WO2024067353A1 - 磁珠分选方法、设备及存储介质 - Google Patents

磁珠分选方法、设备及存储介质 Download PDF

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Publication number
WO2024067353A1
WO2024067353A1 PCT/CN2023/120444 CN2023120444W WO2024067353A1 WO 2024067353 A1 WO2024067353 A1 WO 2024067353A1 CN 2023120444 W CN2023120444 W CN 2023120444W WO 2024067353 A1 WO2024067353 A1 WO 2024067353A1
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WIPO (PCT)
Prior art keywords
liquid
liquid bag
magnetic
bag
magnetic platform
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PCT/CN2023/120444
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English (en)
French (fr)
Inventor
商院芳
郭霄亮
欧映廷
刘福京
张金鑫
Original Assignee
深圳赛桥生物创新技术有限公司
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Publication of WO2024067353A1 publication Critical patent/WO2024067353A1/zh

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326Magnetic particles
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302Apparatus specially adapted for immunological test procedures
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses

Definitions

  • the present application relates to the field of magnetic bead sorting technology, and in particular to a magnetic bead sorting method, device and storage medium.
  • the flow rate of the liquid passing through each region when flowing in the liquid bag is not consistent, and then the magnetization of the corresponding regions of each cross-sectional area of the liquid bag is also inconsistent.
  • the utilization rate of the magnet is low, and the magnet is not sufficient for the adsorption of the immune magnetic bead cells; and the adsorbed immune magnetic bead cells will be accumulated in large quantities near the area with low flow rate, which will also cause insufficient adsorption of the magnet.
  • the embodiments of the present application provide a magnetic bead sorting method, device and storage medium to solve the problems of low magnetic field utilization in the prior art.
  • a magnetic bead sorting method comprising:
  • the magnetic platform is controlled to swing according to preset swing parameters, so that the immunomagnetic bead cells adsorbed by the magnetic platform are evenly distributed, and at the same time, other substances in the liquid bag except the adsorbed immunomagnetic bead cells are suspended in the liquid;
  • a controller is used to execute the magnetic bead sorting method.
  • a magnetic bead sorting device comprises a pressing device, a mixing device and the above-mentioned controller, wherein the controller is connected to the pressing device and the mixing device.
  • a computer-readable storage medium stores computer-readable instructions, wherein the computer-readable instructions implement the above-mentioned magnetic bead sorting method when executed by a processor.
  • the above-mentioned magnetic bead sorting method, equipment and storage medium includes: placing an empty liquid bag on a magnetic platform, inputting a liquid containing immunomagnetic bead cells into the liquid bag, and adsorbing the immunomagnetic bead cells in the liquid bag through the magnetic platform; controlling the swing of the magnetic platform according to preset swing parameters to make the immunomagnetic bead cells adsorbed by the magnetic platform evenly distributed, and at the same time making other substances in the liquid bag except the adsorbed immunomagnetic bead cells suspended in the liquid; performing a waste liquid discharge operation to make the liquid in the liquid bag except the adsorbed immunomagnetic bead cells flow into the waste liquid bag; performing a washing operation on the remaining immunomagnetic bead cells in the liquid bag; after injecting a heavy suspension into the liquid bag and taking out the liquid bag containing the immunomagnetic bead cells, determining that the magnetic bead sorting is completed.
  • the present application can control the swing of the magnetic platform according to the preset swing parameters, thereby shaking the liquid (such as cell liquid) in a large-capacity or large-flux liquid bag, so that the immunomagnetic bead cells are evenly distributed on the bottom of the liquid bag without accumulating in a local position, so that the magnetic platform can closely fit the unaccumulated immunomagnetic bead cells in the liquid bag after shaking, so as to achieve full absorption of the immunomagnetic bead cells by the magnetic platform.
  • the liquid such as cell liquid
  • the waste liquid discharge operation and the cleaning operation are used to separate other substances except the immunomagnetic bead cells from the liquid bag, so as to finally collect and obtain the immunomagnetic bead cells.
  • the present application improves the utilization rate of the magnetic field and realizes the efficient and stable separation and collection of immunomagnetic bead cells by magnetic bead sorting.
  • FIG1 is a flow chart of a magnetic bead sorting method according to an embodiment of the present application.
  • FIG2 is a flow chart of step S20 of the magnetic bead sorting method in one embodiment of the present application.
  • FIG3 is a schematic diagram of a partial explosion structure of a mixing device in one embodiment of the present application.
  • FIG4 is a schematic diagram of the assembly structure of a mixing device in one embodiment of the present application.
  • FIG5 is a schematic diagram of an exploded structure of a pressing device in one embodiment of the present application.
  • FIG6 is a schematic diagram of the assembly structure of a pressing device in one embodiment of the present application.
  • FIG. 7 is a schematic diagram of a computer device in an embodiment of the present application.
  • the reference numerals in the specification are as follows: 1. Pressing device; 10. Magnetic platform; 101. Base; 1011. Lifting hole; 1012. Guide hole; 102. Magnetic block; 103. first rotating shaft; 20, lifting mechanism; 201, lifting assembly; 2011, first lifting block; 2012, second lifting block; 2013, limit plate; 2014, rotating shaft; 202, lifting rod; 203, rising drive assembly; 2031, second motor; 2032, second driving wheel; 2033, second driven wheel; 2034, second synchronous belt; 2035, second rotating shaft; 2036, cam; 2037, mounting bearing; 2038, cam bracket; 2039, second mounting hole; 2040, bearing follower; 2041, Fixed plate; 2042, sensing block; 2043, photoelectric sensor; 30, covering mechanism; 301, cover plate; 302, first adsorption part; 303, second adsorption part; 40, pressing mechanism; 401, guide shaft; 402, spring; 403, linear bearing; 4011, block; 50, liquid bag; 2, mixing device; 21, first motor; 22, reducer; 23, first driving wheel;
  • a magnetic bead sorting method comprising the following steps:
  • the magnetic platform 10 can be a magnetic platform constructed by an electromagnet or a permanent magnet.
  • the magnetic platform 10 shown in FIG5 may include a base 101 provided with a lifting through hole 1011, and a permanent magnet block 102 or an electromagnet installed on the base 101; wherein, the base 101 is provided with a mounting groove, and the magnetic block 102 is fixedly installed in the mounting groove.
  • the magnetic platform 10 can be fitted with the contact surface of the liquid bag 50 so that the liquid is in close contact with the magnetic field of the magnetic platform 10, thereby adsorbing the immunomagnetic bead cells on the contact surface; and the liquid bag 50 is made of non-magnetic material and will not be adsorbed by magnetic force, so it will not be affected by the magnetic field of the magnetic platform 10 below it.
  • the empty liquid bag 50 is placed on the magnetic platform 10 (such as the magnetic block 102), and the cell fluid in the sample container (the cell fluid refers to the mixed fluid formed after the cells, magnetic beads and antibodies are incubated) flows into the empty liquid bag 50. That is, the sample container contains the cell fluid formed after the cells, magnetic beads and antibodies are incubated, and the cell fluid contains the immunomagnetic beads, wherein the immunomagnetic beads Cells are the target objects that need to be collected in the magnetic bead sorting method of the present application, and other substances in the cell fluid except the immunomagnetic bead cells need to be discharged into the waste liquid bag 50.
  • S20 Control the magnetic platform 10 to swing according to the preset swing parameters, so that the immunomagnetic bead cells adsorbed by the magnetic platform 10 are evenly distributed, and at the same time, other substances in the liquid bag 50 except the adsorbed immunomagnetic bead cells are suspended in the liquid; it can be understood that when processing a large volume of cell fluid, due to the large area of the liquid bag 50, the flow rate of the liquid passing through each area when flowing in the liquid bag 50 is not consistent, which leads to inconsistent magnetization of each area of the liquid bag 50. Therefore, in the area with low flow rate, the adsorbed immunomagnetic bead cells will accumulate in large quantities (near the area with low flow rate).
  • the adsorbed immunomagnetic bead cells and, in addition to the adsorbed immunomagnetic bead cells, some of the other substances will also adhere to the adsorbed immunomagnetic bead cells.
  • the area where the immunomagnetic bead cells (and other adhered substances) are accumulated (because there are many other immunomagnetic bead cells and other adhered substances accumulated between the magnetic platform 10 and the immunomagnetic bead cells that are still not adsorbed in the liquid, which will cause the adsorption distance to become larger and the magnetic adsorption force to become weaker) will be difficult to adsorb the immunomagnetic bead cells that are still not adsorbed in the liquid. This will lead to the loss of immunomagnetic bead cells and low magnetic field utilization.
  • the substance is no longer adhered but suspended in the liquid (easy to be discharged when performing the waste liquid discharge operation, and will not prevent the immunomagnetic bead cells that are still not adsorbed from being adsorbed by the magnetic platform); at the same time, excessive shaking is also avoided (when excessively shaken, due to the weak magnetic force, a large number of adsorbed immunomagnetic bead cells will be separated from the magnetic platform 10, and then some immunomagnetic bead cells cannot be re-adsorbed and cause loss, and may even kill the immunomagnetic bead cells due to excessive shaking). Therefore, in this application, the angular velocity and angle of the preset swing parameters for shaking are required to be finely controlled.
  • the preset swing parameters can be the swing angular velocity, swing angle, swing time, angular acceleration, and the angle of the magnetic platform 10 after the swing is completed.
  • the swing angle of the magnetic platform 10 can be within ⁇ 35 degrees (that is, the magnetic platform 106 swings to the opposite sides, and the angle of its swing toward one side is within the range of 0-35 degrees, and more than 35 degrees will kill the immunomagnetic bead cells), preferably ⁇ 25 degrees.
  • S40 Perform a cleaning operation on the remaining immunomagnetic bead cells in the liquid bag 50; in this step, since some other substances may be adhered to the remaining immunomagnetic bead cells in the liquid bag 50, in order to make the collected immunomagnetic bead cells relatively pure, the cleaning pipeline can be opened to perform a cleaning operation on other adhered substances, so that only the immunomagnetic bead cells are retained in the liquid bag 50 due to being adsorbed by the magnetic platform 10.
  • the present application can control the swing of the magnetic platform 10 according to the preset swing parameters, thereby shaking the liquid (such as cell fluid) in the large-capacity or large-flux liquid bag 50, so that the immunomagnetic bead cells are evenly distributed on the bottom surface of the liquid bag 50 and are not accumulated in local positions (such as near the area with low flow rate), so that the magnetic platform 10 can be closely attached to the unaccumulated immunomagnetic bead cells in the liquid bag 50 after shaking, so as to achieve the full adsorption of the immunomagnetic bead cells by the magnetic platform 10 and avoid the loss of the immunomagnetic bead cells; at the same time, other substances other than the adsorbed immunomagnetic bead cells in the liquid bag 50 can also be suspended in the liquid (for example, other substances adhering to the adsorbed immunomagnetic bead cells are shaken to separate from the immunomagnetic bead cells, and then suspended in the liquid, so as to facilitate the discharge of the substances when performing the waste liquid discharge operation,
  • the waste liquid discharge operation and the cleaning operation are used to separate the substances other than the immunomagnetic bead cells from the liquid bag 50, so as to finally collect the immunomagnetic bead cells.
  • This application improves the utilization rate of the magnetic field and realizes the efficient and stable separation and collection of immunomagnetic bead cells through magnetic bead sorting.
  • This application can directly perform magnetic bead sorting on large-capacity immunomagnetic bead cells, realize a large-capacity magnetic bead sorting process in a short time, and can not damage the cell viability, and no manual operation is required in the process, which improves the efficiency of large-capacity magnetic bead sorting.
  • the step S10 i.e., placing the empty fluid bag 50 on the magnetic platform 10 and placing the immunomagnetic
  • the liquid of the beads is input into the liquid bag 50, and the immune magnetic beads in the liquid of the liquid bag 50 are adsorbed by the magnetic platform 10, including:
  • the empty liquid bag 50 is placed on the magnetic platform 10 of the pressing device 1; as shown in Figure 5, the pressing device 1 includes a covering mechanism 30 installed on the magnetic platform 10 and a pressing mechanism 40 connected to the covering mechanism 30; when the covering mechanism 30 is closed, the liquid bag 50 is located in the accommodation space between the covering mechanism 30 and the magnetic platform 10; the covering mechanism 30 is installed on the magnetic platform 10, and the covering mechanism 30 can cover or open the above-mentioned accommodation space (when the liquid bag 50 placed in the accommodation space expands and causes a high protrusion height, the covering mechanism 30 may not be able to cover because it is lifted up by the liquid bag 50, and forced closing may crush the liquid bag 50 or damage the immune magnetic bead cells or anuclear immune cells therein), and when there is no interference from other external forces, the covering mechanism 30 can move downward as the pressing mechanism 40 is pulled down, thereby making the size of the accommodation space for placing the liquid bag 50 between the magnetic platform 10 and the covering mechanism 30 adjustable.
  • the liquid containing the immunomagnetic bead cells is input into the liquid bag 50; in the above process, a flow control component (not shown) can be provided between the liquid bag 50 and the sample container, and after the flow control component is turned on, the liquid containing the immunomagnetic bead cells is automatically input into the liquid bag 50; or the liquid containing the immunomagnetic bead cells can be input into the liquid bag 50 by placing the sample container at a higher position and squeezing the sample container.
  • the flow control component can include a peristaltic pump that can provide power for the flow of the liquid, and a pinch valve that serves as a switch for the flow control component, and can also include a flow regulating valve to control the flow rate of the liquid, or a sensor for monitoring the flow rate and pressure of the liquid flow.
  • the pressing mechanism 40 is controlled to drive the closed closing mechanism 30 to move downward, so as to flatten the liquid bag 50 placed in the accommodation space between the magnetic platform 10 and the closing mechanism 30, increase the contact surface between the bottom surface of the liquid bag 50 and the magnetic platform 10, and then adsorb the immunomagnetic beads in the liquid bag 50 on the contact surface through the magnetic platform 10. Understandably, after the closing mechanism 30 is closed, the pressing mechanism 40 can drive the closed closing mechanism 30 to move downward and evenly flatten the liquid bag 50, so as to increase the contact surface formed by the adhesion between the liquid bag 50 and the magnetic platform 10, and then allow the liquid in the liquid bag 50 to be evenly distributed on the magnetic platform 10 through the contact surface to contact with it.
  • the liquid bag 50 is flattened to increase the contact area between the bottom surface of the liquid bag 50 and the magnetic platform 10.
  • the magnetic platform 10 can more fully adsorb the immunomagnetic bead cells in the liquid bag 50 through the increased contact area, thereby avoiding the escape of the immunomagnetic bead cells, further improving the utilization rate of the magnetic field, and achieving efficient and stable capture of the immunomagnetic bead cells while being easy to operate.
  • the pressing device 1 further includes a lifting mechanism 20 connected to the capping mechanism 30; further, in the step S10, after the liquid containing the immunomagnetic bead cells is input into the liquid bag 50, it also includes:
  • the lifting mechanism 20 is controlled to drive the covering mechanism 30 to rise, so as to increase the storage space between the magnetic platform 10 and the covering mechanism 30 for placing the liquid bag 50; in this embodiment, after the liquid bag 50 is placed in the storage space, due to the high height of the expansion of the liquid in the liquid bag 50, the covering mechanism 30 is pushed open by the liquid bag 50 placed in the storage space, resulting in the covering mechanism 30 being unable to close. At this time, the lifting mechanism 20 is controlled to open and drive the covering mechanism 30 to rise, so that the distance between the magnetic platform 10 and the covering mechanism 30 will increase, and then, the storage space will increase with the increase of the distance.
