CN116445257A - Disposable cell separation appliance and cell separation device - Google Patents

Abstract

The invention discloses a disposable cell separation device, which comprises a transfer container, a rotary joint and a separation container connected with the rotary joint, wherein the transfer container is communicated with the separation container through a pipeline, the transfer container is provided with a ventilation connecting part for enabling the inside of the transfer container to be ventilated to generate positive pressure or negative pressure, and the pipeline is provided with a first butt joint part for connecting an initial container, a second butt joint part for connecting a buffer solution container and a third butt joint part for connecting a collecting container. The disposable cell separation device is also disclosed, materials do not directly pass through the positive and negative pressure device in the feeding and discharging process, the materials are not subjected to repeated extrusion action of the positive and negative pressure device, cell damage in the feeding and discharging conveying process is avoided, and the cell yield and the cell activity are greatly improved. The disposable cell separation device and the cell separation device have the advantages of avoiding cell damage caused by the suction device, greatly improving the cell yield and the cell activity, and the like.

Description

Disposable cell separation appliance and cell separation device

Technical Field

The invention relates to the technical field of cell medicine preparation, in particular to a disposable cell separation device and a cell separation device.

Background

The separation of cells from suspensions (e.g. blood or bone marrow) is becoming more and more common in medical treatment. To perform such treatment, cells are removed from the patient and then isolated to provide the desired target cells, which are stimulated/treated/expanded prior to introducing the cells into the same or a different patient. For example, PBMC are separated in the field for a long time, PBMC are peripheral blood mononuclear cells, human peripheral blood contains lymphocytes, monocytes, dendritic cells and other small amount of cells, PBMC are separated, screened and separated by a blood cell separation pipeline system, a large amount of immune cells can be obtained for cell therapy, a laboratory generally adopts manual operation in early stage, suspension to be separated is injected into a separation container and then is mounted on a centrifuge, after separation of the centrifuge, the separated cells are harvested by an injector and other devices, and now in order to avoid pollution of the cells, a fully-automatic cell centrifuge and matched disposable consumables are gradually developed, wherein the interior of the disposable consumables is a container, a pipeline and other devices which are directly contacted with the cells, the interior of the disposable consumables is airtight and not contacted with the external environment, and the disposable consumables are packaged in an airtight sterile bag before use.

When the disposable consumable is used for cell separation, suspension liquid to be separated and solution required for separation are injected into the disposable consumable in a sterile environment, or a container filled with the suspension liquid is butted in a disposable product, and then the whole disposable consumable is mounted on centrifugal equipment for full-automatic cell centrifugation, so that the problem that manual operation is easy to pollute can be effectively avoided. However, in the existing pipeline systems for blood cell separation and the like, cell fluid is directly pumped through a peristaltic pump, for example, a pipeline system for blood separation is disclosed in the application number of CN202121194589.5, the peristaltic pump directly conveys the cell fluid, and the peristaltic pump conveys the cell fluid through an extrusion hose, so that cell damage is easily caused, and the cell yield and the cell activity are reduced.

Disclosure of Invention

The invention aims to solve the technical problem of overcoming the defects of the prior art and providing a disposable cell separation device and a cell separation device which can avoid cell damage caused by a suction device and greatly improve the yield and the activity of cells.

In order to solve the technical problems, the invention adopts the following technical scheme:

the utility model provides a disposable cell separation utensil, includes transfer container, rotary joint and the separation container of being connected with rotary joint, transfer container and separation container pass through the pipeline intercommunication, transfer container is equipped with the ventilation connecting portion that makes its inside ventilation produce malleation or negative pressure, the pipeline is equipped with the first butt joint portion that is used for connecting initial container, is used for connecting the second butt joint portion of buffer container and is used for connecting the third butt joint portion of collecting container.

As a further improvement of the above technical scheme:

the first docking portion is docked with an initial container, and/or the second docking portion is docked with a buffer container, and/or the third docking portion is docked with a collection container.

The collection container is provided with a sampling interface and/or a first gas filter.

The pipeline is provided with a fourth butt joint part for connecting the waste liquid container.

The fourth butt joint part is butt-jointed with a waste liquid container.

