. The cell sorting device according to claim 1, characterized in that: The first sorting space contains first iron beads; the magnetic field generating mechanism is used to enhance or eliminate the magnetic field of the first iron beads.
7. The cell sorting device according to claim 2, characterized in that: The cell sorting device further comprises a frame and a panel mechanism, wherein the panel mechanism comprises a fluid path panel; the fluid filter and the cell sorting tube set are both mounted on the fluid path panel; the fluid path panel is mounted on the frame, and a containing space is formed between the fluid path panel and the frame; The motion module and the magnet are both installed in the accommodating space.
8. The cell sorting device according to claim 7, characterized in that: The panel mechanism further comprises at least one bubble sensor installed on the liquid surface panel and used for real-time monitoring of the flow state of the sample liquid; and / or The panel mechanism further comprises a pressure sensor mounted on the liquid surface panel and used for real-time monitoring of the sample liquid pressure; and / or The panel mechanism further includes a driving pump installed on the liquid path panel and used for driving the sample liquid to flow.
9. The cell sorting device according to claim 7, characterized in that: The cell sorting device further comprises a weighing mechanism mounted on the frame; the weighing mechanism comprises a supporting assembly and at least one group of weighing assemblies, the supporting assembly comprising a bracket mounted on the frame and used to support the weighing assemblies; each group of the weighing assemblies comprises a mounting support mounted on the bracket, a weighing sensor mounted on the mounting support, and a hook detachably mounted on the weighing sensor for hanging a sample; and / or The cell sorting device further comprises a human-computer interaction component mounted on the rack and used for touch operation or parameter display; and / or The cell sorting device also includes a controller; the controller is connected to the motion module to control the motion module to drive the magnet to approach or move away from the magnetic sorting column in the cell sorting tube group.
10. The cell sorting device according to claim 7, characterized in that: The liquid circuit panel includes a first mounting block, and the end surface of the first mounting block facing away from the accommodating space is recessed to form a first mounting groove; the magnetic separation column is installed in the first mounting groove; the first mounting block is provided with a groove connected to the accommodating space, and the motion module is used to drive the magnet to insert into the groove to approach the magnetic separation column, or to escape from the groove to move away from the magnetic separation column.
11. The cell sorting device according to claim 7, characterized in that: The liquid circuit panel includes a mounting bracket for mounting the magnetic separation column, an insertion hole arranged on at least one side of the mounting bracket and connected to the accommodating space, and a protective cover covering the mounting bracket and the insertion hole; the motion module is used to drive the magnet to insert from the accommodating space into the insertion hole to approach the magnetic separation column, or to retract from the insertion hole into the accommodating space to move away from the magnetic separation column.
12. The cell sorting device according to claim 7, characterized in that: The cell sorting tube group also includes a separation column; the separation column is installed on the liquid path panel, and the fluid filter is connected to the magnetic sorting column through the separation column; a second sorting space is provided in the separation column for the sample liquid filtered by the fluid filter to flow through; the second sorting space contains second iron beads; the separation column is used to separate specific cells from the sample liquid flowing through by the second iron beads, and then output the remaining sample liquid to the first sorting space.
13. The cell sorting device according to claim 12, characterized in that: The liquid circuit panel comprises a second mounting block, the end surface of the second mounting block facing away from the accommodating space is recessed to form a second mounting groove; the separation column is mounted in the second mounting groove.
14. A cell sorting method, characterized in that: The cell sorting device according to any one of claims 1 to 11 performs cell sorting according to the cell sorting method, wherein the cell sorting method comprises: Controlling the sample liquid to flow from the sample container into the fluid filter so as to filter impurities in the sample liquid through the fluid filter; After confirming that the magnetic field generating mechanism has enhanced the magnetic field in the first sorting space, the sample liquid filtered by the fluid filter is controlled to flow into the first sorting space of the magnetic sorting column, and the magnetically labeled cells in the sample liquid flowing through are adsorbed in the first sorting space through the enhanced magnetic field in the first sorting space.
15. The cell sorting method according to claim 14, characterized in that: The cell sorting tube set further comprises a separation column; the fluid filter is connected to the magnetic separation column through the separation column; a second sorting space is provided in the separation column for the sample liquid filtered by the fluid filter to flow through; a second iron bead is contained in the second sorting space; After controlling the sample liquid to flow from the sample container into the fluid filter so as to filter impurities in the sample liquid through the fluid filter, the method further includes: Controlling the sample liquid filtered by the fluid filter to flow into the second sorting space, so as to separate specific cells from the sample liquid flowing through the second sorting space by the second iron beads; The controlling the sample liquid filtered by the fluid filter to flow into the first separation space of the magnetic separation column comprises: The sample fluid after being filtered by the fluid filter and separated into specific cells by the separation column is controlled to flow from the second sorting space into the first sorting space.
16. The cell sorting method according to claim 15, characterized in that: After the magnetically labeled cells in the sample liquid flowing through are adsorbed in the first sorting space by the enhanced magnetic field in the first sorting space, the method further includes: Outputting the sample liquid flowing out of the first sorting space into a negative separation container; After detecting that the sample liquid in the sample container has been exhausted, injecting the cleaning liquid from the cleaning container into the fluid filter, the second sorting space and the first sorting space in sequence, so as to output the remaining sample liquid in the fluid filter, the second sorting space and the first sorting space to the negative separation container; After the cleaning liquid is continuously injected for a preset time, the injection of the cleaning liquid is stopped, and the remaining cleaning liquid in the fluid filter, the second sorting space and the first sorting space is output to the negative separation container.
17. The cell sorting method according to claim 16, characterized in that: After outputting the remaining cleaning liquid in the fluid filter, the second sorting space and the first sorting space to the negative separation container, the method further includes: Eliminating the magnetic field in the first sorting space by the magnetic field generating mechanism; The cleaning liquid is injected into the first sorting space from the cleaning container so that the magnetically labeled cells no longer adsorbed by the magnetic field are suspended in the cleaning liquid in the first sorting space, and then the cleaning liquid containing the magnetically labeled cells is output to the positive selection container.
18. The cell sorting method according to claim 16, characterized in that: Before controlling the sample liquid to flow from the sample container into the fluid filter, the method further comprises: The cleaning liquid is injected from the cleaning container into the fluid filter, the second sorting space and the first sorting space in sequence so that the fluid filter, the second sorting space and the first sorting space are filled with the cleaning liquid, and the cleaning liquid flowing out of the first sorting space is output to the waste liquid container.
19. The cell sorting method according to claim 18, characterized in that: After outputting the remaining cleaning liquid in the fluid filter, the second sorting space and the first sorting space to the negative separation container, the method further includes: Eliminating the magnetic field in the first sorting space by the magnetic field generating mechanism; After the first sorting space is connected to the air, the waste liquid container and the cleaning container are controlled to open alternately, so that the cleaning liquid in the cleaning container and the cleaning liquid collected in the waste liquid container alternately enter the first sorting space, so that the magnetically labeled cells that are no longer adsorbed by the magnetic field are suspended in the cleaning liquid in the first sorting space, and then the cleaning liquid containing the magnetically labeled cells is output to the positive selection container.
20. A computer device comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, characterized in that: When the processor executes the computer program, the cell sorting method according to any one of claims 14 to 19 is implemented.