  • the covering mechanism 30 After the covering mechanism 30 rises to a preset height for covering, the covering mechanism 30 is controlled to cover; that is, when the covering mechanism 30 rises to the preset height, the accommodating space between the covering mechanism 30 and the magnetic platform 10 is large enough, and the covering mechanism 30 will no longer be lifted up by the liquid bag 50, but can be covered normally.
  • the pressing mechanism 40 is controlled to drive the closed covering mechanism 30 to move downward, so as to flatten the liquid bag 50 placed in the accommodation space, increase the contact surface between the bottom surface of the liquid bag 50 and the magnetic platform 10, and then adsorb the immunomagnetic beads in the liquid bag 50 on the contact surface through the magnetic platform 10. That is, after the covering mechanism 30 is closed, the pressing mechanism 40 can drive the closed covering mechanism 30 to move downward and evenly flatten the liquid bag 50, so that the contact surface formed by the contact between the liquid bag 50 and the magnetic platform 10 is increased, and then the liquid in the liquid bag 50 is evenly distributed on the magnetic platform 10 through the contact surface to contact with it.
  • the magnetic platform 10 is provided with a lifting hole 1011
  • the lifting mechanism 20 includes a lifting assembly 201 arranged on the top of the magnetic platform 10, a lifting rod 202 whose top passes through the lifting hole 1011 and is fixedly connected to the lifting assembly 201, and a rising drive assembly 203 arranged below the magnetic platform 10 and connected to the end of the lifting rod 202 away from the lifting assembly 201;
  • the covering mechanism 30 includes a cover plate 301 rotatably connected to the lifting assembly 201; wherein the cover plate
  • the shape of 301 can be set according to the specific shape of the magnetic platform 10.
  • the shape of the lifting component 201 can be set according to the needs.
  • the lifting component 201 can be a frame structure placed on the top of the magnetic platform 10 (or it can be composed of multiple components set separately, but it can move up and down at the same time with the lifting rod 202), and can be driven by the lifting drive component 203 to move in the up and down direction.
  • the lifting component 201 includes a first lifting block 2011 arranged at the first end of the magnetic platform 10, two second lifting blocks 2012 spaced apart on the second end of the magnetic platform 10 away from the first end, a limit plate 2013 connected between the first lifting block 2011 and the second lifting block 2012, and a rotating shaft 2014 connected between the two second lifting blocks 2012; the cover plate 301 is rotatably connected to the rotating shaft 2014.
  • the limit plates 2013 are two pieces arranged in parallel on opposite sides of the magnetic platform 10, so that a limit frame is formed between the first lifting block 2011, the two second lifting blocks 2012 and the two limit plates 2013 to prevent the liquid bag 50 from escaping from the side of the accommodating space.
  • the limit frame (that is, the main component of the lifting assembly 201) can be lifted up and down synchronously with the cover plate 301.
  • control of the lifting mechanism 20 to drive the covering mechanism 30 to rise includes: controlling the start of the rising drive assembly 203, so as to drive the lifting rod 202 through the rising drive assembly 203 to drive the lifting assembly 201 and the cover plate 301 to slide and rise along the lifting through hole 1011, so as to increase the accommodation space between the magnetic platform 10 and the cover plate 301 for placing the liquid bag 50.
  • the covering mechanism 30 is rotatably mounted on the lifting assembly 201, and will move with the up and down movement of the lifting assembly 201, and the rising drive assembly 203 can reversely drive the lifting assembly 201 to move up along the lifting through hole 1011 through the lifting rod 202, so as to drive the cover plate 301 to move up, thereby increasing the accommodation space between the magnetic platform 10 and the cover plate 301 for placing the liquid bag 50, and thus facilitating the covering of the cover plate 301.
  • the covering mechanism 30 also includes a first adsorption portion 302 disposed on the cover plate 301, and a second adsorption portion 303 disposed on the lifting assembly 201 at a position opposite to the first adsorption portion 302, and the cover plate 301 is covered with the lifting assembly 201 by the adsorption of the first adsorption portion 302 and the second adsorption portion 303.
  • at least one of the first adsorption portion 302 and the second adsorption portion 303 is a magnet, for example, both can be magnets, or one can be a magnet and the other can be a metal having adsorption properties with magnets.
  • the number combination of the first adsorption portion 302 and the second adsorption portion 303 as well as the specific shape and size can be set according to demand, and are not limited here, and the magnet in this application can also refer to an electromagnet.
  • the second adsorption part 303 is an electromagnet
  • the first adsorption part 302 is an iron block.
  • the magnetism of the electromagnet can be removed by energizing the electromagnet of the second adsorption part 303.
  • the electromagnet of the second adsorption part 303 and the first adsorption part 302 (iron block) on the cover 301 do not have the magnetic adsorption function and are in a separated state.
  • the cover 301 can be opened; and after the second adsorption part 303 is powered off, the electromagnet as the second adsorption part 303 generates magnetism.
  • the first adsorption part 302 of the cover 301 will be adsorbed by the second adsorption part 303, thereby completing the closing of the cover 301.
  • the rising drive assembly 203 includes a second motor 2031, a second driving wheel 2032, a second driven wheel 2033, a second synchronous belt 2034, a second rotating shaft 2035, a cam 2036, a mounting bearing 2037 and a cam bracket 2038 having a second mounting hole 2039; the cam bracket 2038 is mounted on the bottom of the magnetic platform 10, the second rotating shaft 2035 is mounted in the second mounting hole 2039 through the mounting bearing 2037, the cam 2036 is fixedly mounted on the second rotating shaft 2035, and the second driving wheel 2032 is mounted on the output shaft of the second motor 2031.
  • the second synchronous belt 2034 is sleeved on the second driving wheel 2032 and the second driven wheel 2033, the second driven wheel 2033 is fixedly mounted on the second rotating shaft 2035, and the top end of the cam 2036 abuts against the lifting rod 202; as shown in Figure 5, the second motor 2031 can be fixed on the magnetic platform 10 by a fixing block; the cam 2036, the cam bracket 2038, and the mounting bearing 2037 on the second rotating shaft 2035 are all symmetrically arranged in two, and the lifting rod 202 is also arranged in parallel in two, and the top ends of the two lifting rods 202 are connected to the lifting assembly 201; and the two cams 2036 abut against the bottom ends of the two lifting rods 202 respectively.
  • the lifting drive component 203 drives the lifting rod 202 to drive the lifting component 201 and the cover plate 301 to slide and rise along the lifting hole 1011, including: controlling the second motor 2031 to start, the second motor 2031 drives the cam 2036 to rotate in sequence through the second driving wheel 2032, the second synchronous belt 2034, the second driven wheel 2033, and the second rotating shaft 2035, and the rotating cam 2036 drives the lifting component 201 and the cover plate 301 to slide and rise along the lifting hole 1011 through the lifting rod 202. That is, after the second motor 2031 starts to rotate, it will drive the second driving wheel 2032 to rotate, and then drive the second driven wheel 2033 to rotate through the second synchronous belt 2034.
  • the rotation of the second driven wheel 2033 will drive the second rotating shaft 2035 and the two cams 2036 installed on the second rotating shaft 2035 to rotate.
  • the lifting rod 202 abutted by the cam 2036 will rotate with the
  • the cover 301 moves upward along with the rotation of the cam 2036, thereby driving the lifting assembly 201 and the cover plate 301 to be lifted as a whole.
  • the second adsorption part 303 is an electromagnet as described in the above embodiment, the electromagnet of the second adsorption part 303 will be powered off.
  • the cover plate 301 will also rise accordingly and gradually become flush until the iron block of the first adsorption part 302 is attracted by the electromagnet of the second adsorption part 303, confirming that the cover plate 301 is closed.
  • the lifting drive assembly 203 further includes a sensing block 2042 mounted on the second rotating shaft 2035 and a photoelectric sensor 2043 mounted on the magnetic platform 10, and the photoelectric sensor 2043 is used to determine that the cover plate 301 rises to the preset height when sensing that the second rotating shaft 2035 drives the sensing block 2042 to rotate to a position facing the photoelectric sensor 2043.
  • the preset height refers to the highest height to which the lifting rod 202 can drive the lifting assembly 201 and the cover plate 301 to rise, and the preset height can be set according to the specific size of the liquid bag 50, and can be realized by changing the size and shape of the cam 2036 according to the needs.
  • the lifting drive assembly 203 further includes a bearing follower 2040 and a fixing plate 2041, wherein the bearing follower 2040 is mounted on the bottom end of the lifting rod 202 through the fixing plate 2041, and the cam 2036 abuts against the bearing follower 2040. That is, the bearing follower 2040 can better transmit the lifting force generated by the rotation of the cam 2036 to the lifting rod 202, thereby making the lifting process of the lifting rod 202 more stable and controllable.
  • a guide through hole 1012 is provided on the magnetic platform 10
  • the pressing mechanism 40 includes a guide shaft 401, a spring 402 and a linear bearing 403 installed in the guide through hole 1012, a stopper 4011 is provided at the bottom end of the guide shaft 401, and the top end of the guide shaft 401 passes through the linear bearing 403 to connect the lifting assembly 201, the spring 402 is sleeved on the guide shaft 401, and the two ends of the spring 402 are respectively abutted against the linear bearing 403 and the stopper 4011;
  • the control of the pressing mechanism 40 to drive the closed covering mechanism 30 to move downward includes: controlling the rising drive assembly 203 to be closed, so as to drive the guide shaft 401 to move downward along the guide through hole 1012 through the elastic force of the spring 402, thereby driving the lifting assembly 201 and the cover plate 301 to move downward.
  • the lifting drive assembly 203 with the cam 2036 can only drive the lifting rod 202 to rise, it does not have the downward pulling force to pull down the lifting assembly 201. Therefore, the above-mentioned pressing mechanism 40 is set, and the spring 402 is in a compressed state. After the second motor 2031 of the lifting drive assembly 203 is turned off (the second motor 2031 is reset), the spring 402 will apply a downward pulling force to the lifting assembly 201 through the guide shaft 401 to overcome its compressed state (the spring 402 drives the guide shaft 401 to move downward along the guide through hole 1012), thereby driving the lifting assembly 201 and the cover plate 301 to move downward.
  • the pressing mechanism 40 may include a plurality of pressing components arranged on the magnetic platform 10, such as four sets of pressing components respectively arranged at the four corners of the square magnetic platform 10.
  • the cover plate 301 will move downward with the lifting component 201 and then squeeze the liquid bag 50 in the direction of the magnetic platform 10, and then gradually flatten the liquid bag 50 so that the liquid therein is evenly distributed on the magnetic platform 10.
  • the liquid bag 50 is flattened by pulling down by the spring 402 instead of the second motor 2031, etc.
  • the liquid bag 50 can be evenly flattened and attached to the magnetic platform 10 by the spring 402, and on the other hand, the elastic force of the spring 402 is even and gentle, and will not squeeze the cells in the liquid bag 50.
  • controlling the magnetic platform 10 to swing according to a preset swing parameter includes:
  • the preset mixing parameters include a mixing angle and a mixing time; wherein the mixing angle is ⁇ 35 degrees, that is, (that is, the magnetic platform 106 swings to opposite sides, and the angle of its swing toward one side is in the range of 0-35 degrees, exceeding 35 degrees will kill the immune magnetic bead cells, so the maximum absolute value of the mixing angle is 35 degrees), preferably ⁇ 25 degrees; and the mixing time can be 25S-35S, preferably 30S.
  • the mixing device 2 includes a first motor 21, a reducer 22, a first driving wheel 23, a first driven wheel 24, a first synchronous belt 25 and a synchronous bracket 27;
  • the reducer 22 is connected to the output shaft of the first motor 21 to increase the output torque while reducing the speed of the first motor 21,
  • the first driving wheel 23 is connected to the rotating shaft 2014 of the reducer 22,
  • the first synchronous belt 25 is sleeved on the first driving wheel 23 and the first driven wheel 24, and the first driven wheel 24 is installed on the magnetic platform 10;
  • the magnetic platform 10 is rotatably installed on the synchronous bracket 27;
  • the first driving wheel 23 is used to drive the first driven wheel 24 to rotate through the first synchronous belt 25 under the drive of the reducer 22, so that the magnetic platform 10 swings around the fulcrum of the synchronous bracket 27 to mix its components
  • the first motor 21 may be a stepper motor. Since the torque output by the first motor 21 may be small and cannot drive the magnetic platform 10 to shake, the present application reduces the speed of the first motor 21 through the reducer 22, thereby increasing the output torque, and finally realizes the linkage of the first driving wheel 23, the first synchronous belt 25 and the first driven wheel 24 to drive the magnetic platform 10 to swing a certain angle, and then the swing of the magnetic platform 10 drives the liquid in the liquid bag 50 loaded on the magnetic platform 10 to mix, thereby realizing that the immunomagnetic bead cells are uniformly adsorbed on the magnetic platform 10, and drives other substances in the liquid bag 50 except the adsorbed immunomagnetic bead cells to be suspended in the liquid with the swing of the magnetic platform 10.
  • the mixing device 2 further includes a bearing 26, a first mounting hole 271 is provided on the synchronous bracket 27, and the magnetic platform 10 includes a first rotating shaft 103, and the first rotating shaft 103 is rotatably mounted in the first mounting hole 271 through the bearing 26; the first driven wheel 24 is mounted on the first rotating shaft 103.
  • the first motor 21 drives the magnetic platform 10 to swing through the linkage of the reducer 222, the first driving wheel 23, the first synchronous belt 25 and the first driven wheel 24, the fulcrum of the swing of the magnetic platform 10 is the bearing 26 on the synchronous bracket 27, that is, the outer ring of the bearing 26 is fixed in the first mounting hole 271, and the inner ring of the bearing 26 is fixed on the first rotating shaft 103.
  • the first rotating shaft 103 rotates, thereby driving the inner ring of the bearing 26 to rotate relative to its outer ring.
  • the magnetic platform 10 can be controlled to swing in opposite directions with the bearing 26 as the fulcrum; by controlling the rotation speed of the first motor 21, the swing angle of the magnetic platform 10 can be controlled; further, after the magnetic platform 10 is swung to complete the shaking, the magnetic platform 10 is controlled to swing and stay at a preset inclination angle, so that the liquid in the liquid bag 50 can flow out from the liquid outlet after the magnetic bead sorting is completed.
  • the mixing device 2 controls the magnetic platform 10 to continuously swing at the mixing angle, including:
  • the operating parameters of the first motor 21 are determined according to the mixing angle; that is, if the mixing angle required by the magnetic platform 10 is determined, the real-time operating parameters of the first motor 21 can be determined based on the previous historical experimental data (the historical experimental data contains the correlation between the historical operating parameters of the first motor 21 and the historical mixing angle) and the above-mentioned mixing angle. Specifically, first, the historical mixing angle that matches the above-mentioned mixing angle is determined in the historical experimental data, and then the historical operating parameters of the first motor 21 associated with the determined historical mixing angle are determined as the operating parameters of the first motor 21 to be operated in real time.
  • the first motor 21 is started and the reducer 22 is driven by the operating parameters to drive the first driving wheel 23 to rotate.
  • the first driving wheel 23 drives the first driven wheel 24 to rotate through the first synchronous belt 25, thereby driving the magnetic platform to swing around the connection point with the synchronous bracket 27.
