Cell separating and harvesting system

Abstract

The utility model provides a cell separating and harvesting system. The cell separating and harvesting system at least comprises a two-way pump, a centrifugal cup, a centrifugal machine, a quantitative tube and an air filtering valve, wherein the two-way pump comprises a first channel and a second channel; the size of the rubber tube arranged in the first channel is the same as that of the rubber tube arranged in the second channel; the first end of the first channel is connected with the upper opening of the centrifugal cup, and the second end of the first channel is at least connected with the first pipeline, the second pipeline and the third pipeline; the first end of the second channel is connected with a lower opening of the centrifugal cup, and the second end of the second channel is at least connected with the fourth pipeline, the fifth pipeline, the sixth pipeline and the seventh pipeline. Based on the structure, the stable continuous flow can be formed by introducing and utilizing the two-way pump, and then the stable continuous flow is matched with the centrifugal machine and the refrigeration centrifugal cabin to transport related fluid, so that the loss and damage of cells in the operation treatment process can be effectively reduced; the operations of separating, concentrating, cleaning, resuspending, subpackaging and the like of the cells in the cell stock solution are efficiently realized.

Description

Technical Field

[0001] This specification belongs to the field of cell separation technology, and in particular to a cell separation and harvesting system. Background Art

[0002] With the development of biotechnology, the production of cell products has received increasing attention.

[0003] Based on the existing cell harvesting system, during the specific separation, preparation, and packaging of cell products, especially during the cell separation and concentration stage, cells are easily discharged along with the supernatant, resulting in serious cell loss; moreover, during specific operations, cells are also easily damaged and inactivated, affecting the quality of the final cell product.

[0004] The above problems cannot be effectively solved by existing cell harvesting systems. Utility Model Content

[0005] This specification provides a cell separation and harvesting system that can effectively reduce cell loss and damage during operation and processing, avoid cell inactivation, and efficiently perform operations such as separation, concentration, washing, resuspension, and packaging of cells in cell stock solution to obtain high-quality cell products.

[0006] This specification provides a cell separation and harvesting system, which at least includes: a two-way pump, a centrifuge cup, a centrifuge, a quantitative tube, and an air filter valve; wherein,

[0007] The two-way pump includes a first channel and a second channel; and the hose provided in the first channel and the hose provided in the second channel have the same size;

[0008] The first end of the first channel is connected to the upper opening of the centrifuge cup, and the second end of the first channel is connected to at least a first pipeline, a second pipeline, and a third pipeline; wherein the first pipeline is used to connect to the cell stock solution bag, the second pipeline is used to connect to the cleaning solution bag, and the third pipeline is connected to the quantitative tube;

[0009] The first end of the second channel is connected to the lower opening of the centrifuge cup, and the second end of the second channel is connected to at least a fourth pipeline, a fifth pipeline, a sixth pipeline, and a seventh pipeline; wherein the fourth pipeline is connected to the quantitative tube, the fifth pipeline is used to connect to the sub-packaging bag, the sixth pipeline is used to connect to the resuspension bag, and the seventh pipeline is used to connect to the waste liquid bag; the distance between the upper opening of the centrifuge cup and the adjacent cup wall is smaller than the distance between the lower opening of the centrifuge cup and the adjacent cup wall;

[0010] The quantitative tube is also connected to the air filter valve through an eighth pipeline; the centrifugal cup is arranged on the centrifuge;

[0011] In addition, a first solenoid valve is provided on the first pipeline, a second solenoid valve is provided on the second pipeline, a third solenoid valve is provided on the third pipeline, a fourth solenoid valve is provided on the fourth pipeline, a fifth solenoid valve is provided on the fifth pipeline, a sixth solenoid valve is provided on the sixth pipeline, and a seventh solenoid valve is provided on the seventh pipeline.

[0012] In one embodiment, a first bubble sensor is disposed adjacent to the second end of the first channel, and a second bubble sensor is disposed adjacent to the first end of the second channel.

[0013] In one embodiment, a third bubble sensor is provided on the eighth pipeline adjacent to the quantitative tube.

[0014] In one embodiment, the centrifugal cup comprises at least: a cup body, and a connecting component disposed above the cup body;

[0015] Wherein, the connecting component is provided with at least a first interface, a second interface, a first flow channel, and a second flow channel;

[0016] The cup body is provided with at least an upper flow channel, a lower flow channel, a central axis flow channel, an upper opening and a lower opening;

[0017] Wherein, the first interface is connected to the first flow channel, the first interface is used to connect to the first channel, and the first flow channel is connected to the upper port through the upper flow channel;

[0018] The second interface is connected to the second flow channel, and the second interface is used to connect to the second channel. The second flow channel is connected to the lower port through the central axis flow channel and the lower flow channel.

[0019] In one embodiment, a guide platform is provided at the intersection of the first flow channel and the upper flow channel.

[0020] In one embodiment, further comprising a refrigerated centrifugal chamber;

[0021] Wherein, the refrigerated centrifugal chamber is connected to a refrigeration module; a temperature sensor is also provided in the refrigerated centrifugal chamber; and the centrifugal cup is provided in the refrigerated centrifugal chamber.

[0022] In one embodiment, the invention further comprises a body, on which a first fluid bag support and a second fluid bag support are provided;

[0023] Among them, the first liquid bag bracket is used to hang the cell raw liquid bag and the cleaning liquid bag; the second liquid bag bracket is used to hang the waste liquid bag, the resuspension liquid bag, and the sub-packaging bag.

[0024] In one embodiment, an operation panel is further provided on the machine body;

[0025] The operation panel is provided with a plurality of control knobs, and the plurality of control knobs are respectively associated with the first solenoid valve, the second solenoid valve, the third solenoid valve, the fourth solenoid valve, the fifth solenoid valve, the sixth solenoid valve, and the seventh solenoid valve;

[0026] Alternatively, the operation panel is a touch screen, and icons respectively associated with the first solenoid valve, the second solenoid valve, the third solenoid valve, the fourth solenoid valve, the fifth solenoid valve, the sixth solenoid valve, and the seventh solenoid valve are displayed on the touch screen.