The pipeline is provided with a fifth butt joint part used for connecting the transition container and/or a sixth butt joint part used for connecting the separation liquid container.

The fifth butt joint part is butt jointed with a transition container.

The sixth butt joint part is butt jointed with a separating liquid container.

A demagnetizing component is arranged between the first butt joint part and the transfer container.

The pipeline is connected with the bottom of the transfer container.

The pipeline is also connected with the top of the transfer container.

The ventilation connecting part is arranged on the side wall or the top wall of the transfer container.

The ventilation connecting part is connected with a positive and negative pressure device.

The positive and negative pressure device comprises a second gas filter and a gas pipe, and the second gas filter is communicated with the transfer container through the gas pipe.

An intermediate container is arranged between the air pipe and the transfer container.

The transfer container is a hard container.

The separation container is connected with the pipeline through a rotary joint.

The rotary joint comprises an inner column and a rotary sleeve, the rotary sleeve is rotationally sleeved outside the inner column, a connecting channel which is communicated with the inner column during relative rotation is arranged in the rotary sleeve and the inner column, the pipeline is communicated with the connecting channel of the rotary joint, and the separating container is communicated with the connecting channel of the rotary sleeve.

The inner column is provided with a first connecting part communicated with the connecting channel, the pipeline is connected with the first connecting part, the rotary sleeve is provided with a second connecting part communicated with the connecting channel, and the separation container is connected with the second connecting part.

The utility model provides a cell separation device, includes installation panel and foretell disposable cell separation utensil, be equipped with a plurality of installation department, a plurality of pinch valve and a plurality of pipe fitting admittedly on the installation panel, transfer container demountable installation is on corresponding installation department, the pipeline is fixed on the pipe fitting admittedly, the pinch valve presss from both sides to locate on the corresponding pipe position.

Compared with the prior art, the invention has the advantages that:

the disposable cell separation device provided by the invention has the advantages that the material does not directly pass through the positive and negative pressure devices in the feeding and discharging process, the repeated extrusion action of the positive and negative pressure devices is avoided, the cell damage in the feeding and discharging conveying process is avoided, and the cell yield and the cell activity are greatly improved.

The cell separation device of the invention has the advantages that the disposable cell separation device is detachably arranged on the installation panel, and the disposable cell separation device is scrapped after being used. The separating container, the initial container, the buffer container and other containers are arranged in the separating device or on the hook. Therefore, the pinch valve is not disposable with the disposable cell separation device, can be used for multiple times, and saves cost.

Drawings

FIG. 1 is a schematic structural view of a disposable cell separation instrument of the present invention.

FIG. 2 is a schematic view showing the structure of a collection container of the disposable cell separation instrument of the present invention.

FIG. 3 is a schematic structural view of a rotary joint of the disposable cell separation instrument of the present invention.

FIG. 4 is a diagram showing the cooperation of the disposable cell separation instrument of the present invention with a peristaltic pump.

Fig. 5 is an enlarged view of fig. 4 a.

FIG. 6 is a packaging view of the disposable cell separation instrument of the present invention.

FIG. 7 is a schematic structural view of a packing bag of the disposable cell separation instrument of the present invention.

FIG. 8 is a front view showing a construction of a cell separation apparatus according to the present invention.

The reference numerals in the drawings denote:

1. a transfer container; 10. a pipeline; 101. a sixth butt joint part; 102. a demagnetizing component; 11. a ventilation connection; 12. a rotary joint; 121. an inner column; 122. a rotating sleeve; 123. a first connection portion; 124. a second connecting portion; 13. a peristaltic pump; 14. packaging bags; 2. a separation vessel; 3. an initial container; 31. a first butt joint part; 4. a separation liquid container; 41. a second butt joint part; 5. a collection container; 51. a third butt joint part; 52. a sampling interface; 53. a first gas filter; 6. a waste liquid container; 61. a fourth butt joint part; 7. positive and negative pressure devices; 70. an air pipe; 71. a second gas filter; 72. an intermediate container; 8. a transition vessel; 81. a fifth docking portion; 9. installing a panel; 91. a mounting part; 92. a pinch valve; 93. and fixing the pipe fitting.

Detailed Description

The invention will be described in further detail with reference to the drawings and the specific examples.