  • the reducer 22 is first driven by the first motor 21, thereby driving the first driving wheel 23, the first synchronous belt 25 and the first driven wheel 24 to rotate together, thereby causing the magnetic platform 10 to swing around the first rotating shaft 103 with the bearing 26 as the fulcrum, and the swing angular velocity, swing angle, and angular acceleration of the swing are matched one by one with each parameter in the above-mentioned swing parameters.
  • the mixing device 2 also includes a dual-axis inclination sensor 28 installed on the magnetic platform 10, and the dual-axis inclination sensor 28 is used to detect the swing parameters of the magnetic platform 10.
  • the dual-axis inclination sensor 28 can detect the swing angle, swing angular velocity, angular acceleration, and the angle of stay after the swing is completed during the entire swinging and shaking process of the mixing device 2.
  • the method further includes:
  • the magnetic platform 10 is placed horizontally for a preset time; the preset time can be set to 5-20 minutes according to demand, preferably 10 minutes.
  • first gentle oscillation parameters which include a first gentle oscillation angle and a first gentle oscillation duration; the absolute value of the first gentle oscillation angle is smaller than the absolute value of the mixing angle; the absolute value of the first gentle oscillation angle is smaller than the absolute value of the mixing angle, for example, when the mixing angle is ⁇ 25 degrees, the first gentle oscillation angle is plus or minus 20 degrees.
  • the mixing device 2 controls the magnetic platform 10 to continue to gently swing at the first gentle swing angle for the first gentle swing duration, so that the other substances in the liquid bag 50 except the adsorbed immunomagnetic bead cells are suspended in the liquid.
  • the accumulated immunomagnetic bead cells can be flattened to become more uniform, and at the same time, the other substances in the liquid bag 50 except the adsorbed immunomagnetic bead cells are suspended in the liquid; and in the present embodiment, when shaking at the first gentle swing angle, the shaking force is relatively gentle, and the immunomagnetic bead cells adsorbed by the magnetic platform 10 will not be shaken, but other substances adhering to the adsorbed immunomagnetic bead cells will only be shaken to separate from the immunomagnetic bead cells, and then suspended in the liquid, so that they can be discharged when the waste liquid discharge operation is performed in step S30.
  • the performing of the waste liquid discharge operation includes:
  • the magnetic platform 10 is controlled to stay at a first preset stay angle so that the liquid bag 50 tilts downward from the liquid inlet toward the liquid outlet; in this embodiment, after the magnetic platform 10 is controlled to swing according to the preset swing parameters and the liquid in the liquid bag 50 is shaken, the first preset stay angle refers to an angle that can make the height of the liquid outlet of the liquid bag 50 on the stationary magnetic platform 10 lower than the height of the liquid inlet, so as to allow the liquid in the liquid bag 50 to flow out of the liquid outlet; specifically, when the magnetic platform 10 stays at the first preset stay angle, the angle between the magnetic platform 10 and the horizontal plane is the first preset stay angle, and the first preset stay angle can be 10-30 degrees, preferably 20 degrees.
  • the waste liquid discharge pipeline includes a pump and a bubble sensor connected between the waste liquid bag 50 and the liquid outlet of the liquid bag 50; that is, the first switch operation refers to opening all the closed valves on the line of the waste liquid bag 50, the pump, the bubble sensor and the liquid bag 50 in the waste liquid discharge pipeline, and turning on the pump (the pump is preferably a peristaltic pump) and the bubble sensor at the same time, and then the waste liquid discharge pipeline is considered to be open.
  • the pump is preferably a peristaltic pump
  • the liquid in the liquid bag 50 except the adsorbed immunomagnetic bead cells is discharged into the waste liquid bag 50 through the waste liquid discharge pipeline; specifically, the pump in the waste liquid discharge channel draws the liquid in the liquid bag 50 except the adsorbed immunomagnetic bead cells into the waste liquid bag 50, and the bubble sensor detects the bubbles in the liquid in the waste liquid discharge pipeline, and then determines whether there is still liquid flowing in the waste liquid discharge pipeline based on the detection result.
  • the waste liquid discharge is confirmed to be completed. That is, when it is determined that no liquid passes through the waste liquid discharge pipeline, it means that the liquid in the liquid bag 50 has been exhausted, so it can be considered that the waste liquid discharge process is completed.
  • step S40 the washing operation of the remaining immunomagnetic bead cells in the fluid bag 50 includes:
  • the magnetic platform 10 is controlled to stay at a second preset stay angle so that the liquid bag 50 tilts upward from the liquid inlet toward the liquid outlet; the second preset stay angle and the first preset stay angle are in opposite directions; in this embodiment, the second preset stay angle refers to an angle that can make the height of the liquid outlet of the liquid bag 50 on the stationary magnetic platform 10 higher than the height of the liquid inlet, so that the cleaning liquid at the subsequent cleaning liquid inlet stays near the liquid inlet after flowing into the liquid bag 50 from the liquid inlet, thereby facilitating the cleaning liquid to penetrate into every corner of the liquid bag 50 from the liquid inlet; specifically, when the magnetic platform 10 stays at the second preset stay angle, the angle between the magnetic platform 10 and the horizontal plane is the second preset stay angle, and the second preset stay angle can be 10-30 degrees, preferably 15-20 degrees.
  • the second switch operation includes closing the passage between the pump and the bubble sensor and the waste liquid bag 50, and connecting the pump and the bubble sensor between the cleaning liquid inlet and the liquid inlet of the liquid bag 50; that is, the second switch operation refers to closing the valve between the pump and the bubble sensor and the waste liquid bag 50 in the waste liquid discharge pipeline, so that the pump and the bubble sensor are not connected to the waste liquid bag 50, and the pump and the bubble sensor are also closed, that is, the waste liquid discharge pipeline is closed; at this time, the closed valves on the line of the cleaning liquid inlet, pump, bubble sensor and liquid bag 50 are opened, and then the pump (the pump is preferably a peristaltic pump) and the bubble sensor are turned on, and the cleaning pipeline is considered to be open at this time.
  • the pump the pump is preferably a peristaltic pump
  • a first preset volume of cleaning fluid is input into the fluid bag 50 through the cleaning pipeline; the first preset volume may be 50-300 ml, preferably 100 ml.
  • Obtain a second gentle swing parameter which includes a second gentle swing angle and a second gentle swing duration; wherein the absolute value of the second gentle swing angle is smaller than the absolute value of the mixing angle, for example, when the mixing angle is ⁇ 25 degrees, the second gentle swing angle is plus or minus 20 degrees.
  • the mixing device 2 controls the magnetic platform 10 to continue to gently swing at the second gentle swing angle for the second gentle swing time, the waste liquid discharge operation is performed again.
  • the accumulated immunomagnetic bead cells can be flattened to become more uniform, and in the present embodiment, when it is shaken at the second gentle swing angle, the shaking force is relatively gentle, and the immunomagnetic bead cells adsorbed by the magnetic platform 10 will not be shaken, but other substances adhering to the adsorbed immunomagnetic bead cells will be shaken to separate from the immunomagnetic bead cells, and then suspended in the cleaning liquid, so as to discharge them when the waste liquid discharge operation is performed again.
  • the purity of the adsorbed immunomagnetic bead cells in the final liquid bag 50 can be further guaranteed.
  • the step of performing the waste liquid discharge operation again can refer to the specific description of the waste liquid discharge operation in the above-mentioned embodiment, which will not be repeated here.
  • the first switch operation is to first close the valve between the pump and the bubble sensor and the cleaning liquid inlet in the cleaning pipeline, so that the pump and the bubble sensor are not connected to the cleaning liquid inlet, and the pump and the bubble sensor are also closed.
  • the sensor that is, the cleaning pipeline is closed; at this time, the closed valves on the waste liquid bag 50, the pump, the bubble sensor and the liquid bag 50 are all opened, and the pump (the pump is preferably a peristaltic pump) and the bubble sensor are turned on at the same time. At this time, it is considered that the waste liquid discharge pipeline is opened again.
  • step S50 injecting the resuspension solution into the fluid bag 50 and taking out the fluid bag 50 containing the immunomagnetic bead cells includes:
  • the magnetic platform 10 is adjusted to be parallel to the horizontal plane; that is, after performing the waste liquid discharge operation again, the magnetic platform 10 is first reset to a horizontal level to facilitate subsequent operations.
  • the third switch operation includes closing the passage between the pump and the bubble sensor and the waste liquid bag 50, and connecting the pump and the bubble sensor between the resuspension liquid inlet and the liquid inlet of the liquid bag 50; that is, the third switch operation refers to closing the valve between the pump and the bubble sensor and the waste liquid bag 50 in the waste liquid discharge pipeline, so that the pump and the bubble sensor are not connected to the waste liquid bag 50, and the pump and the bubble sensor are also closed, that is, the waste liquid discharge pipeline is closed; at this time, the closed valves on the line of the resuspension liquid inlet, pump, bubble sensor and liquid bag 50 are opened, and then the pump (the pump is preferably a peristaltic pump) and the bubble sensor are turned on, and the resuspension liquid input pipeline is considered to be opened.
  • the pump is preferably a peristaltic pump
  • the resuspension of a second preset volume is input into the fluid bag 50 via the resuspension input pipeline; understandably, the second preset volume can be set according to demand, such as 0-300 ml.
  • the fourth switch operation includes closing the passage between the pump and the bubble sensor and the resuspension inlet, and controlling the pump and the bubble sensor to be connected to the atmosphere through the sterile air filter; that is, the fourth switch operation refers to closing the valve between the pump and the bubble sensor and the resuspension inlet in the resuspension input pipeline, so that the pump and the bubble sensor are not connected to the resuspension inlet; at this time, the valves closed on the line of the sterile air filter, the pump, the bubble sensor and the liquid bag 50 are all opened, and the resuspension input pipeline is considered to be opened; then, the liquid bag 50 can be connected to the atmosphere through the pump, the bubble sensor and the sterile air filter.
  • the resuspension remaining in the pipeline can be emptied under the action of the pump and enter the liquid bag 50, without wasting the resuspension in the pipeline.
  • the price of the resuspension is high, and the above operation in this embodiment will greatly reduce the cost of the magnetic bead sorting process.
  • the bubble sensor determines that no liquid passes through, it is determined that the resuspension is completely injected into the liquid bag; understandably, when the bubble sensor detects the bubbles in the pipeline and then determines based on the detection result that no liquid flows through the pipeline, it can be considered that the resuspension has been completely injected into the liquid bag 50.
  • the liquid bag 50 containing the immunomagnetic bead cells is taken out from the magnetic platform 10. That is, in this embodiment, after the pipeline is emptied, the liquid outlet and the liquid inlet of the liquid bag 50 are heat-sealed, that is, the liquid outlet and the liquid inlet are heat-sealed using a heat sealer, and then the liquid bag 50 is taken out from the magnetic platform 10, and the magnetic bead sorting process is completed.
  • the immunomagnetic bead cells in the resuspension in the liquid bag 50 are the target objects of collection. At this time, the collection has been completed and the subsequent cultivation process can be carried out.
  • the step of inputting the second preset volume of the resuspension into the fluid bag 50 through the resuspension input pipeline comprises:
  • the resuspension is injected into the liquid bag 50 through the resuspension input pipeline; that is, in this embodiment, after the resuspension input pipeline is opened, the resuspension can be injected into the liquid bag 50 through the opened resuspension input pipeline.
  • the weight change information of the liquid bag 50 is obtained by a weighing sensor, and the actual capacity of the injected heavy suspension is determined according to the weight change information of the liquid bag 50; or the volume-number of revolutions data corresponding to the pump is obtained, and the actual capacity of the injected heavy suspension is determined according to the actual number of revolutions of the pump and the volume-number of revolutions data; that is, in this embodiment, the difference between the current weight and the original weight of the liquid bag 50 can be determined by the weight change information of the liquid bag 50, and then the actual capacity of the injected heavy suspension can be determined according to the difference and the density of the heavy suspension; and in another embodiment, it can also be based on historical data, that is, the volume of the heavy suspension input into the liquid bag 50 corresponding to each revolution of the pump obtained in historical tests, that is, the volume-number of revolutions data, and then, after obtaining the actual number of revolutions of the pump, the actual capacity of the injected heavy suspension can be determined.
  • the second preset capacity of the resuspension has been input into the fluid bag 50. That is, since only the second preset capacity of the resuspension needs to be injected, after determining that the second preset capacity of the resuspension has been injected according to the above method, it can be confirmed that the second preset capacity of the resuspension has been input into the fluid bag 50, and then the subsequent fourth switch operation and other steps are performed.
  • the second preset capacity of the resuspension can be used. Assume that the capacity is set to be slightly smaller than the capacity of the resuspension that actually needs to be injected into the liquid bag 50 (the difference between the two can be a constant value obtained by experiment). In this way, the second pre-capacity plus the resuspension discharged from the pipeline into the liquid bag 50 can actually inject the final required capacity of the resuspension.
  • the present application also provides a magnetic bead sorting device, comprising a pressing device 1, a mixing device 2 and a controller for executing the above-mentioned magnetic bead sorting method, wherein the controller is connected to the pressing device 1 and the mixing device 2.
  • controller is used to perform the following steps:
  • the magnetic platform is controlled to swing according to preset swing parameters, so that the immunomagnetic bead cells adsorbed by the magnetic platform are evenly distributed, and at the same time, other substances in the liquid bag except the adsorbed immunomagnetic bead cells are suspended in the liquid;
  • the step of placing an empty fluid bag on a magnetic platform, injecting a liquid containing immunomagnetic bead cells into the fluid bag, and adsorbing the immunomagnetic bead cells in the fluid bag liquid through the magnetic platform comprises:
  • the pressing device comprises a covering mechanism installed on the magnetic platform and a pressing mechanism connected to the covering mechanism;
  • the pressing mechanism is controlled to drive the closed closing mechanism to move downward to flatten the liquid bag placed in the accommodating space between the magnetic platform and the closing mechanism, thereby increasing the contact surface between the bottom surface of the liquid bag and the magnetic platform, and then adsorbing the immunomagnetic bead cells in the liquid bag on the contact surface through the magnetic platform.
  • the pressing device further includes a lifting mechanism connected to the capping mechanism; further, after the liquid containing the immunomagnetic bead cells is input into the liquid bag, the controller is further configured to perform the following steps:
  • the lifting mechanism is controlled to drive the covering mechanism to rise, so as to increase the accommodation space between the magnetic platform and the covering mechanism for placing the liquid bag;
  • the pressing mechanism is controlled to drive the closed closing mechanism to move downward to flatten the liquid bag placed in the containing space, thereby increasing the contact surface between the bottom surface of the liquid bag and the magnetic platform, and then the immune magnetic bead cells in the liquid bag are adsorbed on the contact surface through the magnetic platform.
  • controlling the magnetic platform to swing according to a preset swing parameter includes:
  • the preset mixing parameters include mixing angle and mixing duration;
  • the mixing device controls the magnetic platform to continuously swing at the mixing angle for the mixing time, so that the immunomagnetic beads are evenly adsorbed on the magnetic platform, and drives other substances in the liquid bag except the adsorbed immunomagnetic beads to be suspended in the liquid with the swing of the magnetic platform.
  • the controller is further configured to perform the following steps:
  • the first gentle swing parameter includes a first gentle swing angle and a first gentle swing duration; an absolute value of the first gentle swing angle is smaller than an absolute value of the mixing angle;
  • the mixing device controls the magnetic platform to continue to gently swing at the first gentle swing angle for the first gentle swing time, so that other substances in the liquid bag except the adsorbed immunomagnetic bead cells are suspended in the liquid.