[0027] In one embodiment, a liquid bag hook is further provided on the side wall of the body for hanging spare sub-packaging bags and / or spare waste liquid bags.

[0028] In one embodiment, the second end of the first channel is further connected to a first expansion pipeline; the second end of the second channel is further connected to a second expansion pipeline.

[0029] Based on the cell separation and harvesting system provided in this specification, the system at least includes: a two-way pump, a centrifuge cup, a centrifuge, a quantitative tube, and an air filter valve; wherein the two-way pump includes a first channel and a second channel; and the hose arranged in the first channel has the same size as the hose arranged in the second channel; the first end of the first channel is connected to the upper opening of the centrifuge cup, and the second end of the first channel is connected to at least the first pipeline, the second pipeline, and the third pipeline; wherein the first pipeline is used to connect the cell stock solution bag, the second pipeline is used to connect the cleaning solution bag, and the third pipeline is connected to the quantitative tube; the first end of the second channel is connected to the lower opening of the centrifuge cup, and the second end of the second channel is connected to at least the fourth pipeline, the fifth pipeline, the sixth pipeline, the third pipeline, the fifth pipeline, the sixth ... first pipeline, the first pipeline, the first pipeline, the first pipeline, the second pipeline, the first pipeline, the second pipeline, the second pipeline, the first pipeline, the second pipeline, the Seven pipelines are connected; wherein the fourth pipeline is connected to the quantitative tube, the fifth pipeline is used to connect the sub-packaging bag, the sixth pipeline is used to connect the resuspension liquid bag, and the seventh pipeline is used to connect the waste liquid bag; the distance between the upper opening of the centrifuge cup and the adjacent cup wall is smaller than the distance between the lower opening of the centrifuge cup and the adjacent cup wall; the quantitative tube is also connected to the air filter valve through the eighth pipeline; the centrifuge cup is arranged on the centrifuge; and a first solenoid valve is arranged on the first pipeline, a second solenoid valve is arranged on the second pipeline, a third solenoid valve is arranged on the third pipeline, a fourth solenoid valve is arranged on the fourth pipeline, a fifth solenoid valve is arranged on the fifth pipeline, a sixth solenoid valve is arranged on the sixth pipeline, and a seventh solenoid valve is arranged on the seventh pipeline. The cell separation and harvesting system based on the above structure can form a stable continuous flow by introducing and utilizing a two-way pump, and then transport the relevant fluid in the form of a stable continuous flow in conjunction with the centrifuge, thereby effectively reducing the loss and damage of cells during the operation and processing process, avoiding cell inactivation, and efficiently completing the separation, concentration, cleaning, resuspension, sub-packaging and other operations of cells in the cell stock solution to obtain a cell product with higher quality. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the embodiments of this specification, the following is a brief introduction to the drawings required for use in the embodiments. The drawings described below are only some of the embodiments recorded in this specification. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0031] Figure 1 This is a schematic diagram of the structure of a cell separation and harvesting system provided in one embodiment of this specification;

[0032] Figure 2 This is a schematic diagram of the structure of a two-way pump in a cell separation and harvesting system provided in one embodiment of this specification;

[0033] Figure 3 This is a schematic diagram of the structural composition of a two-way pump connected to a centrifuge cup in a cell separation and harvesting system provided in one embodiment of the present specification;

[0034] Figure 4 This is a schematic diagram of the structure of a centrifuge cup in a cell separation and harvesting system provided in one embodiment of this specification;

[0035] Figure 5 This is another schematic diagram of the structure of a cell separation and harvesting system provided in one embodiment of this specification;

[0036] Figure 6 This is a schematic diagram of the structure of a refrigerated centrifuge chamber in a cell separation and harvesting system provided in one embodiment of this specification;

[0037] Figure 7 This is a schematic diagram of an improved structure of a centrifuge cup in a cell separation and harvesting system provided in one embodiment of this specification;

[0038] Figure 8 This is another structural diagram of a cell separation and harvesting system provided in one embodiment of this specification;

[0039] Figure 9 This is a schematic diagram of the body structure of a cell separation and harvesting system provided in one embodiment of this specification. DETAILED DESCRIPTION

[0040] To help those skilled in the art better understand the technical solutions in this specification, the following will provide a clear and complete description of the technical solutions in the embodiments of this specification, in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of this specification, not all of them. All other embodiments derived by those skilled in the art based on the embodiments in this specification without creative effort shall fall within the scope of protection of this specification.

[0041] Considering that based on existing system equipment, when separating and packaging cells, most of them use conventional peristaltic pumps to create negative pressure in the centrifuge cup to generate a pressure differential with the outside world; the cell stock solution containing cells is then sucked into the centrifuge cup through this pressure differential for subsequent cell separation. However, the fluid movement generated by the pressure differential is often unstable and can easily lead to sudden interruptions or sudden changes in flow rate due to factors such as changes in liquid volume or pressure, affecting separation and packaging. In addition, when the cell stock solution is pumped into the centrifuge cup based on the above system equipment, since the inside of the centrifuge cup is in a negative pressure state, the cell stock solution will suddenly accelerate the flow rate due to the pressure differential at the moment it enters the centrifuge cup, causing the cells in the cell stock solution to be discharged from the centrifuge cup along with the cell stock solution before they have time to separate and adhere to the wall, resulting in cell loss. In addition, based on the above system equipment, it is necessary to maintain a large negative pressure in the centrifuge cup for a long time, which will cause the cells in the centrifuge cup to be subjected to a large surface tension, thereby affecting cell activity and even causing cell inactivation.