Embodiment one:

fig. 1 to 7 show an embodiment of the disposable cell separation instrument of the present invention, which comprises a relay container 1, a rotary joint 12, and a separation container 2 connected to the rotary joint 12, wherein the relay container 1 communicates with the separation container 2 through a pipe 10, the relay container 1 is provided with a ventilation connection part 11 for ventilating the inside thereof to generate positive pressure or negative pressure, and the pipe 10 is provided with a first docking part 101 for connecting an initial container, a second docking part 31 for connecting a buffer container 3, and a third docking part 51 for connecting a collection container 5. The initial container second docking portion 31.

When in use, the disposable cell separation instrument is arranged on the installation panel 9 shown in fig. 4, the pinch valve 92 on the installation panel 9 is clamped on the corresponding pipe position, and the on-off of the pipeline 10 of the corresponding section is controlled through the pinch valve 92. In the cell separation process, an initial container containing blood is connected with a first butt joint part 101, a buffer solution container 3 containing buffer solution is connected with a second butt joint part 31, a collecting container 5 is connected with a third butt joint part 51, and a positive and negative pressure device 7 is connected with a ventilation connection part 11 under a sterile environment; the pipeline 10 between the initial container and the transfer container 1, the buffer liquid container 3 and the transfer container 1, the separation container 2 and the transfer container 1, and the collection container 5 and the transfer container 1 are clamped and disconnected through the pipe clamping valve 92, then the transfer container 1 is pumped by the positive and negative pressure device 7 to generate negative pressure, then the pipeline 10 between the initial container and the transfer container 1 and/or between the buffer liquid container 3 and the transfer container 1 is released and opened through the pipe clamping valve 92, under the action of the negative pressure, the blood and/or the buffer liquid in the initial container and/or the buffer liquid container 3 enters the transfer container 1, then the pipeline 10 between the initial container and the transfer container 1, the buffer liquid container 3 and the transfer container 1 is clamped and disconnected through the pipe clamping valve 92, the pipeline 10 between the transfer container 1 and the separation container 2 is released and opened, and then the transfer container 1 is inflated by the positive and negative pressure device 7 to generate positive pressure, so that the materials in the transfer container 1 enter the separation container 2.

After the blood separation of the separation container 2 is completed, the pipeline 10 between the initial container and the transfer container 1, the buffer liquid container 3 and the transfer container 1, the collecting container 5 and the transfer container 1, and the pipeline 10 between the separation container 2 and the transfer container 1 are clamped and closed through the pinch valve 92, then the transfer container 1 is pumped by the positive and negative pressure device 7 to generate negative pressure, then the pipeline 10 between the separation container 2 and the transfer container 1 is released and opened through the pinch valve 92, under the negative pressure effect, the target cells in the separation container 2 enter the transfer container 1, then the pipeline 10 between the separation container 2 and the transfer container 1 is clamped and disconnected through the pinch valve 92, the pipeline 10 between the transfer container 1 and the collecting container 5 is released and opened, and then the transfer container 1 is inflated by the positive and negative pressure device 7 to generate positive pressure, so that the target cells in the transfer container 1 enter the collecting container 5. Therefore, materials (blood and cells) do not directly pass through the positive and negative pressure device 7 in the feeding and discharging process, are not subjected to repeated extrusion action of the positive and negative pressure device 7, so that cell damage in the feeding and discharging conveying process is avoided, and the cell yield and the cell activity are greatly improved.

In this embodiment, the first docking portion 31 is docked with the initial container, and/or the second docking portion 31 is docked with the buffer container 3, and/or the third docking portion 51 is docked with the collection container 5. In this way, in the subsequent use, it is unnecessary to prepare an initial container that can be docked with the first docking portion 31, to prepare the buffer container 3 that can be docked with the second docking portion 31, and to prepare the collection container 5 that can be docked with the third docking portion 51.

In this embodiment, the collection container 5 is provided with a sampling interface 52 and/or a first gas filter 53. Sampling detection is facilitated by the provision of sampling interface 52. By providing a first gas filter 53 for balancing the gas pressure in the collection vessel 5.