  • the mixing device includes a first motor, a reducer, a first driving wheel, a first driven wheel, a first synchronous belt and a synchronous bracket;
  • the reducer is connected to the output shaft of the first motor to increase the output torque while reducing the speed of the first motor;
  • a driving wheel is connected to the rotating shaft of the reducer, the first synchronous belt is sleeved on the first driving wheel and the first driven wheel, the first driven wheel is mounted on the magnetic platform; the magnetic platform is rotatably mounted on the synchronous bracket;
  • the mixing device controls the magnetic platform to continuously swing at the mixing angle, comprising:
  • the first motor is started and drives the reducer with the operating parameters to drive the first driving wheel to rotate.
  • the first driving wheel drives the first driven wheel to rotate through the first synchronous belt, thereby driving the magnetic platform to swing around the connection point with the synchronous bracket.
  • the performing of the waste liquid discharge operation includes:
  • the waste liquid discharge pipeline includes a pump and a bubble sensor connected between a waste liquid bag and a liquid outlet of the liquid bag;
  • the washing operation of the remaining immunomagnetic bead cells in the fluid bag comprises:
  • the second switch operation includes closing the passage between the pump and the bubble sensor and the waste liquid bag, and connecting the pump and the bubble sensor between the cleaning liquid inlet and the liquid inlet of the liquid bag;
  • the second gentle swing parameter includes a second gentle swing angle and a second gentle swing duration
  • the mixing device controls the magnetic platform to gently swing continuously at the second gentle swing angle for the second gentle swing time, the waste liquid discharge operation is performed again.
  • the step of injecting a resuspension solution into the fluid bag and removing the fluid bag containing the immunomagnetic bead cells comprises:
  • the third switch operation includes closing the passage between the pump and the bubble sensor and the waste liquid bag, and connecting the pump and the bubble sensor between the resuspension liquid inlet and the liquid inlet of the liquid bag;
  • the fourth switch operation includes closing the passage between the pump and the bubble sensor and the resuspension liquid inlet, and controlling the pump and the bubble sensor to communicate with the atmosphere through the sterile air filter;
  • the liquid bag containing the immunomagnetic bead cells is taken out from the magnetic platform.
  • the step of inputting a second preset volume of the resuspension into the fluid bag through the resuspension input pipeline comprises:
  • Each module in the above-mentioned controller can be implemented in whole or in part by software, hardware and a combination thereof.
  • the above-mentioned modules can be embedded in or independent of the processor in the computer device in the form of hardware, or can be stored in the memory in the computer device in the form of software, so that the processor can call and execute the operations corresponding to the above modules.
  • the controller can be regarded as one or more computer devices, as shown in Figure 7, the computer device includes a processor, a memory, a network interface and a database connected by 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, computer-readable instructions and a database.
  • the internal memory provides an environment for the operation of the operating system and computer-readable instructions in the readable storage medium.
  • the database of the computer device is used to store the data used in the magnetic bead sorting method in the above-mentioned embodiment.
  • the network interface of the computer device is used to communicate with an external terminal through a network connection. When the computer-readable instructions are executed by the processor, a magnetic bead sorting method is implemented.
  • the readable storage medium provided in this embodiment includes a non-volatile readable storage medium and a volatile readable storage medium.
  • one or more readable storage media storing computer-readable instructions are provided, and the readable storage media provided in this embodiment include non-volatile readable storage media and volatile readable storage media; computer-readable instructions are stored on the readable storage medium, and when the computer-readable instructions are executed by one or more processors, the one or more processors implement the above-mentioned magnetic bead sorting method.
  • the one or more processors implement the following steps:
  • the magnetic platform is controlled to swing according to preset swing parameters, so that the immunomagnetic bead cells adsorbed by the magnetic platform are evenly distributed, and at the same time, other substances in the liquid bag except the adsorbed immunomagnetic bead cells are suspended in the liquid;
  • the step of placing an empty fluid bag on a magnetic platform, injecting a liquid containing immunomagnetic bead cells into the fluid bag, and adsorbing the immunomagnetic bead cells in the fluid bag liquid through the magnetic platform comprises:
  • the pressing device comprises a covering mechanism installed on the magnetic platform and a pressing mechanism connected to the covering mechanism;
  • the pressing mechanism is controlled to drive the closed closing mechanism to move downward to flatten the liquid bag placed in the accommodating space between the magnetic platform and the closing mechanism, thereby increasing the contact surface between the bottom surface of the liquid bag and the magnetic platform, and then adsorbing the immunomagnetic bead cells in the liquid bag on the contact surface through the magnetic platform.
  • the pressing device further includes a lifting mechanism connected to the capping mechanism; further, after the liquid containing the immunomagnetic bead cells is input into the liquid bag, when the computer-readable instructions are executed by one or more processors, the one or more processors further implement the following steps:
  • the lifting mechanism is controlled to drive the covering mechanism to rise, so as to increase the accommodation space between the magnetic platform and the covering mechanism for placing the liquid bag;
  • the pressing mechanism is controlled to drive the closed closing mechanism to move downward to flatten the liquid bag placed in the containing space, thereby increasing the contact surface between the bottom surface of the liquid bag and the magnetic platform, and then the immune magnetic bead cells in the liquid bag are adsorbed on the contact surface through the magnetic platform.
  • controlling the magnetic platform to swing according to a preset swing parameter includes:
  • the preset mixing parameters include mixing angle and mixing duration;
  • the mixing device controls the magnetic platform to continuously swing at the mixing angle for the mixing time, so that the immunomagnetic beads are evenly adsorbed on the magnetic platform, and drives other substances in the liquid bag except the adsorbed immunomagnetic beads to be suspended in the liquid with the swing of the magnetic platform.
  • the one or more processors further implement the following steps:
  • the first gentle swing parameter includes a first gentle swing angle and a first gentle swing duration; an absolute value of the first gentle swing angle is smaller than an absolute value of the mixing angle;