[0042] In order to address the root cause of the above-mentioned problems, the applicant, through creative work, considered introducing and using a dual-channel dual-pass pump to replace the conventional peristaltic pump, and at the same time making corresponding improvements to the relevant structures of the system to cooperate with the operation of the dual-pass pump in the cell separation and packaging process. In this way, the dual-pass pump can be used to make the liquid inlet and outlet speeds of the centrifuge cup relatively consistent, so that the pressure in the centrifuge cup is relatively constant, thereby forming a stable continuous flow. Furthermore, the above-mentioned stable continuous flow can be used to complete operations such as separation, concentration, washing, resuspension, and packaging in the cell separation and packaging process. On the one hand, it can make the liquid flow rate when entering the centrifuge cup stable and reliable, so that the cells in the cell stock solution have sufficient time to enter the adherent state under the action of centrifugal force after entering the centrifuge cup, achieving separation, and effectively reducing the loss of cells during the separation operation; on the other hand, it can also effectively avoid the cells in the centrifuge cup from being inactivated due to the negative pressure. In this way, the cell separation and packaging can be completed relatively efficiently, and a high-quality cell product can be obtained.

[0043] See Figure 1 As shown, the embodiment of this specification provides a cell separation and harvesting system, which may at least include: a two-way pump, a centrifuge cup, a centrifuge, a quantitative tube, an air filter valve and other structures; wherein,

[0044] The two-way pump may specifically include a first channel and a second channel; and the hose provided in the first channel has the same size as the hose provided in the second channel;

[0045] The first end of the first channel is connected to the upper opening of the centrifuge cup, and the second end of the first channel is connected to at least a first pipeline, a second pipeline, and a third pipeline; wherein the first pipeline is used to connect to the cell stock solution bag, the second pipeline is used to connect to the cleaning solution bag, and the third pipeline is connected to the quantitative tube;

[0046] The first end of the second channel is connected to the lower opening of the centrifuge cup, and the second end of the second channel is connected to at least a fourth pipeline, a fifth pipeline, a sixth pipeline, and a seventh pipeline; wherein the fourth pipeline is connected to the quantitative tube, the fifth pipeline is used to connect to the sub-packaging bag, the sixth pipeline is used to connect to the resuspension bag, and the seventh pipeline is used to connect to the waste liquid bag; the distance between the upper opening of the centrifuge cup and the adjacent cup wall is smaller than the distance between the lower opening of the centrifuge cup and the adjacent cup wall;

[0047] The quantitative tube is also connected to the air filter valve through an eighth pipeline; the centrifugal cup is arranged on the centrifuge;

[0048] In addition, a first solenoid valve (which can be expressed as ①) is provided on the first pipeline, a second solenoid valve (which can be expressed as ②) is provided on the second pipeline, a third solenoid valve (which can be expressed as ③) is provided on the third pipeline, a fourth solenoid valve (which can be expressed as ④) is provided on the fourth pipeline, a fifth solenoid valve (which can be expressed as ⑤) is provided on the fifth pipeline, a sixth solenoid valve (which can be expressed as ⑥) is provided on the sixth pipeline, and a seventh solenoid valve (which can be expressed as ⑦) is provided on the seventh pipeline.

[0049] Specifically, the first solenoid valve, the second solenoid valve, the third solenoid valve, the fourth solenoid valve, the fifth solenoid valve, the sixth solenoid valve, and the seventh solenoid valve can be used to control the on / off of the pipelines in which they are located.

[0050] Specifically, the above-mentioned two-way pump (or two-way peristaltic pump) can be a two-channel peristaltic pump. Figure 2 As shown, the dual-channel pump may include at least a motor, a roller, a first channel, and a second channel. The first and second channels may utilize hoses of the same size (e.g., the same diameter). Because the first and second channels are driven by the same motor and roller, and have the same diameter, the fluid velocity in the first channel is the same as the fluid velocity in the second channel.

[0051] Accordingly, the introduction and use of a two-way pump in a cell separation and harvesting system can make the liquid inlet and outlet speeds of the centrifuge cup relatively consistent, maintain the pressure in the centrifuge cup constant, and thus form a stable continuous flow.

[0052] Specifically, the cell stock solution bag can store the cell stock solution to be separated and concentrated. The cleaning solution bag can store the cleaning solution used to clean the residual liquid on the cells. The resuspension solution bag can store the resuspension solution used to resuspend the separated cells.

[0053] The waste liquid bag can be an empty liquid bag for storing waste liquid generated during the operation of the system. The subpackaging bag can be an empty liquid bag for storing the target liquid containing cells (or cell liquid product, cell product, etc.) obtained by final separation and concentration during the operation of the system.

[0054] Furthermore, in addition to the first pipeline, the second pipeline, and the third pipeline, according to the specific application scenario and processing requirements, the second end of the above-mentioned first channel can also be connected to a first extension pipeline other than the above-mentioned pipelines; wherein, the first extension pipeline can specifically be connected to other liquid bags such as other cell raw liquid bags.

[0055] Similarly, in addition to the fourth pipeline, the fifth pipeline, the sixth pipeline, and the seventh pipeline, the second end of the second channel can also be connected to a second extension pipeline; wherein the second extension pipeline can specifically be connected to other liquid bags such as other waste liquid bags.

[0056] Specifically, the air filter valve may be connected to the external environment to inhale and filter air fluid from the external environment; or to discharge air fluid to the external environment.

[0057] Specifically, the centrifuge is connected to a centrifuge cup, and the internal motor can drive the centrifuge cup to rotate, so that the cells in the solution in the centrifuge cup can be pressed against the wall of the centrifuge cup due to the centrifugal force, and enter the wall-adherent state.

[0058] Specifically, the quantitative tube can be understood as a connected structure with a known and fixed volume. For example, the volume of the quantitative tube can be recorded as V.

[0059] For details, see Figure 1 As shown, the first pipeline, the second pipeline, and the third pipeline may first converge at a node; and then the node is connected to the first channel of the two-way pump through corresponding pipelines.

[0060] Similarly, the fourth pipeline, the fifth pipeline, the sixth pipeline, and the seventh pipeline may first converge at a node; and then the node may be connected to the second channel of the two-way pump through corresponding pipelines.

[0061] For details, see Figure 3 As shown, the first channel can be connected to the upper opening of the centrifuge cup, and the second channel can be connected to the lower opening of the centrifuge cup.