In this embodiment, the line 10 is provided with a fourth docking portion 61 for connecting the waste liquid container 6. In this way, at the time of subsequent use, it is not necessary to prepare the waste liquid container 6 which can be docked with the fourth docking portion 61.

In this embodiment, the fourth docking portion 61 docks with the waste liquid container 6. The separation vessel 2 is configured to interface the waste liquid vessel 6 with the fourth interface 61 during separation, and is configured to collect the waste liquid discharged from the separation vessel 2.

In this embodiment, the line 10 is provided with a fifth docking 81 for connecting to the transition vessel 8. Since the initial container contains several times more blood than the separation container 2, and the separation can generally be accomplished at one time. Accordingly, a fifth docking portion 81 is provided for connecting the transition container 8, and in use, the transition container 8 is connected to the fifth docking portion 81. Thus, the blood of the initial container can be divided into a plurality of parts to be output, one part of blood is output at a time and enters the separation container 2, the separation container 2 separates one part of blood at a time, the target cells after the separation of the separation container 2 are output to the transition container 8 for unified collection, and after all parts of blood are separated, the target cell liquid which is uniformly collected in the transition container 8 is returned to the separation container 2 for re-separation.

In the present embodiment, the fifth docking portion 81 is docked with the transition container 8. In this way, at the time of subsequent use, it is no longer necessary to prepare the transition container 8 which can be docked with the fifth docking portion 81.

In this embodiment, the pipe 10 is provided with a sixth docking portion 41 for connecting the separation liquid container 4. The sixth docking portion 41 is used to connect with the separation liquid container 4, so that it is unnecessary to prepare the separation liquid container 4 that can be docked with the sixth docking portion 41 at the time of subsequent use.

In the present embodiment, the sixth docking portion 41 docks with the separation liquid container 4. In the separation vessel 2, the separation liquid can be supplied into the separation vessel 2 by abutting the separation liquid vessel 4 against the sixth abutting portion 41 during the separation process.

In this embodiment, a demagnetizing component 102 is disposed between the first butt joint 101 and the pipeline 10. Since the beads are generally mixed in the cell liquid contained in the cell liquid container (initial container), the beads need to be removed during discharging, and therefore, a demagnetization module 102 is provided between the sixth docking portion 41 and the pipeline 10 to remove the beads in the cells.

In this embodiment, the pipeline 10 is connected to the bottom of the transfer vessel 1. The pipeline 10 is also connected with the top of the transfer container 1.

The pipeline 10 connects the top and bottom of the transfer container 1, and since the separation container 2 needs to be fed with liquid (material flows from the initial container into the separation container 2) and discharged with liquid (material flows from the separation container 2 into the collection container 5), when fed with liquid, the liquid enters the transfer container 1 from the initial container through the pipeline 10 and the top of the transfer container 1, then enters the separation container 2 through the bottom of the transfer container 1 and the pipeline 10, and when discharged with liquid, the liquid enters the transfer container 1 from the separation container 2 through the pipeline 10 and the top of the transfer container 1, then enters the collection container 5 through the bottom of the transfer container 1 and the pipeline 10, so that the liquid is prevented from entering from the bottom of the transfer container 1, regardless of the feeding or discharging of the liquid. If the effluent of the separation vessel 2 enters from the bottom of the transfer vessel 1, a large amount of bubbles are finally sucked into the transfer vessel 1, and bursting of the bubbles may adversely affect the cells.

In this embodiment, the ventilation connection 11 is provided on a side wall or a top wall of the transfer container 1. Thus, during the positive pressure process, gas enters from the side wall or the top wall of the transfer container 1, for example, the ventilation connection part 11 is arranged at the bottom of the transfer container 1, and when the transfer container 1 is filled with liquid, the liquid can enter the positive-negative pressure device 7 and even leak through the ventilation connection part 11.

In the present embodiment, the positive/negative pressure device 7 is connected to the ventilation connection portion 11. The positive-negative pressure device 7 includes a second gas filter 71 and a gas pipe 70, and the second gas filter 71 communicates with the relay tank 1 through the gas pipe 70. When in use, the air pipe 70 is arranged in the peristaltic pump 13 (as shown in fig. 4 and 5), the peristaltic pump 13 can be ventilated or pumped to the transfer container 1 through the air pipe 70 when in operation, so that positive pressure or negative pressure in the transfer container 1 is realized, the second air filter 71 is used for filtering impurities in air to prevent internal pollution of the culture appliance, and in addition, particles possibly occur when the peristaltic pump 13 clamps the air pipe 70 when in operation, the second air filter 71 can be arranged between the peristaltic pump 13 and the ventilation connecting part 11.