  • the mixing device controls the magnetic platform to continue to gently swing at the first gentle swing angle for the first gentle swing time, so that other substances in the liquid bag except the adsorbed immunomagnetic bead cells are suspended in the liquid.
  • the mixing device includes a first motor, a reducer, a first driving wheel, a first driven wheel, a first synchronous belt and a synchronous bracket;
  • the reducer is connected to the output shaft of the first motor to increase the output torque while reducing the speed of the first motor
  • the first driving wheel is connected to the rotating shaft of the reducer
  • the first synchronous belt is sleeved on the first driving wheel and the first driven wheel
  • the first driven wheel is installed on the magnetic platform
  • the magnetic platform is rotatably installed on the synchronous bracket;
  • the mixing device controls the magnetic platform to continuously swing at the mixing angle, comprising:
  • the first motor is started and drives the reducer with the operating parameters to drive the first driving wheel to rotate.
  • the first driving wheel drives the first driven wheel to rotate through the first synchronous belt, thereby driving the magnetic platform to swing around the connection point with the synchronous bracket.
  • the performing of the waste liquid discharge operation includes:
  • the waste liquid discharge pipeline includes a pump and a bubble sensor connected between a waste liquid bag and a liquid outlet of the liquid bag;
  • the washing operation of the remaining immunomagnetic bead cells in the fluid bag comprises:
  • the second switch operation includes closing the passage between the pump and the bubble sensor and the waste liquid bag, and connecting the pump and the bubble sensor between the cleaning liquid inlet and the liquid inlet of the liquid bag;
  • the second gentle swing parameter includes a second gentle swing angle and a second gentle swing duration
  • the mixing device controls the magnetic platform to gently swing continuously at the second gentle swing angle for the second gentle swing time, the waste liquid discharge operation is performed again.
  • the step of injecting a resuspension solution into the fluid bag and removing the fluid bag containing the immunomagnetic bead cells comprises:
  • the third switch operation includes closing the passage between the pump and the bubble sensor and the waste liquid bag, and connecting the pump and the bubble sensor between the resuspension liquid inlet and the liquid inlet of the liquid bag;
  • the fourth switch operation includes closing the passage between the pump and the bubble sensor and the resuspension liquid inlet, and controlling the pump and the bubble sensor to communicate with the atmosphere through the sterile air filter;
  • the liquid bag containing the immunomagnetic bead cells is taken out from the magnetic platform.
  • the step of inputting a second preset volume of the resuspension into the fluid bag through the resuspension input pipeline comprises:
  • Non-volatile memory may include read-only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM) or flash memory.
  • Volatile memory may include random access memory (RAM) or external cache memory.
  • RAM random access memory
  • DRAM dynamic RAM
  • SDRAM synchronous DRAM
  • DDRSDRAM double data rate SDRAM
  • ESDRAM enhanced SDRAM
  • SLDRAM synchronous link (Synchlink) DRAM
  • RDRAM direct memory bus dynamic RAM
  • RDRAM memory bus dynamic RAM

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Abstract

本申请公开了一种磁珠分选方法、设备及存储介质,该方法包括:将空的液袋放置在磁性平台上,将包含免疫磁珠细胞的液体输入至液袋中,通过磁性平台吸附液袋液体中的免疫磁珠细胞;根据预设摆动参数控制磁性平台摆动,令被磁性平台吸附的免疫磁珠细胞均匀分布,同时令液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中;执行排废液操作,令液袋中除被吸附的免疫磁珠细胞之外的液体流入废液袋;对液袋中剩余的免疫磁珠细胞执行清洗操作;向液袋中注入重悬液并取出包含免疫磁珠细胞的液袋之后,确定磁珠分选完成。本申请中被磁性平台吸附的免疫磁珠细胞均匀分布而不会局部堆积,提升了磁场利用率,实现了高效稳定地分离收集免疫磁珠细胞。

Description

磁珠分选方法、设备及存储介质
本申请要求于2022年9月27日提交中国专利局、申请号为202211182777.5,发明名称为“磁珠分选方法、设备及存储介质”的中国专利申请的优先权,其全部内容通过引用结合在本申请中。
技术领域
本申请涉及磁珠分选技术领域,尤其涉及一种磁珠分选方法、设备及存储介质。
背景技术
目前,磁珠分选技术中,需要通过磁铁吸住已经与磁珠结合的免疫磁珠细胞(部分细胞表面抗原具有与连接有磁珠的特异性抗体结合的特性,该部分细胞在外加磁场中,可以通过抗原与磁珠相连,进而形成免疫磁珠细胞),进而将未被磁铁吸住的其他物质(比如不能与磁珠结合的细胞等)抽离,进而分离免疫磁珠细胞。发明人意识到,现有技术中,通常使用微流控芯片与磁场相结合的方式进行磁珠分选,该方案存在处理容量小的问题,如此,在处理大容量的细胞液时,由于液袋面积过大,液体在液袋中流动时经过各区域的流速并不一致,进而导致液袋各截面积对应区域的磁化也不一致,比如,部分区域的流速过大时将会由于免疫磁珠细胞与磁场接触不够导致免疫磁珠细胞逃逸,如此,磁铁利用率低,磁铁对免疫磁珠细胞的吸附并不充分;且被吸附的免疫磁珠细胞将会大量堆积在流速低的区域附近,同样会导致磁铁吸附不充分。
申请内容
本申请实施例提供一种磁珠分选方法、设备及存储介质,以解决现有技术中磁场利用率低等问题。
一种磁珠分选方法,包括:
将空的液袋放置在磁性平台上,将包含免疫磁珠细胞的液体输入至所述液袋中,通过所述磁性平台吸附所述液袋液体中的免疫磁珠细胞;
根据预设摆动参数控制所述磁性平台摆动,以令被所述磁性平台吸附的免疫磁珠细胞均匀分布,同时令所述液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中;
执行排废液操作,以令所述液袋中除被吸附的免疫磁珠细胞之外的液体流入废液袋;
对所述液袋中剩余的免疫磁珠细胞执行清洗操作;
向所述液袋中注入重悬液并取出包含免疫磁珠细胞的所述液袋之后,确定磁珠分选完成。
一种控制器,所述控制器用于执行上述磁珠分选方法。
一种磁珠分选设备,包括压合装置、混匀装置以及上述控制器,所述控制器连接所述压合装置以及所述混匀装置。
一种计算机可读存储介质,所述计算机可读存储介质存储有计算机可读指令,其中,所述计算机可读指令被处理器执行时实现上述磁珠分选方法。
上述磁珠分选方法、设备及存储介质,所述方法包括:将空的液袋放置在磁性平台上,将包含免疫磁珠细胞的液体输入至所述液袋中,通过所述磁性平台吸附所述液袋液体中的免疫磁珠细胞;根据预设摆动参数控制所述磁性平台摆动,以令被所述磁性平台吸附的免疫磁珠细胞均匀分布,同时令所述液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中;执行排废液操作,以令所述液袋中除被吸附的免疫磁珠细胞之外的液体流入废液袋;对所述液袋中剩余的免疫磁珠细胞执行清洗操作;向所述液袋中注入重悬液并取出包含免疫磁珠细胞的所述液袋之后,确定磁珠分选完成。
本申请可以根据预设摆动参数控制磁性平台摆动,进而实现将大容量或大通量的液袋中的液体(比如细胞液)摇匀,使得免疫磁珠细胞在液袋底面均匀分布而不在局部位置堆积,从而使得磁性平台可以对摇匀之后的液袋中未堆积的免疫磁珠细胞近距离贴合,以实现磁性平台对免疫磁珠细胞的充分吸 附,避免免疫磁珠细胞的流失;同时,还可以令所述液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中(比如,将黏附在已被吸附的免疫磁珠细胞上的其他物质摇晃到与免疫磁珠细胞脱离,进而使其悬浮在液体中,以便于在执行排废液操作时将其排出,同时不会阻挡仍然未被吸附的免疫磁珠细胞被磁性平台吸附)。进而,最终通过排废液操作和清洗操作实现从液袋中将除免疫磁珠细胞之外的其他物质进行分离,以最终收集得到免疫磁珠细胞。本申请提升了磁场利用率,实现了通过磁珠分选方式高效稳定地分离和收集免疫磁珠细胞。
本申请的一个或多个实施例的细节在下面的附图和描述中提出,本申请的其他特征和优点将从说明书、附图以及权利要求变得明显。
附图说明
为了更清楚地说明本申请实施例的技术方案,下面将对本申请实施例的描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本申请的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动性的前提下,还可以根据这些附图获得其他的附图。
图1是本申请一实施例中磁珠分选方法的流程图;
图2是本申请一实施例中磁珠分选方法的步骤S20的流程图;
图3是本申请一实施例中混匀装置的部分爆炸结构示意图;
图4是本申请一实施例中混匀装置的装配结构示意图;
图5是本申请一实施例中压合装置的爆炸结构示意图;
图6是本申请一实施例中压合装置的装配结构示意图;
图7是本申请一实施例中计算机设备的示意图。
说明书中的附图标记如下:
1、压合装置;10、磁性平台;101、底座;1011、顶升通孔;1012、导向通孔;102、磁块;103、
第一转轴;20、顶升机构;201、升降组件;2011、第一升降块;2012、第二升降块;2013、限位板;2014、转动轴;202、顶升杆;203、上升驱动组件;2031、第二电机;2032、第二主动轮;2033、第二从动轮;2034、第二同步带;2035、第二转轴;2036、凸轮;2037、安装轴承;2038、凸轮支架;2039、第二安装孔;2040、轴承随动器;2041、固定板;2042、感应块;2043、光电传感器;30、盖合机构;301、盖板;302、第一吸附部;303、第二吸附部;40、压合机构;401、导向轴;402、弹簧;403、直线轴承;4011、挡块;50、液袋;2、混匀装置;21、第一电机;22、减速机;23、第一主动轮;24、第一从动轮;25、第一同步带;26、轴承;27、同步支架;271、第一安装孔;28、双轴倾角传感器。
具体实施方式
下面将结合本申请实施例中的附图,对本申请实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例是本申请一部分实施例,而不是全部的实施例。基于本申请中的实施例,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例,都属于本申请保护的范围。
在一实施例中,如图1所示,提供一种磁珠分选方法,包括如下步骤:
S10:将空的液袋50放置在磁性平台10上,将包含免疫磁珠细胞的液体输入至所述液袋50中,通过所述磁性平台10吸附所述液袋50液体中的免疫磁珠细胞;其中,所述磁性平台10可以为通过电磁铁或者永磁体构建的具有磁性的平台。比如,如图5所示的磁性平台10可以包括设置有顶升通孔1011的底座101,以及安装在所述底座101上的永磁体磁块102或者电磁铁;其中,所述底座101上设有安装槽,而磁块102被固定安装在该安装槽中。可理解地,磁性平台10可以通过与液袋50的接触面贴合,使得液体与磁性平台10的磁场近距离接触,进而将免疫磁珠细胞吸附在接触面上;而液袋50由非磁性材料制成,不会被磁力吸附,因此不会受到其下方磁性平台10的磁场影响。
在本申请的该步骤中,将空的液袋50放到磁性平台10(比如磁块102)上面,将样本容器中的细胞液(细胞液是指由细胞、磁珠以及抗体孵育后形成的混合液)流入空的液袋50中。也即,样本容器中盛放的是由细胞、磁珠以及抗体孵育后形成的细胞液,细胞液中包含免疫磁珠细胞,其中免疫磁珠 细胞是本申请的磁珠分选方法最终需要进行收集的目标对象,而细胞液中除免疫磁珠细胞之外的其他物质均需要排除到废液袋50中。
S20:根据预设摆动参数控制所述磁性平台10摆动,以令被所述磁性平台10吸附的免疫磁珠细胞均匀分布,同时令所述液袋50中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中;可理解地,由于在处理大容量的细胞液时,由于液袋50面积过大,液体在液袋50中流动时经过各区域的流速并不一致,进而导致液袋50各区域的磁化也不一致,因此,在流速低的区域,被吸附的免疫磁珠细胞将会大量堆积(在流速低的区域附近),并且,除被吸附的免疫磁珠细胞之外的其他物质,亦会有一部分黏附在已被吸附的免疫磁珠细胞上,如此,堆积免疫磁珠细胞(以及被黏附的其他物质)的区域(由于磁性平台10与液体中仍然未被吸附的免疫磁珠细胞中间堆积了很多其他免疫磁珠细胞以及被黏附的其他物质,会导致可吸附距离变大且磁吸附力变弱)将很难再对液体中依旧未被吸附的免疫磁珠细胞进行吸附,如此,会导致免疫磁珠细胞的流失,磁场利用率低;在该实施例中,需要避免让免疫磁珠细胞以及黏附的其他物质堆积在一起,从而避免造成免疫磁珠细胞未被磁性平台10吸住导致其流失,同时,磁性平台10的磁力也不能太强(磁力太强会杀死细胞,因此不能通过增加磁力来解决上述免疫磁珠细胞流失的问题),因此,需要设置合适的预设摆动参数,进而柔和摆动并摇匀液袋50中的液体,使得堆积的免疫磁珠细胞不再堆积而是均匀分布,并且令所述液袋50中除被吸附的免疫磁珠细胞之外的其他物质不再被黏附而是悬浮在液体中(易于在执行排废液操作时被排出,且不会阻挡仍然未被吸附的免疫磁珠细胞被磁性平台吸附);同时,也避免摇晃过度(在过度摇晃时,由于磁力较弱,会造成大量已被吸附的免疫磁珠细胞与磁性平台10脱离,进而使得部分免疫磁珠细胞不能被重新吸附而导致流失,甚至可能因为力度过大的摇晃而杀死免疫磁珠细胞),因此,本申请中对于摇匀的预设摆动参数中的角速度和角度等都需进行精细化的控制。具体地,首先需要获取预设摆动参数,预设摆动参数可以为磁性平台10的摆动角速度、摆动角度、摆动时间、角加速度和摆动完后停留的角度等。具体地,磁性平台10的摆动角度的范围为±35度以内均可(也即磁性平台106向相对两侧摆动,且其朝向其中一侧摆动的角度为0-35度范围内,超过35度会杀死免疫磁珠细胞),优选为±25度。