[0062] For further information, see Figure 4 As shown, the distance between the upper opening and its adjacent cup wall (for example, the right cup wall) is smaller than the distance between the lower opening and its adjacent cup wall (for example, the left cup wall).

[0063] When implementing it specifically, Figure 3 and Figure 4 As can be seen, when the dual-channel pump rotates in a first direction, liquid can be pumped into the centrifuge cup through the first channel via the upper opening of the centrifuge cup; simultaneously, liquid can be discharged from the centrifuge cup through the second channel via the lower opening of the centrifuge cup. Because the liquid flow rates in the first and second channels are the same, the pressure within the centrifuge cup can be maintained constant, eliminating a pressure differential and thereby forming a stable continuous flow. Furthermore, this stable continuous flow allows liquid to be pumped into the centrifuge cup at a stable and uniform rate while simultaneously being discharged from the centrifuge cup.

[0064] Specifically, for example, in the cell separation and concentration stage, while the cell stock solution is pumped into the centrifuge cup based on the first channel of the above-mentioned two-way pump, the supernatant remaining after the cells in the cell stock solution are separated by centrifugal force is discharged from the centrifuge cup at the same flow rate based on the second channel of the two-way pump, thereby forming a stable continuous flow in the centrifuge cup and related pipelines.

[0065] This stable continuous flow allows the cell concentrate to be pumped into the centrifuge cup at a steady and uniform rate, while the supernatant, after cell separation, is simultaneously discharged from the centrifuge cup. This eliminates the need to rely on a pressure differential within the centrifuge cup to pump the cell concentrate, as is the case with existing systems.

[0066] This allows the cell stock solution to enter the centrifuge cup continuously, stably, and at a uniform speed, allowing the cells in the cell stock solution to cling to the cup wall under the influence of centrifugal force for ample time, achieving separation of the cells from the supernatant. This also prevents the cell stock solution from being directly flushed out of the centrifuge cup due to unstable flow rate or sudden excessive flow rate when entering the centrifuge cup, thus causing cell loss. Furthermore, it effectively prevents the cell stock solution from being squeezed by the pressure differential after entering the centrifuge cup, which could cause cell damage or even inactivation.

[0067] In addition, because the distance between the upper opening of the centrifuge cup and the cup wall of the centrifuge cup is relatively close, when the centrifuge drives the centrifuge cup to rotate, the cells in the cell fluid entering through the upper opening are more likely to stick to the cup wall (enter the wall-adherent state) under the action of centrifugal force, and it is relatively more difficult for them to be directly discharged from the centrifuge cup with the cell fluid, thereby effectively reducing the loss of cells and better achieving the separation of cells and supernatant (which can be simply referred to as cell separation). At the same time, after the centrifuge cup undergoes the above-mentioned cell separation, the supernatant separated from the cell fluid can be referred to Figure 4The fluid path shown in the figure discharges the centrifuge cup through the lower opening of the centrifuge cup, achieving concentration of the cell fluid (which can be simply referred to as cell concentration). Because the lower opening of the centrifuge cup is relatively far from the cup wall, the distance between the adherent cells in the centrifuge cup and the discharge opening is longer, making it more difficult for the adherent cells to be discharged from the centrifuge cup along with the liquid, thereby further reducing cell loss.

[0068] Furthermore, when the two-way pump rotates in the second direction, gas can be pumped into the centrifuge cup through the second channel via the lower opening of the centrifuge cup; at the same time, liquid can be discharged from the centrifuge cup through the first channel via the upper opening of the centrifuge cup. Furthermore, because liquid is discharged out of the centrifuge cup through the upper opening of the centrifuge cup, and the upper opening of the centrifuge cup is relatively close to the cup wall, a relatively large amount of liquid can be discharged from the centrifuge cup.

[0069] In addition, by forming a stable continuous flow, a more effective water cooling system can be formed. The stable continuous flow can promptly conduct away the heat generated by the rotation of the centrifuge cup, thereby achieving auxiliary cooling of the centrifuge cup and further reducing cell inactivation due to excessive temperature.

[0070] In some embodiments, see Figure 5 As shown, a first bubble sensor (which may be indicated as P1) may be provided near the second end of the first channel, and a second bubble sensor (which may be indicated as P2) may be provided near the first end of the second channel.

[0071] Specifically, a third bubble sensor (which may be expressed as P3) may be further provided at a position adjacent to the quantitative tube on the eighth pipeline.

[0072] The first bubble sensor can be used to detect whether the fluid passing through the first channel of the two-way pump is gas or liquid. The second bubble sensor can be used to detect whether the fluid passing through the second channel of the two-way pump is gas or liquid. The third bubble sensor can be used to detect whether the fluid flowing out of the metering tube is gas or liquid.

[0073] In some embodiments, a flow rate detector may be provided on the pipeline between the second channel of the two-way pump and the lower opening of the centrifuge cup to detect the velocity of the fluid flowing into the centrifuge cup. The flow rate detector may be electrically connected to the two-way pump.

[0074] Accordingly, the two-way pump can receive and dynamically adjust the rotation speed of the two-way pump according to the flow rate collected by the flow rate detector, so that the fluid can be pumped into the centrifuge cup at an appropriate speed.

[0075] In some embodiments, an angular velocity detector may be provided on the centrifuge cup to detect the angular velocity of the centrifuge cup when rotating with the centrifuge, wherein the angular velocity detector may be electrically connected to the centrifuge.

[0076] Accordingly, the centrifuge can receive and determine the actual rotation speed of the centrifuge cup according to the angular velocity collected by the angular velocity detector, and then adjust the rotation speed of the centrifuge in a targeted manner.

[0077] In some embodiments, see Figure 5 As shown, the above-mentioned cell separation and harvesting system may further include a refrigerated centrifuge chamber;

[0078] The refrigerated centrifugal chamber may be connected to a refrigeration module; a temperature sensor may be provided in the refrigerated centrifugal chamber; and the centrifugal cup may be provided in the refrigerated centrifugal chamber.