In this embodiment, an intermediate container 72 is provided between the air pipe 70 and the relay container 1. The middle container 72 is used for adding the isolation liquid into the separation container 2 when the cells are concentrated, the isolation liquid is positioned at the bottom layer of the separation container 2 in the centrifugal layering process of the separation container 2 and is filled between the cell liquid and the inner wall of the separation container 2, so that the target cells are prevented from being directly extruded on the inner wall of the separation container 2 in the centrifugal separation process, the physical damage to the target cells in the cell centrifugation process is greatly reduced, and the yield of collecting the target cells is high and the concentration volume is large. The spacer fluid may be human albumin or other fluid having a density greater than the density of the cells of interest and which does not damage the cells of interest.

In this embodiment, the transfer container 1 is a rigid container. In this way, the relay container 1 is not deformed in the positive and negative pressure state.

In this embodiment, the separation vessel 2 is connected to the pipeline 10 via a swivel joint 12. In this way, the pipe 10 is prevented from being entangled during the rotational operation of the separation vessel 2.

In this embodiment, as shown in fig. 3, the rotary joint 12 includes an inner column 121 and a rotary sleeve 122, the rotary sleeve 122 is rotatably sleeved outside the inner column 121, a connecting channel which is kept in communication during relative rotation is arranged in the rotary sleeve 122 and the inner column 121, the pipeline 10 is communicated with the connecting channel of the rotary joint 12, and the separation vessel 2 is communicated with the connecting channel of the rotary sleeve 122. In this way, the pipe 10 can be kept stationary with the inner column 121 without being entangled during the rotational operation of the separation vessel 2.

In this embodiment, the inner column 121 is provided with a first connecting portion 123 communicating with the connecting channel thereof, the pipeline 10 is connected with the first connecting portion 123, the rotating sleeve 122 is provided with a second connecting portion 124 communicating with the connecting channel thereof, and the separation vessel 2 is connected with the second connecting portion 124.

In this embodiment, as shown in FIGS. 6 and 7, the disposable cell culture apparatus further comprises a packing bag 14, and each container and the tube 10 are packed in the packing bag 14.

In this embodiment, the pipe 10 and the container may be connected by a Luer (Luer) or a two-way connector, that is, the connection portion is a Luer (Luer) or a two-way connector, or the pipe 10 and the container may be connected by a connection device, for example, a hot-melt welding machine.

Embodiment two:

fig. 8 shows an embodiment of the cell separation apparatus of the present invention, which comprises a mounting panel 9 and the disposable cell separation device of the first embodiment, wherein the mounting panel 9 is provided with a plurality of mounting portions 91, a plurality of pinch valves 92 and a plurality of fixing pipes 93, the transfer container 1 is detachably mounted on the corresponding mounting portions 91, the pipeline 10 is fixed on the fixing pipes 93, and the pinch valves 92 are clamped on the corresponding pipe positions. The disposable cell separation device is detachably arranged on the mounting panel 9, and is scrapped after being used. The separating vessel 2 and the containers such as the initial vessel, the buffer vessel 3 and the like are provided in the separating apparatus or on the hook. In this way, pinch valve 92 is not disposable with a disposable cell separation apparatus, and can be used multiple times, saving costs.

While the invention has been described in terms of preferred embodiments, it is not intended to be limiting. Many possible variations and modifications of the disclosed technology can be made by anyone skilled in the art, or equivalent embodiments with equivalent variations can be made, without departing from the scope of the invention. Therefore, any simple modification, equivalent variation and modification of the above embodiments according to the technical substance of the present invention shall fall within the scope of the technical solution of the present invention.