S30:执行排废液操作,以令所述液袋50中除被吸附的免疫磁珠细胞之外的液体流入废液袋50;在该步骤中,为了顺利分离并收集免疫磁珠细胞,可以通过开启排废液管路,将液袋50中除免疫磁珠细胞之外的其他物质通过排废液管路排除到废液袋50中。
S40:对所述液袋50中剩余的免疫磁珠细胞执行清洗操作;在该步骤中,由于液袋50中剩余的免疫磁珠细胞上可能还粘附有一些其他物质,因此,为了使得收集的免疫磁珠细胞相对纯净,可以通过开启清洗管路,对粘附的其他物质进行清洗操作,以使得仅有免疫磁珠细胞由于被磁性平台10吸附而被保留在液袋50中。
S50:向所述液袋50中注入重悬液并取出包含免疫磁珠细胞的所述液袋50之后,确定磁珠分选完成。也即,将重悬液注入液袋50中,是为了使得免疫磁珠细胞浮起而便于在对其进行培育之前避免其死亡。可理解地,上述重悬液亦可以替换为培养基等可以使得免疫磁珠细胞保持活性的液体均可。
本申请可以根据预设摆动参数控制磁性平台10摆动,进而实现将大容量或大通量的液袋50中的液体(比如细胞液)摇匀,使得免疫磁珠细胞在液袋50底面均匀分布而不在局部位置(比如流速低的区域附近)堆积,从而使得磁性平台10可以对摇匀之后的液袋50中未堆积的免疫磁珠细胞近距离贴合,以实现磁性平台10对免疫磁珠细胞的充分吸附,避免免疫磁珠细胞的流失;同时,还可以令所述液袋50中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中(比如,将黏附在已被吸附的免疫磁珠细胞上的其他物质摇晃到与免疫磁珠细胞脱离,进而使其悬浮在液体中,以便于在执行排废液操作时将其排出,同时不会阻挡仍然未被吸附的免疫磁珠细胞被磁性平台10吸附)。进而,最终通过排废液操作和清洗操作实现从液袋50中将除免疫磁珠细胞之外的其他物质进行分离,以最终收集得到免疫磁珠细胞。本申请提升了磁场利用率,实现了通过磁珠分选方式高效稳定地分离和收集免疫磁珠细胞。本申请可以直接对大容量的免疫磁珠细胞进行磁珠分选,实现短时间内的大容量磁珠分选过程,并且能够不损伤细胞活率,且该过程中也无需人工操作,提高了大容量磁珠分选的效率。
在一实施例中,所述步骤S10,也即所述将空的液袋50放置在磁性平台10上,并将包含免疫磁 珠细胞的液体输入至所述液袋50中,通过所述磁性平台10吸附所述液袋50液体中的免疫磁珠细胞,包括:
将空的所述液袋50放置在压合装置1的所述磁性平台10上;如图5所示,所述压合装置1包括安装在所述磁性平台10上的盖合机构30以及与所述盖合机构30连接的压合机构40;所述盖合机构30盖合时,所述液袋50位于所述盖合机构30与所述磁性平台10之间的容纳空间中;盖合机构30安装在磁性平台10上,盖合机构30可以盖合或者打开上述容纳空间(容纳空间中放置的液袋50膨胀而导致凸出高度较高时,盖合机构30可能因为被液袋50顶起而无法盖合,强行盖合可能会压破液袋50或伤害其中的免疫磁珠细胞或无核免疫细胞),且在不受到其他外力干涉时,盖合机构30可以随着压合机构40的下拉而下移,进而使得磁性平台10与所述盖合机构30之间用于放置液袋50的容纳空间的大小可调。
将包含免疫磁珠细胞的液体输入至所述液袋50中;上述过程中,可以通过在液袋50和样本容器之间设置流量控制组件(图未示),并在将流量控制组件开启之后,将包含免疫磁珠细胞的液体自动输入至所述液袋50中;亦可以通过将样本容器放在较高位置并挤压样本容器将包含免疫磁珠细胞的液体输入至所述液袋50中。其中,流量控制组件可以包括可以为液体流动提供动力的蠕动泵,以及作为流量控制组件开关的夹管阀,也可以包括流量调节阀等控制液体流动流量,或用于监测液体流动的流速和压力的传感器等。
在所述盖合机构30盖合后,控制所述压合机构40带动已盖合的所述盖合机构30下移,以压平放置在所述磁性平台10与所述盖合机构30之间的容纳空间内的所述液袋50,增大所述液袋50的底面与所述磁性平台10之间的接触面,进而通过所述磁性平台10将所述液袋50中的免疫磁珠细胞吸附在所述接触面上。可理解地,在盖合机构30盖合之后,可以通过压合机构40带动已盖合的盖合机构30下移并均匀压平液袋50,以使得液袋50与磁性平台10之间贴合所形成的接触面增大,进而让液袋50中的液体均匀地通过该接触面分布在磁性平台10上与其接触。本实施例中通过对液袋50执行压平操作,增大了液袋50的底面与所述磁性平台10之间的接触面,进而,磁性平台10可以通过增大的接触面更为充分地吸附液袋50中的免疫磁珠细胞,避免了免疫磁珠细胞的逃逸,进一步提升了磁场利用率,在操作简便的前提下实现了高效稳定地捕获免疫磁珠细胞。
在一实施例中,所述压合装置1还包括与所述盖合机构30连接的顶升机构20;进一步地,所述步骤S10中,所述将包含免疫磁珠细胞的液体输入至所述液袋50中之后,还包括:
在所述盖合机构30被鼓胀的所述液袋50顶起而无法盖合时,控制所述顶升机构20带动所述盖合机构30上升,以增大所述磁性平台10与所述盖合机构30之间用于放置所述液袋50的容纳空间;在该实施例中,在容纳空间中放置有液袋50之后,由于液袋50中液体膨胀的高度较高,盖合机构30被放置在容纳空间中的液袋50顶开,导致盖合机构30无法盖合时,此时将控制顶升机构20开启并带动盖合机构30上升,如此,磁性平台10与盖合机构30之间的距离将会增大,进而,容纳空间随着距离的增大而增大。
在所述盖合机构30上升到可盖合的预设高度之后,控制所述盖合机构30盖合;也即,当盖合机构30上升到预设高度之后,盖合机构30和磁性平台10之间的容纳空间已经足够大,盖合机构30将不再被液袋50顶起,而是可以正常盖合。
控制所述压合机构40带动已盖合的所述盖合机构30下移,以压平放置在所述容纳空间中的所述液袋50,增大所述液袋50的底面与所述磁性平台10之间的接触面,进而通过所述磁性平台10将所述液袋50中的免疫磁珠细胞吸附在所述接触面上。也即,在盖合机构30盖合之后,可以通过压合机构40带动已盖合的盖合机构30下移并均匀压平液袋50,以使得液袋50与磁性平台10之间贴合所形成的接触面增大,进而让液袋50中的液体均匀地通过该接触面分布在磁性平台10上与其接触。
在一实施例中,如图5和图6所示,所述磁性平台10上设有顶升通孔1011,所述顶升机构20包括设置在所述磁性平台10顶部的升降组件201、顶端穿过所述顶升通孔1011与所述升降组件201固定连接的顶升杆202,以及设置在所述磁性平台10的下方并连接所述顶升杆202远离升降组件201一端的上升驱动组件203;所述盖合机构30包括转动连接在所述升降组件201上的盖板301;其中,盖板 301的形状可以根据磁性平台10的具体形状进行设置即可。升降组件201的形状可以根据需求设定,比如,升降组件201可以为放置在磁性平台10顶部的一个框架结构(或为分离设置的多个组件组成亦可,但可以随着顶升杆202的带动同时上下移动),可以被上升驱动组件203带动在上下方向上移动。在一实施例中,所述升降组件201包括设置在所述磁性平台10第一端的第一升降块2011、间隔分布在所述磁性平台10上远离所述第一端的第二端的两个第二升降块2012、连接在所述第一升降块2011与所述第二升降块2012之间的限位板2013,以及连接在两个所述第二升降块2012之间的转动轴2014;所述盖板301转动连接在所述转动轴2014上。具体地,限位板2013为平行设置在磁性平台10相对两侧的两块,如此,第一升降块2011、两个第二升降块2012以及两块限位板2013之间围成了一个限位框,用于防止液袋50从容纳空间的侧面脱出,该限位框(也即是升降组件201的主要组成部分)可以实现和盖板301同步上下升降。
进一步地,所述控制所述顶升机构20带动所述盖合机构30上升,以增大所述磁性平台10与所述盖合机构30之间用于放置所述液袋50的容纳空间,包括:控制所述上升驱动组件203启动,以通过所述上升驱动组件203驱动所述顶升杆202带动所述升降组件201以及所述盖板301沿所述顶升通孔1011滑动上升,以增大所述磁性平台10与所述盖板301之间用于放置液袋50的容纳空间。也即,盖合机构30转动安装在升降组件201上,将会随着升降组件201的上下移动而移动,而上升驱动组件203可以通过顶升杆202反带动升降组件201沿顶升通孔1011上移,如此,可以带动盖板301上移,进而使得磁性平台10与所述盖板301之间用于放置液袋50的容纳空间增大,进而方便盖合盖板301。
进一步地,如图5和图6所示,所述盖合机构30还包括设置在所述盖板301上的第一吸附部302,以及设置在所述升降组件201上与所述第一吸附部302相对位置的第二吸附部303,所述盖板301通过所述第一吸附部302和所述第二吸附部303的吸附与所述升降组件201盖合。其中,第一吸附部302和第二吸附部303中的至少一个为磁铁,比如,可以均为磁铁,或者一个为磁铁,另一个为具有与磁铁吸附特性的金属亦可。上述第一吸附部302和第二吸附部303的数量组合以及具体形状和大小可以根据需求进行设定,在此并不做限定,且本申请中的磁铁亦可以是指电磁铁。在一具体的实施例中,第二吸附部303为电磁铁,第一吸附部302为铁块,此时,对第二吸附部303的电磁铁进行通电,就可以去除电磁铁的磁性,此时,第二吸附部303的电磁铁与盖板301上的第一吸附部302(铁块)并不具有磁性吸附功能而处于与分离状态,如此,盖板301可以打开;而在第二吸附部303断电之后,作为第二吸附部303的电磁铁产生磁性,此时,在没有外力阻挡的情况下,盖板301上的铁块处于该电磁铁的磁性吸引范围内时,盖板301的第一吸附部302将被第二吸附部303吸附,从而完成盖板301的盖合。
在一实施例中,如图5和图6所示,所述上升驱动组件203包括第二电机2031、第二主动轮2032、第二从动轮2033、第二同步带2034、第二转轴2035、凸轮2036、安装轴承2037和具有第二安装孔2039的凸轮支架2038;所述凸轮支架2038安装在所述磁性平台10的底部,所述第二转轴2035通过所述安装轴承2037安装在所述第二安装孔2039中,所述凸轮2036固定安装在所述第二转轴2035上,所述第二主动轮2032安装在所述第二电机2031的输出轴上,所述第二同步带2034套接在所述第二主动轮2032与所述第二从动轮2033上,所述第二从动轮2033固定安装在所述第二转轴2035上,所述凸轮2036的顶端与所述顶升杆202抵接;如图5所示,第二电机2031可以通过固定块固定在磁性平台10上;第二转轴2035上的凸轮2036、凸轮支架2038、和安装轴承2037均对称设置为两个,顶升杆202也平行设置为两个,且两个顶升杆202的顶端均连接在升降组件201上;而两个凸轮2036分别与两个顶升杆202的底端抵接。
进一步地,所述通过所述上升驱动组件203驱动所述顶升杆202带动所述升降组件201以及所述盖板301沿所述顶升通孔1011滑动上升,包括:控制所述第二电机2031启动,所述第二电机2031顺次通过所述第二主动轮2032、所述第二同步带2034、所述第二从动轮2033、所述第二转轴2035带动所述凸轮2036转动,转动的所述凸轮2036通过所述顶升杆202带动所述升降组件201以及所述盖板301沿所述顶升通孔1011滑动上升。也即,第二电机2031启动旋转之后,将带动第二主动轮2032旋转,进而通过第二同步带2034来带动第二从动轮2033转动,而第二从动轮2033的转动将带动第二转轴2035以及安装在第二转轴2035上的两个凸轮2036转动,此时,被凸轮2036抵接的顶升杆202将随 着凸轮2036的转动而上移,进而带动升降组件201和盖板301整体抬升,此时,若如上述实施例中所述,第二吸附部303为电磁铁,则将对第二吸附部303的电磁铁进行断电处理,如此,在升降组件201上升的过程中,盖板301也会随之上升,逐渐平齐,直至第一吸附部302的铁块与第二吸附部303的电磁铁吸上,确认盖板301盖合。
进一步地,如图5所示,所述上升驱动组件203还包括安装在所述第二转轴2035上的感应块2042以及安装在所述磁性平台10上的光电传感器2043,所述光电传感器2043用于在感应到所述第二转轴2035带动所述感应块2042转动到正对所述光电传感器2043的位置时,确定所述盖板301上升到所述预设高度。其中,预设高度是指顶升杆202可以带动升降组件201和盖板301上升到的最高高度,该预设高度可以根据液袋50的具体尺寸进行设定,具体可以根据需求更换凸轮2036尺寸和形状等实现。
在一实施例中,如图5所示,所述上升驱动组件203还包括轴承随动器2040和固定板2041,所述轴承随动器2040通过所述固定板2041安装在所述顶升杆202的底端,所述凸轮2036与与所述轴承随动器2040抵接。也即,轴承随动器2040可以更好地将凸轮2036转动产生的顶升力传递给顶升杆202,进而使得顶升杆202的上升过程更为平稳可控。
在一实施例中,如图5和图6所示,所述磁性平台10上设有导向通孔1012,所述压合机构40包括导向轴401、弹簧402以及安装在所述导向通孔1012中的直线轴承403,所述导向轴401的底端设有挡块4011,所述导向轴401的顶端穿过所述直线轴承403连接所述升降组件201,所述弹簧402套接在所述导向轴401上,且所述弹簧402的两端分别与所述直线轴承403以及所述挡块4011抵接;进一步地,所述控制所述压合机构40带动已盖合的所述盖合机构30下移,包括:控制所述上升驱动组件203关闭,以通过所述弹簧402的弹力带动所述导向轴401沿所述导向通孔1012下移,进而带动所述升降组件201和所述盖板301下移。也即,在该实施例中,由于具有凸轮2036的上升驱动组件203仅能带动顶升杆202上升,而不具备对升降组件201下拉的下拉力。因此,设置上述压合机构40,弹簧402处于压缩状态,在上升驱动组件203的第二电机2031关闭(第二电机2031复位)之后,弹簧402为克服其压缩状态将通过导向轴401给升降组件201施加下拉力(弹簧402带动导向轴401沿导向通孔1012下移),进而带动升降组件201和盖板301下移。可理解地,将一个导向轴401、一个弹簧402以及一个直线轴承403作为一组压合组件,则上述压合机构40可以包含设置在磁性平台10上的多个压合组件,比如分别设置在方形的磁性平台10四角的四组压合组件,如此,在四组压合组件的四个弹簧402同时对升降组件201施加下拉力作用下,盖板301将会随着升降组件201下移进而朝向磁性平台10的方向挤压液袋50,进而逐渐压平液袋50使其中的液体均匀分布在磁性平台10上。在本申请中,通过弹簧402下拉压平液袋50而不是第二电机2031等,一方面通过弹簧402即可以让液袋50均匀压平贴合至磁性平台10,另一方面,弹簧402的弹力均匀轻柔,不会挤压坏液袋50内的细胞。
在一实施例中,如图2所示,所述步骤S20中,所述根据预设摆动参数控制所述磁性平台10摆动,包括:
S201,获取预设混匀参数;所述预设混匀参数包括混匀角度和混匀时长;其中,所示混匀角度为±35度,也即,(也即也即磁性平台106向相对两侧摆动,且其朝向其中一侧摆动的角度为0-35度范围内,超过35度会杀死免疫磁珠细胞,因此混匀角度的绝对值的最大值为35度),优选为±25度;而所述混匀时长可以为25S-35S,优选为30S。
S202,令混匀装置2控制所述磁性平台10以所述混匀角度持续摆动所述混匀时长,以使得免疫磁珠细胞被均匀吸附在所述磁性平台10上,且带动所述液袋50中除被吸附的免疫磁珠细胞之外的其他物质随所述磁性平台10的摆动悬浮在液体中。可理解地,在一具体实施例中,如图3、图4和图5所示,所述混匀装置2包括第一电机21、减速机22、第一主动轮23、第一从动轮24、第一同步带25以及同步支架27;所述减速机22连接第一电机21的输出轴以在降低所述第一电机21转速的同时增大输出转矩,所述第一主动轮23连接所述减速机22的转动轴2014,所述第一同步带25套接在所述第一主动轮23和所述第一从动轮24上,所述第一从动轮24安装在所述磁性平台10上;所述磁性平台10转动安装在所述同步支架27上;所述第一主动轮23用于在所述减速机22的驱动下通过所述第一同步带25带动所述第一从动轮24转动,进而使得所述磁性平台10绕所述同步支架27的支点摆动以混匀其装 载的所述液袋50中的液体。具体地,第一电机21可以为步进电机,由于第一电机21输出的转矩可能较小而不能带动磁性平台10摇晃,因此,本申请通过减速机22对第一电机21转速进行降低,进而加大增大输出转矩,最终实现通过第一主动轮23、第一同步带25以及第一从动轮24的联动带动磁性平台10摆动一定角度,进而通过磁性平台10的摆动带动磁性平台10上装载的液袋50中的液体混匀,进而实现使得免疫磁珠细胞被均匀吸附在所述磁性平台10上,且带动所述液袋50中除被吸附的免疫磁珠细胞之外的其他物质随所述磁性平台10的摆动悬浮在液体中。