[0079] Specifically, the refrigeration module can intelligently control the temperature inside the refrigerated centrifuge chamber so that the cells in the centrifuge cup are within a stable and appropriate threshold temperature range, thereby preventing the cells from being inactivated due to excessively high temperatures.

[0080] The threshold temperature range may be greater than or equal to 2 degrees Celsius and less than or equal to 8 degrees Celsius.

[0081] Based on the above structure, during the separation and concentration stage, the cells in the centrifuge cup can be cooled in time by the refrigerated centrifuge chamber so that the cells in the centrifuge cup are always within the appropriate threshold temperature range, avoiding damage or even inactivation of the cells in the centrifuge cup due to excessive temperature.

[0082] For details, see Figure 6 As shown, a temperature sensor may be further provided in the refrigerated centrifugal chamber for detecting the temperature in the refrigerated centrifugal chamber in real time.

[0083] The temperature sensor may be electrically connected to the refrigeration module.

[0084] In specific implementation, the refrigeration module can intelligently and dynamically adjust the refrigeration power according to the temperature data collected by the temperature sensor, and effectively maintain the temperature of the centrifuge cup in the refrigerated centrifuge chamber within a suitable threshold temperature range.

[0085] In some embodiments, in order to cooperate with the above-mentioned cell separation and harvesting system and better complete operations such as separation, concentration, and washing, the structure of the centrifuge cup is further improved. For details, please refer to Figure 7 shown.

[0086] Specifically, the centrifugal cup may include at least: a cup body, and structures such as a connecting component arranged above the cup body;

[0087] Wherein, the connecting component may be provided with at least a first interface, a second interface, a first flow channel, a second flow channel, etc.;

[0088] The cup body may be provided with at least an upper flow channel, a lower flow channel, a central axis flow channel, an upper opening, a lower opening, etc.;

[0089] The first interface can be connected to the first flow channel, and the first interface can be specifically used to connect to the first channel. The first flow channel can be connected to the upper port through the upper flow channel;

[0090] The second interface can be connected to the second flow channel. The second interface can be specifically used to connect to the second channel. The second flow channel can be connected to the lower port through the central axis flow channel and the lower flow channel in sequence.

[0091] For details, please refer to Figure 7 As shown, the above-mentioned connecting component can be specifically provided with a dual-channel F-type connector, wherein one connector serves as a first interface and is communicated with a first flow channel provided inside the connecting component, and the other connector serves as a second interface and is communicated with a second flow channel provided inside the connecting component.

[0092] For details, please refer to Figure 7 As shown, an upper flow channel can be provided near the top of the centrifuge cup body; the upper flow channel is connected to the first flow channel. An upper opening is formed on the upper flow channel at a position close to the cup wall. In a specific implementation, fluid outside the centrifuge cup can enter the centrifuge cup through the first opening, pass through the first flow channel, and then flow through the upper flow channel along the cup wall to the cup bottom.

[0093] A lower flow channel may be provided near the bottom of the cup body of the centrifugal cup; wherein a lower opening is provided on the lower flow channel at a position farther from the cup wall. The distance between the lower opening and the cup wall (for example, it may be noted as L2) is greater than the distance between the upper opening and the cup wall (for example, it may be noted as L1). In addition, a central axis flow channel is provided close to the bottom of the cup body and along the central axis of the cup body. wherein the central axis flow channel is connected to the lower flow channel and is also connected to the second flow channel. in a specific implementation, the fluid at the bottom of the centrifugal cup may flow into the lower flow channel through the lower opening, and then along the central axis flow channel, enter the second flow channel, and flow out of the centrifugal cup through the second interface.

[0094] In some embodiments, a guide platform (eg, a T-shaped guide platform) may be further provided at the intersection of the first flow channel and the upper flow channel.

[0095] Furthermore, a large sealing ring can be provided near the upper part of the guide table; a small sealing ring can be provided near the lower part of the guide table; in addition, a bearing or other structure can be provided above the large sealing ring to cooperate with the cell separation and harvesting system for high-speed centrifugal rotation.

[0096] Based on the above structure, fluid can be better input into the centrifuge cup and fluid can be discharged from the centrifuge cup.

[0097] Specifically, the centrifuge cup may further include a base, wherein the base may be fixedly mounted on the centrifuge, and the cup body may be mounted on the base.

[0098] In specific operation, based on the aforementioned centrifuge cup, when rotating in conjunction with the cell separation and harvesting system, fluid enters the centrifuge cup through the first port and flows through the upper flow channel from the upper opening along the cup wall to the bottom of the cup. Because the upper opening is relatively close to the cup wall, centrifugal force allows cells to adhere to the cup wall more easily during the separation and concentration phase, resulting in a significantly greater number of cells being separated. Simultaneously, the separated supernatant flows along the cup wall into the cup body, enters the lower flow channel through the lower opening, and then exits the centrifuge cup through the second port, sequentially passing through the central axial flow channel and the second flow channel.

[0099] When fluid flows from the upper opening, through the upper flow channel and the first flow channel in sequence, and out of the centrifuge cup from the first interface, since the distance between the upper opening and the cup wall is relatively close, relatively more cleaning liquid can be discharged from the centrifuge cup during the cleaning stage.

[0100] Specifically, for example, assuming that the radius of the cup body is R, the height is H, the distance between the upper opening and the cup wall is L1, and the distance between the lower opening and the cup wall is L2.

[0101] If the liquid is discharged through the lower port, the remaining liquid volume in the cup can be expressed as: V 下 =π(2RL2-L2 2 )H.

[0102] On the contrary, if the liquid is discharged through the upper mouth, the volume of the remaining liquid in the cup can be expressed as: V 上 =π(2RL1-L1 2 )H.

[0103] Since L1 is smaller than L2, V 下 >V 上 .

[0104] It can be seen that based on the above centrifuge cup, the degree of liquid discharge from the centrifuge cup can be flexibly adjusted by adjusting the interface used when discharging the liquid in conjunction with the cell separation and harvesting system according to specific circumstances and processing requirements.