Claims (20)

1. A disposable cell separation device, characterized in that: including transfer container (1), rotary joint (12) and separation container (2) of being connected with rotary joint (12), transfer container (1) and separation container (2) are through pipeline (10) intercommunication, transfer container (1) are equipped with and make its inside ventilation produce ventilation connecting portion (11) of malleation or negative pressure, pipeline (10) are equipped with first interfacing part (101) that are used for connecting initial container, second interfacing part (31) that are used for connecting buffer container (3) and third interfacing part (51) that are used for connecting collection container (5).

2. The disposable cell separation apparatus according to claim 1, wherein: the first docking portion (101) is docked with an initial container, and/or the second docking portion (31) is docked with a buffer container (3), and/or the third docking portion (51) is docked with a collection container (5).

3. The disposable cell separation apparatus according to claim 2, wherein: the collection container (5) is provided with a sampling interface (52) and/or a first gas filter (53).

4. The disposable cell separation apparatus according to claim 1, wherein: the pipeline (10) is provided with a fourth butt joint part (61) for connecting the waste liquid container (6).

5. The disposable cell separation instrument according to claim 4, wherein: the fourth butt joint part (61) is butt-jointed with a waste liquid container (6).

6. The disposable cell separation apparatus according to claim 1, wherein: the pipeline (10) is provided with a fifth butt joint (81) for connecting a transition container (8) and/or a sixth butt joint (41) for connecting a separation liquid container (4).

7. The disposable cell separation apparatus according to claim 6, wherein: the fifth butt joint part (81) is butt-jointed with a transition container (8).

8. The disposable cell separation apparatus according to claim 6, wherein: the sixth butt joint part (41) is butt-jointed with a separating liquid container (4).

9. The disposable cell separation apparatus according to claim 1, wherein: a demagnetizing component (102) is arranged between the first butt joint part (101) and the transfer container (1).

10. The disposable cell separation apparatus according to claim 1, wherein: the pipeline (10) is connected with the bottom of the transfer container (1).

11. The disposable cell separation apparatus according to claim 10, wherein: the pipeline (10) is also connected with the top of the transfer container (1).

12. The disposable cell separation instrument according to any one of claims 1 to 11, wherein: the ventilation connecting part (11) is arranged on the side wall or the top wall of the transfer container (1).

13. The disposable cell separation instrument according to any one of claims 1 to 11, wherein: the ventilation connecting part (11) is connected with a positive and negative pressure device (7).

14. The disposable cell separation apparatus according to claim 13, wherein: the positive and negative pressure device (7) comprises a second gas filter (71) and a gas pipe (70), and the second gas filter (71) is communicated with the transfer container (1) through the gas pipe (70).

15. The disposable cell separation apparatus according to claim 14, wherein: an intermediate container (72) is arranged between the air pipe (70) and the transfer container (1).

16. The disposable cell separation instrument according to any one of claims 1 to 11, wherein: the transfer container (1) is a hard container.

17. The disposable cell separation instrument according to any one of claims 1 to 11, wherein: the separation container (2) is connected with the pipeline (10) through a rotary joint (12).

18. The disposable cell separation apparatus according to claim 17, wherein: the rotary joint (12) comprises an inner column (121) and a rotary sleeve (122), the rotary sleeve (122) is rotationally sleeved outside the inner column (121), a connecting channel which is communicated with the inner column (121) in a relative rotation manner is arranged in the rotary sleeve (122), the pipeline (10) is communicated with the connecting channel of the rotary joint (12), and the separating container (2) is communicated with the connecting channel of the rotary sleeve (122).

19. The disposable cell separation apparatus according to claim 18, wherein: the inner column (121) is provided with a first connecting part (123) communicated with a connecting channel of the inner column, the pipeline (10) is connected with the first connecting part (123), the rotary sleeve (122) is provided with a second connecting part (124) communicated with the connecting channel of the rotary sleeve, and the separation container (2) is connected with the second connecting part (124).

20. A cell separation device, characterized in that: the disposable cell separation device comprises a mounting panel (9) and any one of claims 1 to 19, wherein a plurality of mounting parts (91), a plurality of pinch valves (92) and a plurality of fixed pipe fittings (93) are arranged on the mounting panel (9), the transit container (1) is detachably mounted on the corresponding mounting parts (91), the pipeline (10) is fixed on the fixed pipe fittings (93), and the pinch valves (92) are clamped on corresponding pipe positions.