在一实施例中,如图3至图5所示,所述混匀装置2还包括轴承26,所述同步支架27上设有第一安装孔271,所述磁性平台10包括第一转轴103,所述第一转轴103通过所述轴承26转动安装在所述第一安装孔271中;所述第一从动轮24安装在所述第一转轴103上。也即,在第一电机21通过减速机222、第一主动轮23、第一同步带25以及第一从动轮24的联动带动磁性平台10摆动时,磁性平台10摆动的支点为同步支架27上的轴承26,也即,轴承26的外圈固定在第一安装孔271内,轴承26的内圈固定在第一转轴103上,随着磁性平台10的摆动,第一转轴103转动,进而带动轴承26的内圈相对于其外圈转动。可理解地,通过控制第一电机21的转动方向不同,可以控制磁性平台10以轴承26为支点向相反方向摆动;通过控制第一电机21的转速,可以控制磁性平台10的摆动角度;进一步地,在磁性平台10摆动完成摇匀之后,控制磁性平台10摆动并停留在一个预设倾斜角度,如此,便于液袋50中的液体在进行磁珠分选完毕之后从出液口流出。
进一步地,所述步骤S202中,所述令混匀装置2控制所述磁性平台10以所述混匀角度持续摆动,包括:
根据所述混匀角度确定所述第一电机21的运行参数;也即,若确定了磁性平台10所需的混匀角度,此时即可根据此前的历史实验数据(历史实验数据中包含了第一电机21历史运行参数和历史混匀角度之间的关联关系)以及上述混匀角度确定所述第一电机21实时的运行参数,具体地,首先根据上述混匀角度在历史实验数据中确定与其匹配的历史混匀角度,进而将与被确定的该历史混匀角度关联的第一电机21历史运行参数确定为第一电机21将要实时运行的运行参数即可。
令所述第一电机21启动并以所述运行参数驱动所述减速机22带动所述第一主动轮23转动,所述第一主动轮23通过所述第一同步带25带动所述第一从动轮24转动,进而带动所述磁性平台绕与所述同步支架27的连接点摆动。在本申请中,首先通过第一电机21带动减速机22,进而带动第一主动轮23、第一同步带25和第一从动轮24一起转动,进而使得磁性平台10以轴承26为支点绕第一转轴103摆动,且其摆动的摆动角速度、摆动角度、角加速度与上述摆动参数中的各参数一一对应匹配。进一步地,如图5所示,所述混匀装置2还包括安装在所述磁性平台10上的双轴倾角传感器28,所述双轴倾角传感器28用于检测所述磁性平台10的摆动参数。其中,双轴倾角传感器28可以在混匀装置2的整个摆动摇匀过程中检测摆动角度、摆动角速度、角加速度和摆动完后停留的角度等。
进一步地,所述步骤S202中令混匀装置2控制所述磁性平台10以所述混匀角度持续摆动混匀时长之后,且在所述步骤S30中执行排废液操作之前,还包括:
令所述磁性平台10水平放置预设时长;预设时长可以根据需求设定为5-20分钟,优选为10分钟。
获取第一轻柔摆动参数,所述第一轻柔摆动参数包括第一轻柔摆动角度和第一轻柔摆动时长;所述第一轻柔摆动角度的绝对值小于所述混匀角度的绝对值;第一轻柔摆动角度的绝对值小于混匀角度的绝对值,比如,在混匀角度为±25度时,第一轻柔摆动角度为正负20度。
令所述混匀装置2控制所述磁性平台10以所述第一轻柔摆动角度持续轻柔摆动第一轻柔摆动时长,以令所述液袋50中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中。在本申请中,磁性平台10以混匀角度摇晃时,可以使得堆积的免疫磁珠细胞摊平变得更为均匀,同时令所述液袋50中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中;而在本实施例中以第一轻柔摆动角度摇晃时,摇晃力度较为轻柔,不会晃动已被磁性平台10吸附的免疫磁珠细胞,而只是是会将黏附在已被吸附的免疫磁珠细胞上的其他物质摇晃到与免疫磁珠细胞脱离,进而使其悬浮在液体中,以便于在步骤S30中执行排废液操作时将其排出。
进一步地,所述步骤S30中,所述执行排废液操作,包括:
控制所述磁性平台10停留在第一预设停留角度,以使得所述液袋50自进液口朝向出液口向下倾斜;在该实施例中,在根据预设摆动参数控制所述磁性平台10摆动并摇匀液袋50中液体之后,第一预设停留角度是指可以使得停留不动的磁性平台10上的液袋50的出液口的高度低于进液口高度的角度,以便于让液袋50中的液体从出液口流出;具体地,所述磁性平台10停留在所述第一预设停留角度时,磁性平台10与水平面之间的夹角即为第一预设停留角度,所述第一预设停留角度可以为10-30度,优选为20度。
执行第一开关操作,以开启排废液管路;其中,所述排废液管路包括连通在废液袋50与所述液袋50的出液口之间的泵以及气泡传感器;也即,第一开关操作是指,将排废液管路中,废液袋50、泵、气泡传感器以及液袋50这一条线路上关闭的阀均打开,同时开启泵(所述泵优选为蠕动泵)以及气泡传感器,此时认为排废液管路开启。
通过所述排废液管路将所述液袋50中除被吸附的免疫磁珠细胞之外的液体排入所述废液袋50;具体地,排废液通道中的泵将液袋50中除被吸附的免疫磁珠细胞之外的的液体抽取到废液袋50中,且气泡传感器对排废液管路的液体中的气泡进行检测,进而根据检测结果确定排废液管路中是否还有液体流过。
在通过所述气泡传感器确定所述排废液管路中无液体通过时,确认排废液完成。也即,在确定排废液管路中无液体通过时,说明液袋50中的液体已经流尽,因此可以认为排废液流程完成。
进一步地,所述步骤S40中,所述对所述液袋50中剩余的免疫磁珠细胞执行清洗操作,包括:
控制所述磁性平台10停留在第二预设停留角度,以使得所述液袋50自进液口朝向出液口向上倾斜;所述第二预设停留角度以及所述第一预设停留角度的方向相反;在该实施例中,第二预设停留角度是指可以使得停留不动的磁性平台10上的液袋50的出液口的高度高于进液口高度的角度,以便于后续清洗液入口的清洗液从进液口流入液袋50之后,停留在进液口附近,进而便于清洗液从进液口开始渗透到液袋50中的各个角落;具体地,所述磁性平台10停留在所述第二预设停留角度时,磁性平台10与水平面之间的夹角即为第二预设停留角度,所述第二预设停留角度可以为10-30度,优选为15-20度。
执行第二开关操作,以开启清洗管路;所述第二开关操作包括关闭所述泵以及所述气泡传感器与所述废液袋50之间的通路,并将所述泵以及所述气泡传感器连通在所述清洗液入口与所述液袋50的进液口之间;也即,第二开关操作是指,将排废液管路中所述泵以及所述气泡传感器与所述废液袋50之间的阀关闭,以使得泵以及气泡传感器均不会与废液袋50连通,同时也关闭泵以及气泡传感器,也即关闭了排废液管路;此时,再将清洗液入口、泵、气泡传感器以及液袋50这一条线路上关闭的阀均打开,再开启泵(所述泵优选为蠕动泵)以及气泡传感器,此时认为清洗管路开启。
通过所述清洗管路将第一预设容量的清洗液输入所述液袋50;所述第一预设容量可以为50-300ml,优选为100ml。
获取第二轻柔摆动参数,所述第二轻柔摆动参数包括第二轻柔摆动角度和第二轻柔摆动时长;其中,第二轻柔摆动角度的绝对值小于混匀角度的绝对值,比如,在混匀角度为±25度时,第二轻柔摆动角度为正负20度。
令所述混匀装置2控制所述磁性平台10以所述第二轻柔摆动角度持续轻柔摆动第二轻柔摆动时长之后,再次执行所述排废液操作。在本申请中,磁性平台10以混匀角度摇晃时,可以使得堆积的免疫磁珠细胞摊平变得更为均匀,而在本实施例中以第二轻柔摆动角度摇晃时,摇晃力度较为轻柔,不会晃动已被磁性平台10吸附的免疫磁珠细胞,而是会将黏附在已被吸附的免疫磁珠细胞上的其他物质摇晃到与免疫磁珠细胞脱离,进而使其悬浮到清洗液中,以便于再次执行排废液操作时将其排出。通过上述清洗操作,可以进一步保证最终得到的液袋50中被吸附的免疫磁珠细胞的纯净度。可理解地,再次执行排废液操作的步骤可参照上述实施例中对于排废液操作的具体说明,在此不再赘述。不同的是,再次执行排废液操作时,其中的第一开关操作中首先要将清洗管路中,所述泵以及所述气泡传感器与所述清洗液入口之间的阀关闭,以使得泵以及气泡传感器均不会与清洗液入口连通,同时也关闭泵以及气泡 传感器,也即关闭了清洗管路;此时,再将废液袋50、泵、气泡传感器以及液袋50这一条线路上关闭的阀均打开,同时开启泵(所述泵优选为蠕动泵)以及气泡传感器,此时认为排废液管路再次开启。
进一步地,所述步骤S50中,所述向所述液袋50中注入重悬液并取出包含免疫磁珠细胞的所述液袋50,包括:
将所述磁性平台10调整至与水平面平行;也即,再次执行排废液操作之后,首先将磁性平台10复位到水平,以便进行后续操作。
执行第三开关操作,以开启重悬液输入管路;所述第三开关操作包括关闭所述泵以及所述气泡传感器与所述废液袋50之间的通路,并将所述泵以及所述气泡传感器连通在所述重悬液入口与所述液袋50的进液口之间;也即,第三开关操作是指,将排废液管路中所述泵以及所述气泡传感器与所述废液袋50之间的阀关闭,以使得泵以及气泡传感器均不会与废液袋50连通,同时也关闭泵以及气泡传感器,也即关闭了排废液管路;此时,再将重悬液入口、泵、气泡传感器以及液袋50这一条线路上关闭的阀均打开,再开启泵(所述泵优选为蠕动泵)以及气泡传感器,此时认为重悬液输入管路开启。
通过所述重悬液输入管路将第二预设容量的重悬液输入所述液袋50;可理解地,第二预设容量可以根据需求设定,比如为0-300ml。
执行第四开关操作;所述第四开关操作包括关闭所述泵以及所述气泡传感器与所述重悬液入口之间的通路,并控制所述泵以及所述气泡传感器通过无菌空气过滤器与大气连通;也即,第四开关操作是指,将重悬液输入管路中所述泵以及所述气泡传感器与所述重悬液入口之间的阀关闭,以使得泵以及气泡传感器均不会与重悬液入口连通;此时,再将无菌空气过滤器、泵、气泡传感器以及液袋50这一条线路上关闭的阀均打开,此时认为重悬液输入管路开启;进而,液袋50可以通过泵、气泡传感器以及无菌空气过滤器与大气连通,此时,在大气压力下,残留在管路中的重悬液能够在泵的作用下排空并进入到液袋50中,不浪费管路中的重悬液,重悬液价格高,本实施例中的上述操作将会大大降低磁珠分选过程的成本。
在通过所述气泡传感器确定无液体通过时,确定重悬液完全注入所述液袋;可理解地,在气泡传感器对管路中的气泡进行检测,进而根据检测结果确定管路中不再有液体流过时,可以认为重悬液已经完全注入液袋50中。
对所述液袋50的出液口和进液口进行热合密封处理之后,从所述磁性平台10上取出包含免疫磁珠细胞的所述液袋50。也即,在该实施例中,排空管路完后,对液袋50的出液口和进液口均进行热合密封处理,也即运用热合仪在出液口和进液口进行热合密封,之后,从磁性平台10上取出液袋50,进而完成磁珠分选过程,液袋50中的重悬液中的免疫磁珠细胞即为收集的目标对象,此时已经完成收集,可以进行后续的培育处理。
进一步地,所述通过所述重悬液输入管路将第二预设容量的重悬液输入所述液袋50,包括:
通过所述重悬液输入管路向所述液袋50中注入重悬液;也即,在该实施例中,开启重悬液输入管路之后,即可通过该开启的重悬液输入管路向液袋50中注入重悬液。
通过称重传感器获取所述液袋50的重量变化信息,并根据所述液袋50的重量变化信息确定注入的重悬液的实际容量;或获取与所述泵对应的体积-转圈数数据,根据所述泵的实际转动圈数以及所述体积-转圈数数据确定注入的重悬液的实际容量;也即,在该实施例中,可以通过液袋50的重量变化信息确定液袋50的当前重量与原始重量之差值,进而根据该差值以及重悬液的密度,确定注入的重悬液的实际容量;而在另一实施例中,还可以根据历史数据,也即泵在历史试验中得到的泵每转一圈对应输入至液袋50中的重悬液的体积,也即体积-转圈数数据,进而,在获取泵转动的实际转动圈数之后,即可确定注入的重悬液的实际容量。
在所述实际容量达到所述第二预设容量时,确认已将所述第二预设容量的重悬液输入所述液袋50。也即,由于仅需要注入第二预设容量的重悬液,因此,在根据上述方法确定已经注入第二预设容量的重悬液之后,即可确认已将所述第二预设容量的重悬液输入所述液袋50,进而执行后续的第四开关操作等步骤。可理解地,由于上述第四开关操作对应的步骤中可以将重悬液输入管路中残留的重悬液排空进入管路中,且该部分重悬液在执行第四开关操作之前将不会计入实际容量中,因此,可以将第二预 设容量设置为略小于液袋50中最终实际需要注入的重悬液的容量(两者之间的差值可以为一个试验得到的常数值),如此,将第二预容量加上从管道中排空进入液袋50中的重悬液即可实际注入最终所需的重悬液的容量。
应理解,上述实施例中各步骤的序号的大小并不意味着执行顺序的先后,各过程的执行顺序应以其功能和内在逻辑确定,而不应对本申请实施例的实施过程构成任何限定。
本申请还提供一种磁珠分选设备,包括压合装置1、混匀装置2以及用于执行上述磁珠分选方法的控制器,所述控制器连接所述压合装置1以及所述混匀装置2。
具体地,所述控制器用于执行以下步骤:
将空的液袋放置在磁性平台上,将包含免疫磁珠细胞的液体输入至所述液袋中,通过所述磁性平台吸附所述液袋液体中的免疫磁珠细胞;
根据预设摆动参数控制所述磁性平台摆动,以令被所述磁性平台吸附的免疫磁珠细胞均匀分布,同时令所述液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中;
执行排废液操作,以令所述液袋中除被吸附的免疫磁珠细胞之外的液体流入废液袋;
对所述液袋中剩余的免疫磁珠细胞执行清洗操作;
向所述液袋中注入重悬液并取出包含免疫磁珠细胞的所述液袋之后,确定磁珠分选完成。
在一实施例中,所述将空的液袋放置在磁性平台上,并将包含免疫磁珠细胞的液体输入至所述液袋中,通过所述磁性平台吸附所述液袋液体中的免疫磁珠细胞,包括:
将空的所述液袋放置在压合装置的所述磁性平台上;所述压合装置包括安装在所述磁性平台上的盖合机构以及与所述盖合机构连接的压合机构;
将包含免疫磁珠细胞的液体输入至所述液袋中;
在所述盖合机构盖合后,控制所述压合机构带动已盖合的所述盖合机构下移,以压平放置在所述磁性平台与所述盖合机构之间的容纳空间内的所述液袋,增大所述液袋的底面与所述磁性平台之间的接触面,进而通过所述磁性平台将所述液袋中的免疫磁珠细胞吸附在所述接触面上。
在一实施例中,所述压合装置还包括与所述盖合机构连接的顶升机构;进一步地,所述将包含免疫磁珠细胞的液体输入至所述液袋中之后,所述控制器还用于执行以下步骤:
在所述盖合机构被鼓胀的所述液袋顶起而无法盖合时,控制所述顶升机构带动所述盖合机构上升,以增大所述磁性平台与所述盖合机构之间用于放置所述液袋的容纳空间;
在所述盖合机构上升到可盖合的预设高度之后,控制所述盖合机构盖合;
控制所述压合机构带动已盖合的所述盖合机构下移,以压平放置在所述容纳空间中的所述液袋,增大所述液袋的底面与所述磁性平台之间的接触面,进而通过所述磁性平台将所述液袋中的免疫磁珠细胞吸附在所述接触面上。
在一实施例中,所述根据预设摆动参数控制所述磁性平台摆动,包括:
获取预设混匀参数;所述预设混匀参数包括混匀角度和混匀时长;
令混匀装置控制所述磁性平台以所述混匀角度持续摆动所述混匀时长,以使得免疫磁珠细胞被均匀吸附在所述磁性平台上,且带动所述液袋中除被吸附的免疫磁珠细胞之外的其他物质随所述磁性平台的摆动悬浮在液体中。
在一实施例中,所述令混匀装置控制所述磁性平台以所述混匀角度持续摆动混匀时长之后,所述执行排废液操作之前,所述控制器还用于执行以下步骤:
令所述磁性平台水平放置预设时长;
获取第一轻柔摆动参数,所述第一轻柔摆动参数包括第一轻柔摆动角度和第一轻柔摆动时长;所述第一轻柔摆动角度的绝对值小于所述混匀角度的绝对值;
令所述混匀装置控制所述磁性平台以所述第一轻柔摆动角度持续轻柔摆动第一轻柔摆动时长,以令所述液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中。
在一实施例中,所述混匀装置包括第一电机、减速机、第一主动轮、第一从动轮、第一同步带以及同步支架;所述减速机连接第一电机的输出轴以在降低所述第一电机转速的同时增大输出转矩,所述第 一主动轮连接所述减速机的转动轴,所述第一同步带套接在所述第一主动轮和所述第一从动轮上,所述第一从动轮安装在所述磁性平台上;所述磁性平台转动安装在所述同步支架上;
所述令混匀装置控制所述磁性平台以所述混匀角度持续摆动,包括:
根据所述混匀角度确定所述第一电机的运行参数;
令所述第一电机启动并以所述运行参数驱动所述减速机带动所述第一主动轮转动,所述第一主动轮通过所述第一同步带带动所述第一从动轮转动,进而带动所述磁性平台绕与所述同步支架的连接点摆动。
在一实施例中,所述执行排废液操作,包括:
控制所述磁性平台停留在第一预设停留角度,以使得所述液袋自进液口朝向出液口向下倾斜;
执行第一开关操作,以开启排废液管路;其中,所述排废液管路包括连通在废液袋与所述液袋的出液口之间的泵以及气泡传感器;
通过所述排废液管路将所述液袋中除被吸附的免疫磁珠细胞之外的液体排入所述废液袋;
在通过所述气泡传感器确定所述排废液管路中无液体通过时,确认排废液完成。
在一实施例中,所述对所述液袋中剩余的免疫磁珠细胞执行清洗操作,包括:
控制所述磁性平台停留在第二预设停留角度,以使得所述液袋自进液口朝向出液口向上倾斜;所述第二预设停留角度以及所述第一预设停留角度的方向相反;
执行第二开关操作,以开启清洗管路;所述第二开关操作包括关闭所述泵以及所述气泡传感器与所述废液袋之间的通路,并将所述泵以及所述气泡传感器连通在所述清洗液入口与所述液袋的进液口之间;
通过所述清洗管路将第一预设容量的清洗液输入所述液袋;
获取第二轻柔摆动参数,所述第二轻柔摆动参数包括第二轻柔摆动角度和第二轻柔摆动时长;
令混匀装置控制所述磁性平台以所述第二轻柔摆动角度持续轻柔摆动第二轻柔摆动时长之后,再次执行所述排废液操作。
在一实施例中,所述向所述液袋中注入重悬液并取出包含免疫磁珠细胞的所述液袋,包括:
将所述磁性平台调整至与水平面平行;
执行第三开关操作,以开启重悬液输入管路;所述第三开关操作包括关闭所述泵以及所述气泡传感器与所述废液袋之间的通路,并将所述泵以及所述气泡传感器连通在所述重悬液入口与所述液袋的进液口之间;
通过所述重悬液输入管路将第二预设容量的重悬液输入所述液袋;