[0105] In some embodiments, see Figure 8 As shown, the cell separation and harvesting system may further include a constant temperature box; wherein the sub-packaging bags are placed in the constant temperature box.

[0106] Specifically, the thermostat can be connected to a refrigeration module. The refrigeration module controls the temperature within the thermostat to maintain it within a threshold temperature range. This effectively protects the target solution in the packaging bag and prevents the cells in the target solution from being inactivated due to excessive temperature.

[0107] In some embodiments, depending on specific application scenarios and processing requirements, the second end of the first channel may be further connected to a first extension pipeline; the second end of the second channel may be further connected to a second extension pipeline.

[0108] The first extension pipeline and the second extension pipeline can be connected to matching fluid bags according to actual needs, and this specification does not limit this.

[0109] In some embodiments, the cell separation and harvesting system may further include a processor. The processor may be electrically connected to the solenoid valves, bubble sensors, temperature sensors, refrigeration modules, two-way pumps, and centrifuges in the system. In practice, the processor may receive and, based on relevant data collected by the bubble sensors and temperature sensors, intelligently control the corresponding solenoid valves, refrigeration modules, two-way pumps, centrifuges, and the like to automatically complete cell separation and packaging.

[0110] In some embodiments, during specific implementation, the processor can first complete the calibration operation of the two-way pump by controlling the corresponding solenoid valve, using a quantitative tube, a two-way pump, a centrifuge, and other structures. Then, by controlling the corresponding solenoid valve, the two-way pump is used to pump a specified volume of cell stock solution from the cell stock solution bag into the centrifuge cup in the form of a continuous flow to achieve the liquid filling operation; at the same time, the centrifuge is used to rotate the centrifuge cup so that the cells in the cell stock solution enter a wall-adherent state under the action of centrifugal force, cling to the cup wall, and separate from the supernatant, thereby achieving the separation operation; and the two-way pump is also used to synchronously discharge the separated supernatant from the centrifuge cup and transport it to the waste liquid bag to achieve the concentration operation. Then, by controlling the corresponding solenoid valve, the two-way pump is used to pump the cleaning solution from the cleaning solution bag into the centrifuge cup in the form of a continuous flow to rinse the separated cells, thereby achieving the cleaning operation. Then, by controlling the corresponding solenoid valve, the two-way pump is used to pump the corresponding volume of resuspension solution from the resuspension solution bag into the centrifuge cup to mix and dissolve the separated cells, thereby achieving the resuspension operation. Finally, by controlling the corresponding solenoid valve, a two-way pump is used to transport the target liquid containing cells in the centrifuge cup to the sub-packaging bag to realize the sub-packaging operation and complete the separation and sub-packaging of the cells.

[0111] In some embodiments, see Figure 9 As shown, the above-mentioned cell separation and harvesting system may further include a body (or fuselage).

[0112] A first fluid bag bracket and a second fluid bag bracket are provided on the body;

[0113] Among them, the first liquid bag bracket is used to hang the cell raw liquid bag and the cleaning liquid bag; the second liquid bag bracket is used to hang the waste liquid bag, the resuspension liquid bag, and the sub-packaging bag.

[0114] The first liquid bag support may be arranged on the right side of the machine body, and the second liquid bag support may be arranged on the left side of the machine body.

[0115] Based on the above structure, the corresponding liquid bag can be conveniently and firmly mounted to complete specific cell separation and harvesting.

[0116] In some embodiments, an operation panel may be further provided on the body;

[0117] The operation panel is provided with a plurality of control knobs, and the plurality of control knobs are respectively associated with the first solenoid valve, the second solenoid valve, the third solenoid valve, the fourth solenoid valve, the fifth solenoid valve, the sixth solenoid valve, and the seventh solenoid valve.

[0118] Specifically, the plurality of control knobs are electrically connected to the first solenoid valve, the second solenoid valve, the third solenoid valve, the fourth solenoid valve, the fifth solenoid valve, the sixth solenoid valve, and the seventh solenoid valve, respectively. When operating, the user can control the solenoid valve associated with the control knob by rotating the corresponding control knob.

[0119] In specific implementation, the user can control the above-mentioned cell separation and harvesting system through the control knob on the operation panel, and perform operations such as calibration, separation, concentration, cleaning, and packaging in sequence to complete the separation and harvesting of cells.

[0120] It should also be pointed out that, compared with conventional system equipment, the cell separation and harvesting system of the above structure can not only realize a more comprehensive variety of functional operations such as calibration, liquid filling, separation, concentration, cleaning, and packaging; it also effectively simplifies the overall structural layout, making the structural layout relatively simpler and clearer, making it easier for users to understand the operation, and while reducing the difficulty of user operation, it helps to reduce the equipment cost of the system.

[0121] Alternatively, the operation panel may be a touch screen; wherein the touch screen may display icons associated with the first solenoid valve, the second solenoid valve, the third solenoid valve, the fourth solenoid valve, the fifth solenoid valve, the sixth solenoid valve, and the seventh solenoid valve, respectively.

[0122] Accordingly, in a specific implementation, the user can control the associated solenoid valve accordingly by touching the relevant icon on the touch screen.

[0123] Specifically, compared with conventional system equipment, the total number of solenoid valves in the above-mentioned cell separation and harvesting system has been reduced from 14 to 7, the number of air filter valves has been reduced from 2 to 1, and the total length of the pipeline has been reduced from 600 cm to 370 cm; the liquid circuit logic is relatively clearer, which is convenient for observation and monitoring during operation; at the same time, it also effectively simplifies the installation of sterile consumables pipelines, greatly reduces the difficulty of operation, reduces human errors caused by complex pipelines, and improves the efficiency and stability of automated cell processing.

[0124] The cell separation and harvesting system provided in this specification comprises at least: a two-way pump, a centrifuge cup, a centrifuge, a quantitative tube, and an air filter valve; wherein the two-way pump comprises a first channel and a second channel; and the hose provided in the first channel has the same size as the hose provided in the second channel; the first end of the first channel is connected to the upper opening of the centrifuge cup, and the second end of the first channel is connected to at least the first pipeline, the second pipeline, and the third pipeline; wherein the first pipeline is used to connect the cell stock solution bag, the second pipeline is used to connect the cleaning solution bag, and the third pipeline is connected to the quantitative tube; the first end of the second channel is connected to the lower opening of the centrifuge cup, and the second end of the second channel is connected to at least the fourth pipeline, the fifth pipeline, the sixth pipeline, and the seventh pipeline The invention relates to a cell separation and harvesting system comprising a first circuit, a second circuit and a second circuit; a first ...

[0125] In some embodiments, during specific implementation, the above-mentioned cell separation and harvesting system can be used to complete corresponding cell separation and harvesting in the following manner: according to a preset calibration rule, the two-way pump is calibrated by controlling the second solenoid valve, the seventh solenoid valve, the fourth solenoid valve, and the two-way pump to determine the hose coefficient of the two-way pump; wherein the hose coefficient is used to characterize the volume of fluid transported by the two-way pump during one rotation; according to a preset separation and concentration rule, based on the hose coefficient of the two-way pump, the first volume of cell stock solution is pumped from the cell stock solution bag into the centrifuge cup in the form of a continuous flow by controlling the first solenoid valve and the two-way pump; at the same time, the cell stock solution in the centrifuge cup is separated into cells and supernatant by controlling the centrifuge, the two-way pump, and the seventh solenoid valve. The supernatant is transferred from the centrifuge cup to the waste liquid bag in the form of a continuous flow; according to the preset cleaning rules, the cleaning liquid is pumped into the centrifuge cup in the form of a continuous flow by controlling the second solenoid valve and the two-way pump to clean the supernatant on the cells; at the same time, the cleaning liquid after cleaning is transferred from the centrifuge cup to the waste liquid bag in the form of a continuous flow by controlling the two-way pump and the seventh solenoid valve; according to the preset resuspension rules, based on the hose coefficient of the two-way pump, the sixth solenoid valve, the two-way pump, and the third solenoid valve are controlled to resuspend the washed cells in the centrifuge cup; according to the preset packaging rules, based on the hose coefficient of the two-way pump, the fifth solenoid valve, the two-way pump, and the third solenoid valve are controlled to transport the target liquid containing cells in the centrifuge cup to the packaging bag.

[0126] Based on the above embodiments, the structural characteristics of the above cell separation and harvesting system can be fully utilized according to the corresponding rules to perform calibration, separation, concentration, washing, resuspension, packaging and other operations in sequence to efficiently complete the separation and harvesting of cells and obtain high-quality cell products.

[0127] In some embodiments, before specific implementation, you can refer to Figure 1 The structural diagram of the cell separation and harvesting system shown in the figure determines the configuration parameters of the relevant liquid bags, pipelines, solenoid valves, etc. according to the specific application scenario and separation and packaging requirements. Then, based on the above system configuration parameters, fully enclosed disposable consumables are used in conjunction with sterile pipe connection machines, heat sealers and other equipment to connect them in sequence and build a cell separation and harvesting system that meets the requirements.

[0128] Specifically, you can first determine the required cell stock liquid bags, cleaning liquid bags, resuspension liquid bags, waste liquid bags, and sub-packaging bags. Then connect the above-mentioned liquid bags to the corresponding sterile fully enclosed disposable consumables pipelines in sequence, and according to the installation prompt information, install the above-mentioned fully enclosed disposable consumables pipelines in the corresponding solenoid valve opening sequence to obtain the required cell separation and harvesting system. Specifically, you can first open the first solenoid valve to combine the cell stock liquid bag and the corresponding pipeline; open the second solenoid valve to combine the cleaning liquid bag and the corresponding pipeline; open the third solenoid valve and the fourth solenoid valve to combine the quantitative tube, the air filter valve and the corresponding pipeline; open the fifth solenoid valve to combine the sub-packaging bag and the corresponding pipeline; open the sixth solenoid valve to combine the resuspension liquid bag and the corresponding pipeline; open the seventh solenoid valve to combine the waste liquid bag and the corresponding pipeline. Then start the two-way pump, install the hose of the first channel and the hose of the second channel according to the installation label; and fix the centrifuge cup to the centrifuge, and ensure that the centrifuge cup is installed stably. Then use a sterile pipe connection machine to connect each liquid bag to the corresponding consumables pipeline in the specified order. From right to left, the liquid bags corresponding to the solenoid valves are: cell stock liquid bag, cleaning liquid bag, filling bag (empty), resuspension liquid bag, and waste liquid bag (empty).

[0129] The consumables piping can be fully enclosed, disposable, and sterilized with ethylene oxide. The consumables also include centrifuge cups. The entire installation process is isolated from the outside world, and the fluid bag is connected using a sterile pipe connection machine to prevent the piping from coming into contact with the outside world.

[0130] In some embodiments, the above-mentioned calibration is performed on the two-way pump by controlling the second solenoid valve, the seventh solenoid valve, the fourth solenoid valve, and the two-way pump according to a preset calibration rule to determine the hose coefficient of the two-way pump. When specifically implemented, the following contents may be included: according to the preset calibration rule, the second solenoid valve and the seventh solenoid valve are opened; and the two-way pump and the centrifuge are started; the two-way pump is controlled to rotate in a first direction to pump a second volume of cleaning liquid into the centrifuge cup along the second pipeline as a calibration liquid; and the centrifuge is stopped; wherein the second volume is greater than the volume of the quantitative tube; the two-way pump is controlled to rotate in the first direction , transfer the calibration liquid in the centrifuge cup along the seventh pipeline to the waste liquid bag; and monitor whether the calibration liquid reaches the seventh solenoid valve; when it is monitored that the calibration liquid reaches the seventh solenoid valve, close the seventh solenoid valve and open the fourth solenoid valve; control the two-way pump to rotate in the first direction, and transfer the calibration liquid in the centrifuge cup along the fourth pipeline to the quantitative tube; and monitor the detection value of the third bubble sensor; when the detection value of the third bubble sensor indicates that liquid is detected, stop the operation of the two-way pump; and obtain the number of rotations of the two-way pump; determine the hose coefficient of the two-way pump according to the volume of the quantitative tube and the number of rotations of the two-way pump.