执行第四开关操作;所述第四开关操作包括关闭所述泵以及所述气泡传感器与所述重悬液入口之间的通路,并控制所述泵以及所述气泡传感器通过无菌空气过滤器与大气连通;
在通过所述气泡传感器确定无液体通过时,确定重悬液完全注入所述液袋;
对所述液袋的出液口和进液口进行热合密封处理之后,从所述磁性平台上取出包含免疫磁珠细胞的所述液袋。
在一实施例中,所述通过所述重悬液输入管路将第二预设容量的重悬液输入所述液袋,包括:
通过所述重悬液输入管路向所述液袋中注入重悬液;
通过称重传感器获取所述液袋的重量变化信息,并根据所述液袋的重量变化信息确定注入的重悬液的实际容量;或获取与所述泵对应的体积-转圈数数据,根据所述泵的实际转动圈数以及所述体积-转圈数数据确定注入的重悬液的实际容量;
在所述实际容量达到所述第二预设容量时,确认已将所述第二预设容量的重悬液输入所述液袋。
关于磁珠分选设备以及控制器的更多具体限定可以参见上文中对于磁珠分选方法的限定,在此不再赘述。上述控制器中的各个模块可全部或部分通过软件、硬件及其组合来实现。上述各模块可以硬件形式内嵌于或独立于计算机设备中的处理器中,也可以以软件形式存储于计算机设备中的存储器中,以便于处理器调用执行以上各个模块对应的操作。可理解地,该控制器可以视为一个或多个计算机设备,如图7所示,该计算机设备包括通过系统总线连接的处理器、存储器、网络接口和数据库。其中,该计 算机设备的处理器用于提供计算和控制能力。该计算机设备的存储器包括可读存储介质、内存储器。该可读存储介质存储有操作系统、计算机可读指令和数据库。该内存储器为可读存储介质中的操作系统和计算机可读指令的运行提供环境。该计算机设备的数据库用于存储上述实施例中磁珠分选方法所使用到的数据。该计算机设备的网络接口用于与外部的终端通过网络连接通信。该计算机可读指令被处理器执行时以实现一种磁珠分选方法。本实施例所提供的可读存储介质包括非易失性可读存储介质和易失性可读存储介质。
在一个实施例中,提供了一个或多个存储有计算机可读指令的可读存储介质,本实施例所提供的可读存储介质包括非易失性可读存储介质和易失性可读存储介质;该可读存储介质上存储有计算机可读指令,该计算机可读指令被一个或多个处理器执行时,使得一个或多个处理器实现上述磁珠分选方法。
具体地,该计算机可读指令被一个或多个处理器执行时,使得一个或多个处理器实现以下步骤:
将空的液袋放置在磁性平台上,将包含免疫磁珠细胞的液体输入至所述液袋中,通过所述磁性平台吸附所述液袋液体中的免疫磁珠细胞;
根据预设摆动参数控制所述磁性平台摆动,以令被所述磁性平台吸附的免疫磁珠细胞均匀分布,同时令所述液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中;
执行排废液操作,以令所述液袋中除被吸附的免疫磁珠细胞之外的液体流入废液袋;
对所述液袋中剩余的免疫磁珠细胞执行清洗操作;
向所述液袋中注入重悬液并取出包含免疫磁珠细胞的所述液袋之后,确定磁珠分选完成。
在一实施例中,所述将空的液袋放置在磁性平台上,并将包含免疫磁珠细胞的液体输入至所述液袋中,通过所述磁性平台吸附所述液袋液体中的免疫磁珠细胞,包括:
将空的所述液袋放置在压合装置的所述磁性平台上;所述压合装置包括安装在所述磁性平台上的盖合机构以及与所述盖合机构连接的压合机构;
将包含免疫磁珠细胞的液体输入至所述液袋中;
在所述盖合机构盖合后,控制所述压合机构带动已盖合的所述盖合机构下移,以压平放置在所述磁性平台与所述盖合机构之间的容纳空间内的所述液袋,增大所述液袋的底面与所述磁性平台之间的接触面,进而通过所述磁性平台将所述液袋中的免疫磁珠细胞吸附在所述接触面上。
在一实施例中,所述压合装置还包括与所述盖合机构连接的顶升机构;进一步地,所述将包含免疫磁珠细胞的液体输入至所述液袋中之后,该计算机可读指令被一个或多个处理器执行时,使得一个或多个处理器还实现以下步骤:
在所述盖合机构被鼓胀的所述液袋顶起而无法盖合时,控制所述顶升机构带动所述盖合机构上升,以增大所述磁性平台与所述盖合机构之间用于放置所述液袋的容纳空间;
在所述盖合机构上升到可盖合的预设高度之后,控制所述盖合机构盖合;
控制所述压合机构带动已盖合的所述盖合机构下移,以压平放置在所述容纳空间中的所述液袋,增大所述液袋的底面与所述磁性平台之间的接触面,进而通过所述磁性平台将所述液袋中的免疫磁珠细胞吸附在所述接触面上。
在一实施例中,所述根据预设摆动参数控制所述磁性平台摆动,包括:
获取预设混匀参数;所述预设混匀参数包括混匀角度和混匀时长;
令混匀装置控制所述磁性平台以所述混匀角度持续摆动所述混匀时长,以使得免疫磁珠细胞被均匀吸附在所述磁性平台上,且带动所述液袋中除被吸附的免疫磁珠细胞之外的其他物质随所述磁性平台的摆动悬浮在液体中。
在一实施例中,所述令混匀装置控制所述磁性平台以所述混匀角度持续摆动混匀时长之后,所述执行排废液操作之前,该计算机可读指令被一个或多个处理器执行时,使得一个或多个处理器还实现以下步骤:
令所述磁性平台水平放置预设时长;
获取第一轻柔摆动参数,所述第一轻柔摆动参数包括第一轻柔摆动角度和第一轻柔摆动时长;所述第一轻柔摆动角度的绝对值小于所述混匀角度的绝对值;
令所述混匀装置控制所述磁性平台以所述第一轻柔摆动角度持续轻柔摆动第一轻柔摆动时长,以令所述液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中。
在一实施例中,所述混匀装置包括第一电机、减速机、第一主动轮、第一从动轮、第一同步带以及同步支架;所述减速机连接第一电机的输出轴以在降低所述第一电机转速的同时增大输出转矩,所述第一主动轮连接所述减速机的转动轴,所述第一同步带套接在所述第一主动轮和所述第一从动轮上,所述第一从动轮安装在所述磁性平台上;所述磁性平台转动安装在所述同步支架上;
所述令混匀装置控制所述磁性平台以所述混匀角度持续摆动,包括:
根据所述混匀角度确定所述第一电机的运行参数;
令所述第一电机启动并以所述运行参数驱动所述减速机带动所述第一主动轮转动,所述第一主动轮通过所述第一同步带带动所述第一从动轮转动,进而带动所述磁性平台绕与所述同步支架的连接点摆动。
在一实施例中,所述执行排废液操作,包括:
控制所述磁性平台停留在第一预设停留角度,以使得所述液袋自进液口朝向出液口向下倾斜;
执行第一开关操作,以开启排废液管路;其中,所述排废液管路包括连通在废液袋与所述液袋的出液口之间的泵以及气泡传感器;
通过所述排废液管路将所述液袋中除被吸附的免疫磁珠细胞之外的液体排入所述废液袋;
在通过所述气泡传感器确定所述排废液管路中无液体通过时,确认排废液完成。
在一实施例中,所述对所述液袋中剩余的免疫磁珠细胞执行清洗操作,包括:
控制所述磁性平台停留在第二预设停留角度,以使得所述液袋自进液口朝向出液口向上倾斜;所述第二预设停留角度以及所述第一预设停留角度的方向相反;
执行第二开关操作,以开启清洗管路;所述第二开关操作包括关闭所述泵以及所述气泡传感器与所述废液袋之间的通路,并将所述泵以及所述气泡传感器连通在所述清洗液入口与所述液袋的进液口之间;
通过所述清洗管路将第一预设容量的清洗液输入所述液袋;
获取第二轻柔摆动参数,所述第二轻柔摆动参数包括第二轻柔摆动角度和第二轻柔摆动时长;
令混匀装置控制所述磁性平台以所述第二轻柔摆动角度持续轻柔摆动第二轻柔摆动时长之后,再次执行所述排废液操作。
在一实施例中,所述向所述液袋中注入重悬液并取出包含免疫磁珠细胞的所述液袋,包括:
将所述磁性平台调整至与水平面平行;
执行第三开关操作,以开启重悬液输入管路;所述第三开关操作包括关闭所述泵以及所述气泡传感器与所述废液袋之间的通路,并将所述泵以及所述气泡传感器连通在所述重悬液入口与所述液袋的进液口之间;
通过所述重悬液输入管路将第二预设容量的重悬液输入所述液袋;
执行第四开关操作;所述第四开关操作包括关闭所述泵以及所述气泡传感器与所述重悬液入口之间的通路,并控制所述泵以及所述气泡传感器通过无菌空气过滤器与大气连通;
在通过所述气泡传感器确定无液体通过时,确定重悬液完全注入所述液袋;
对所述液袋的出液口和进液口进行热合密封处理之后,从所述磁性平台上取出包含免疫磁珠细胞的所述液袋。
在一实施例中,所述通过所述重悬液输入管路将第二预设容量的重悬液输入所述液袋,包括:
通过所述重悬液输入管路向所述液袋中注入重悬液;
通过称重传感器获取所述液袋的重量变化信息,并根据所述液袋的重量变化信息确定注入的重悬液的实际容量;或获取与所述泵对应的体积-转圈数数据,根据所述泵的实际转动圈数以及所述体积-转圈数数据确定注入的重悬液的实际容量;
在所述实际容量达到所述第二预设容量时,确认已将所述第二预设容量的重悬液输入所述液袋。
关于可读存储介质的具体限定可以参见上文中对于磁珠分选方法的限定,在此不再赘述。
本领域普通技术人员可以理解实现上述实施例方法中的全部或部分流程,是可以通过计算机可读指令来指令相关的硬件来完成,所述的计算机可读指令可存储于一非易失性可读取存储介质或易失性可读存储介质中,该计算机可读指令在执行时,可包括如上述各方法的实施例的流程。其中,本申请所提供的各实施例中所使用的对存储器、存储、数据库或其它介质的任何引用,均可包括非易失性和/或易失性存储器。非易失性存储器可包括只读存储器(ROM)、可编程ROM(PROM)、电可编程ROM(EPROM)、电可擦除可编程ROM(EEPROM)或闪存。易失性存储器可包括随机存取存储器(RAM)或者外部高速缓冲存储器。作为说明而非局限,RAM以多种形式可得,诸如静态RAM(SRAM)、动态RAM(DRAM)、同步DRAM(SDRAM)、双数据率SDRAM(DDRSDRAM)、增强型SDRAM(ESDRAM)、同步链路(Synchlink)DRAM(SLDRAM)、存储器总线(Rambus)直接RAM(RDRAM)、直接存储器总线动态RAM(DRDRAM)、以及存储器总线动态RAM(RDRAM)等。
所属领域的技术人员可以清楚地了解到,为了描述的方便和简洁,仅以上述各功能单元、模块的划分进行举例说明,实际应用中,可以根据需要而将上述功能分配由不同的功能单元、模块完成,即将所述装置的内部结构划分成不同的功能单元或模块,以完成以上描述的全部或者部分功能。
以上所述实施例仅用以说明本申请的技术方案,而非对其限制;尽管参照前述实施例对本申请进行了详细的说明,本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本申请各实施例技术方案的精神和范围,均应包含在本申请的保护范围之内。

Claims (12)

  1. 一种磁珠分选方法,其中,包括:
    将空的液袋放置在磁性平台上,将包含免疫磁珠细胞的液体输入至所述液袋中,通过所述磁性平台吸附所述液袋液体中的免疫磁珠细胞;
    根据预设摆动参数控制所述磁性平台摆动,以令被所述磁性平台吸附的免疫磁珠细胞均匀分布,同时令所述液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中;
    执行排废液操作,以令所述液袋中除被吸附的免疫磁珠细胞之外的液体流入废液袋;
    对所述液袋中剩余的免疫磁珠细胞执行清洗操作;
    向所述液袋中注入重悬液并取出包含免疫磁珠细胞的所述液袋之后,确定磁珠分选完成。
  2. 如权利要求1所述的磁珠分选方法,其中,所述将空的液袋放置在磁性平台上,并将包含免疫磁珠细胞的液体输入至所述液袋中,通过所述磁性平台吸附所述液袋液体中的免疫磁珠细胞,包括:
    将空的所述液袋放置在压合装置的所述磁性平台上;所述压合装置包括安装在所述磁性平台上的盖合机构以及与所述盖合机构连接的压合机构;
    将包含免疫磁珠细胞的液体输入至所述液袋中;
    在所述盖合机构盖合后,控制所述压合机构带动已盖合的所述盖合机构下移,以压平放置在所述磁性平台与所述盖合机构之间的容纳空间内的所述液袋,增大所述液袋的底面与所述磁性平台之间的接触面,进而通过所述磁性平台将所述液袋中的免疫磁珠细胞吸附在所述接触面上。
  3. 如权利要求2所述的磁珠分选方法,其中,所述压合装置还包括与所述盖合机构连接的顶升机构;
    所述将包含免疫磁珠细胞的液体输入至所述液袋中之后,还包括:
    在所述盖合机构被鼓胀的所述液袋顶起而无法盖合时,控制所述顶升机构带动所述盖合机构上升,以增大所述磁性平台与所述盖合机构之间用于放置所述液袋的容纳空间;
    在所述盖合机构上升到可盖合的预设高度之后,控制所述盖合机构盖合;
    控制所述压合机构带动已盖合的所述盖合机构下移,以压平放置在所述容纳空间中的所述液袋,增大所述液袋的底面与所述磁性平台之间的接触面,进而通过所述磁性平台将所述液袋中的免疫磁珠细胞吸附在所述接触面上。
  4. 如权利要求1所述的磁珠分选方法,其中,所述根据预设摆动参数控制所述磁性平台摆动,包括:
    获取预设混匀参数;所述预设混匀参数包括混匀角度和混匀时长;
    令混匀装置控制所述磁性平台以所述混匀角度持续摆动所述混匀时长,以使得免疫磁珠细胞被均匀吸附在所述磁性平台上,且带动所述液袋中除被吸附的免疫磁珠细胞之外的其他物质随所述磁性平台的摆动悬浮在液体中。
  5. 如权利要求4所述的磁珠分选方法,其中,所述令混匀装置控制所述磁性平台以所述混匀角度持续摆动混匀时长之后,所述执行排废液操作之前,还包括:
    令所述磁性平台水平放置预设时长;
    获取第一轻柔摆动参数,所述第一轻柔摆动参数包括第一轻柔摆动角度和第一轻柔摆动时长;所述第一轻柔摆动角度的绝对值小于所述混匀角度的绝对值;
    令所述混匀装置控制所述磁性平台以所述第一轻柔摆动角度持续轻柔摆动第一轻柔摆动时长,以令所述液袋中除被吸附的免疫磁珠细胞之外的其他物质悬浮在液体中。
  6. 如权利要求4所述的磁珠分选方法,其中,所述混匀装置包括第一电机、减速机、第一主动轮、第一从动轮、第一同步带以及同步支架;所述减速机连接第一电机的输出轴以在降低所述第一电机转速的同时增大输出转矩,所述第一主动轮连接所述减速机的转动轴,所述第一同步带套接在所述第一主动轮和所述第一从动轮上,所述第一从动轮安装在所述磁性平台上;所述磁性平台转动安装在所述同步支架上;
    所述令混匀装置控制所述磁性平台以所述混匀角度持续摆动,包括:
    根据所述混匀角度确定所述第一电机的运行参数;
    令所述第一电机启动并以所述运行参数驱动所述减速机带动所述第一主动轮转动,所述第一主动轮通过所述第一同步带带动所述第一从动轮转动,进而带动所述磁性平台绕与所述同步支架的连接点摆动。
  7. 如权利要求1所述的磁珠分选方法,其中,所述执行排废液操作,包括:
    控制所述磁性平台停留在第一预设停留角度,以使得所述液袋自进液口朝向出液口向下倾斜;
    执行第一开关操作,以开启排废液管路;其中,所述排废液管路包括连通在废液袋与所述液袋的出液口之间的泵以及气泡传感器;
    通过所述排废液管路将所述液袋中除被吸附的免疫磁珠细胞之外的液体排入所述废液袋;
    在通过所述气泡传感器确定所述排废液管路中无液体通过时,确认排废液完成。
  8. 如权利要求7所述的磁珠分选方法,其中,所述对所述液袋中剩余的免疫磁珠细胞执行清洗操作,包括:
    控制所述磁性平台停留在第二预设停留角度,以使得所述液袋自进液口朝向出液口向上倾斜;所述第二预设停留角度以及所述第一预设停留角度的方向相反;
    执行第二开关操作,以开启清洗管路;所述第二开关操作包括关闭所述泵以及所述气泡传感器与所述废液袋之间的通路,并将所述泵以及所述气泡传感器连通在所述清洗液入口与所述液袋的进液口之间;
    通过所述清洗管路将第一预设容量的清洗液输入所述液袋;
    获取第二轻柔摆动参数,所述第二轻柔摆动参数包括第二轻柔摆动角度和第二轻柔摆动时长;
    令混匀装置控制所述磁性平台以所述第二轻柔摆动角度持续轻柔摆动第二轻柔摆动时长之后,再次执行所述排废液操作。
  9. 如权利要求7所述的磁珠分选方法,其中,所述向所述液袋中注入重悬液并取出包含免疫磁珠细胞的所述液袋,包括:
    将所述磁性平台调整至与水平面平行;
    执行第三开关操作,以开启重悬液输入管路;所述第三开关操作包括关闭所述泵以及所述气泡传感器与所述废液袋之间的通路,并将所述泵以及所述气泡传感器连通在所述重悬液入口与所述液袋的进液口之间;
    通过所述重悬液输入管路将第二预设容量的重悬液输入所述液袋;
    执行第四开关操作;所述第四开关操作包括关闭所述泵以及所述气泡传感器与所述重悬液入口之间的通路,并控制所述泵以及所述气泡传感器通过无菌空气过滤器与大气连通;
    在通过所述气泡传感器确定无液体通过时,确定重悬液完全注入所述液袋;
    对所述液袋的出液口和进液口进行热合密封处理之后,从所述磁性平台上取出包含免疫磁珠细胞的所述液袋。
  10. 如权利要求9所述的磁珠分选方法,其中,所述通过所述重悬液输入管路将第二预设容量的重悬液输入所述液袋,包括:
    通过所述重悬液输入管路向所述液袋中注入重悬液;
    通过称重传感器获取所述液袋的重量变化信息,并根据所述液袋的重量变化信息确定注入的重悬液的实际容量;或获取与所述泵对应的体积-转圈数数据,根据所述泵的实际转动圈数以及所述体积-转圈数数据确定注入的重悬液的实际容量;
    在所述实际容量达到所述第二预设容量时,确认已将所述第二预设容量的重悬液输入所述液袋。
  11. 一种磁珠分选设备,其中,包括压合装置、混匀装置以及用于执行如权利要求1至10任一项所述的磁珠分选方法的控制器,所述控制器连接所述压合装置以及所述混匀装置。
  12. 一种计算机可读存储介质,所述计算机可读存储介质存储有计算机可读指令,其中,所述计算机可读指令被处理器执行时实现如权利要求1至10任一项所述的磁珠分选方法。
PCT/CN2023/120444 2022-09-27 2023-09-21 磁珠分选方法、设备及存储介质 WO2024067353A1 (zh)

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