[0131] The first direction may specifically be a direction of flowing in from the first channel and flowing out from the second channel.

[0132] The second direction may specifically be a direction of flowing in from the second channel and flowing out from the first channel.

[0133] The various embodiments in this specification are described in a progressive manner. Similar or identical parts between the various embodiments can be referenced across them. Each embodiment focuses on the differences from other embodiments. In particular, the system embodiments are generally similar to the related embodiments, so the description is relatively simple. For relevant parts, reference can be made to the description of the related embodiments. Throughout this specification, reference to the terms "one embodiment," "some embodiments," "example," "specific example," or "some examples" means that the specific features, structures, materials, or characteristics described in conjunction with that embodiment or example are included in at least one embodiment or example of the embodiments in this specification. In this specification, the schematic representations of these terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, those skilled in the art may combine and integrate the different embodiments or examples, and features of different embodiments or examples, described in this specification, without conflict.

[0134] The above description is merely an example of the embodiments of this specification and is not intended to limit the embodiments of this specification. For those skilled in the art, various modifications and variations of the embodiments of this specification are possible. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the embodiments of this specification shall be included within the scope of the claims of the embodiments of this specification.

Claims

1. A cell separation and harvesting system, characterized in that: At least: Two-way pump, centrifugal cup, centrifuge, quantitative tube, air filter valve; among them, The two-way pump includes a first channel and a second channel; and the hose provided in the first channel and the hose provided in the second channel have the same size; The first end of the first channel is connected to the upper opening of the centrifuge cup, and the second end of the first channel is connected to at least a first pipeline, a second pipeline, and a third pipeline; wherein the first pipeline is used to connect to the cell stock solution bag, the second pipeline is used to connect to the cleaning solution bag, and the third pipeline is connected to the quantitative tube; The first end of the second channel is connected to the lower opening of the centrifuge cup, and the second end of the second channel is connected to at least a fourth pipeline, a fifth pipeline, a sixth pipeline, and a seventh pipeline; wherein the fourth pipeline is connected to the quantitative tube, the fifth pipeline is used to connect to the sub-packaging bag, the sixth pipeline is used to connect to the resuspension bag, and the seventh pipeline is used to connect to the waste liquid bag; the distance between the upper opening of the centrifuge cup and the adjacent cup wall is smaller than the distance between the lower opening of the centrifuge cup and the adjacent cup wall; The quantitative tube is also connected to the air filter valve through an eighth pipeline; the centrifugal cup is arranged on the centrifuge; In addition, a first solenoid valve is provided on the first pipeline, a second solenoid valve is provided on the second pipeline, a third solenoid valve is provided on the third pipeline, a fourth solenoid valve is provided on the fourth pipeline, a fifth solenoid valve is provided on the fifth pipeline, a sixth solenoid valve is provided on the sixth pipeline, and a seventh solenoid valve is provided on the seventh pipeline.

2. The cell separation and harvesting system according to claim 1, characterized in that: A first bubble sensor is disposed adjacent to the second end of the first passage, and a second bubble sensor is disposed adjacent to the first end of the second passage.

3. The cell separation and harvesting system according to claim 1, characterized in that A third bubble sensor is provided on the eighth pipeline at a position adjacent to the quantitative tube.

4. The cell separation and harvesting system according to claim 1, characterized in that The centrifugal cup at least includes: a cup body, and a connecting component arranged above the cup body; Wherein, the connecting component is provided with at least a first interface, a second interface, a first flow channel, and a second flow channel; The cup body is provided with at least an upper flow channel, a lower flow channel, a central axis flow channel, an upper opening and a lower opening; Wherein, the first interface is connected to the first flow channel, the first interface is used to connect to the first channel, and the first flow channel is connected to the upper port through the upper flow channel; The second interface is connected to the second flow channel, and the second interface is used to connect to the second channel. The second flow channel is connected to the lower port through the central axis flow channel and the lower flow channel.

5. The cell separation and harvesting system according to claim 4, characterized in that: A flow guide platform is provided at the intersection of the first flow channel and the upper flow channel.

6. The cell separation and harvesting system according to claim 1, characterized in that: Also included is a refrigerated centrifugal chamber; Wherein, the refrigerated centrifugal chamber is connected to a refrigeration module; a temperature sensor is also provided in the refrigerated centrifugal chamber; and the centrifugal cup is provided in the refrigerated centrifugal chamber.

7. The cell separation and harvesting system according to claim 1, characterized in that: It also includes a body, on which a first fluid bag support and a second fluid bag support are provided; Among them, the first liquid bag bracket is used to hang the cell raw liquid bag and the cleaning liquid bag; the second liquid bag bracket is used to hang the waste liquid bag, the resuspension liquid bag, and the sub-packaging bag.

8. The cell separation and harvesting system according to claim 7, characterized in that: An operation panel is also provided on the machine body; The operation panel is provided with a plurality of control knobs, and the plurality of control knobs are respectively associated with the first solenoid valve, the second solenoid valve, the third solenoid valve, the fourth solenoid valve, the fifth solenoid valve, the sixth solenoid valve, and the seventh solenoid valve; Alternatively, the operation panel is a touch screen, and icons respectively associated with the first solenoid valve, the second solenoid valve, the third solenoid valve, the fourth solenoid valve, the fifth solenoid valve, the sixth solenoid valve, and the seventh solenoid valve are displayed on the touch screen.

9. The cell separation and harvesting system according to claim 7, characterized in that: A liquid bag hook is also provided on the side wall of the machine body for hanging spare sub-packaging bags and / or spare waste liquid bags.

10. The cell separation and harvesting system according to claim 1, characterized in that: The second end of the first channel is further connected to a first expansion pipeline; the second end of the second channel is further connected to a second expansion pipeline.

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